Myocardial protection with verapamil during ischaemia and reperfusion: dissociation between myocardial salvage and the degree of ATP depletion during ischaemia

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Abstract
Study objective – The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion. Design – In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg·kg−1 intraperitoneal) and controls during a 45 min left coronary artery occlusion and 60 min reperfusion. In separate groups of animals, haemodynamic measurements were taken at baseline, during ischaemia, and during reperfusion. Infarct size was determined by staining with triphenyltetrazolium chloride. Experimental material – Female Sprague-Dawley rats were used (control group n = 25, experimental group n = 24). Measurements and main results – Infarct size was significantly reduced in the verapamil group compared to controls: 9.9(SEM 2.3)%, n = 19 v 28.5(2.7)%, n = 19, pv 61.4(1.8)%, n = 11, NS; 67.7(2.7)%, n = 10 v 69.7(2.9)%, n = 11, NS (% of baseline value). After 60 min reflow, there was significant recovery of phosphocreatine [91.1(4.2)% of baseline, pConclusions – Pretreatment with verapamil extends the ischaemic time after which reperfusion results in myocardial salvage in this model of ischaemia and reperfusion. This protective effect is independent of the haemodynamic determinants of myocardial oxygen demand and the degree of ATP and phosphocreatine depletion during the ischaemic period. In this model of reversible ischaemia, 31P magnetic resonance spectroscopy is useful for quantitating both the size of the ischaemic region during coronary artery occlusion and infarct size after reperfusion.

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