Page 533 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Fluid and Diuretic Therapy in Heart Failure 521

problems. 57 Neurohormones and cytokines, angiotensin with the type and severity of heart failure. 46,141 However,
in particular, are considered central to the progression of it is clear that with deterioration in cardiac function,
renal disease in heart failure. 80 Aggressive therapy of heart sodium- and water-retaining mechanisms are
failure may slow progression of renal disease in humans. 89 exacerbated, and further expansion of the plasma volume
The renal response to decreased cardiac output is cen- occurs. Blunting the renal response generally requires
tral to the pathogenesis of edema and effusions in heart appropriate medical treatment of CHF, progressive
failure. Studies of induced right-sided heart failure and restriction of dietary sodium, and administration of
spontaneous CHF in dogs have demonstrated avid reten- diuretics.
tion of administered salt loads. 9,84 Numerous In CHF, the vasoconstrictive and sodium-retaining
mechanisms have been identified for persistent sodium mechanisms overwhelm local and systemic vasodilator
retention in CHF (see Figure 21-3). These alterations and natriuretic systems. Distention of the atria and
include redistribution of renal blood flow, 9,131 enhanced ventricles signals release of atrial natriuretic peptide
tubular sodium reabsorption, 8,91,102 release of (ANP) and brain natriuretic peptide (BNP). These
prostaglandins, 36,38,111 greater renal sympathetic nerve peptides of cardiac origin stimulate formation of cyclic
activity,* increased renal interstitial pressure, 58,101 and GMP, leading to diuresis, vasodilatation, and improved
increased hormonal activity. The last includes increases ventricular relaxation. 107,113 Although increased
in vasopressin (ADH), 16,136 angiotensin II, and aldoste- circulating concentrations of ANP and BNP can be
{
rone (see Box 21-4). Presumably, these mechanisms also measured in dogs with experimentally induced and spon-
operate in animals with spontaneous heart failure. 134 taneous CHF,* it also has been shown that the renal
Particular emphasis has been placed on the increased response to these hormones is blunted or antagonized.
21,104,135
concentrations of renin, angiotensin II, and aldosterone If dogs or people with CHF are treated with
found in patients with CHF. 121 There are a number of pharmacologic doses of ANP, however, or if the degrada-
triggers for the release of renin in the cardiac patient. 113 tion of ANP is reduced by administration of a neutral
One mechanism is the stimulation of renal ß-adrenergic endopeptidase inhibitor, diuresis may follow. 104,110
receptors by sympathetic efferent traffic activated in Other vascular-modulating factors, such as the vasodila-
response to hypotension. Renin also is released in tor nitric oxide, are more difficult to assess in CHF,
response to reduced renal blood flow related to heart fail- but metabolites of this endothelial-derived substance
ure or volume depletion caused by diuretic therapy of reportedly are decreased in some dogs with mitral
CHF. 182 Severe sodium restriction, especially in dogs regurgitation. 126
with signs of heart disease but without overt CHF, can
lead to renin release. 127 Clinically, the effects of angioten- CARDIOVASCULAR DRUGS
sin II and aldosterone can be mitigated in part by drugs AND RENAL FUNCTION
that inhibit formation of angiotensin II (angiotensin-
converting enzyme [ACE] inhibitors such as enalapril
and benazepril) or drugs that block the AT-1 receptor EFFECTS OF DIURETICS ON
of angiotensin II, such as losartan and candesartan. RENAL FUNCTION
Other factors promote renal fluid retention in CHF. Diuretics used in management of CHF prevent reabsorp-
Changes in intrarenal blood flow can lead to redistribu- tion of solute and water, leading to increased urine flow.
tion of flow to the salt-conserving juxtamedullary Diuretics are essential to both the short- and long-term
nephrons. 16,91,93 Increased filtration fraction maintains management of CHF. While there are no blinded clinical
the glomerular filtration rate (GFR) but predisposes to trials evaluating the efficacy of furosemide, experienced
renal tubular reabsorption of water (see Chapter 2). Argi- clinicians repeatedly observe the short-term benefit of
nine vasopressin (ADH) also plays a role. In CHF, furosemide diuresis in veterinary patients with life-threat-
increases in plasma ADH concentration probably repre- ening pulmonary edema. In a 3-week study of dogs with
sent nonosmotic release in response to low ABP. 122 CHF, pulmonary wedge pressure, an estimate of left atrial
Increased thirst (mediated by angiotensin II), when com- pressure, declined within hours after initiating furose-
bined with increases in ADH, can contribute to free- mide and remained below baseline after 21 days of ther-
water retention and hyponatremia. 35,99,120 Endothelin apy. 71 Despite the lack of study in terms of chronic
is another hormone released from endothelial cells in efficacy, diuretics are a mainstay for acute and chronic
CHF. 132,176 This hormone reduces renal blood flow, treatment of CHF in dogs, cats, and humans. 70 They
the GFR, and urinary sodium excretion. 98,122 The reduce preload by decreasing cardiac filling (venous)
sequence in which these mechanisms are activated varies pressures and chronically prevent the excessive dietary
9
sodium retention characteristic of CHF, allowing for a
*References 23, 66, 90, 114, 151, 168. new steady state of sodium balance to develop. 70
{ References 22, 27, 37, 51, 54, 63, 68, 70a, 77, 86, 88, 116, 118, 137,
138, 159. *References 4, 24, 29, 59, 96, 133, 175.