The effect of an adenosine and lidocaine intravenous infusion on myocardial high-energy phosphates and pH during regional ischemia in the rat model in vivo.
We have previously shown that an intravenous infusion of adenosine and lidocaine (AL) solution protects against death and 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 microg.(kg body mass)-1.min-1; L: 608 microg.(kg body mass)-1.min-1) was administered intravenously 5 min before and during 30 min coronary artery ligation. Two controls died from ventricular fibrillation; 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 reperfusion period. AL-treated rats maintained relatively constant ATP throughout ischemia and reperfusion ranging from 95% +/- 6% to 121% +/- 10% of baseline. Owing to increased variability in controls, these results were not found to be significant. In contrast, control [PCr] was significantly reduced in controls compared with AL-treated rats during ischemia at 10 min (68% +/- 7% vs. 99% +/- 6%), at 15 min (68% +/- 10% vs. 93% +/- 2%), and 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 intramyocardial pH between each group were not significantly different during ischemia and fell by about 1 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. There was no significant difference in the heart rate, mean arterial pressure, and rate-pressure product between the controls and AL treatment during ischemia and reperfusion. We conclude that AL cardioprotection appears to be associated with the preservation of myocardial high-energy phosphates, downregulation of the heart at the expense of a high acid-load during ischemia, and with a rapid recovery of myocardial pH during reperfusion.
Canyon
Sarah J
SJ
Department of Physiology and Pharmacology, James Cook University, Townsville, Queensland, 4811 Australia.
Dobson
Geoffrey P
GP
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004338:Drug Combinations; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats
D002316:Cardiotonic Agents; D004338:Drug Combinations; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D008012:Lidocaine; D000241:Adenosine