Clinical Aspects of CV System

6.7.1 Circulatory Adjustments During Exercise

Physiological adaptation associated with exercise physical conditioning is a mechanism by which exercise capacity can be optimized.

During strenuous exercise, the metabolic needs of work­ing muscle increase dramatically. The pumping ability of the heart to eject sufficient blood to meet the needs of the exercising horse and provide effective redistribution of the blood to working skeletal muscle is essential. During exer­cise, increases in heart rate are brought about by increases in sympathetic activity. This sympathetic activation also increases cardiac contractility, so the ventricles empty more completely with each beat. In addition, sympathetic activa­tion shortens the duration of systole, which helps to preserve diastolic filling time. In summary, under sympathetic action, the heart not only contracts more frequently (increased rate) and more forcefully (increased contractility), but also contracts and relaxes more quickly (helping to preserve dia­stolic filling time).

Cardiac output: Exercise demands an increased cardiac out­put to meet the oxygen requirements to fuel working muscle energetics. Because maximal heart rate is attained during severe exercise, stroke volume may limit the increase in cardiac output during exercise. During sub- maximal exercise, cardiac output increases close to line­arly with workload, and this is principally due to increased heart rate.

Heart rate: The substantial increase in cardiac output is primarily due to the very high heart rates. In the trained thoroughbred, average resting heart rate is around 35 bpm. During maximal exercise, heart rate can increase to 240-250 bpm in the racing thoroughbred. In the dog, resting heart rates can be less than 100 bpm, particularly in the racing greyhound, rising to 300 bpm or more during maximal exercise. Heart rate rises rapidly at the onset of exercise, reaching a maximum in 30-45 s, and then often drops before reaching a plateau during steady-state work. In addition, heart rate during submaximal exercise is affected by apprehension and anxiety. The psychogenic component of the heart rate response to exercise is pro­portionately larger at lower, relative workloads.

Stroke volume: Stroke volume is increased or unchanged during exercise in the dog and increased during submaxi- mal exercise in the horse. Maintenance of stroke volume during exercise occurs by several physiological mechanisms. Increased sympathetic nervous activity dur­ing exercise results in both tachycardia and reduced end-systolic ventricular volumes by increasing myocardial contractility, thereby making the ventricular emptying more effective. Venous return during exercise is supplemented by mobilization of the splenic reserve of blood volume, increased negativity of intrathoracic pres­sure, and muscle movement. Increased stretch of myocardial fibers within physiologic limits leads to an increase in developed pressure and stroke volume. The increases in left ventricular end-diastolic pressure and contractility during exercise, along with the increased venous return, assist in the maintenance of stoke volume, despite the decreased filling time associated with short­ened diastole at increased heart rates.

Myocardial contractility: During strenuous exercise in the dog and pony, marked augmentation of myocardial con­tractility is observed, along with pronounced increases in both ventricular preload (increased end-diastolic volume) and afterload (mean arterial pressure). The net result is an increase in myocardial oxygen consumption, which is met by increases in both coronary blood flow and increased oxygen extraction.

Blood flow: The main changes in distribution of blood flow during exercise are (1) enhanced pulmonary blood flow from opening of previously closed pulmonary capillaries,

(2) coronary vasodilation resulting in increased coronary flow to provide oxygen for myocardial contraction,

(3) vasodilation in working skeletal muscles that elevates capillary red blood cell flux, (4) vasoconstriction in the nonworking muscles and the splanchnic vasculature, and (5) increased blood flow to the skin. These cardiovascular adaptations elevate the oxygen supply to tissues with increased oxygen requirements during exercise and body thermoregulation. Blood flow to the skin is dependent on body temperature as well as environmental temperature and humidity.

Blood pressure: During submaximal exercise, systemic arte­rial blood pressure is maintained relatively constant by arterial baroreceptors. During strenuous exercise, cardiac output increases up to 16-fold in the horse and significant increases in mean systemic arterial pressure occur.

6.7.2 Cardiac and Circulatory Changes at Parturition

During a normal birth, the newborn emerges from the birth canal at about the time the placenta is detaching from the uterine wall. Placental gas exchange probably continues well into third-stage labor.

The newborn heart, especially the left ventricle, must cope with significant hemodynamic challenges including a rapid rise in systemic arterial blood pressure and a marked increase in pulmonary venous return to the left atrium. In spite of the structural and biochemical immaturity of the newborn heart, the left ventricle supports a two- to threefold increase in cardiac output, increased stroke volume, and high heart rate. This response is supported by an increase in the left ventricular contractile state.

The newborn left ventricle demonstrates a high level of contractility but operates more nearly at maximal contractile capacity than does the adult heart. Hence, the contractile reserve of the newborn ventricle is much less than that in the adult heart.

This limits the ability of the newborn heart to respond to further increases in diastolic volume or arterial blood pres­sure. Myocardial mass increases rapidly during the neonatal period due to hypertrophy.

At birth, the thickness of the right ventricular wall may be equal to that of the left ventricular wall, reflecting the high right ventricular pressure in the fetus.

After birth, the fall in pulmonary vascular resistance due to inflation and oxygenation of the lung leads to a dramatic increase in pulmonary arterial blood flow and, consequently, to a marked increase in pulmonary venous flow returning to the left atrium. The increase in left atrial volume, combined with increased peripheral vascular resistance and blood pres­sure, causes left atrial pressure to increase above right atrial pressure. At about the same time, the umbilical vessels rup­ture because the animal struggles to stand or the umbilical cord is torn by the mother. Umbilical blood flow is arrested by local vasoconstriction in the umbilical vessels. The loss of the low-resistance placental circulation increases systemic vascular resistance, which results in an increased pressure in the aorta, left ventricle, and left atrium. As a result of these changes, aortic pressure exceeds pulmonary arterial pressure, and left atrial pressure exceeds right atrial pressure. There­fore, blood flow through the ductus arteriosus and foramen ovale reverses. Flow reversal in the foramen ovale causes a flap valve to close and occlude the foramen. Over succeeding days to weeks, this valve becomes adherent to the wall of the atrium, thus permanently closing the foramen physiologically or as functional closure. True and permanent anatomic clo­sure of the foramen ovale is due to fibrosis, which requires a period of weeks after birth. In a minority of instances, true closure fails to occur, resulting in a patent foramen ovale. It is important to note that a patent foramen ovale may not be functionally open during life, provided that left atrial pressure continues to exceed right atrial pressure.

6.7.2.1 Patent Ductus Arteriosus

Abnormal, persistent patency of the ductus arteriosus after birth is termed patent ductus arteriosus and is one of the most frequently noted forms of congenital cardiovascular disease in the dog. If the ductus arteriosus remains patent after delivery, changing pressures in the pulmonary artery and aorta change the direction of blood flow across the ductus arteriosus from a right-to-left pattern (pulmonary artery to aorta) in the fetus to a left-to-right pattern (aorta to pulmonary artery) in the neonate. The ductus venosus closes before or at birth depending on the species.

6.7.2.2 Canine Puerperal Tetany (Eclampsia)

Puerperal hypocalcemia is an acute, life-threatening condi­tion most often seen in small-breed bitches with large litters and usually occurring at peak lactation, 2-3 weeks after whelping. Hypocalcemia most likely results due to inade­quate dietary calcium intake and from loss of calcium into the milk. This imbalance in calcium metabolism occurs because of the decreased calcium mobilization from bone into the serum pool together with the efflux of calcium leaving through the mammary glands. In bitches, the excitation-contraction coupling is maintained at the neuro­muscular junction. Low concentration of calcium in the extracellular fluid has an excitatory effect on nerve and mus­cle cells, because it lowers the threshold potential, hence requiring a stimulus of lesser magnitude to depolarize. Tet­any results due to spontaneous repetitive firing of motor nerve fibers. Tachycardia, prolongation of the QT interval, and ventricular premature contractions may be seen on the ECG.

6.7.3 Heart Failure

Heart failure is cardiogenic circulatory failure with sustained inability of the heart to produce a stroke volume to adequately meet the tissue metabolic demands. Heart failure refers to any condition which limits the ability of the heart to deliver a normal cardiac output due to depressed cardiac contractility. Depressed cardiac contractility can result from coronary artery disease, cardiac hypoxia, myocarditis, toxins, drugs, or electrolyte imbalances. If the decrease in contractil­ity affects both sides of the heart, the condition is called bilateral heart failure, and if failure is restricted primarily to either the left ventricle or the right ventricle, it is called left­sided heart failure or right-sided heart failure.

It is useful from a pathophysiological perspective to cate­gorize heart failure on the basis of where the primary defect occurs in the cardiac cycle. Systolic dysfunction or systolic failure refers to heart failure in which diastolic filling of the ventricle is normal but cardiac output (usually stroke volume) is still decreased. Diastolic dysfunction or diastolic failure refers to heart failure due to abnormal cardiac filling with normal ventricular contractility (normal systolic function).

Cardiac failure may actually be classified according to whether stroke volume is reduced (low-output cardiac fail­ure) or increased (high-output cardiac failure). Some clinical patients with heart failure are affected with conditions characterized by excessive need for tissue perfusion. Heart failure may be present in these patients because a normal or even high cardiac output cannot meet tissue needs. Feline hyperthyroidism, chronic anemia, congenital left-to-right shunts (patent ductus arteriosus), and arteriovenous fistulas are examples of conditions observed in veterinary patients that may result in high-output heart failure.

6.7.3.1 Causes of Systolic Dysfunction

A frequent cardiac disease producing systolic failure in vet­erinary medicine is dilated cardiomyopathy, which may be heritable (e.g., Doberman Pinscher cardiomyopathy) or acquired (e.g., dietary taurine deficiency in cats). Other acquired causes of myocardial failure, such as myocarditis or myocardial infarction, are occasionally observed. Valvular insufficiencies can reduce stroke volume by allowing retro­grade flow of blood, abnormal shunting of blood (e.g., arte­riovenous fistula or patent ductus arteriosus), or tissue perfusion needs may rise excessively (e.g., feline hyperthy­roidism producing high-output cardiac failure).

6.7.3.2 Causes of Diastolic Dysfunction

Some conditions reduce cardiac output by interfering with ventricular filling, producing diastolic dysfunction. These may be lesions (e.g., vena caval thrombosis or atrioventricu­lar valvular stenosis) that reduce inflow during diastole, or excessive hypertrophy of ventricular muscle mass in hyper­trophic cardiomyopathy can reduce chamber compliance and limit preload. Similarly, pericardial diseases (e.g., constric­tive pericarditis or pericardial hemorrhage) may limit cardiac expansion and reduce cardiac filling.

6.7.3.3 Compensatory Responses to Heart Failure

In response to the cardiac failure, many compensatory mechanisms are mediated through the activation of arterial baroreceptors and renin-angiotensin-aldosterone mechanism.

6.7.4 Shock

Shock refers to a state of peripheral circulatory failure characterized by inadequate peripheral tissues perfusion resulting in cardiovascular collapse, leading to organ and tissue dysfunction. It is generally characterized by systemic hypotension, inadequate tissue perfusion, oliguria, cellular hypoxia, and generalized dysfunction of cells, tissues, and organs. Shock and its consequences are often reversible with appropriate therapy in its early stages. Eventually, however, sustained tissue hypoperfusion leads to irreversible cell injury progressing to cell death and organ dysfunction. In the absence of effective interventional therapy, shock generally progresses through defined stages, frequently resulting in fatality. Shock usually results from inadequate cardiac out­put, decreased tissue perfusion, and reduced venous return. Cardiac abnormalities that decrease the pumping ability of the heart include cardiac arrhythmias, myocardial infarction, and severe heart valve dysfunction.

6.7.4.1 Classification of Shock

Circulatory shock is classified into three main types: cardio­genic, hypovolemic, and septic shock.

Cardiogenic shock: It is the end-stage result of progressive heart failure, with the primary causative mechanism being a failure of cardiac output that cannot be compensated by other factors. Cardiogenic shock is caused by a severe decline in cardiac output. There are a variety of feedback mechanisms that serve to maintain arterial blood pressure within normal limits, despite a decline in cardiac function. However, if the disease process causing heart failure progresses in severity, these compensatory mechanisms may fail to sustain arterial blood pressure. The consequent systemic hypotension can lead to tissue hypoperfusion and cellular hypoxia, initiating the early stages of cardiogenic shock. In the absence of effective intervention, death may result.

Hypovolemic shock: Low cardiac output due to a reduction in circulating blood volume (e.g., severe dehydration or hemorrhage) leads to hypovolemic shock. Hypovolemic shock results due to a precipitous fall in cardiac output caused by the decrease in blood volume (30% or more of total blood volume) upon hemorrhage, fluid loss, or fluid sequestration. All these factors lead to decrease preload and stroke volume. However, circulatory collapse from decreased effective circulating blood volume may also be caused by peripheral vasodilation with venous pooling of blood. Mechanisms causing this latter form of hypovolemic shock include neurogenic shock, which may occur secondary to central nervous system injury, anaphylactic shock caused by a systemic allergic response associated with IgE-triggered histamine release, and anes­thetic shock caused by anesthetic overdose.

The proximate cause of the cardiovascular collapse in hypovolemic shock is the inadequacy of blood volume to sustain venous return and cardiac preload. With a marked decrement in preload, stroke volume declines quickly and tachycardia is unable to restore cardiac output. In the early stage of hypovolemic shock, peripheral vasoconstriction sustains perfusion of vital organs (i.e., brain, heart, and kidney) at the expense of nonvital tissues (e.g., skin and abdominal viscera). Later, cell and organ dysfunction ensue and, untreated, hypovolemic shock is generally terminal.

Septic shock: This refers to a bacterial infection that is widely disseminated through the blood from one tissue to another and causing extensive damage by the blood­borne microbes or microbial toxins. It may be caused due to peritonitis, generalized infection, or generalized gan­grenous infection. Circulatory shock caused by endotoxic Gram-negative bacilli is relatively common in all veteri­nary species. Circulatory shock produced by endotoxemia is referred to as endotoxic shock. Endotoxic shock is the most common form of septic shock. It is initiated by a complex interaction between endotoxin and monocytes that results in a cascade of events. The earliest stage of endotoxic shock is generally a hyperdynamic in which increased cardiac output predominates. Generally, periph­eral vasodilation occurs secondary to a variety of inflam­matory mediators produced by activated monocytes, the condition being referred to as systemic inflammatory response syndrome (SIRS). Although cardiac output may be normal or elevated initially, extreme peripheral vasodi­lation and cardiac depressant factors eventually lead to hypotension and cardiovascular collapse as the syndrome progresses, ultimately leading to death (in the absence of effective intervention).

Anaphylactic shock and histamine shock: Anaphylaxis refers to the allergic condition in which the cardiac output and arterial pressure often decrease drastically. It results primarily from an antigen-antibody reaction that takes place immediately after an antigen to which the individual is sensitive enters the circulation. The principal effects include the release histamine or a histamine-like substance from the basophils in blood and mast cells in the pericapillary tissues. The histamine causes (1) increased capillary permeability, leading to rapid loss of fluid and protein into the tissue spaces; (2) arteriolar dilation, resulting in greatly reduced arterial pressure; and (3) venous dilation leading to an increase in vascular capacity, thus causing a marked decrease in venous return. The net effect is increased reduction in venous return, and sometimes it is so serious that the animal dies within minutes.

Shock may also be classified on the basis of the level of cardiac output as low- or high-output shock. Low-output shock is generally either cardiogenic or hypovolemic in ori­gin. High-output shock is generally associated with septice­mia or endotoxemia (septic shock). Once circulatory shock reaches a critical level of severity, despite its initiating cause, the shock itself promotes and aggravates further shock. That is, the inadequate blood flow causes the body tissues includ­ing the heart and circulatory system to undergo deterioration, resulting in greater decrease in cardiac output, and a vicious circle ensues, with progressively increasing circulatory shock, poor adequate tissue perfusion, increased shock, and so forth until death.

The sympathetic reflex compensations have an important role in maintaining the arterial pressure. After hemorrhage, decrease in arterial pressure as well as decreases in pressures in the pulmonary arteries and thoracic veins cause powerful sympathetic reflexes. These reflexes activate the sympathetic vasoconstrictor system, resulting in enhanced heart activity and arteriolar constriction throughout the systemic circula­tion, thereby increasing the total peripheral resistance. The veins and venous reservoirs constrict, thus helping to main­tain adequate venous return despite diminished blood volume.

6.7.4.2 Stages of Shock

Shock has been divided into three stages based on the response to therapy:

Stage 1: Compensated circulatory shock

In nonprogressive stage (compensated stage), without the external therapy, the normal circulatory compensatory mechanisms eventually cause full recovery. In this stage, tissue perfusion is inadequate. With cardiogenic and hypovolemic shock, hypotension is also present. In compensated septic shock, cardiac hyperfunction is gener­ally present and arterial blood pressure is normal (or possibly elevated). In this stage, neurohumoral responses maintain adequate tissue perfusion to vital organs, preventing their hypoxia. Adapting control mechanisms include the arterial baroreceptor system, renin-angiotensin- aldosterone system, and antidiuretic hormone. The result is tachycardia, heightened sympathetic stimulation of the ven­tricular myocardium, peripheral vasoconstriction with increased total peripheral resistance, reduced venous capac­itance, and oliguria with renal retention of salt and water. Untreated, an animal in this stage of shock often advances to the second, progressive stage.

If shock is not severe enough to cause its own progression, the animal eventually recovers. Therefore, this lesser degree shock is called nonprogressive shock. Further on, it is also called compensated shock, as the sympathetic reflexes and other factors provide sufficient compensation to stop the circulation from getting worse.

Stage 2: Progressive circulatory shock

This refers to the progressive stage, wherein without therapy, the shock becomes steadily worse. With failure of ade­quate treatment of an animal with compensated shock or with further insult to the circulatory system, progression to stage 2 often occurs. Compensatory mechanisms now fail to sustain arterial blood pressure, and tissue perfusion falls precipitously. Without intervention, cellular hypoxia and organ dysfunction will predominate. At this stage, appro­priate therapy (e.g., intravenous fluid or transfusion ther­apy in hypovolemic shock; therapy for heart failure in cardiogenic shock; or intravenous fluid and antimicrobial therapy in septic shock) may restore cardiovascular func­tion. Untreated, this stage advances to terminal cardiovas­cular collapse.

Stage 3: Irreversible circulatory shock

During this stage, due to extensive progression of the shock, it becomes life threatening. Without therapeutic interven­tion, shock tends to progress inexorably toward this irre­versible stage and death. In stage 3, widespread cellular injury due to hypoxia causes a failure of vascular smooth muscle, endothelial cells, and ventricular myocardium. This leads to a loss of vascular tone, extravasation of fluid into the intestinal lumen in some species (e.g., dogs), and stasis of blood in vascular beds. Blood stasis causes intravascular activation of the clotting cascade producing a syndrome known as disseminated intravascu­lar coagulation (DIC). Intestinal ischemia disrupts the mucosal barrier, leading to entry of bacteria or bacterial by-products (e.g., endotoxin) into the circulation, ulti­mately superimposing endotoxic shock on all forms of shock in this terminal, irreversible stage. Despite efforts at therapeutic intervention at this stage, death of the patient is the result.

6.7.5 Hypertension

Systemic hypertension refers to persistently elevated sys­temic arterial blood pressure. In dogs and cats, secondary hypertension commonly occurs wherein the cause is associated with another disease. Examples of conditions associated with the development of hypertension in dogs and cats include chronic kidney disease, hyperthyroidism, diabetes mellitus, hyperadrenocorticism, pheochromocy­toma, and hyperaldosteronism and medications such as corticosteroids cyclosporine, phenylpropanolamine, and erythropoietin. Most cases of systemic hypertension in dogs and cats are associated with chronic kidney disease, wherein abnormal patterns of intrarenal blood flow or renal artery stenosis may lead to reduced pressure within renal afferent arterioles, causing increased renin release and activation of the RAAS and finally increased arterial blood pressure. Epi­sodic release of adrenaline and noradrenaline from adrenal medulla in Pheochromocytomas leads to peripheral vasocon­striction, tachycardia, and hypertension. In dogs suffering with Cushing syndrome or hyperadrenocorticism, overpro­duction of glucocorticoids occurs, leading to increased blood volume and overproduction of renin, contributing to the development of systemic hypertension. In cats, the most common adrenocortical disorder is primary hyperaldosteronism, wherein excess production of aldoste­rone leads to sodium retention and potassium depletion resulting in expansion of blood volume, increased stroke volume, and thus arterial blood pressure. Hyperthyroidism due to benign tumor is relatively common in geriatric cats, wherein the thyroid hormone enhances cardiac function and sensitivity of the myocardium to catecholamines leading to tachycardia and increased stroke volume, resulting in sys­temic hypertension. Animals with diabetes mellitus may develop systemic hypertension as a result of blood volume expansion associated with hyperglycemia and increased pro­duction of renin.

6.7.6 Hemorrhage

Hemorrhage refers to the excess blood loss due to rupture of blood vessels. Hemorrhage is classified into four categories, based on the cause: capillary hemorrhage, internal hemor­rhage, accidental hemorrhage, and postpartum hemorrhage.

6.7.6.1 Integrated Response to Hemorrhage

Compensatory responses to progressive blood loss involve activation of multiple reflex systems involving both neural and humoral components, which work in concert to restore cardiac output and perfusion pressure. The integrated response to hemorrhage is shown in Fig. 6.6. An initial blood loss up to 10% of total blood volume results in little or no decrease in arterial blood pressure. Reduced blood volume after mild hemorrhage decreases venous return, ven­tricular filling, and cardiac output. The decrease in blood volume and venous return reduces stretch and thus “unloads” volume receptors on the low-pressure side of the circulation (cardiopulmonary receptors).

During hemorrhage, the arterial blood pressure falls and baroreceptors stop discharging impulses, which increases the vasomotor tone and finally leads to vasoconstriction. Heart rate, cardiac contractility, and total peripheral resistance increase, and venoconstriction promotes venous return to the heart. The arteriolar constriction in response to hemor­rhage is most pronounced in the reservoir organs such as cutaneous, skeletal muscle, and splanchnic beds, favoring maintenance of blood flow into systemic circulation, espe­cially in the cerebral and coronary circulations. Arteriolar constriction decreases the capillary pressure, which facilitates the tissue fluid to enter the capillaries, thereby helping to compensate the blood loss. As hemorrhage progresses, increased sympathetic activity, especially to the kidney, results in vasoconstriction, decreased glomerular filtration rate, and decreased urine volume. Decreased stretch of the atrium due to reduced blood volume results in diminished secretion of ANP, while decreased renal perfusion pressure promotes secretion of renin and stimulation of the renin- angiotensin-aldosterone system. In addition, both cardiopul­monary and arterial baroreflex mechanisms promote increased circulating levels of angiotensin II, vasopressin, and aldosterone. These humoral changes promote sodium and water reabsorption in the kidney. As levels of ADH and angiotensin II continue to rise, direct vasoconstrictor effects of these peptides contribute to increased total peripheral resistance. With more severe hemorrhage, peripheral chemoreceptors sense hypoxia due to inadequate blood flow to the carotid body and contribute to further increases in sympathetic outflow. In addition, increased ventilation due to chemoreflex activation assists in promoting venous return. If cerebral ischemia occurs, elevated PaCO₂ and decreased blood pH activate chemosensitive neurons in the brain, which results in a massive activation of the sympathoadrenal systems. The compensatory mechanisms restore arterial pres­sure and cardiac output following mild-to-moderate hemor­rhage. The longer term processes are critical for complete restoration of blood volume.

Pronounced renal and splanchnic vasoconstrictions during severe hemorrhage help maintain adequate perfusion of the heart and brain. However, if prolonged, vasoconstriction in these circulations can result in irreversible damage. A patient may survive the initial blood loss, but die several days later due to acute renal failure due to falling of arterial blood pressure and damage to renal tubules. Prolonged intestinal ischemia may result in liver damage, an increase in intestinal blood loss, and the release of potent vasodilatory endotoxins

Fig. 6.6 Integrated response to hemorrhage. The central and peripheral chemoreceptors and baroreceptors signals to the cardiovascular center in the medulla, which in turn initiates the sequential events leading to the compensatory mechanisms for hemorrhage

into the general circulation. Decompensation during hemor­rhagic shock is the irreversible process which aggravates hypotension and leads to circulatory failure and death.

Learning Outcomes

• General organization of CVS and hemodynamics of circulation

The circulatory system is the transport system of the body. The three basic components of the circulatory system are the heart (the pump), the blood vessels (the passageways), and the blood (the transport medium). The heart functions as a dual pump that provides the driving pressure for blood to flow through the systemic circulation (between the heart and peripheral organs/tissues) and pulmonary circu­lation (between the heart and lungs).

• Electrical activity of heart

The self-excitable heart initiates its rhythmic contractions. Autorhythmic cells are 1% of the car­diac muscle cells; they do not contract but are specialized to initiate and conduct action potentials. The other 99% of cardiac cells are contractile cells that contract in response to the spread of an action potential initiated by autorhythmic cells.

(continued)

The cardiac impulse originates at the SA node, the pacemaker of the heart, and spreads throughout the right and left atria and ventricles facilitated by specialized conduction pathways.

• Regulation of heart and mean arterial pressure

Cardiac output and total peripheral resistance deter­mine the heart activity and the blood pressure. Reg­ulation of cardiac output, in turn, depends on the heart rate and stroke volume regulation, whereas total peripheral resistance is influenced primarily by the degree of arteriolar vasoconstriction. Short­term regulation of blood pressure is carried out mainly by the baroreceptor reflex. The

baroreceptors present in the carotid sinus and aortic arch continuously monitor MAP. Long-term control of blood pressure involves renal maintenance of proper plasma volume and renin-angiotensin-aldo- sterone system.

• Regional circulation

Coronary blood vessels are the dedicated blood vessels that supply the heart muscles. During sys­tole, the contracting heart muscles compress the coronary vessels and hence most coronary blood flow occurs during diastole. The pulmonary circula­tion is a high-flow, low-resistance pathway for the blood to flow between the lungs and heart to provide oxygenation of the venous blood. Fetal circulation differs from the adult in that the fetus receives oxygenated blood and nutrients from the placenta, and fetal lungs and liver are bypassed.

Exercises

Objective Questions

Q1. Which type of channel is most closely with the move­ment of cations during the depolarization phase of the atrioventricular (AV) nodal action potential?

Q2. What is the resting membrane potential of the SA node?

Q3. Which phase of cardiac cycle is associated with the slow rate of blood flow from the atria to the ventricles?

Q4. What is the cause of the “c” wave of atrial pressure?

Q5. Which component of the circulatory system has the largest distribution of distribution of blood volume?

Q6. What causes elevation of blood pressure during a mass sympathetic discharge in dog?

Q7. What is meant by lusitropic reserve of cardiac muscle?

Q8. Which channels are activated by cholinergic M2 receptors in the heart?

Q9. Name the heart sound that occurs during the period of isovolumetric contraction.

Q10. Identify the property of SA node which makes it to act as a pacemaker.

Q11. What is the amount of oxygen extracted by the cardiac muscles from the blood?

Q12. Which of the vessels does not have sympathetic control?

Q13. What causes positive bathmotropic effect on heart?

Q14. On what factor does the force of contraction within physiological limit in the heart directly depend on?

Q15. What is the influence of increased vagal tone on heart? Q16. Name the physiologists who proposed that an increase in pressure inside most small arteries unexpectedly results in a vasoconstriction.

Q17. An increase in the heart rate during inspiration and a decrease during expiration are known as?

Q18. Which organ receives the maximum amount of cardiac output under resting condition?

Q19. Which volume is directly related to preload in heart function?

Q20. Name the reflex that causes increase in heart rate due to increase in venous return or blood volume.

Subjective Questions

Q1. Discuss the functional anatomy of the myocardial and pacemaker cells and the special properties of the car­diac muscle cells.

Q2. Write briefly on the autorhythmicity and conduction system of the heart.

Q3. Explain the various phases of cardiac cycle and associated events.

Q4. Discuss the different control mechanisms of cardiac output regulation.

Q5. Explain the short-term regulation of blood pressure.

Q6. Describe in detail about the long-term regulation of blood pressure.

Q7. Write a note on the role of capillary circulation and exchange dynamics.

Q8. Describe in detail the various methods to estimate the cardiac output.

Q9. Discuss in detail about the lymphatic circulation.

Q10. Write briefly on the cerebral circulation.

Q11. Write note on the coronary circulation.

Q12. Discuss in brief on the fetal circulation.

Q13. Discuss in detail about the special features of pulmo­nary circulation.

Q14. Describe the etiology of shock and the various stages involved.

Q15. Describe the various circulatory changes occurring during exercise.

Answer to Objective Questions

A1. Slow voltage-gated calcium channels

A2. -55 to -60 mV

A3. Diastasis

A4. Bulging of AV valves into the atrium

A5. Veins

A6. Contraction of the capacitance vessels

A7. Ability to relax

A8. K⁺ channels

A9. First heart sound

A10. Low resting membrane potential and leakiness to Na⁺ ions

A11. 15 mL O₂/100 mL

A12. Cerebral vessels

A13. Stimulation of sympathetic nerves

A14. Initial length of the cardiac muscle

A15. Bradycardia

A16. Sir William Bayliss

A17. Respiratory sinus arrhythmia

A18. Liver

A19. Venous return

A20. Bainbridge reflex

Keywords for Answer to Subjective Questions

A1. Contractile myofibrils, syncytium, desmosomes, gap junctions, conductivity, contractivity, all or none prin­ciple staircase phenomenon, refractory period, extrasystoles

A2. Leaky sodium channels, low resting membrane poten­tial, nodal cells, Purkinje cells, transitional cells, sino­atrial node, atrioventricular node, Purkinje fibers, Bundle of his

A3. Isometric contraction, maximum ejection, reduced ejection, protodiastole, isovolumetric relaxation, rapid filling, reduced filling, atrial systole, pressure changes, volume changes, sound changes, electrical changes

A4. Intrinsic regulation, heterometric regulation, homeometric autoregulation, extrinsic regulation, ner­vous control, reflex control, chemical regulation, humoral control

A5. Nervous regulation, reflex mechanism, baroceptor reflex, atrial volume receptor reflex, Bainbridge reflex, psychogenic responses, local control myogenic theory, metabolic theory

A6. Regulation by extracellular fluid volume renin­angiotensin mechanism

A7. Continuous capillaries, discontinuous capillaries, fenestrated capillaries, diffusion

A8. Transthoracic or esophageal echocardiography, indica­tor dilution technique, Fick method, pressure recording analytical method (PRAM)

A9. Lymph capillaries, lymphangions, thoracic and right lymphatic ducts

A10. Circulus arteriosus cerebri, blood-brain barrier, hypoxia-stimulated cerebral vasodilation

A11. Right and left coronary arteries, coronary sinus, ante­rior coronary veins, arteriosinusoidal vessels, collateral coronary arteries, and Thebesian veins

A12. Ductus arteriosus, foramen ovale and ductus arteriosus, ductus venosus

A13. Low-resistance, low-pressure system, relatively great distensibility and collapsibility of the pulmonary vessels

A14. Circulatory failure, cardiogenic, hypovolemic and sep­tic shock, anaphylactic shock and histamine shock, compensated circulatory shock, progressive circulatory shock, irreversible circulatory shock

A15. Sympathetic activation, increased end-diastolic vol­ume, increased pulmonary blood flow, increased coro­nary flow, increased blood flow to the skin, coronary vasodilation

Further Reading

Textbooks

Berne RM, Levy MN (2000) Cardiovascular physiology, 8th edn. Mosby Year Book, St Louis, MO, pp 5-52

Boron WF, Boulpaep EL (eds) (2008) Medical physiology, 2nd edn. Saunders Elsevier, Philadelphia

Boulpaep EL (2009) Organization of the cardiovascular system. In: Boron WF, Boulpaep EL (eds) Medical physiology, 2nd edn. Saunders Elsevier, Philadelphia

Braunwald E, Ross J Jr, Sonnenblick EJ (1968) Mechanisms of contrac­tion of the normal and failing heart. Little, Brown, Boston

Cohen PF (1985) Cardiac pumping action and its regulation. In: Cohen PF, Brown EJ Jr, Vlay SC (eds) Clinical cardiovascular physiology. W.B. Saunders, Philadelphia

Dzialowski EM, Crossley DA (2015) Chapter 11 - The cardiovascular system. In: Scanes CG (ed) Sturkie’s avian physiology, 6th edn. Academic, pp 193-283

Erickson HH, Detweiler DK (2004) Control mechanisms of the circula­tory system. In: Reece WO (ed) Dukes’ physiology of domestic animals, 12th edn. Cornell University Press, Ithaca, NY, pp 275-302 Ganong WF, Barrett KE, Barman SM, Boitano S, Brooks HL (2015) Review of medical physiology. McGraw-Hill Medical, New York

Grant AO (2009) Cardiac ion channels. Circ Arrhyth Electrophysiol 2: 185-194

Hall JE (2015) Guyton and Hall textbook of medical physiology, 13th edn. W B Saunders

Katz AM (2011) Physiology of the heart, 5th edn. Wolters Kluwer Lippincott Williams & Wilkins, Philadelphia

King AS (1999) The cardiorespiratory system. Blackwell Science, Oxford

Mohrman DE (2010) Cardiovascular physiology, 7th edn. McGraw- Hill, New York

Monfredi O, Maltsev VA, Lakatta EG (2013) Modern concepts concerning the origin of the heartbeat. Physiology 28:74-92

Pappano AJ, Wier WG (2013) Cardiovascular physiology, 10th edn. Mosby, Philadelphia

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Marengo FD, Marquez MT, Bonazzola P, Ponce-Hornos JE (1999) The heart extrasystole: an energetic approach. Am J Physiol 276(45): H309-H316