Key Points
- To evaluate the long-term cardioprotective effects of combined versus single-agent ETA receptor blockade and ACE inhibition on hemodynamics, neurohormonal activation, and cardiac remodeling in post-infarction heart failure.
- Rats were treated with placebo, the ETA receptor antagonist LU135252 (30 mg/kg/day), the ACE inhibitor trandolapril (0.3 mg/kg/day), or both agents in combination for 11 weeks, initiating therapy 7 days after extensive myocardial infarction.
- Evaluations included left ventricular hemodynamics, sympathetic activation, matrix metalloproteinase-2 activity, collagen mRNA expression, and markers of hypertrophy.
- Only combination therapy significantly decreased left ventricular end-diastolic pressure (P<0.01), enhanced LV dP/dt(max) (P<0.01), and normalized sympathetic activation (P<0.05), despite all active regimens yielding comparable left ventricular systolic pressures.
- Combination therapy was superior to monotherapy in suppressing type I and III collagen mRNAs, MMP-2 zymographic activity, and myocardial fibrosis, while uniquely preventing right ventricular hypertrophy and ANF mRNA upregulation (P<0.01).
Structured PICO
Does combined ETA receptor blockade and ACE inhibition improve hemodynamics and cardiac remodeling in rats with CHF after MI?
PPopulationRats with congestive heart failure (CHF) after extensive myocardial infarction (MI)
IInterventionCombination of ETA antagonist LU135252 (30 mg/kg/d) and ACE inhibitor trandolapril (0.3 mg/kg/d) for 11 weeks, starting 7 days after MI
CComparatorPlacebo, LU135252 (30 mg/kg/d) alone, or trandolapril (0.3 mg/kg/d) alone
OOutcomeHemodynamics, neurohormonal activation, and cardiac remodelingsurrogate
In a rat model of post-MI heart failure, combined ETA receptor blockade and ACE inhibition provided additive benefits on hemodynamics, fibrosis, and fetal gene expression compared to monotherapy.