Intracoronary nifedipine improved contractile function recovery (17% vs -2%, p<0.01) and prevented ventricular fibrillation (0% vs 50%, p<0.01) in dogs with myocardial reperfusion injury.
RCT
randomized
Does intracoronary nifedipine improve sarcoplasmic reticulum function and contractile recovery in dogs undergoing myocardial ischemia and reperfusion?
In a canine model of ischemia-reperfusion, nifedipine prevented sarcoplasmic reticulum Ca2+ ATPase pump dysfunction and improved contractile recovery.
Absolute Event Rate: 17% vs -2%
p-value: p=<0.01
OBJECTIVE: Sarcoplasmic reticulum dysfunction may contribute to calcium (Ca2+) overload during myocardial reperfusion. The aim of this study was to investigate its role in reperfusion injury. METHODS: Open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion were randomized to intracoronary infusions of 0.9% saline, vehicle, or the Ca2+ channel antagonist, nifedipine (50 micrograms/min from 2 minutes before to 5 minutes after reperfusion). After each experiment, transmural myocardial biopsies were removed from ischemic/reperfused and nonischemic myocardium in the beating state and analyzed for (i) sarcoplasmic reticulum protein content (Ca2+ ATPase, phospholamban, and calsequestrin) by immunoblotting and (ii) Ca2+ uptake by sarcoplasmic reticulum vesicles with and without 300 micromolar ryanodine or the Ca2+ ATPase activator, antiphospholamban (2D12) antibody. RESULTS: Contractile function did not recover in controls and vehicle-treated dogs after ischemia and reperfusion (mean systolic shortening, -2 +/- 2%), but completely recovered in nifedipine-treated dogs (17 +/- 2%, p = NS vs. baseline, p < 0.01 vs. control). Ventricular fibrillation occurred in 50% of controls and vehicle dogs and 0% of nifedipine-treated dogs (p < 0.01). Ca2+ uptake by the sarcoplasmic reticulum vesicles was severely reduced in ischemic/reperfused myocardium of controls and vehicle dogs (p < 0.01 vs. nonischemic). Ryanodine and the 2D12 antibody improved, but did not reverse the low Ca2+ uptake. Protein content was similar in ischemic/reperfused and nonischemic myocardium. In contrast, Ca2+ uptake and the responses to ryanodine and 2D12 antibody were normal in ischemic/reperfused myocardium from nifedipine-treated dogs. CONCLUSION: Dysfunction of the sarcoplasmic reticulum Ca2+ ATPase pump correlates with reperfusion injury. Reactivation of Ca2+ channels at reperfusion contributed to Ca2+ pump dysfunction. Ca2+ pump injury may be a critical event in myocardial reperfusion injury.
Smart et al. (Sat,) conducted a rct in Myocardial reperfusion injury. Nifedipine vs. 0.9% saline or vehicle was evaluated on Mean systolic shortening (p=<0.01). Intracoronary nifedipine improved contractile function recovery (17% vs -2%, p<0.01) and prevented ventricular fibrillation (0% vs 50%, p<0.01) in dogs with myocardial reperfusion injury.
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