Cardiac Physiology

Question 1

Diastole is ventricular relaxation, and it occurs in four distinct phases: …

Answer 1

(1) isovolumic relaxation;

(2) the rapid filling phase (i.e., the LV chamber filling at variable left ventricular pressure);

(3) slow filling, or diastasis;

(4) final filling during atrial systole

Question 2

Laplace’s law states that

Answer 2

wall stress (σ) is the product of pressure (P) and radius (R) divided by wall thickness (h):

σ=P × R/2h

Question 3

The work of the heart can be divided into
external and internal work.
External work is …, whereas internal work is … I

Wall stress is directly proportional to the … work of the heart

Answer 3

expended to eject blood under pressure

expended within the ventricle to change the shape of the heart and to prepare it for ejection

internal

Question 4

External work, or stroke work, is a product of the …

Answer 4

SV and pressure (P) developed during ejection of the SV.

Stroke work = SV × P or (LVEDV – LVESV) × P

Question 5

Describe the treppe, which means staircase in
German, phenomenon

Answer 5

In isolated cardiac muscle, an increase in the frequency of stimulation induces an increase in the force of contraction.

• At between 150 and 180 stimuli per
  minute, maximal contractile force is reached in an isolated heart muscle at a fixed muscle length

Question 6

Cardiac output is the amount of blood pumped by the heart per unit of time (Q˙ ) and is determined by four factors:

Answer 6

• Heart rate
• Myocardial contractility
• Preload
• Afterload.

Question 7

Phases of cellular action potentials and major associated currents in ventricular myocytes. The initial phase (0) spike and overshoot are caused by …; The rapid upstroke is followed by a transient repolarization (phase 1). Phase (1) is a period of brief and limited repolarization that is largely attributable to the activation of …; the plateau phase is caused (2) by …, and repolarization (phase 3) by outward potassium (K+) currents.
Phase 4, the resting potential (Na+ efflux, K+ influx), is maintained by …

Answer 7

a rapid inward sodium (Na+) current

a transient outward K+ current, ito

a net influx of Ca2+ through L-type Ca2+ channels and the efflux of K+ through several K+ channels —the inwardly rectifying ik, the delayed
rectifier ik1, and ito

Na+-K+-adenosine triphosphatase (ATPase)

Question 8

Pacemaker currents during phase 4 are the result of an increase in the three inward currents and a decrease in the two outward currents. The three inward currents that contribute to spontaneous pacemaker
activity include two carried by Ca2+,…, and one
that is a mixed cation current, …

The two outward currents are the delayed rectifier K+ current, ik, and the inward
rectifying K+ current, ik1. When compared with the fastresponse action potential, phase 0 is much less steep, phase 1 is absent, and phase 2 is indistinct from phase 3 in the slow-response action potential

Answer 8

iCaL and iCaT

If

Question 9

In SA node cells, the pacemaker …
current is the principal determinant of duration
diastolic depolarization, and it is encoded by four members of the hyperpolarization-activated cyclic nucleotide-gated gene (HCN1-4) family

Answer 9

If

Question 10

The … is the ATP-dependent pump that actively pumps the majority of the Ca2+ back into the SR after its release

Answer 10

sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pump

Question 11

The contractile apparatus within the cardiomyocyte consists of contractile and regulatory proteins. The thin-filament … and the thick-filament … are the two principal contractile proteins

Answer 11

actin

myosin

Question 12

The regulatory troponin heterotrimer
complex is found at regular intervals along tropomyosin. The heterotrimer troponins are made up of …

Answer 12

troponin C (TnC), the Ca2+ receptor; TnI, an inhibitor of actin-myosin interaction; and TnT, which links the troponin complex to tropomyosin

Question 13

The Frank-Starling relationship states that an increase in end-diastolic volume results in enhanced systolic function. At the cellular level, the key component for the Frank-Starling relationship is a length-dependent shift in …

Answer 13

Ca2+ sensitivity

• Several possible mechanisms for this change
  in Ca2+ sensitivity have been implicated, including Ca2+ sensitivity: as a function of myofilament lattice spacing, involving positive cooperativity in cross-bridge binding to actin, and
  dependence on a strain of the elastic protein titin

Question 14

M2 receptors are the predominant muscarinic receptor subtype found in the mammalian heart. In the coronary circulation, M3 receptors have been identified. Moreover, non-M2 receptors have also been reported to exist in the heart. In general, for intracellular signaling, M1, M3, and M5 receptors couple to … protein and activate the … system.

On the other hand, the M2 and M4 receptors couple to the …, to inhibit adenylyl cyclase. M2 receptors can couple to certain K+ channels and influence the activity of Ca2+ channels, If
current, phospholipase A2, phospholipase
D, and tyrosine kinases

Answer 14

Gq/11

phospholipase C-diacylglycerol-inositol phosphate

pertussis toxin-sensitive G protein, Gi/o

Question 15

In contrast to vagal innervation, sympathetic innervation of the heart is more predominant in the …

Answer 15

ventricle than in the atrium

Question 16

Hormones with cardiac actions can be
synthesized and secreted by cardiomyocytes or produced by other tissues and delivered to the heart. They act on specific receptors expressed in cardiomyocytes. Most of these hormone receptors are plasma membrane GPCRs. NonGPCRs include the …

Answer 16

• natriuretic peptide receptors, which are guanylyl cyclase-coupled receptors
• the glucocorticoid and mineralocorticoid receptors, which bind androgens and aldosterone and are nuclear zinc finger transcription factors

Question 17

Angiotensin II effects on the herat

Answer 17

Angiotensin II stimulates two separate receptor subtypes, AT1 and AT2, both of which are present in the heart.

AT1 receptors are the predominant subtype expressed in the normal adult human heart. Stimulation of AT1 receptors induces a positive chronotropic and inotropic effect.
Angiotensin II also mediates cell growth and proliferation in cardiomyocytes and fibroblasts, and induces the release of the growth factors aldosterone and catecholamines through
the stimulation of AT1 receptors. Activation of AT1 receptors is directly involved in the development of cardiac hypertrophy and heart failure, as well as adverse remodeling of the
myocardium.

In contrast, AT2 receptor activation is counterregulatory and generally antiproliferative. Expression of AT2 receptors, however, is relatively scant in the adult heart because AT2 receptors are most abundant in the fetal heart and decline with development. In response to injury and ischemia, AT2 receptors become upregulated. The precise role of AT2 receptors in the heart remains to be defined

Question 18

Is a recently discovered cardiac hormone that was originally isolated from pheochromocytoma tissue. It increases the accumulation of cAMP and has direct positive chronotropic and inotropic effects.
With interspecies and regional variations,
has also been shown to increase nitric oxide production, and it functions as a potent vasodilator.

Answer 18

Adrenomedullin

Question 19

How does menopause affect the cardiovascular system?

Answer 19

Cardiac contractility is more intense in premenopausal women than in age-matched men, and withdrawal of hormone replacement therapy in postmenopausal women leads to a reduction in cardiac contractile function. The
gender dimorphism in heart function and its adaptive responses to injury and disease states are partly mediated by sex steroid hormones. Indeed, healthy premenopausal women exhibit a lower cardiovascular risk compared to men, which suggests a mechanism for sex hormones in the modulation of cardiac function

Question 20

The nucleus …, located in the cardiovascular center of the … , receives impulses from stretch receptors located in the carotid sinus and the aorta arch through afferents of the glossopharyngeal and vagus nerves

Answer 20

solitarius

medulla

Question 21

At an arterial partial O2 pressure (PaO2) of less than 50 mm Hg or in conditions of acidosis,
the chemoreceptors send their impulses along the sinus nerve of … (a branch of the glossopharyngeal nerve) and the tenth cranial nerve to the chemosensitive area of
the medulla. This area responds by stimulating the …

In addition, activation of the parasympathetic system ensues and leads to a reduction in heart rate and myocardial contractility.

In the case of persistent hypoxia, the CNS will be directly stimulated, with a resultant increase in …

Answer 21

Hering

respiratory centers and thereby increasing ventilatory drive

sympathetic activity

Question 22

Explain the Bainbridge Reflex

Answer 22

The Bainbridge reflex is elicited by stretch receptors located in the right atrial wall and the cavoatrial junction. An increase in right-sided filling pressure sends vagal afferent signals to the cardiovascular center in the medulla. These afferent signals inhibit parasympathetic activity, thereby increasing the heart rate. Acceleration of the heart rate also results from a direct effect on the SA node by stretching the atrium. The changes in heart rate are dependent on the underlying heart rate before stimulation

Question 22

Explain the Bezold-Jarisch reflex

Answer 22

The Bezold-Jarisch reflex responds to noxious ventricular stimuli sensed by chemoreceptors and mechanoreceptors within the left ventricular wall by inducing the triad of hypotension, bradycardia, and coronary artery dilatation.

The activated receptors communicate along unmyelinated vagal afferent type C fibers. These fibers reflexively increase parasympathetic tone. Because it invokes bradycardia, the Bezold-Jarisch reflex is thought of as a cardioprotective
reflex. This reflex has been implicated in the physiologic response to a range of cardiovascular conditions such as myocardial ischemia or infarction, thrombolysis, or revascularization and syncope.

Natriuretic peptide receptors stimulated by endogenous ANP or BNP may modulate the
Bezold-Jarisch reflex. Thus, the Bezold-Jarisch reflex may be less pronounced in patients with cardiac hypertrophy or atrial fibrillation

Question 23

Explain the Valsalva maneuver

Answer 23

Forced expiration against a closed glottis produces increased intrathoracic pressure, increased central venous pressure, and decreased venous return. Cardiac output and
blood pressure will be decreased after the Valsalva maneuver. This decrease will be sensed by baroreceptors and will reflexively result in an increase in heart rate and myocardial contractility through sympathetic stimulation.

When the glottis opens, venous return increases and causes the heart to respond by vigorous contraction and an increase in blood pressure. This increase in arterial blood pressure will,
in turn, be sensed by baroreceptors, thereby stimulating the parasympathetic efferent pathways to the heart.

Question 24

Explain the cushing reflex

Answer 24

The Cushing reflex is a result of cerebral ischemia caused by increased intracranial pressure. Cerebral ischemia at the medullary vasomotor center induces initial activation of the
sympathetic nervous system. Such activation will lead to an increase in heart rate, arterial blood pressure, and myocardial contractility in an effort to improve cerebral perfusion. As a result of the high vascular tone, reflex bradycardia mediated by baroreceptors will ensue

Question 25

Explain the oculocardiac reflex

Answer 25

The oculocardiac reflex is provoked by pressure applied to the globe of the eye or traction on the surrounding structures. Stretch receptors are located in the extraocular muscles. Once activated, stretch receptors will send afferent signals through the short- and long-ciliary nerves. The ciliary nerves will merge with the ophthalmic division of the trigeminal nerve at the ciliary ganglion. The trigeminal nerve will carry these impulses to the gasserian ganglion, thereby resulting in increased parasympathetic tone
and subsequent bradycardia. The incidence of this reflex during ophthalmic surgery ranges from 30% to 90%

• Administration of an antimuscarinic drug such as glycopyrrolate or atropine reduces the incidence of bradycardia during eye surgery