Effect of adenosine and lidocaine intravenous infusion on myocardial high-energy phosphates and pH during regional ischemia in the rat model in vivo

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The effect of adenosine and lidocaine intravenous infusion on myocardial high-energy
phosphates and pH during regional ischemia in the rat model in vivo

 

Sarah J. Canyon PhD and Geoffrey P. Dobson^* PhD

Department of Physiology and Pharmacology,
James Cook University,
Townsville, Queensland, Australia 4811

Abstract

We have previously shown that an intravenous infusion of adenosine and lidocaine (AL) solution protects against death, severe arrhythmias and reduces infarct size in the in vivo rat model of regional ischemia. The aim of this study was to examine the relative changes of myocardial high-energy phosphates (ATP and PCr) and pH in the left ventricle during ischemia-reperfusion using 31P NMR in AL-treated rats (n=7) and controls (n=6). The AL solution (A: 305 mg/kg/min plus L: 608 mg/kg/min) was administered intravenously 5 min before and during 30 min coronary artery ligation. Two controls died from ventricular fibrillation, and no deaths were recorded in AL treated rats. In controls that survived, ATP fell to 73?? 29% of baseline by 30 min ischemia and decreased further to 68?? 28% during reperfusion followed by a sharp recovery at the end of the test period. However, due to increased variability in controls these results were not found to be significant. In contrast, AL-treated rats maintained relatively constant ATP throughout ischemia and reperfusion ranging from 95?± 6% to 121?± 10% of baseline. Control [PCr] was significantly reduced in controls compared to AL-treated rats during ischemia at 10 min (68 ± 7% vs. 99 ± 6%), at 15 min (68 ± 10% vs 93 ± 2%), at 20 min (67 ± 15% vs. 103 ± 5%) and during reperfusion at 10 min (56 ± 22% vs. 99 ± 7%), at 15 min (60 ± 10% vs. 98 ± 7%) and at 35 min (63 ± 14 vs. 120 ± 11%) (P < 0.05). Interestingly, changes in intra-myocardial pH between each group were not significantly different during ischemia and fell by about one pH unit to 6.6. During reperfusion, pH in AL-treated rats recovered to baseline in 5 min but not in controls, which recovered to only around pH 7.1. We conclude that AL cardioprotection appears to be associated with the preservation of myocardial high-energy phosphates and down-regulation of the heart at the expense of a high acid-load during ischemia, and with a rapid recovery of myocardial pH during reperfusion.

 

Key words: adenosine; lidocaine; myocardial ischemia; metabolism; pH; ATP; PCr; ³¹P NMR