The autorhythmicity inherent in cardiac cells keeps the heart beating at a regular pace; however, the heart is regulated by and responds to outside influences as well. Neural and endocrine controls are vital to the regulation of cardiac function. In addition, the heart is sensitive to several environmental factors, including electrolytes.

Heart Rate and its Control

Heart rates (HR) vary considerably, not only with exercise and fitness levels, but also with age. Newborn resting HRs may be 120 bpm. HR gradually decreases until young adulthood and then gradually increases again with age.

Maximum HRs are normally in the range of 200–220 bpm, although there are some extreme cases in which they may reach higher levels. As one ages, the ability to generate maximum rates decreases. This may be estimated by taking the maximal value of 220 bpm and subtracting the individual’s age. So a 40-year-old individual would be expected to reach a maximum rate of approximately 180, and a 60-year-old person would achieve a HR of 160.

Correlation Between Heart Rates and Cardiac Output

Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the heart increases. However, as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased filling time. CO will initially stabilize as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV. Consider this phenomenon in a healthy young individual. Initially, as HR increases from resting to approximately 120 bpm, CO will rise. As HR increases from 120 to 160 bpm, CO remains stable, since the increase in rate is offset by decreasing ventricular filling time and, consequently, SV. As HR continues to rise above 160 bpm, CO decreases as SV falls faster than HR increases.

Cardiovascular Centers

Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata . The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioacceleratory nerves, and the cardioinhibitory centers decrease heart activity via parasympathetic stimulation as one component of the vagus nerve. The ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. During rest, both centers provide slight stimulation to the heart, contributing to autonomic tone. This is a similar concept to tone in skeletal muscles. Normally, vagal stimulation predominates as, left unregulated, the SA node would initiate a sinus rhythm of ~100 bpm.

At the nodes sympathetic stimulation causes the release of the neurotransmitter norepinephrine (NE) at the neuromuscular junction of the cardiac nerves. NE binds to the beta-1 receptors which primarily opens ligand-gated sodium ion channels, allowing an influx of positively charged ions. Some cardiac medications (for example, beta blockers) work by blocking these receptors, thereby slowing HR and are one possible treatment for hypertension.

Parasympathetic stimulation originates from the cardioinhibitory region with impulses traveling via the vagus nerve (cranial nerve X). The vagus nerve sends branches to both the SA and AV nodes to decrease HR. Parasympathetic stimulation releases the neurotransmitter acetylcholine (ACh) at the neuromuscular junction. ACh slows HR by opening ligand-gated potassium ion channels to slow the rate of spontaneous depolarization and increase the time before the next spontaneous depolarization occurs. Without any nervous stimulation, the SA node would establish a sinus rhythm of ~100 bpm. Since resting rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows HR. This is like driving a car with one foot on the brake pedal. To speed up, you would just need to remove your foot from the brake and let the engine increase speed. In the case of the heart, decreasing parasympathetic stimulation decreases the release of ACh, which allows HR to increase up to ~100 bpm. Any increases beyond this rate would require sympathetic stimulation.

Other Factors Influencing Heart Rate and Force of Contraction

Using a combination of autorhythmicity and innervation, the cardiovascular centers can provide relatively precise control over HR. However, there are several other factors that have an impact on HR as well, including epinephrine, NE, levels of various ions including calcium, potassium, and sodium. Many of these factors also influence contractility which refers to the force of contraction of the heart muscle.  After reading this section, the importance of maintaining homeostasis should become even more apparent.

Epinephrine and Norepinephrine

The catecholamines, epinephrine and NE, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The other component is sympathetic stimulation. Epinephrine and NE have similar effects: binding to the beta-1 receptors and opening ligand-gated sodium channels. The rate of depolarization is increased by this additional influx of positively charged ions, so the threshold is reached more quickly increasing heart rate. However, massive releases of these hormones coupled with sympathetic stimulation may lead to arrhythmias.

Sodium and Potassium

Altered sodium and potassium concentrations can slow HR. The relationship between electrolytes and HR is complex, but maintaining electrolyte balance is critical to the normal wave of depolarization. Of the two ions, potassium has the greater clinical significance. Hypokalemia (low potassium levels) leads to arrhythmias, whereas hyperkalemia (high potassium levels) causes the heart to become weak and flaccid, and ultimately to fail. Initially, both hyponatremia (low sodium levels) and hypernatremia (high sodium levels) may lead to tachycardia. Severely high hypernatremia may lead to fibrillation, which may cause cardiac output to cease. Severe hyponatremia leads to both bradycardia and other arrhythmias.

Adapted from Anatomy & Physiology by Lindsay M. Biga et al, shared under a Creative Commons Attribution-ShareAlike 4.0 International License, chapter 19