Enhanced reduction of myocardial infarct size by combined ACE inhibition and AT1‐receptor antagonism
Why the study?
Does the combination of ramiprilat and candesartan reduce myocardial infarct size more than either drug alone in a pig model of ischaemia/reperfusion?
Population
46 enflurane-anaesthetized pigs subjected to 90 min low-flow ischaemia and 120 min reperfusion
Comparison
Combined ramiprilat and candesartan vs Placebo, ramiprilat alone, or candesartan alone
Design
Preclinical
Follow-up
120 min reperfusion
Authors
Discussion
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Implication
May enhance experimental cardioprotection beyond monotherapy; leaves open translation to human ischemia/reperfusion injury.
Key Points
- To determine whether combining an ACE inhibitor with an AT1-receptor antagonist produces a greater reduction in myocardial infarct size than monotherapy during ischaemia and reperfusion.
- Forty-six enflurane-anaesthetized pigs (N=46) were subjected to 90 minutes of regional low-flow ischaemia followed by 120 minutes of reperfusion.
- Pigs were assigned to receive placebo (n=10), ramiprilat (n=10), candesartan (n=10), ramiprilat plus candesartan (n=10), or the combination pretreated with the bradykinin-B2-receptor antagonist icatibant (n=6).
- Systemic haemodynamics, subendocardial blood flow using microspheres, and infarct size via TTC-staining were assessed, with left ventricular pressure decreases readjusted by aortic constriction.
- Infarct size as a percentage of the area at risk was 20.0±3.3% in the placebo group, 9.8±2.6% with ramiprilat alone, 10.6±3.1% with candesartan alone, and 6.7±2.1% with combined therapy (P<0.05 vs all other groups).
- Pretreatment with icatibant prior to combined ramiprilat and candesartan completely abolished the reduction of infarct size (22.8±6.1%, n=6).
Structured PICO
Does the combination of ramiprilat and candesartan reduce myocardial infarct size more than either drug alone in a pig model of ischaemia/reperfusion?
P
Population
46 enflurane-anaesthetized pigs subjected to 90 min low-flow ischaemia and 120 min reperfusion
I
Intervention
Combined ramiprilat (ACE inhibitor) and candesartan (AT1-receptor antagonist)
C
Comparator
Placebo, ramiprilat alone, or candesartan alone
O
Outcome
Myocardial infarct size as a percentage of the area at risksurrogate
The combination of an ACE inhibitor and an AT1-receptor antagonist enhances the reduction of myocardial infarct size following ischaemia/reperfusion compared to monotherapy, an effect mediated by bradykinin.
Cite This Study
Weidenbach et al. (2000) studied this question.