Protective effect of verapamil in ischemic porcine hearts: Analysis of ultrastructural and metabolic changes using in-vivo[formula omitted] spectroscopy

Abstract

To assess the protective effect of verapamil on ischemic myocardium, the changes in high energy phosphates, inorganic phosphate, and intracellular pH were serially and quantitatively measured in ischemic porcine hearts without collateral circulation using 31 P-NMR spectroscopy, together with ultrastructural examination. Twenty-six farm pigs weighing 11 to 14 kg were anesthetized with fluothane and were divided into control (C) group and verapamil pretreatment (V) group. In V group 0.2 mg/kg of verapamil was administered for 20 mins before occlusion of the anterior descending cornary artery. 31 P-NMR spectra were serially obtained throughout the experiment, and ultrastructural examination was done at 20-min occlusion and at 120-minute occlusion in each group. At 10-min ischemia, creatin phosphate was significantly preserved in V group ( C V = 11 ± 4% 16 ± 5% P < 0.05 ). At 20 min ischemia, ATP was significantly preserved ( C V = 60 ± 9% 73 ± 8% P < 0.05 ), and intracellular pH was significantly higher in V group ( C V = 6.4 ± 0.2 6.6 ± 0.1 P < 0.05 ). Morphologically, clumping of the nuclear chromatin, mitochondrial swelling and decrease in glycogen were milder in V group at 20 min ischemia. However, these beneficial effects disappeared at 120 min ischemia. Thus pretreatment with verapamil attenuated depletion of high energy phosphates, progression of acidosis, and ultrastructural changes. There was no significant difference of rate pressure product and regional blood flow between hearts with and without pretreatment of verapamil. Therefore, this protective effect may be due to the energy sparing effect or other direct subcellular effect of verapamil on ischemic myocyte.