15.3C: The Heartbeat - Biology

15.3C: The Heartbeat - Biology

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During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.

The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.

The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.

When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles. The contraction of the heart in response to this electrical activity creates systole. A period of recovery follows called diastole.

  • The heart muscle and S-A node become recharged.
  • The heart muscle relaxes.
  • The atria refill.

The Electrocardiogram

The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG.

Ventricular Fibrillation

The ventricles can maintain a beat even without a functioning A-V node, although the beat is slower. There is, however, a danger that impulses arising in the ventricles may become disorganized and random. If this happens, they begin to twitch spasmodically, a condition called ventricular fibrillation. Blood flow ceases and unless the heart rhythm is restarted, death follows swiftly. In fact, ventricular fibrillation is the immediate cause of as much as 25% of all deaths.

Hospital emergency rooms, ambulances, commercial air craft and many other public places are now equipped with defibrillators which, by giving the heart a jolt of direct current, may restore its natural rhythm and save the victim's life.

Artificial Pacemakers

These are devices that generate rhythmic impulses that are transmitted to the heart by fine wires. Thanks to miniaturization and long-lived batteries, pacemakers can be implanted just under the skin and reached through a small incision when maintenance is needed.

Auxiliary Control of the Heart

Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.

  • One sends nerve impulses down accelerans nerves.
  • The other sends nerve impulses down a pair of vagus nerves

The Accelerans Nerve

The accelerans nerve is part of the sympathetic branch of the autonomic nervous system, and like all post-ganglionic sympathetic neurons releases noradrenaline at its endings on the heart. It increases the rate and strength of the heartbeat and thus increase the flow of blood. Its activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25–30 liters/minute.


The 24 Feb 2000 issue of the New England Journal of Medicine reports on a family some of whose members have inherited a mutant gene for the transporter that is responsible for reuptake of noradrenaline back into the neuron that released it. Those with the mutation are prone to bouts of rapid heartbeat and fainting when they suddenly stand up.

Vigorous exercise accelerates heartbeat in two ways:

  • As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay by the accelerans nerve to the heart.
  • As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.

Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure.

The Vagus Nerves

The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat. Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these by way of the vagus nerves to the heart. Heartbeat and blood pressure diminish.

MicroRNA in cardiovascular biology and disease

MicroRNAs (miRNAs) are members of a non-coding RNA family. They act as negative regulators of protein translation by affecting messenger RNA (mRNA) stability they modulate numerous signaling pathways and cellular processes, and are involved in cell-to-cell communication. Thus, studies on miRNAs offer an opportunity to improve our understanding of complex biological mechanisms. In the cardiovascular system, miRNAs control functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of disorders like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into circulation. Manipulation of miRNA activity may influence the course of a disease. Therefore, miRNAs have become an active field of research for developing new diagnostic and therapeutic tools. This review discusses emerging functions of miRNAs in cardiogenesis, heart regeneration and the pathophysiology of cardiovascular diseases.

Keywords: cardiovascular disease heart development heart regeneration microRNA.



Blowflies Calliphora vicina Robineau-Desvoidy 1830 were obtained and used directly from the field or their offspring larvae were reared on decomposing chicken meat or liver. After capture or eclosion, the flies were kept in a tissue-covered cylindrical flight cage (45×60 cm, diameter×height). They could feed ad libitum on a mixture of honey, soft cheese and water. The reared flies were not used for experiments before the full development of flight muscles (Auber, 1969), at approximately 5 days to 1 month old. The measurements lasted several days. Only data from flies that survived the experiments in a vital condition were considered. They only exhibited clear resting rhythms after careful treatment during preparation, especially after the insertion of electrodes and dorsal punctures for pressure measurements. The tethered flies willingly seized a Styrofoam ball, which allowed them to run and to groom. During tethered flight they lost the ball, but could recapture it from a dish-like support below the fly. Between the experimental runs, the flies received water and food on the running ball. Most flies could be released after the experiments with the punctures sealed by a layer of Fixogum rubber cement (Marabu, Tamm, Germany). Before and after the experiments, the mass of the flies was determined. In both sexes the mass depended on feeding status. In females this was approximately 50 to 125 mg, depending also on the maturation stage of eggs. The males had a lower mass of approximately 45 to 90 mg. The mean (±s.d.) mass of F1 offspring was 66±21 mg (N=26). Males were more difficult to equip with sensors because of their smaller size. Therefore, females were preferred in the experiments (supplementary material Tables S1-S3). Moreover, the largest flies were females from the field, which had entered the house (mean ± s.d. mass=87±25 mg, N=23).

Recording of heartbeat by thermistors

Thermistors allow the measurement of pulses of the tubular heart below the intact body surface without fixing the insect in a stationary setup. The method utilises the effects of natural or artificial thermal gradients on unheated thermistors (T-method) (Wasserthal, 1980) or convective/conductive effects on slightly heated thermistors (C-method). For measurements of heat-marked heart pulses, Veco micro-thermistors (2 kΩ at 25°C, diameter 0.1 mm Victory Engineering Corp., Springfield, NJ, USA) were attached with surgical tape to the cuticle of abdominal tergite 3 or 4 above the corresponding heart segments. With the thermistor at ambient temperature, the pulse direction was clearly recognised when the hemolymph of the thorax was raised by a change in temperature (ΔT) of 1.5 to 2.5°C using a soldering bit, which at the same time served to fix the fly at the mesonotum. Backward (retrograde) pulses transported heat to the abdominal heart (Fig. 1A). As an alternative method, heat was applied by a laser beam (5 mW He-Ne Laser, heating the hemolymph by a ΔT of 1.5 to 2°C anteriorly, between or behind the measuring thermistors (Fig. 2). Alternatively, in the C-method, the thermistors were heated by a ΔT of 1.7 to 1.8°C supplying the Wheatstone bridge current with a higher voltage (1.5 V instead of 0.25 V as in the T-method). This allowed the visualisation of heart pulses and local hemolymph accumulation by their convective and conductive effects. As a disadvantage of the C-method, the single pulses tended to disappear in the steep changes in temperature. The pulses were, however, visualised using a band-pass filter, which suppressed events slower than 0.5 Hz and noise above 20 Hz. Using this procedure, the pulse rates were analysed on a broad data basis (Table 1, supplementary material Table S1). Data were evaluated from fully resting flies at a mean temperature of 21°C, without phases of grooming, feeding or running. The interpretation of the temperature effects on this C-method has been tested in physical simulation experiments (Wasserthal, 1980). This non-invasive method has been introduced in connection with records of moth hearts and pulsatile organs (Wasserthal, 1976) and has been reviewed (Miller, 1979). It has already been successfully applied in Lepidoptera, Coleoptera, Hymenoptera and Diptera (Wasserthal, 1982b Wasserthal, 1996 Wasserthal, 1999 Hetz et al., 1999 Lubischer et al., 1999 Slama and Miller, 2001). This method allowed the thermistors to be mounted without anaesthesia and was preferred as a reference recording in combination with other techniques.

Heartbeat frequency and duration of sequences, pulse periods and pauses in Calliphora vicina

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(A) Setup for parallel recording of heartbeat and abdominal movements. A thermistor at the third tergite under heat marking of the thoracic hemolymph by a soldering bit records the pulse direction. Two infrared reflex coupler devices (RCDs) register the changes in distance to the microprismatic reflector foils (RFs) caused by abdominal movements. Sensors and reflectors are not to scale. (B) Cross-section of the anterior mesothorax with the position of the outlet to the hemolymph pressure sensor. (C) Cross-section of the posterior mesothorax with the outlet to the tracheal air pressure sensor. DLM, dorsal longitudinal muscle DVM, dorso-ventral muscle.

(A) Setup for parallel recording of heartbeat and abdominal movements. A thermistor at the third tergite under heat marking of the thoracic hemolymph by a soldering bit records the pulse direction. Two infrared reflex coupler devices (RCDs) register the changes in distance to the microprismatic reflector foils (RFs) caused by abdominal movements. Sensors and reflectors are not to scale. (B) Cross-section of the anterior mesothorax with the position of the outlet to the hemolymph pressure sensor. (C) Cross-section of the posterior mesothorax with the outlet to the tracheal air pressure sensor. DLM, dorsal longitudinal muscle DVM, dorso-ventral muscle.

Extracellular electrical resistance measurements

As a more direct measurement of heartbeat, paired steel electrodes were placed on the left and right side of the anterior heart chamber-pericardial complex and at the fourth heart segment. The changes in electrical resistance, which were recorded, resulted from alterations in the distance between the heart muscle and the recording electrode and from changes in the electrical conductance across the dorsal vessel. Contraction of the heart (=systole) resulted in a negative peak. The V2A-steel electrodes were 20 μm in diameter and their insertion through the inter-segmental fold directly beside the heart tube produced no lasting damage. Although the immediate contact of the recording electrode to the heart was essential, the reference electrode was implanted at a greater distance, usually 1 to 2 mm from the recording electrode. The electrical signal was low-pass-filtered by 20 Hz and amplified with a custom-made amplifier. This minimally invasive technique was also used to verify the data obtained by the more cautious thermistor method and was found to be superior for recording pulse velocity. This method has been introduced under the name ‘impedance conversion measurement’ and has been used successfully to record heart pulses in hawkmoths and bumble bees (Heinrich and Bartholomew, 1971 Heinrich, 1976) (for details, see Miller, 1979).

Periodic heartbeat reversal in Calliphora vicina recorded with thermistors (T-method) above heart segments 3 and 4, and local heating by a laser beam. (A) Heating at the metathorax shorter pulse periods at the third and fourth segments exhibit warming pulses. (B) Heating between the thermistors temperatures of the anterior and posterior thermistor sites are inverse. (C) Heating at the fifth abdominal tergite longer pulse periods exhibit warming pulses, and hence are forwards (white bars), whereas shorter ones are backwards (black bars).

Periodic heartbeat reversal in Calliphora vicina recorded with thermistors (T-method) above heart segments 3 and 4, and local heating by a laser beam. (A) Heating at the metathorax shorter pulse periods at the third and fourth segments exhibit warming pulses. (B) Heating between the thermistors temperatures of the anterior and posterior thermistor sites are inverse. (C) Heating at the fifth abdominal tergite longer pulse periods exhibit warming pulses, and hence are forwards (white bars), whereas shorter ones are backwards (black bars).

Recording of abdominal movements

Abdominal movements were video recorded from the lateral view (Canon EX1, Ohta-ku, Tokyo, Japan) at 25 frames s -1 , and then transformed into time-lapse movies with 18× acceleration using ImageJ software (National Institutes of Health, Bethesda, MD, USA) (supplementary material Movie 1). In addition, positional changes of the third abdominal tergites and sternites were measured using position-sensitive infrared (IR) reflex coupling devices (RCDs (Fig. 1A). The IR beam was reflected by a microprismatic reflection foil (3M Scotchlite 5870, St Paul, MN, USA). The reflection foil was not attached directly to the sclerites but 20 mm behind the abdomen on the thermistor wires and to another wire glued to the sternite. The RCDs were installed with micromanipulators opposite the reflex foils. The operating distance range between the RCD and the reflecting foil was between 2.5 and 3.5 mm. A step of 1 μm corresponded to a 50 mV sensor output. However, because the movement of the tergites and sternites was not simply an up and down movement but rather an inclination, the angle with which the fine copper wire with the fixed reflection foil moved towards or away from the RCD was used to scale the ordinate (in degrees). By application of the foil on the thread, the lever effect offered the advantage of a mechanical amplification of sclerite movements. In some individuals, activity of the thoracic spiracular valves was observed with a binocular microscope after removal of the filter structures or recorded with a digital camera (Canon 60D).

Hemolymph pressure measurements

Hemolymph pressure was recorded in the dorsal hemocoel below the mesoscutum (Fig. 1B) and dorso-laterally below the fourth tergite of the abdomen. The notal cuticle was perforated in CO2-narcotised flies and connected to a pressure transducer (Capto SP 844, 3193 Horten, Norway sensitivity: Δ1 mV=26.5 Pa). A metal or plastic cylinder glued to the punctured cuticle allowed the insertion and adjustment of the tip of the syringe needle of the sensor setup in the insect. To facilitate abdominal movements, the syringe was connected to a flexible plastic tube. The pressure sensor was attached by a plastic dome to a 1 ml syringe containing saline (Ephrussi and Beadle, 1936). Saline was needed to transmit the hemolymph pressure to the sensor and to avoid air bubbles. An eventual excess of saline, which increased hemolymph pressure, was always reduced by the flies within the next 2 to 9 h by the observed excretion of fluid. The influence of the hemolymph volume increase on the pressure curves and heartbeat periodicity was tested by application of 10 or 20 μl saline laterally on the abdomen. By puncturing the intersegmental membrane, the droplet was sucked in. The flies always restored the original negative hemocoelic pressure by diuresis, as normally occurs after eclosion and wing inflation (Cottrell, 1962). The hemolymph pressure data were calibrated using a mechanical barometer PMK04 A109 -2.5 to +1.5 kPa (PKP Prozess Messtechnik, Wiesbaden, Germany). The delay between mechanically applied pulses and the pressure response was below 1 ms for hemolymph pressure.

Measurements of intratracheal pressure

The intratracheal pressure was measured within the (meso)scutellar and abdominal air sacs. The cuticle was perforated and the air sac directly adhering to the inner cuticle was punctured (Fig. 1C). This procedure was performed after a few minutes of CO2 anaesthesia to avoid damage and loss of hemolymph. The flies recuperated within minutes and spent up to the next 3 h grooming. The resting heartbeat or pressure cycles became obvious only when not obscured by motion effects. The resulting dorsal ‘artificial spiracle’ was tightly connected to a plastic cone (tip of an Eppendorf pipette with inner diameter of 1.6 mm, outer diameter of 2.3 mm) with Pattex glue (Henkel, Düsseldorf, Germany). The cone served as a holder. One or two polyethylene tubes (1 mm external diameter and 0.5 mm internal diameter) were inserted into the cone. The space around these tubes was tightly sealed using Fixogum. The adapter cone allowed the fly to be connected to the pressure sensor (Sensym SCXL 004 DN, Sensortechniques, Puchheim, Germany). The dead space of the external system of the pressure sensing system with a connecting tube of 48-81 mm length was approximately 10-16 μl. These differences in tube length had no measurable effect (delay or dampening of signal) when changing from shorter to longer tubes. The intratracheal pressure data were calibrated using an electronic calibration manometer (total scale ±1 kPa, Manocal P, Besançon, France). The delay between mechanically applied pulses and the pressure response was approximately 1 ms for air pressure.

Data acquisition and analyses

Data were continuously recorded on an Apple PowerMac or PowerBook (Apple, Cupertino, CA, USA) using a custom-made amplifier and a PowerLab AD-Interface with Chart 5.54 software (CB Sciences, Milford, MA, USA). The sampling rate was 200 Hz. A software-integrated low-pass input filter was used to minimise noise in the electrophysiological measurements. An integrated band-pass filter allowed me to resolve pulses in the temperature recordings. A Student's t-test was used to determine the significance between means of the duration of forward and backward pulse periods, heartbeat frequency, hemolymph pressure amplitude, intratracheal pressure and the delay between the heart pulse and tracheal pressure pulse. The linear regression curves in supplementary material Fig. S1 were calculated using Excel (Microsoft Corporation, Redmond, WA, USA).


Normal heart sounds are associated with heart valves closing:

S1 Edit

The first heart sound, or S1, forms the "lub" of "lub-dub" and is composed of components M1 (mitral valve closure) and T1 (tricuspid valve closure). Normally M1 precedes T1 slightly. It is caused by the closure of the atrioventricular valves, i.e. tricuspid and mitral (bicuspid), at the beginning of ventricular contraction, or systole. When the ventricles begin to contract, so do the papillary muscles in each ventricle. The papillary muscles are attached to the cusps or leaflets of the tricuspid and mitral valves via chordae tendineae (heart strings). When the papillary muscles contract, the chordae tendineae become tense and thereby prevent the backflow of blood into the lower pressure environment of the atria. The chordae tendineae act a bit like the strings on a parachute, and allow the leaflets of the valve to balloon up into the atria slightly, but not so much as to evert the cusp edges and allow backflow of blood. It is the pressure created from ventricular contraction that closes the valve, not the papillary muscles themselves. The contraction of the ventricle begins just prior to AV valves closing and prior to the opening of the semilunar valves. The sudden tensing of the chordae tendineae and the squeezing of the ventricles against closed semilunar valves, send blood rushing back toward the atria, and the parachute-like valves catch the rush of blood in their leaflets causing the valve to snap shut. The S1 sound results from reverberation within the blood associated with the sudden block of flow reversal by the valves. The delay of T1 even more than normally causes the split S1 which is heard in a right bundle branch block. [1]

S2 Edit

The second heart sound, or S2, forms the "dub" of "lub-dub" and is composed of components A2 (aortic valve closure) and P2 (pulmonary valve closure). Normally A2 precedes P2 especially during inspiration where a split of S2 can be heard. It is caused by the closure of the semilunar valves (the aortic valve and pulmonary valve) at the end of ventricular systole and the beginning of ventricular diastole. As the left ventricle empties, its pressure falls below the pressure in the aorta. Aortic blood flow quickly reverses back toward the left ventricle, catching the pocket-like cusps of the aortic valve, and is stopped by aortic valve closure. Similarly, as the pressure in the right ventricle falls below the pressure in the pulmonary artery, the pulmonary valve closes. The S2 sound results from reverberation within the blood associated with the sudden block of flow reversal. [2]

Splitting of S2, also known as physiological split, normally occurs during inhalation because the decrease in intrathoracic pressure increases the time needed for pulmonary pressure to exceed that of the right ventricular pressure. A widely split S2 can be associated with several different cardiovascular conditions, and the split is sometimes wide and variable whereas, sometimes wide and fixed. The wide and variable split occurs in Right bundle branch block, pulmonary stenosis, pulmonary hypertension and ventricular septal defects. The wide and fixed splitting of S2 occurs in atrial septal defect. Pulmonary S2 (P2) will be accentuated (loud P2) in pulmonary hypertension and pulmonary embolism. S2 becomes softer in aortic stenosis. [3]

The rarer extra heart sounds form gallop rhythms and are heard in both normal and abnormal situations. [4]

S3 Edit

Rarely, there may be a third heart sound also called a protodiastolic gallop, ventricular gallop, or informally the "Kentucky" gallop as an onomatopoeic reference to the rhythm and stress of S1 followed by S2 and S3 together (S1=Ken S2=tuck S3=y). [5]

"lub-dub-ta" or "slosh-ing-in" If new, indicates heart failure or volume overload.

It occurs at the beginning of diastole after S2 and is lower in pitch than S1 or S2 as it is not of valvular origin. The third heart sound is benign in youth, some trained athletes, and sometimes in pregnancy but if it re-emerges later in life it may signal cardiac problems, such as a failing left ventricle as in dilated congestive heart failure (CHF). S3 is thought to be caused by the oscillation of blood back and forth between the walls of the ventricles initiated by blood rushing in from the atria. The reason the third heart sound does not occur until the middle third of diastole is probably that during the early part of diastole, the ventricles are not filled sufficiently to create enough tension for reverberation. [6]

It may also be a result of tensing of the chordae tendineae during rapid filling and expansion of the ventricle. In other words, an S3 heart sound indicates increased volume of blood within the ventricle. An S3 heart sound is best heard with the bell-side of the stethoscope (used for lower frequency sounds). A left-sided S3 is best heard in the left lateral decubitus position and at the apex of the heart, which is normally located in the 5th left intercostal space at the midclavicular line. A right-sided S3 is best heard at the lower left sternal border. The way to distinguish between left and right-sided S3 is to observe whether it increases in intensity with inhalation or exhalation. A right-sided S3 will increase on inhalation, while a left-sided S3 will increase on exhalation. [7]

S3 can be a normal finding in young patients but is generally pathologic over the age of 40. The most common cause of pathologic S3 is congestive heart failure. [8]

S4 Edit

S4 when audible in an adult is called a presystolic gallop or atrial gallop. This gallop is produced by the sound of blood being forced into a stiff or hypertrophic ventricle. [9]

"ta-lub-dub" or "a-stiff-wall"

It is a sign of a pathologic state, usually a failing or hypertrophic left ventricle, as in systemic hypertension, severe valvular aortic stenosis, and hypertrophic cardiomyopathy. The sound occurs just after atrial contraction at the end of diastole and immediately before S1, producing a rhythm sometimes referred to as the "Tennessee" gallop where S4 represents the "Ten-" syllable. [5] It is best heard at the cardiac apex with the patient in the left lateral decubitus position and holding his breath. The combined presence of S3 and S4 is a quadruple gallop, also known as the "Hello-Goodbye" gallop. At rapid heart rates, S3 and S4 may merge to produce a summation gallop, sometimes referred to as S7. [10] Atrial contraction must be present for production of an S4. It is absent in atrial fibrillation and in other rhythms in which atrial contraction does not precede ventricular contraction. [11]

This occurs when the ventricles are almost full the atria contracts, pumping more blood into the ventricles. The contraction completes ventricular filling, c.

The cardiac cycle begins when the deoxygenated blood from the upper part of the body 7 and the lower body 8 enters into the hearts through the superior vena .

Jennifer Datus Anatomy and Physiology II Essay Questions Test 2 Professor Vernet 1. The beginning of the cardiac cycle starts with deoxygenated blood from.

Hemogloblin (Hb) function primarily is to transport oxygen, partial pressure of oxygen is the determining factor of how much O2 binds to hemoglobin. The maxi.

In the atria due to the increase of a pressure, it is filled. The atrioventricular valves open this allows the blood to pass to the ventricles. The valves in.

After the blood leaves the lungs, it goes into the left atrium where it is then passed into the left ventricle to be pumped to the rest of the body. The left.

The heart has 4 sections inside: left and right atria and left and right ventricle. The right atrium receives blood that is low on oxygen molecules from the.

When the ventricles fill with blood, they too contract together in ventricular systole. The atria and ventricles contract as units but the right and left sid.

The blood vessel, vein, has the duty to deliver deoxygenated blood to the heart. The deoxygenated blood pass into the heart from the right atrium with the he.

CO-DIRFTs through different reactions are shown in Fig.15, and the Cu+-CO peak areas are listed in Table 2. It’s obvious that the amount of active Cu+ sites .

We can stop lead exposure – but we must take action

In the 1970s, the government banned lead from paint and began phasing it out of gasoline, two major public health successes that lowered blood lead levels by about 80%. But the war has not yet been won. Forty years later, the CDC estimates that 500,000 children in the United States have blood lead levels above 5 ug/dl, the threshold for public health intervention.

It’s clear that lead is still a major public health concern, but the response to the latest lead crisis in Flint was sorely lacking. We now know that children under 6 drinking Flint River water were 46% more likely to have blood lead levels above 5 ug/dl. State and local officials used misdirection to minimize this situation, refusing to acknowledge the problem. These actions were not merely negligent – they were criminal, and multiple individuals have been indicted for these activities.

In failing to take action to reduce lead exposure, we are allowing children to encounter a poison that irreversibly damages their bodies. Lead exposure sets children up for every disadvantage in life. Even worse, it is most common in children already disadvantaged due to low socioeconomic status. It is unconscionable to allow this poison to continue to threaten human health – in Flint, across the United States, and around the globe.

Despite these sobering problems, there is hope for the future. A 2009 analysis suggests that every dollar spent on lead removal may have an economic benefit of $17-$220, including increased economic productivity and decreased education and health care costs. This cost-benefit ratio is similar to that of vaccines, a major public health triumph. Since a diet rich in calcium, iron, and vitamin C can lower children’s absorption of lead, hunger prevention programs like SNAP and local food banks also reduce the negative effects of lead exposure.

What can you do to fight lead and environmental pollutants? The American Academy of Pediatrics has excellent resources on lead in the home, including how to screen your water for lead. Blood lead testing is recommended for children under 6 and is commonly covered by insurance. Numerous nonprofit organizations have made lead poisoning a policy priority, and the World Health Organization holds International Lead Poisoning Prevention Week each October. To finally win the war on lead, we must use our voices to advocate for a healthier future.

Mary E. Gearing is a PhD candidate in the Biological and Biomedical Sciences program at Harvard. Follow her on Twitter @megearing.

For more information:

Due to space constraints, some of lead’s biological effects were not covered in this piece. For a more complete picture of lead’s impact on children, please see the WHO guide and other resources listed below. To learn more about the effects of very high lead levels, please see the histories of lead poisoning in the United States.

The Effects of Lead on Children

A Guide to Childhood Lead Poisoning – World Health Organization
Lead Exposure in Children – American Academy of Pediatrics

Have an adult help you do further research by visiting the following websites. These websites offer more information on pulses and heart rates:

  • Topend Sports Network. (2013, August 20). Fitness Testing: Measuring Heart Rate. Retrieved August 20, 2013.
  • Cleveland Clinic Heart and Vascular Institute. (n.d.). Pulse and Target Heart Rate. Retrieved June 12, 2008.

This website will give you more information about how the heart and blood vessels work.

Sociality, Hierarchy, Health: Comparative Biodemography: A Collection of Papers (2014)

Susan C. Alberts, * Elizabeth A. Archie, * Laurence R. Gesquiere, Jeanne Altmann, James W. Vaupel, and Kaare Christensen

The male-female health-survival paradox&mdashthe phenomenon observed in modern human societies in which women experience greater longevity and yet higher rates of disability and poor health than men&mdashhas far-reaching economic, sociological, and medical implications. Prevailing evidence indicates that men die at younger ages than women, despite better health, because of both biological and environmental differences that include behavioral, cultural, and social factors (Wingard, 1984 Verbrugge, 1985, 1989 Kinsella and Gist, 1998 Kinsella, 2000 Case and Paxson, 2005 Oksuzyan et al., 2008 Lindahl-Jacobsen et al., 2013). The male-female health-survival paradox is very well documented in late 20th century high-income countries (Crimmins et al., 2011 Thorslund et al., 2013 Oksuzyan et al., 2014). For instance, cross-national comparisons between the United States, Europe (Denmark), and Japan found consistent but opposite sex differences in survival and health: Men had higher mortality rates at all ages in all three countries, but men also exhibited a substantial advantage in handgrip strength and in activity of daily living at older ages&mdashphenotypes that in both sexes are positively correlated with survival (Oksuzyan et al., 2010).

The mortality part of the paradox, the female survival advantage, has been well documented earlier than the 20th century. In fact, in the very first

lifetables that were categorized by sex, estimated by Struyck (1740) and Deparcieux (1746), female life expectancy exceeded that of males. More than 250 years later, Thorslund et al. (2013) reported on life expectancy data at age 65 for 16 Western countries and Japan, covering various parts of the period from 1751 to 2007. During the 19th century in Western societies, women generally had a constant, higher life expectancy than men at age 65, although the difference was less than 1 year. The 20th century saw rapid country-specific rises in life expectancy, increasing the male-female gap to approximately 4 years, but with variance across countries. During the last three decades, however, all 16 countries experienced a simultaneous narrowing of the gap to 0.5-1 years. This suggests that country-specific factors may have driven the rise in female advantage in life expectancy, whereas factors shared by all countries may underlie the simultaneous fall (Thorslund et al., 2013). There is general agreement that changes in cigarette smoking is the largest identifiable factor in explaining changes in the sex gap in mortality in the developed countries (Pampel, 2003 Payne, 2004 Preston and Wang, 2006 Jacobsen et al., 2008 Leon, 2011 Lindahl-Jacobsen et al., 2013).

With regard to the health part of the paradox, the female disadvantages in health and functioning, research on contemporary populations generally suggests that men are physically stronger, report fewer diseases, and have fewer limitations in the activities of daily living at older ages than women. However, the issue of sex differences in morbidity is more complex than the pattern in activities of daily living and physical performance tests because of variation in the definitions of diseases, diagnostic procedures, and age-related change in incidence and prevalence of many diseases. For example, the incidence of coronary heart disease starts to rise earlier for men than for women, but the sex difference in heart disease is small at the oldest ages. Women generally have a significantly higher mean number of reported disabling, nonlethal conditions than men (Hjertestatistik, 2004 Crimmins et al., 2011). Hence, sex differences in morbidity depend on disease definitions, the measure of severity, and age trajectories of the particular diseases.

It is generally not clear whether sex differences in health also occur in populations that experience living conditions and cultures very different from contemporary Western societies. For instance, historical populations with very different cultural practices, such as low-risk male behavior combined with high fertility (and hence high risk of female mortality), might have experienced much less of a male-female health-survival paradox than modern human populations, which are characterized by high-risk male behavior but relatively low fertility. As another example, in human populations with extremely high male mortality relative to female mortality, male health might also be more compromised than it is in high-income Western societies.

It is even less clear whether the male-female health-survival paradox is preserved across species: Somewhat surprisingly, no systematic investigations of the paradox exist for nonhuman animals. Research on aging in wild or semi-natural vertebrate populations has generally focused on demographic senescence alone (increases in mortality rates with age), rather than on declines in health or functioning with age (Brunet-Rossinni and Austad, 2006). Research on aging in insects has focused on the molecular basis of aging variation across species and between males and females (reviewed in Keller and Jemielty, 2006) and more recently on how the social environment influences aging, particularly in honey bees (Amdam, 2011). In spite of the significant advances made by these various studies on vertebrates and invertebrates, much remains unknown about the evolutionary significance and proximate mechanisms underlying male-female differences in lifespan. Studies of mortality in animal populations suggest that males experience higher mortality than females in many species, particularly mammals (Promislow and Harvey, 1990 Forsyth et al., 2004 Clutton-Brock and Isvaran, 2007), but they also suggest that this may not be a general rule in either vertebrates or invertebrates (McDonald, 1993 Allman et al., 1998 Carey, 2003). Data regarding the second element of the paradox, sex differences in health, are sparser than mortality data. Some data have arisen from animal models of particular human traits or conditions (e.g., menopause: Bellino and Wise, 2003 memory loss: Picq, 2007 Parkinson disease: Smith and Cass, 2007), but such studies rarely involve systematic investigations of sex differences in these health measures with age.

A relatively recent evolutionary framework predicts that, in many species, males will tend to have worse health than females of the same age, as well as shorter lifespans, because in many cases the most important component of male fitness is mating success rather than investment in health maintenance (Rolff, 2002 Zuk and Stoehr, 2002 Stoehr and Kokko, 2006). This framework thus posits an explicit tradeoff between investment in mating activity and investment in somatic maintenance. Furthermore, males in many species gain substantial fitness benefits from seeking additional mates while females generally do not (Bateman, 1948). The energetic demands of obtaining additional mates will often require the sacrifice of somatic maintenance in general and immune function in particular. The consequence is that males are predicted to show compromised immune function and health relative to females, while females maximize fitness by investing in immune function and thus enhancing longevity. Importantly, this framework, sometimes called &ldquoBateman&rsquos Principle for Immunity,&rdquo predicts no health-survival paradox, but instead predicts that females in many vertebrate species will experience both greater health and greater longevity than males. Nonetheless, it represents one of the few well-developed evolutionary frameworks for predictions about male-female differences in

health, and has received some empirical support for instance, Nunn and colleagues (2009) found a positive association between sex differences in a measure of immune function and sex differences in investment in mating. However, very few data on health and functioning over the lifespan exist for animals of either sex in any species.

Here we provide a comparative perspective on the male-female health-survival paradox. First, we examine health and survival patterns in humans living in unusual demographic circumstances to determine whether they show a non-paradoxical pattern. Specifically, we summarize recent evidence on the health-survival paradox in a 20th century Russian population and on female survival advantages in the late 19th and early 20th century Mormon population and other historic and prehistoric populations.

Second, we examine age-specific changes in health-related measures in a nonhuman primate in which male life expectancy is short relative to females, to determine whether they conform to the paradoxical pattern described in humans. Specifically, we provide a detailed analysis of age-related declines in health and physical functioning in a wild baboon population in southern Kenya. Baboons are a good choice of species from a comparative evolutionary perspective because baboons, like humans, are diurnal, ecologically flexible omnivores that evolved in a savannah environment. Males in our study population experience both a higher initial mortality rate than females at the beginning of adulthood and a faster acceleration in age-specific mortality with increasing age (Alberts and Altmann, 2003 Bronikowski et al., 2011). By comparing the health trajectories of males and females, we examine whether baboons, like many human societies, experience a health-survival paradox.

At the beginning of the 21st century, it is well established that females, on average, outlive men in all countries around the globe (Barford et al., 2006). In high-income countries, they generally do so despite more disabilities and worse self-reported health. In this section, we explore patterns of all-cause mortality in four sets of populations, working our way backwards in time to shed light on whether:

  1. the male health advantage is present in a contemporary Russian population with extreme excess male mortality
  2. the female survival advantage was present in the late 19th and early 20th century Mormon population living in Utah, in which

male risk-taking behavior was minimized by societal norms and fertility was high

The Male-Female Health-Survival Pattern in a Contemporary Russian Population

Life expectancy in Russia is lagging behind that in the United States and Europe, and this difference has been very pronounced since the 1960s (Shkolnikov and Meslé, 1996 Meslé, 2004 Oksuzyan et al., 2014). In Russia in 2009, life expectancy was 74.7 years for women and 62.7 years for men. The female-male gap in life expectancy in Russia increased from 8.3 years in 1953 to the maximum level of 13.6 years in 2005 with a decline in 1986-1987 (to 9.4 years) in connection with Gorbachev&rsquos anti-alcohol campaign and a steeper reduction in male than female mortality (Human Mortality Database Field, 2000). Although a narrowing of the sex difference in life expectancy in Russia has occurred since 2006, the sex gap of 11.9 years in 2009 was second only to Kazakhstan as the highest in the world.

In Russia, the main contributors to the declining life expectancy for younger and middle-aged adults from 1988 to 2000 were deaths due to cardiovascular diseases, violence, accidents, and alcohol-related causes (Meslé, 2004 Zaridze et al., 2014). Also, higher mortality rates were observed in Russia at older ages than in other European countries, suggesting worse health in Russia than in old-aged populations elsewhere. A study conducted in the 1990s showed that middle-aged Russians and Swedes had similar prevalence of poor self-rated health and disability, but after about age 45, the prevalence of good general health and the level of physical functioning were substantially lower in Russia compared to Sweden (Bobak et al., 2004). Another study of Russian men and women in the 1990s showed a much steeper decline with age in the probability of being healthy, in comparison not only to the populations in Western Europe, but also to the former communist Eastern European countries (Andreev et al., 2003).

Recently, we have studied sex gaps in mortality rates in Denmark, Russia, and Moscow, as well as sex differences in several health outcomes in Denmark and Moscow among individuals aged 55 to 89 years (Oksuzyan et al., 2014). Pronounced male excess mortality in Russia led us to expect smaller male advantages in selected health domains in Russia compared to Denmark.

The Human Mortality Database and the Russian Fertility and Mortality Database were used to examine sex differences in all-cause death rates in Denmark, Russia, and Moscow in 2007-2008. Self-reported health data were obtained from the Study of Middle-Aged Danish Twins (n = 4,314), the Longitudinal Study of Aging Danish Twins (n = 4,731), and the study of Stress, Aging, and Health in Russia (n = 1,800). In both Moscow and Denmark there was a consistent female advantage in survival at ages 55-89 years and a male advantage in self-rated health, physical ability, and depression symptomatology. Only on cognitive tests did men perform similarly to, or worse than, women. In other words, on the large majority of health indicators, Muscovite males performed better than females. This occurred despite Muscovite men having twice the mortality of Muscovite women at ages 55-69 years, a male-female ratio almost twice as large as that seen in Denmark. Hence, the male-female health-survival paradox is very pronounced in this contemporary Russian population.

Sex Differences in Survival in the Late 19th and Early 20th Century Utah Population

Behavioral factors have been proposed as a key source of female-male differences in mortality, with risk-taking behaviors&mdashincluding cigarette smoking and alcohol consumption&mdash occurring more frequently among men than among women. Cigarette smoking is the largest identifiable factor in explaining changing sex gaps in mortality, but it is well known that cigarette smoking alone cannot explain the sex difference in mortality for instance, male non-smokers have higher mortality than female non-smokers (Wang and Preston, 2009).

With this background, we hypothesized that the late 19th and early 20th century Utah male-female survival difference should be among the lowest observed and smaller than that in Denmark and Sweden (Lindahl-Jacobsen et al., 2013). This hypothesis is based on the fact that many residents in Utah in this period were active in the Mormon Church, which proscribes the use of alcohol and tobacco, and whose members would therefore have a healthier lifestyle than the general population with regard to typical male risk factors. This lifestyle was common among members of the Church during the early settlement years, though it was not enforced until the 1860s (Alexander, 1981) and was not institutionalized until 1906 with the Word of Wisdom (Bush, 1993 Alexander, 1996). Females, on the other hand, had a very high fertility level, which was associated with increased maternal mortality risks (Skolnick et al., 1978). We anticipated that the female longevity advantage would grow over the last half of the 19th and early part of the 20th centuries, as their elevated fertility declined during the demographic transition. Denmark and Sweden were chosen as com-

FIGURE 15-1 Cohort life expectancy in Utah (A), Sweden (B), and Denmark (C) and the sex differences in each population (D).
SOURCE: Lindahl-Jacobsen et al. (2013).

parison countries because many descendants of both nations were widely represented among the early migrants to Utah and because these countries have high-quality cohort mortality data spanning back as early as 1850.

As seen in Figure 15-1 and contrary to our expectation, the sex difference in cohort life expectancy was similar or larger in Utah than in Denmark and Sweden, except during the early frontier settlement era (1850-1870), which was distinguished by a series of food shortages and hardships associated with migration and the vagaries of establishing communities (Skolnick et al., 1978). Active male Mormons had longer life expectancy than other groups in Utah (approximately 2 years at age 50), while the difference was minimal for females, suggesting that male Mormons benefitted from a healthy lifestyle. Still, sex differences in cohort life expectancy at the age of 50 years were similar for individuals actively affiliated with the Mormon Church and for individuals living in the general population in Denmark and Sweden. This comparison confirms that even under the particular circumstances found in Utah during the historical period, women had a survival advantage similar to that seen in European populations at that time.

The Female Survival Advantage Was Present in Other 19th and 20th Century Populations

The male-female life-expectancy gap was smaller in the past than it is today, as indicated for time periods in Figure 15-2a for France, and as illustrated for cohorts in Figure 15-1d. In the 1850s, the male-female gap in eo (life expectancy at birth, a measure of mortality conditions in a given year of birth see Figure 15-2) was 1.6 years for France and only 0.4 years for Belgium. The gap was 1.8 years in the Netherlands and 2 years in

FIGURE 15-2 Male vs. female life expectancy over time (A) and male vs. female death rates over age (B and C).
NOTES: In A, for the French population, the difference plotted is female minus male life expectancy (eo for females - eo for males = ed) at ages 0 (ed(0)), 15 (ed(15)) and 65 (ed(65+)) as well as the difference in partial life expectancy between age 15 and 65 (ed(15-64)). Each point pertains to a decade of data: for example, the point for 1850 pertains to 1850-9. In B the ratio of male to female death rates is plotted for five populations. In C the difference between male and female death rates is plotted for the same five populations. Note that A, B, and C all pertain to mortality conditions in the specified decades, whereas the graphs in Figure 15-1 pertain to cohorts followed from birth through time. In contrast to the cohort life expectancy values in Figure 15-1, which reflect the lifespans of people born in various years, the period life expectancy values in Figure 15-2 are measures of mortality conditions in the specified decade.

The brain is a heterogeneous tissue composed of various highly interconnected cell types. Each type has a particular pattern of expression and is differentially located in the brain regions. In some pathological situations such as brain injury, cascades of metabolic, cellular and molecular events ultimately lead to brain cell death, tissue damage and atrophy. To better understand these cellular processes it is important to obtain information regarding the spatial and temporal patterns of gene expression. In this chapter, we will describe the method of intracardial perfusion of a mouse prior to brain removal. We will then describe the detailed methodology for the detection of proteins and mRNA utilizing immunohistochemistry (IHC) and in situ hybridization (ISH) respectively in brain sections respectively.

The brain is composed of areas of gray and white matter and consists of various regions, including the cerebral cortex, the thalamus, the hypothalamus, the brain stem, and the cerebellum. The sensory areas of the cerebral cortex are involved in perception of sensory information: motor areas control execution of voluntary movements and association areas deal with complex integrative functions such as memory, personality traits, and intelligence. The limbic system promotes a range of emotions including pleasure, pain, affection, fear, and anger. The thalamus relays almost all sensory input to the cerebral cortex: it contributes to motor functions by transmitting information from the cerebellum and basal nuclei to motor areas of the cerebral cortex. It also plays a role in maintaining consciousness. The hypothalamus controls and integrates activities of the autonomic nervous system: it regulates emotional and behavioral patterns and circadian rhythms. The cerebellum smoothes and coordinates contractions of skeletal muscles, regulates posture and balance, and may have a role in cognition and language processing.

The brain is a heterogeneous tissue that contains neurons, neuroglia, and other cell types that vary among anatomical regions. Nonneuronal cell types are broadly categorized into (1) astrocytes, (2) radial glia, (3) oligodendrocytes, (4) ependymal cells, and (5) microglia. The role of each cell type is well defined moreover, their interaction is essential for the neuronal function of the central nervous system. The cellular communication is substantially involved in the establishment of the majority of neurological disorders (Pham and Gupta, 2009).

Brain function is determined by the communication between electrically excitable neurons and the surrounding glial cells, which perform many tasks in the brain.

Oligodendrocytes are one type of glial cell that form an insulating protective myelin sheath around the axons of neurons that enables saltatory nerve conduction. A loss of myelin in defined areas of brain leads to an impairment of axonal conductance. This is what happens in many forms of myelin disorders, such as multiple sclerosis, and it results in a permanent loss of neuron impulse transmission. It is evident that the demyelinated region contains inflammatory cells such as infiltrating lymphocytes and macrophages and activated microglia. These cells might potentiate or even initiate a damage cascade leading to continuous neurodegeneration.

Microglia are the resident phagocytic cells in the brain, taking part in immune-mediated defense mechanisms and clearing damaged cell debris (Ransohoff and Cardona, 2010 Ransohoff and Perry, 2009). Previously, it was thought that microglia, in their resting state, are relatively quiescent. More recent work suggests that microglia are constantly active and surveying their surroundings (Hughes, 2012 Nimmerjahn et al., 2005). Microglia are now implicated in synapse pruning during both development and throughout adulthood, and therefore play a role in regulating homeostatic synaptic plasticity (Schafer et al., 2012).

Together with astrocytes, another type of glial cell, microglia can release neuromodulatory chemicals that influence neuronal firing and intracellular signaling. When first described, astrocytes were seen merely as structural scaffolding to support and fill the gaps between neurons. However, recent evidence suggests that astrocytes serve as much more than a nutrient supply or supportive scaffolding to protect neural networks (Nedergaard et al., 2003). Astrocytes are highly secretory cells, participating in rapid brain communication by releasing factors that modulate neurotransmission (Haydon and Carmignoto, 2006 Huang et al., 2004 Pascual et al., 2012) and more recently have been suggested to possess their own repertoire of gliotransmitters (Bezzi et al., 2004 Cali et al., 2008 Cali and Bezzi, 2010 Domercq et al., 2006 Jourdain et al., 2007 Prada et al., 2011 Santello et al., 2011). Astrocytes also express a wide variety of functional neurotransmitter receptors essential for sensing neuronal activity (Verkhratsky et al., 1998).

When a local inflammatory reaction is triggered in the brain, the increased levels of proinflammatory mediators such as tumor necrosis factor-alpha and prostaglandin 2 can deeply alter the properties of glial network and thus of neuronal network (Bezzi and Volterra, 2001). The important roles played by glial cells in normal and pathological brain functioning are growing, and a more complete picture of neuron–glia interactions is beginning to emerge.

Cellular behaviors such as proliferation, differentiation, migration, and cell death are studied during brain development and in pathological situations. To better understand the developmental processes involved, it is important to obtain information regarding the spatial and temporal patterns of gene expression.

Over the past three decades, animal models have been developed to replicate the various aspects of human brain injury to better understand the underlying pathophysiology and to explore potential treatments. Among more recent models for traumatic brain injury, four specific models are widely used in research: fluid percussion injury (Dixon et al., 1987), controlled cortical impact injury (Dixon et al., 1991 Lighthall, 1988), weight drop impact acceleration injury (Marmarou et al., 1994), and blast injury (Cernak et al., 1996 Leung et al., 2008). Rodents are mostly used in traumatic brain injury research because of their modest cost, small size, and standardized outcome measurements.

In this chapter, we will describe the method of intracardial perfusion and an appropriate method to dissect and remove the brain of a mouse. We will then describe methods for the detection of protein (immunohistochemistry, IHC) and messenger RNA (mRNA) (in situ hybridization, ISH) in brain sections.

Research for Your Health

The NHLBI is part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discoveries to improve health and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders, including heart conditions. Learn about current and future NHLBI efforts to improve health through research and scientific discovery.

Learn about the following ways the NHLBI continues to translate current research and science into improved health for people who have heart conditions. Research on this topic is part of the NHLBI's broader commitment to advancing heart and vascular disease scientific discovery.

  • Long-standing Leader in Heart Research. For more than 70 years, the NHLBI has led the fight against heart and vascular diseases. During this period, steady, long-term investments in heart research have led to a greater understanding of how the heart works. These basic insights into the normal biology of the heart are essential for making biomedical discoveries that improve health for people who have heart and vascular diseases. In addition, research from the NHLBI's landmark effort, the Framingham Heart Study, has formed the basis of cardiovascular disease (CVD) prevention and health promotion guidelines and educational programs.
  • NHLBI Systematic Evidence Review of Lifestyle Interventions to Reduce Cardiovascular Risk. The NHLBI conducted a rigorous systematic review of evidence on the effect of dietary patterns, nutrient intake, and levels and types of physical activity on reducing CVD risk in adults. Results were incorporated into clinical guidelines for managing blood cholesterol and blood pressure in 2013. Visit Lifestyle Interventions to Reduce Cardiovascular Risk: Systematic Evidence Review from the Lifestyle Work Group for more information.
  • NHLBI Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. We support the development of guidelines based on up-to-date research to evaluate and manage children and adolescents' risk of heart disease, including overweight and obesity. Visit Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report for more information.
  • Collaborating to Improve Women's Heart Disease Awareness.The Heart Truth® is a national education program for women that raises awareness about heart disease and its risk factors, including high blood pressure. It also educates and motivates women to take action to prevent the disease. The NHLBI sponsors The Heart Truth in partnership with many national and community organizations.
  • Studying Innovations to Improve Heart and Vascular Disease Outcomes. The Cardiothoracic Surgical Trials Network (CTSN) is an international clinical research enterprise that studies heart valve disease, arrhythmias, heart failure, coronary artery disease, and the complications of surgery. The CTSN's efforts extend from early translational research to the completion of six randomized clinical trials, three large observational studies, and multiple ancillary studies with more than 14,000 participants.

Learn about some of the pioneering research contributions we have made over the years that have improved clinical care.

  • Increased risk of heart disease among American Indians. The Strong Heart Study is the largest and longest study on heart disease and its risk factors in American Indians. The study found that heart disease among American Indians has increased over the past 50 years and is now double the rate of heart disease in the general U.S. population.
  • Pioneered techniques to measure heart function. NHLBI-funded investigators pioneered a technique to measure electrical activity from the sinoatrial (SA) node, also called the pacemaker of the heart. This procedure is now used to look for problems with the SA node and to locate the SA node during surgery to avoid damaging it.
  • Environment contributes to heart disease risk. Over the past 30 years, findings from the NHLBI-funded Coronary Artery Risk Development in Young Adults (CARDIA) study have contributed substantially to our knowledge about the important roles lifestyle and environmental factors play in the development of cardiovascular disease later in life. Research from CARDIA found that living in racially segregated neighborhoods is associated with higher blood pressure among black adults, while moving away from segregated areas is associated with a decrease in blood pressure.
  • The heart helps controls blood pressure. NHLBI-funded researchers found that when blood pressure and the amount of blood in the body rises, the heart makes a hormone that does two things: it causes the blood vessels to widen, and it makes the kidneys remove more water from the blood so that blood pressure returns to normal. This discovery made it possible for doctors to use the hormone as a biomarker to help diagnose patients who have heart failure.
  • Understanding hardening of the arteries.The Atherosclerosis Risk in Communities (ARIC) study is investigating the causes of atherosclerosis, a disease marked by plaque buildup in the arteries, and the clinical outcomes in adults from four U.S. communities. Another goal of the study is to measure how cardiovascular risk factors, medical care, and outcomes vary by race, sex, place, and time.

In support of our mission, we are committed to advancing heart research, in part, through the following ways.

  • We perform research. Our Division of Intramural Research (DIR) and its Cardiovascular Branch, which includes investigators from the Cell and Developmental Biology Center and the Cardiac Physiology Laboratory, perform research on the heart.
  • We fund research. The research we fund today will help improve our future health. Our Division of Cardiovascular Sciences oversees much of the research on the heart we fund, helping us to understand how the heart normally develops, functions, and repairs itself so that we can better prevent and treat heart conditions. The Center for Translation Research and Implementation Science translates these discoveries into clinical practice. Search the NIH RePORTer to learn about research the NHLBI is funding to improve heart health.
  • We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) program includes participants who have heart conditions, such as coronary artery disease and atrial fibrillation, to help us understand how genes contribute to differences in disease severity and how patients respond to treatment. The NHLBI Strategic Vision highlights ways in which we may support research over the next decade.

Learn about exciting research areas the NHLBI is exploring about the heart.