Page 84 - Small Animal Internal Medicine, 6th Edition

56 PART I Cardiovascular System Disorders

Eventually, decompensation and myocardial failure develop. catecholamines. β-blocking agents can reverse β 1 -receptor
In patients with primary myocardial diseases, initial cardiac downregulation but may worsen heart failure. Cardiac β 2 -
VetBooks.ir pressure and volume loads are normal; however, intrinsic and α 1 -receptors also are present but are not downregulated;
these are thought to contribute to myocardial remodeling
defects of the heart muscle lead to observed hypertrophy or
secondary dilation.
(β 3 -receptors) may promote further myocardial function
Cardiac hypertrophy and other remodeling changes begin and arrhythmogenesis. Another cardiac receptor subtype
long before heart failure becomes manifest. Biochemical deterioration through a negative inotropic effect.
abnormalities involving cell energy production, calcium Normal feedback regulation of sympathetic nervous and
fluxes, and contractile protein function can contribute to this hormonal systems depends on arterial and atrial barorecep-
process. Eventually, ventricular function progressively dete- tor function. Baroreceptor responsiveness becomes attenu-
riorates as contractility and relaxation become more ated in chronic heart failure, which contributes to sustained
deranged. Clinical heart failure can be considered a state of sympathetic and hormonal activation and reduced inhibi-
decompensated hypertrophy. tory vagal effects. Baroreceptor function can improve with
reversal of heart failure, increased myocardial contractil-
SYSTEMIC RESPONSES ity, decreased cardiac loading conditions, or inhibition of
Neurohormonal Mechanisms angiotensin II and aldosterone (which directly attenuate
Neurohormonal (NH) responses contribute to cardiac baroreceptor sensitivity). Digoxin has a positive effect on
remodeling and also have more far-reaching effects. Over baroreceptor sensitivity.
time, excessive activation of NH “compensatory” mecha- The renin-angiotensin system (RAAS) has far-reaching
nisms leads to the clinical syndrome of CHF. Although these effects. Whether systemic renin-angiotensin-aldosterone
mechanisms support circulation in the face of acute hypo- activation always occurs before overt congestive failure is
tension and hypovolemia, their chronic activation acceler- unclear and may depend on the underlying etiology. Renin
ates the deterioration of cardiac function. Major NH changes release from the renal juxtaglomerular apparatus occurs sec-
in heart failure include increased sympathetic nervous tone, ondary to low renal artery perfusion pressure, renal
+
attenuated vagal tone, renin-angiotensin-aldosterone system β-adrenergic receptor stimulation, and reduced Na delivery
activation, and increased release of vasopressin (antidiuretic to the macula densa of the distal renal tubule. Stringent
hormone, ADH-) and endothelin. These NH systems work dietary salt restriction and diuretic or vasodilator therapy
independently and also interact together to increase vascular can promote renin release. Renin facilitates conversion of the
volume (by enhancing sodium and water retention and precursor peptide angiotensinogen to angiotensin I (an inac-
thirst) as well as vascular tone (Fig. 3.1). The expanded vas- tive form). Angiotensin-converting enzyme (ACE), found in
cular volume increases ventricular filling (preload), which the lung and elsewhere, converts angiotensin I to the active
then enhances cardiac output. However, this comes at the angiotensin II and is involved in the degradation of certain
cost of increased venous and capillary pressure, which pro- vasodilator kinins. There are also alternative pathways for
motes interstitial fluid accumulation. Although increased angiotensin II generation.
lymphatic flow helps moderate the effects of rising venous Angiotensin II has several important effects, including
pressure, continued volume retention eventually leads to potent vasoconstriction and stimulation of aldosterone
edema and effusions. Prolonged systemic vasoconstriction release from the adrenal cortex. Additional effects of angio-
increases the workload on the heart, can reduce forward tensin II include increased thirst and salt appetite, facilita-
cardiac output, and may exacerbate valvular regurgitation. tion of neuronal norepinephrine synthesis and release,
The extent to which these mechanisms are activated varies blockade of neuronal norepinephrine reuptake, stimulation
with the severity and etiology of heart failure. In general, as of vasopressin (ADH) release, and increased adrenal epi-
failure worsens, NH activation increases. Increased produc- nephrine secretion. Inhibition of ACE can reduce NH activa-
tion of endothelins and proinflammatory cytokines, as well tion and promote vasodilation and diuresis. Local production
as altered expression of vasodilatory and natriuretic factors, of angiotensin II also occurs in the heart, vasculature, adrenal
also contributes to the complex interplay among these NH glands, and other tissues in dogs and cats. Local activity
mechanisms and their consequences. affects cardiovascular structure and function by enhancing
The effects of sympathetic stimulation (such as increased sympathetic effects and promoting tissue remodeling that
contractility, heart rate, and venous return) can initially can include hypertrophy, inflammation, and fibrosis. Tissue
increase cardiac output. However, over time, these effects chymase is thought to be more important in the conversion
become detrimental by increasing afterload stress and myo- to active angiotensin II than ACE in the myocardium and
cardial oxygen requirements, contributing to cellular damage extracellular matrix.
and myocardial fibrosis, and enhancing the potential for Aldosterone promotes sodium and chloride reabsorption,
cardiac arrhythmias. Persistent sympathetic stimulation as well as potassium and hydrogen ion secretion in the renal
reduces cardiac sensitivity to catecholamines. Downregula- collecting tubules; the concurrent water reabsorption aug-
tion (reduced number) of myocardial β 1 -receptors and other ments vascular volume. Increased aldosterone concentration
changes in cellular signaling can help protect the myocar- can promote hypokalemia, hypomagnesemia, and impaired
dium against the cardiotoxic and arrhythmogenic effects of baroreceptor function. It can potentiate the effects of