Compensatory Mechanisms

In the setting of a sustained loss of myocardium, a number of mechanisms aid the heart when faced with an increased hemodynamic burden and reduced CO. They include the Frank-Starling mechanism, tachycardia and increased afterload, and cardiac hypertrophy and remodeling (Table 6-2). ,7

Table 6-2 Beneficial and Detrimental Effects of the Compensatory Responses in Heart Failure

Compcnsfllorv Rnpnnw

Bintftdtl Efiull oF ComptniiHon

Dfltri mvnti I Fllnli «1 i"n in |icjimtion

intreased piofcail ([hioujh sodium and wiler reiention}

OfuidndlVvIa FiartiiariHig (rBthaflJsm

hitauriiiyindsyitRfiHc¿ongeickhn ¿r.d Menu fbrmdtbn

WO

Vasoconsuiictlon

r^jlncaoeiJ El^andpeiluslorun [he Uco of reduced CO

increased MVO

Increased afterload decreases SV and luMher achates the compewrtpri iOifxjhsn^

Tactycardia and increased s yi\lPiK 1ili(y GJjtMtfSNi? aahfation}

^hoflcned [ijylulit niirKj time

¿^-Receptor downiiegftilatlon. :lenea<ed ipfepmr sensitivity [•nv ipK.-jion of venrnciji.ir Hrhyfhmiis Increased pisltof mytxanWl cell dtsilh

ViTirriaiLji I |:- ■ i r i: jh->--i1111 remodeling

Reduced moocafdial wall stress

QlWtpllC [¡f.furif 1 Kjn

Systolic dysfunction !ncr«u«l ri+of nrvxiiriial «11 dwih Increased riAcf rr^Scaitfdl Ischemia tjCN«^ .VrfiyNiiilhl rrtft

Bf, blood pressure; GQ cardiac ourpui; WWO, myocardial oxygen consumption SUS, synrtuiherk: nervoui sysiem SV, strafee volume.

Bf, blood pressure; GQ cardiac ourpui; WWO, myocardial oxygen consumption SUS, synrtuiherk: nervoui sysiem SV, strafee volume.

Preload and the Frank-Starling Mechanism

In the setting of a sudden decrease in CO, the natural response of the body is to decrease blood flow to the periphery in order to maintain perfusion to the vital organs such as the heart and brain. Therefore, renal perfusion is compromised due to both the decreased CO, as well as shunting of blood away from peripheral tissues. This results in activation of the renin-angiotensin-aldosterone system (RAAS). The decrease in renal perfusion is sensed by the juxtaglomerular cells of the kidneys leading to the release of renin and initiation of the cascade for production of angiotensin II (AT2). AT2 stimulates the synthesis and release of aldosterone. Aldosterone in turn stimulates sodium and water retention in an attempt to increase intravascular volume, and hence preload. In a healthy heart, a large increase in CO is usually accomplished with just a small change in preload. However, in a failing heart, alterations in the contractile filaments reduce the ability of cardiomyocytes to adapt to increases in preload. Thus, an increase in preload actually impairs contractile function in the failing heart and results in a further decrease in CO.

Tachycardia and Increased Afterload

Another mechanism to maintain CO when contractility is low is to increase HR. This is achieved through sympathetic nervous system (SNS) activation and the agonist effect of norepinephrine on P-adrenergic receptors in the heart. Sympathetic activation also enhances contractility by increasing cytosolic calcium concentrations. SV is relatively fixed in HF, thus HR becomes the major determinant of CO. Although this mechanism increases CO acutely, the chronotropic and inotropic responses to sympathetic activation increase myocardial oxygen demand, worsen underlying ischemia, contribute to proarrhythmia, and further impair both systolic and diastolic function.

Activation of both the RAAS and the SNS also contribute to vasoconstriction in an attempt to redistribute blood flow from peripheral organs such as the kidneys to

coronary and cerebral circulation. However, arterial vasoconstriction leads to impaired forward ejection of blood from the heart due to an increase in afterload. This results in a decrease in CO and continued stimulation of compensatory responses, creating a vicious cycle of neurohormonal activation.

Cardiac Hypertrophy and Remodeling

Ventricular hypertrophy, an adaptive increase in ventricular muscle mass due to growth of existing myocytes, occurs in response to an increased hemodynamic burden such as volume or pressure overload.5 Hypertrophy can be concentric or eccentric.

Concentric hypertrophy occurs in response to pressure overload such as in long-standing hypertension or pulmonary hypertension, whereas eccentric hypertrophy occurs after an acute MI. Eccentric hypertrophy involves an increase in myocyte size in a segmental fashion, as opposed to the global hypertrophy occurring in concentric hypertrophy. Although hypertrophy helps to reduce cardiac wall stress in the short term, continued hypertrophy accelerates myocyte cell death through an overall increase in myocardial oxygen demand.

Cardiac remodeling occurs as a compensatory adaptation to a change in wall stress and is largely regulated by neurohormonal activation, with AT2 and aldosterone being key stimuli. The process entails changes in myocardial and extracellular matrix composition and function, which results in both structural and functional alterations to the heart. In HF, the changes in cardiac size, shape, and composition are pathologic and detrimental to heart function. In addition to myocyte size and extracellular matrix changes, heart geometry shifts from an elliptical to a less efficient spherical shape. Even after remodeling occurs, the heart can maintain CO for many years. However, heart function will continue to deteriorate until progression to clinical HF. The timeline for remodeling varies depending on the cardiac insult. For example, in the setting of an acute MI, remodeling starts within a few days.5 Chronic remodeling, however, is what progressively worsens HF and therefore is a major target of drug therapy.

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