Key result
Cariporide improves early functional recovery by ~43% but provides no long-term myocardial salvage.
Why the study?
The long-term effects of cariporide on cardiac function and metabolism after ischemia/reperfusion were not well characterized in a canine model.
Does cariporide improve functional recovery and reduce infarct volume in a canine model of cardiac ischemia/reperfusion?
Does cariporide improve functional recovery and reduce infarct volume in a canine model of cardiac ischemia/reperfusion?
Absolute Event Rate: 90.5% vs 63.5%
Cariporide provides transient early functional recovery but fails to offer long-term myocardial salvage or metabolic protection in a canine ischemia/reperfusion model.
Cariporide yields no long-term functional, metabolic, or infarct-size benefit in this canine model; leaves open NHE inhibition efficacy in human reperfusion injury.
PURPOSE: To examine with magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) the long-term effects of cariporide in a canine cardiac ischemia/reperfusion model. MATERIALS AND METHODS: Twenty-two beagles underwent a 2-hour occlusion followed by 10 days of reperfusion. Cine MRI and (31)P MRS were performed to monitor function and metabolism of the heart in the control (N = 10) and cariporide (N = 12) groups. Radioactively labeled microspheres were injected to determine coronary blood flow, and contrast-enhanced ex vivo MRI assessed infarct volumes. RESULTS: Cariporide produced a significant reduction vs. controls, in intracellular pH, during ischemia (P < 0.05) and at days 3 and 10 postreperfusion (P < 0.0005). Functional recovery of the myocardium was significantly improved immediately upon reperfusion (percent of baseline: 63.5% +/- 3.5% for controls, 90.5% +/- 7.2% for cariporide) and at day 3, but not by day 10. Normalized infarct ratios (IRs) were similar for controls and cariporide (0.58 +/- 0.08, 0.58 +/- 0.06, respectively). CONCLUSION: Cariporide augments early functional recovery, while delaying normalization of intracellular pH following ischemia/reperfusion, but confers neither long-term functional or metabolic protection nor, most importantly, myocardial salvage.
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Thompson et al. (2002) studied Cardiac ischemia/reperfusion (n=22). Cariporide vs. Control was evaluated on Functional recovery of the myocardium immediately upon reperfusion (percent of baseline). Cariporide significantly improved early functional recovery immediately upon reperfusion (90.5% vs 63.5% of baseline) but conferred no long-term functional protection or myocardial salvage.
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