The Cardiovascular System in Animals

The sinoatrial (SA) node is the pacemaker of the heart. The heartbeat originates with a wave of depolarization that begins in the SA node at the juncture of the cranial vena cava and the right atrium. At rest, the SA node discharges approximately 30 times/minute in horses, > 120 times/minute in cats (typically 180–220 times/minute in a hospital setting), and 60–120 times/minute in dogs, depending on the animal's size.

In general, the larger the species, the slower the rate of SA node discharge and the slower the heart rate. Birds can have a resting heart rate of approximately 115–130 bpm, with active heart rates up to 670 bpm, depending on size and species. Hummingbirds can have an active heart rate of > 1,200 bpm.

The rate of SA nodal discharge increases when norepinephrine (released from sympathetic nerves) or epinephrine (released from the adrenal medulla) binds to the beta-1-adrenergic receptors on the SA node (sympathetic stimulation). This cardioacceleration (positive chronotropic effect) may be blocked by beta-adrenergic blocking agents (eg, propranolol, atenolol, metoprolol, esmolol, carvedilol).

The rate of SA nodal discharge decreases when acetylcholine released by parasympathetic (vagus) nerves binds to cholinergic receptors on the SA node (vagal stimulation). This vagally mediated cardiodeceleration (negative chronotropic effect) may be blocked by a parasympatholytic (vagolytic) compound (eg, atropine, glycopyrrolate).

When the SA node discharges and the wave of depolarization traverses the atria toward the atrioventricular (AV) node, the P wave of the ECG is produced. Subsequently, the atria contract, ejecting a small volume (15–20% of cardiac output) of remaining blood into the respective ventricles. Atrial repolarization (T_awave) is typically difficult to visualize in small animals because of its low voltage deflection.

Once the wave of depolarization reaches the atrioventricular (AV) node, the speed of conduction is slowed through the nodal tissue, giving the atria time to contract and eject more blood into the ventricles and allowing for atrioventricular synchrony. Depolarization then travels rapidly via a specialized conduction system (ie, bundle of His, right and left bundle branches, Purkinje network) to the ventricular subendocardium and ventricular septum. From these points, it travels slowly through the ventricular myocardium, producing the QRS complex of the ECG (representing ventricular depolarization) with subsequent mechanical ventricular contraction.

The process of ventricular activation varies between domestic mammals, which are characterized as either category A (dog, human, monkey, cat, rat) or category B (goat, horse, cow, pig, sheep) based on the time and order of the 3 fronts (waves) of depolarization. Animals in category B have more extensive Purkinje fiber networks throughout the ventricular myocardium into the epicardium; thus the wave front does not spread from endocardium to epicardium as in category A mammals. For this reason, chamber enlargement cannot be determined from a base-apex lead on large animals, and the ECG is used only to assess the cardiac rhythm (see sinus rhythm, ECG, horse).

The wave of ventricular depolarization in avian species spreads from subepicardial to endocardial through the myocardium, starting from the right ventricular apex; thus, in lead II the polarity of the QRS complex is mainly negative, similar to horses. In order to meet high energy demands, birds have a higher cardiac mass (at least 2 times that of other mammals their size) and higher cardiac output with larger-diameter Purkinje fibers and smaller cardiomyocyte size, lending to faster depolarization rate and faster sinus nodal discharge rates (higher heart rates).

The delay between the electrical activity visualized on the ECG and mechanical function is due to the transmission time of impulses through the conduction system, which allows contraction of cardiomyocytes to occur in synchrony. Under rare conditions, there may be depolarization without contraction, which is called electromechanical dissociation.

Sinus rhythm, ECG, horse

Image

Courtesy of Dr. Kursten V. Pierce.

The interval on an ECG between the onset of the P wave and the onset of the QRS complex is termed the PQ or PR interval. It is a measure of the time it takes for the electrical wave of depolarization to begin at the SA node, traverse the AV node, and reach the ventricles. Factors that speed or slow the rate of discharge of the SA node (chronotropy) also speed or slow conduction through the AV node (dromotropy). Thus, as the heart rate increases, the PR interval shortens; when heart rate slows, the PR interval lengthens. (See ECG, normal sinus rhythm.)

Normal sinus rhythm, labeled ECG, dog

Image

Courtesy of Dr. Kursten V. Pierce.

The T wave of the ECG represents repolarization of the ventricles. It is affected by electrolyte imbalances (eg, hypo- or hyperkalemia, hypo- or hypercalcemia) or myocardial injury.

In quiet, healthy animals, the cyclic variation of the heart rate with respiration is termed respiratory sinus arrhythmia (RSA; see RSA image, dog); it results from decreased vagal activity during inspiration (increase in SA node discharge rate with resultant increase in heart rate) and increased vagal activity during expiration (decrease in SA node discharge rate with resultant decrease in heart rate).

Respiratory sinus arrhythmia, ECG, dog

Image

Courtesy of Dr. Kursten V. Pierce.

Heart rate variability synchronized with respirations is a good indicator of cardiac health. Animals rarely have active CHF with RSA; however, primary SA nodal dysfunction or comorbid conditions that increase vagal activity (such as primary respiratory or neurological disease) may cause RSA to persist. RSA is uncommonly documented in cats in the hospital setting because of their higher sympathetic tone.

In addition to variations in vagal tone with respiration, other mechanisms contribute to RSA, including response of the cardiopulmonary receptors and baroreceptors (eg, Frank-Starling mechanism, Bainbridge reflex). Therefore, vagolytic compounds, as well as excitement, pain, fever, and congestive heart failure (CHF), usually abolish or diminish RSA.

Heart rate is also inversely related to systemic arterial blood pressure. When blood pressure increases, heart rate decreases; when blood pressure decreases, heart rate increases. This relation, known as Marey's law, occurs by the following mechanism: when high-pressure arterial baroreceptors in the aortic and carotid sinuses detect increases in blood pressure, they send increased afferent volleys (burst of simultaneous nerve impulses) to the medulla oblongata, which increases vagal efferents to the SA node and causes the heart rate to decrease.

However, in heart failure, the baroreceptors (laden with Na⁺/K⁺-ATPase) become fatigued, which reduces the afferent signals to the medulla oblongata. This results in less vagal efferent signaling. Thus, dogs in CHF have a decrease in heart rate variability and frequently present with an underlying sinus tachycardia.

Interpretation of ECGs should be performed in a systematic manner, including assessing the heart rate and rhythm, evaluating waveforms (P, QRS, T) and segments (PQ/PR, ST, QT), and assessing for presence of a P wave for every QRS wave and vice versa. An in-depth review of ECG interpretation is beyond the scope of this discussion.

The force with which the ventricles contract is determined by many factors, including both end-diastolic volume (preload), which is the volume of blood within the ventricles just before they begin to contract, and myocardial contractility (inotropy), which is the rate of cycling of the microscopic myocardial contractile units. Note that afterload (tension/load the ventricle must overcome to eject blood) can also affect force of contraction, at least initially (Anrep effect). Preload, afterload, and contractility determine stroke volume. Cardiac output is equal to heart rate times stroke volume.

Preload is determined primarily by the blood volume and the stiffness or compliance of the atrial wall, which determine the end-diastolic pressure generated in the atria. Stated another way, this can be considered the "filling pressure" driving blood flow into the ventricles when the AV valves open.

Myocardial contractility is determined by the availability of ATP and calcium, which allows myosin-actin cross-bridging to occur. The rate of energy liberation from ATP is determined, in part, by the amount of norepinephrine binding to beta-1-adrenergic receptors in the myocardium. One of the most important factors in heart failure is the downregulation (decreased number) of myocardial beta-1-receptors and resultant loss of contractility.

Oxygen is essential for the production of energy that permits all body functions. The amount of oxygen available for production of this energy is termed the tissue oxygen content. The myocardial oxygen content is a balance between how much oxygen is delivered to the heart minus how much oxygen the heart consumes.

The amount of oxygen delivered to the heart depends on how well the lungs function, how much Hgb is present to carry oxygen, and how much blood carrying oxygenated Hgb flows through the heart muscle via the coronary arteries. If pulmonary function is normal and there is sufficient Hgb, coronary blood flow will determine how much oxygen is delivered to the myocardium. Coronary blood flow is determined by the difference in mean pressure between the aorta (normally 100 mm Hg) and the right atrium (normally 5 mm Hg), into which coronary blood empties. Because coronary flow is greatest during diastole, slower heart rates (which preferentially increase diastolic interval) are associated with improved myocardial oxygen delivery.

The amount of oxygen consumed by the heart is termed myocardial oxygen consumption. It is determined, principally, by wall tension and heart rate.

Wall tension is expressed by LaPlace's law, in which tension increases with increases in ventricular pressure and/or diameter, and tension decreases with increases in ventricular wall thickness. Tension increases with conditions that increase afterload (resistance to ventricular ejection), such as pulmonary valve stenosis, subaortic stenosis, systemic or pulmonary hypertension. Wall tension also increases with conditions that cause increased preload (volume), including mitral valve insufficiency, left-to-right shunting defects, and dilated cardiomyopathy.

In the absence of a stenotic lesion, afterload is determined by the relative stiffness of the arteries and the degree of constriction of the arterioles. The tone of vascular smooth muscle depends on many factors, some of which constrict muscle (eg, adrenergic agonists, angiotensin II, vasopressin, endothelin, norepinephrine) and some of which relax muscle (eg, atriopeptin, bradykinin, adenosine, nitric oxide). Afterload is often increased in heart failure, and therapy is often directed at decreasing it.

Increases in heart rate result in increasing myocardial oxygen consumption while decreasing time for diastole when coronary blood flow is greatest. This combination can set the stage for an imbalance in myocardial oxygen demand and supply, leading to myocardial ischemia. Cardiac failure is characterized by an increase in sympathetic tone and relative increases in heart rate, along with changes to wall thickness and chamber volume that render the myocardium less efficient.

Oxygen is responsible for the production of the vast majority of ATP, which fuels both myocardial contraction and relaxation. Calcium must be released rapidly by intracellular stores (sarcoplasmic reticulum) via calcium-induced calcium release to allow for excitation-contraction coupling, and equally rapid removal of calcium back into the sarcoplasmic reticulum is necessary for relaxation. Both processes of calcium cycling are energy dependent.

In heart failure and cardiomyopathy, inappropriate handling of calcium may result in arrhythmogenesis and may also be the most important factor that leads to both reduced force of contraction and reduced rate of relaxation (ie, reduced systolic and diastolic function).

Blood flow from the heart, termed cardiac output, is via both the left and right ventricles. Cardiac output is determined by the heart rate and ventricular stroke volume. Stroke volume (SV) is the amount of blood pumped out of each ventricle with each contraction and is determined by 3 factors: preload, contractility, and afterload. Cardiac output equals heart rate times stroke volume (CO = HR × SV). Blood flows through the systemic arterial (left ventricular) or pulmonary arterial (right ventricular) trees and is critical to satisfactory cardiac function and consequent adequate perfusion of organs with blood and oxygen. Normal cardiac output for dogs and cats is 100–200 mL/kg/minute and 120 mL/kg/minute, respectively.

Most (> 90%) of the hindrance to blood flow is from the degree of constriction of arterioles, termed vascular resistance; however, some interference is from the stiffness of the portion of the great arteries closest to the ventricles, termed impedance. The ventricles eject a stroke volume into the proximal portion of the great arteries, which expand to accommodate the stroke volume and then recoil after ventricular relaxation to continue the propulsion of blood through the arterioles into the capillaries. The aortic and pulmonic valves close after ventricular relaxation to prevent backflow.

One of the most important features of heart failure that leads to morbidity is increased resistance of arterial, arteriolar, and venous smooth muscle because of increased angiotensin II, vasopressin, and endothelin. If the left ventricle is unable to eject a normal stroke volume or cardiac output, it is reasonable that ventricular function might be improved by decreasing vascular resistance. Decreasing afterload (arterial vasodilation) is one therapeutic goal in heart failure therapy.