Page 86 - Small Animal Internal Medicine, 6th Edition

58 PART I Cardiovascular System Disorders

reduced effective circulating volume and other nonosmotic Renal Effects
stimuli (including sympathetic stimulation and angiotensin Renal efferent glomerular arteriolar constriction, mediated
VetBooks.ir II) cause continued release of ADH in patients with heart by sympathetic stimulation and angiotensin II, helps main-
tain glomerular filtration in the face of reduced cardiac
failure. The continued release of ADH contributes to the
dilutional hyponatremia sometimes found in patients with
hydrostatic pressures develop in the peritubular capillaries,
heart failure. output and renal blood flow. Higher oncotic and lower
Increased circulating concentrations of other substances enhancing the reabsorption of tubular fluid and sodium.
with a role in abnormal cardiovascular hypertrophy and/or Angiotensin II–mediated aldosterone release further pro-
fibrosis, including cytokines (e.g., TNF α ) and endothelins, motes sodium and water retention. Continued activation of
also have been detected in animals with severe heart failure. these mechanisms leads to clinical edema and effusions.
Endothelin is a potent vasoconstrictor whose precursor Afferent arteriolar vasodilation mediated by endogenous
peptide is produced by vascular endothelium. Endothelin prostaglandins and natriuretic peptides can partially offset
production is stimulated by hypoxia and vascular mechani- the effects of efferent vasoconstriction, but progressive
cal factors and also by angiotensin II, ADH, norepinephrine, impairment of renal blood flow leads to renal insufficiency.
cytokines (including TNF α and interleukin-I), and other Diuretics not only can magnify azotemia and electrolyte loss
factors. but also further reduce cardiac output and activate NH
Endogenous mechanisms that oppose the vasoconstrictor mechanisms.
responses also are activated. These include natriuretic pep-
tides, adrenomedullin, nitric oxide (NO), and vasodilator Other Effects of Heart Failure
prostaglandins. Normally, a balance between vasodilator and Reduced exercise capacity occurs in patients with heart
vasoconstrictor effects maintains circulatory homeostasis, as failure. Although cardiac output may be fairly normal at rest,
well as renal solute excretion. As heart failure progresses, the the ability to increase cardiac output in response to exercise
influence of the vasoconstrictor mechanisms predominates is impaired. Inadequate forward output, poor diastolic filling,
despite increased activation of vasodilator mechanisms. and pulmonary edema or pleural effusion can interfere with
Natriuretic peptides are synthesized in the heart and exercise ability. Furthermore, impaired peripheral vasodi-
play an important role in regulating blood volume and lation during exercise contributes to inadequate skeletal
pressure. Atrial natriuretic peptide (ANP) is synthesized muscle perfusion and fatigue. Excessive peripheral sympa-
by atrial myocytes as a prohormone, which is then cleaved thetic tone, angiotensin II (both circulating and locally pro-
to the active peptide after its release. Mechanical stretch duced), and vasopressin can contribute to impaired skeletal
of the atrial wall stimulates ANP release. Brain natriuretic muscle vasodilatory capacity in patients with CHF. Increased
peptide (BNP) also is synthesized in the heart, mainly by vascular wall sodium content and interstitial fluid pressure
the ventricles in response to myocardial dysfunction or stiffen and compress vessels. Other mechanisms can include
ischemia. Natriuretic peptides promote diuresis, natriure- impaired endothelium-dependent relaxation, increased
sis, and peripheral vasodilation. They act to antagonize the endothelin concentration, and vascular wall changes induced
effects of the RAAS, and also can alter vascular permeabil- by the growth factor effects of various NH vasoconstrictors.
ity and inhibit growth of smooth muscle cells. Natriuretic ACE inhibitor (ACEI) therapy, with or without spironolac-
peptides are degraded by neutral endopeptidases. Circulat- tone, may improve endothelial vasomotor function and exer-
ing concentrations of ANP, BNP, and their precursor pep- cise capacity. Pulmonary endothelial function is improved
tides (such as NT-proBNP) increase in patients with heart by ACEIs in dogs with CHF.
failure. This increase has been correlated with pulmonary
capillary wedge pressure and severity of heart failure in both GENERAL CAUSES OF HEART FAILURE
dogs and people. Adrenomedullin is another natriuretic The causes of heart failure are quite diverse. It can be useful
and vasodilatory peptide produced in the adrenal medulla, to think of them in terms of underlying pathophysiology. In
heart, lung, and other tissues thought to play a role in most cases of heart failure, the major initiating abnormality
heart failure. entails myocardial (systolic pump) failure, systolic pressure
NO, produced by the vascular endothelium in response overload, volume overload, or reduced ventricular compli-
to endothelial-nitric oxide synthetase (NOS), is a functional ance (impaired filling). Nevertheless, several pathophysio-
antagonist of endothelin and angiotensin II. This response is logic abnormalities often coexist. Both systolic and diastolic
impaired in patients with heart failure. At the same time, function abnormalities are common in patients with
myocardial inducible–NOS expression is enhanced; myocar- advanced failure.
dial NO release has negative effects on myocyte function. Myocardial failure is characterized by poor ventricular
Intrarenal vasodilator prostaglandins oppose the action of contractile function. It most commonly occurs from idio-
angiotensin II on the renal vasculature. The use of prosta- pathic dilated cardiomyopathy (DCM) but also from known
glandin synthesis inhibitors in dogs or cats with severe heart causes of impaired myocardial contractility. Valvular insuf-
failure could potentially reduce glomerular filtration (by ficiency may or may not be present initially but usually
increasing afferent arteriolar resistance) and enhance sodium develops as the affected ventricle dilates. Persistent tachyar-
retention. rhythmias, some nutritional deficiencies, and other cardiac