Page 280 - Feline Cardiology

Chapter 19: Congestive Heart Failure 287

Pharmacodynamic effects of furosemide and improved exercise abilities in dogs with CHF due to
In the cat, acute diuresis occurs 5 minutes after intrave- naturally occurring DCM or mitral valve disease
nous injection of furosemide, with a peak diuretic effect (Ettinger et al. 1998; IMPROVE Study Group 1995;
seen at 15 minutes (Friedman and Roch-Ramel 1977). COVE Study Group 1995; BENCH Study Group 1999).
In a study of normal anesthetized cats, urinary flow rate Hemodynamic benefits in dogs with CHF include mild
increased by 6, 15, and 18-fold after intravenous injec- reductions in heart rate, mean arterial pressure, pulmo-
tions of 0.2 mg/kg, 1 mg/kg, and 5 mg/kg of furosemide nary artery pressure, and marginal reduction of pulmo-
(Friedman and Roch-Ramel 1977). Renal blood flow nary capillary pressure (IMPROVE Study Group 1995).
was increased up to 45% of control in a dose-dependent There is only one prospective, randomized, blinded
manner without altering glomerular filtration rate, indi- multicenter study that has evaluated the effect of enala-
cating balanced dilation of afferent and efferent renal pril compared to diltiazem or atenolol, on survival in
arterioles (Friedman and Roch-Ramel 1977). The symptomatic cats with congestive heart failure or arte-
increase in renal blood flow is abolished by pretreatment rial thromboembolism. 118 cats were enrolled, includ-
with inhibitors of prostaglandin synthesis including ing 57 cats with HCM and 37 cats with HOCM. Although
indomethacin (Kirschenbaum et al. 1974). Nonsteroidal no treatment improved survival, there was a trend
anti-inflammatory drugs also lessen the diuretic response toward improved survival in the enalapril group
to furosemide by increasing solute reabsorption at the (p = 0.06), and effects may have been underestimated
thick ascending loop of Henle, and this potential con- due to the low power of the study (∼30 cats/group) (Fox
tributor to diuretic resistance, particularly in cats taking 2003). Early use of ACE inhibitors as monotherapy in
aspirin or clopidogrel for anticoagulation, has not been asymptomatic cats with HCM does not appear to be Congestive Heart Failure
investigated in this species (Chennavasin et al. 1980). warranted, based on a placebo-controlled, blinded, ran-
domized, prospective clinical study in 26 Maine coon
Adjunctive physiologic effects of furosemide cats with familial HCM (MacDonald et al. 2006).
Furosemide causes a dose-dependent direct venodilator Drug properties of ACE inhibitors
effect that occurs 5 minutes after intravenous injection,
prior to onset of diuresis (Bayne and Williamson 1979). The negatively charged group of the ACE inhibitor binds
The venodilation appears to be mediated by a local vas- to the zinc ions of ACE, preventing access by ACE sub-
cular prostaglandin synthesis and local release of nitric strates including angiotensin I and the vasodilator bra-
oxide (de Berrazueta et al. 2007). Acute pulmonary dykinin (Zhu et al. 1997; Brown and Vaughan 1998;
venodilation decreases preload and lessens pulmonary Wong et al. 2004). By inhibiting the action of ACE,
edema accumulation. Furosemide also causes broncho- angiotensin II formation is reduced and bradykinin (a
dilation in horses and people, although no studies have vasodilator) is increased. The potency and duration of
evaluated this in dogs or cats (Niven 2003; Rubie et al. an ACE inhibitor depends on its binding characteristics
1993). In horses with recurrent airway obstruction, rather than its tissue penetrating properties (Shu et al.
1 mg/kg furosemide IV reduced pulmonary resistance 1997; Zeitz et al. 2003). The majority of ACE inhibitors
and increased lung compliance acutely within 15 minutes are administered as a pro-drug (i.e., enalapril), which is
after administration, which persisted for 5 hours. This metabolized by the liver into the active drug (i.e., enala-
effect was mediated by prostanoids rather than by a prilat). Most ACE inhibitors, except benazepril and
diuretic effect. Sometimes cats are incorrectly diagnosed ramipril, are eliminated entirely by the kidneys, and
with congestive heart failure yet improve after furose- reduction of dosage is necessary in the face of renal
mide administration. An intriguing postulate is that dysfunction (Vuong and Annis 2003). Benazepril is
they improve due to furosemide induced bronchodila- mainly metabolized by the liver (85%), and pharmaco-
tion, but this has not been studied in cats. kinetics are unaffected by renal dysfunction (King et al.
2002). Likewise, 87% of ramiprilat was eliminated in
Angiotensin Converting Enzyme the feces in healthy cats, although no studies have
Inhibitors (ACEIs) been done to evaluate whether pharmacokinetics are
ACE inhibitors are the standard of care for treatment of altered by renal dysfunction (Desmoulins et al. 2008).
congestive heart failure in dogs as well as people, but Gastrointestinal absorption of ACE inhibitors is not
studies are lacking in cats (Ettinger et al. 1998; IMPROVE affected by presence of food. The clinical relevance of
Study Group 1995; COVE Study Group 1995; BENCH renal versus hepatic elimination of ACE inhibitors
Study Group 1999). Several clinical trials have identified applies to cats with acute oliguric or anuric renal failure,
improved survival, clinical reduction in heart failure who may be unable to effectively eliminate renally
class, fewer hospitalizations, reduced morbidity scores, excreted ACE inhibitors. Cats with both congestive heart