Is microvascular protection by cariporide and ischemic preconditioning causally linked to myocardial salvage?

Abstract

Two independent cardioprotective interventions, Na+/H+ exchange inhibition and ischemic preconditioning (PC), were investigated with respect to differential effects on microvascular and myocardial salvage in anesthetized rabbits (30 min of ischemia, 180 min of reperfusion). Cariporide (Car, 300 μg/kg) administered before occlusion and PC reduced infarct size (IS) as measured by triphenyltetrazolium staining [control, 46.0 ± 4.2% of risk area (RA); Car, 17.6 ± 3.7% ( P< 0.01); PC, 27.5 ± 4.1% ( P < 0.01)] and concomitantly decreased the area of anatomic no reflow (ANR) as measured by thioflavin S staining [control, 40.4 ± 3.7%; Car, 19.0 ± 2.9% ( P < 0.01); PC, 26.9 ± 3.4% ( P < 0.05)]. Regional myocardial blood flow (RMBF, measured by radioactive microspheres) in the RA, which deteriorated between 30 and 180 min of reperfusion (control, from 79 ± 6 to 26 ± 2% of nonischemic flow), was shifted to higher values with both treatments [Car, from 110 ± 12 to 49 ± 7% ( P < 0.05); PC, from 109 ± 8 to 38 ± 6% ( P < 0.05)]. However, neither intervention uncoupled the close relationship between IS and ANR ( r= 0.92–0.95) or RMBF. Car given at reperfusion did not alter IS, ANR, RMBF, or the close interrelationships. Because size and spatial distribution of no reflow and myocardial necrosis remained closely coupled with independent cardioprotective interventions, a potential causal connection between microvascular and myocardial salvage is discussed.

Coronary microvascular reperfusion injury and no-reflow in acute myocardial infarction

“…34 In an experimental series, the no-reflow zone was confined to the zone of infarction and tended to be slightly smaller in size in the majority of hearts. Infarct size seemed to be the major determinant of the amount of no-reflow irrespective of the duration of coronary occlusion.…”

The Coronary Circulation as a Target of Cardioprotection

“…[243][244][245] Still, correlations cannot resolve questions of causality, and the lack of adequate techniques to make serial measurements of infarcted tissue and no-reflow with reasonable spatial resolution is largely responsible that causality between myocardial infarction and coronary microvascular no-reflow is not established. 246 With microembolization of atherosclerotic debris, plugging of platelet/leukocyte aggregates and vasoconstriction in response to soluble mediators, the resulting coronary microvascular obstruction could be cause to myocardial infarction.…”

Cardiac protection during acute myocardial infarction: Where do we stand in 2004?

“…Sodium-hydrogen exchange inhibitors. A number of studies with the sodium-hydrogen exchange (NHE) inhibitor agent cariporide were positive in experimental models (61,62). In our studies, 30 min of coronary artery occlusion and 3 h of reperfusion cariporide reduced infarct size by 55% in a rabbit model.…”