Ischemic postconditioning fails to reduce infarct size in pig models of intermediate and prolonged ischemia

Abstract

ABSTRACT Introduction and objectives: Ischemic postconditioning (iPost, coronary intermittent re-occlusion maneuvers immediately after PCI-mediated reperfusion) has been proposed to limit infarct size (IS). However, a few experimental and clinical contradictory results have been reported. We hypothesized that iPost cardioprotection is affected by the duration of ischemia. Our objective was to assess IS in the presence/absence of iPost in a pig model of myocardial infarction of variable ischemia duration. Methods: Large white pigs (n = 38) underwent angioplasty balloon-induced coronary ischemia followed by reperfusion. Two set of experiments were carried out: intermediate (30 min) and prolonged (40 min) ischemia. In both, pigs were allocated on a 1:1 ratio to receive iPost (4 cycles of “1 min balloon inflation followed by 1 min deflation” upon reperfusion) or control. Animals underwent contrast-enhanced multiparametric cardiac magnetic resonance scan on day 7. Primary outcome measure was cardiac magnetic resonance-based IS (% of left ventricular mass). The interaction between treatment allocation and ischemia duration was assessed using a 2-way ANOVA test. Results: iPost was not associated with smaller IS in any of the ischemia duration protocols (intermediate ischemia: 0.3% [0.0–3.9] vs 0.9% [0.0–2.6] in iPost and control, respectively; P = .378; long ischemia: 31.1% [27.3–32.8] vs 27.3% [25.1–27.5]; P = .248). When both ischemia-duration protocols were combined, iPost was not associated with smaller IS (3.9% [0.0–30.9] vs 4.6% [0.2–25.1]; P = .672). T1 relaxation times were longer in animals undergoing iPost compared to controls (1306.2 ms [1190.7–1492.7] vs 1240.7 ms [1167.1–1304.5]; P = .024). Conclusions: In a pig model of reperfused myocardial infarction of variable ischemia duration, iPost failed to reduce IS. T1 relaxation times were longer in animals undergoing iPost indicative of the potential harm involved in this procedure.

Keywords

• Reperfusion injury
• Ischemic postconditioning
• Cardioprotection
• Myocardial infarction