Page 542 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

530 FLUID THERAPY

HOME THERAPY spaniels. 87 Other studies have shown efficacy for
benazepril, 82 including the relatively large BENCH study
Chronic therapy of CHF targets the kidney, heart, and
of dogs with CHF caused by mitral regurgitation or
vascular tree, while attempting to minimize neurohor- 130
dilated cardiomyopathy. In the latter trial, benazepril
monal injury to cardiac and vascular tissues. By combin-
dosages of 0.5 mg/kg every 24 hours or every 12 hours
ing diuretics (usually furosemide and spironolactone)
both were effective and well tolerated in terms of renal
with an ACE inhibitor and dietary sodium restriction,
function. Other ACE inhibitors, such as ramipril, have
fluid retention is prevented. In dogs, cardiac performance
is enhanced by administration of pimobendan. 62 Further been approved in countries outside of North America
for management of canine heart failure. Based on clinical
cardiac protection may be achieved by gradual up-titra- 3,145
tion of a ß-adrenergic blocker such as carvedilol or observations, cats with chronic CHF also can benefit
bucindolol, but definitive data supporting this therapy from ACE inhibition, but a blinded, controlled, prospec-
is unavailable. Digoxin may still be useful for dogs with tive study has not yet been published. The dosage of ACE
atrial fibrillation or as a drug that will reduce sympathetic inhibitors in cats with CHF is similar if slightly lower than
that for dogs (enalapril, 0.25 mg/kg once or twice daily,
and heighten parasympathetic activity. Specific heart
increased after 1 or 2 weeks to 0.25 to 0.5 mg/kg every
rhythm disturbances such as atrial fibrillation or ventricu-
12 hours orally). Renal function should be monitored
lar tachycardia require additional antiarrhythmic drug
before and after any dosage change.
treatments. Many of these treatments impact renal func-
Spironolactone is prescribed frequently for dogs and
tionandfluidandelectrolytebalanceinthecardiacpatient.
occasionally for cats with chronic heart failure. Although
The rationale for medical therapy is considered below.
diuretic effects of this drug are minimal, ACE inhibition
A fundamental feature of CHF is dominance of vaso-
does not fully inhibit aldosterone formation in advanced
constrictive, sodium-retaining mechanisms over compet-
ing vasodilator-natriuretic systems. 46,137,139 Chronic CHF. One clinical study demonstrated the potential value
activation of the sympathetic nervous system, increased of spironolactone in canine valvular heart disease in mixed
10
formation of endothelin, and progressive stimulation of populations of dogs with and without CHF ; however,
in the author’s opinion, these survival benefits have not
the RAAS injures the myocardium, blood vessels, and
the kidney. 22,67,119,160 Neurohormonal activation clearly been demonstrated conclusively in well-defined patient
populations. In cats spironolactone has been used for
occurs in many dogs with spontaneous heart disease,
especially those with advanced heart failure. 85,125,155,178 antifibrotic effects in hypertrophic cardiomyopathy, but
at least one study failed to show clear benefit in terms
Many laboratory and clinical investigations in humans 97
of fibrosis or diastolic function.
have emphasized the beneficial effect that pharmacologic
As with the ACE inhibitors and spironolactone, ß-
blockade of the RAAS has in limiting the progression of
myocardial disease and reducing morbidity and mortality adrenergic blockers also improve left ventricular ejection
in CHF. 26,113,154 Another therapeutic advance is aldoste- fraction and inhibit myocardial remodeling and fibrosis in
rone blockade at the tissue level by administration of an humans and in animal models of myocardial fail-
1,14,42,147,148,185
aldosterone antagonist (spironolactone or ure. b-blockers are now standard therapy
eplerenone). 129,181 A tissue RAAS is present in the canine for human heart failure. However, this approach has not
been widely accepted in veterinary medicine, with the
heart, and the local chymases that convert angiotensin to
possible exception of left ventricular systolic dysfunction
its active form may not be inhibited by ACE inhibitors.
leading to the “preclinical” (before CHF) phase of cardiac
Aldosterone antagonism produces modest but measur-
failure. One problem with use of b-blockers in veterinary
able survival benefits in human patients with CHF
patients relates to the advanced state of CHF so often
and has been shown to reduce left ventricular remodeling
in dogs with experimentally induced heart failure. 161 observed. Furthermore, aside from canine model studies
and a known benefit on reducing dynamic outflow
Aldosterone also blunts baroreceptor reflexes in dogs,
obstruction in cardiomyopathy, there is no pivotal evi-
an effect that can be partially reversed by administration
of digitalis glycosides. 177 dence supporting b-blockade in spontaneous animal
Two prospective North American studies of dogs with diseases. An ongoing clinical trial with bucindolol may
CHF have demonstrated the efficacy of enalapril at address some of the outstanding questions regarding effi-
0.5 mg/kg orally every 24 hours or every 12 hours, 25,71 cacy and safety in dogs. Another issue relates to the spe-
cific ß-blocker because not every drug is equally
and another investigation demonstrated the relative renal
cardioprotective. Metoprolol, carvedilol, and atenolol
safety of monotherapy with enalapril in dogs with asymp-
5
tomatic valvular heart disease. That study also showed a have been evaluated in canine models of heart fail-
1,42,105,147,148,185
ure, Currently, the author confines
modest trend for delay in onset of CHF in dogs with
5b use of b-blockers in dogs with heart failure to those with
advanced chronic valvular disease, although no benefit
was observed in another study of Cavalier King Charles echocardiographically demonstrated impaired systolic
function but without overt CHF. We most often