Cardioplegia, CPD Cardioplegia, Blood Cardioplegia, Microplegia, Micro Cardioplegia, Myocardial Protection, Myocardial Protection Cardioplegia - Adenocaine and the Thermacor 1200 from Smisson-Cartledge Biomedical

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

Please contact us for more information

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

Sarah J. Canyon PhD and Geoffrey P. Dobson PhD

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

Abstract

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), tachycardias or cardiac ischemia with a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common anti-arrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats (n=49) were anesthetized with sodium pentobarbital (60 mg/ml/kg i.p.) and instrumented for regional coronary occlusion (30 min) and reperfusion (120min). Heart rate, blood pressure and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 minutes prior to ischemia and extended throughout ischemia terminating at the start of reperfusion. After 120 min hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls (n=12), 50% of adenosine only (305 µg/kg/min, n=8), 0% in lidocaine only (608 µg/kg/min, n=8), and 0% in AL at any dose (152, 305 or 407 µg/kg/min adenosine plus 608 µg/kg/min lidocaine, n = 7, 8, 6). VT occurred in 100% of saline controls (18 ± 9 episodes), 50% of the Adeno-only (11 ± 7 episodes), and 83% of Lido-only treatment (23 ± 11 episodes), 60% of Low-dose AL (2 ± 1 episodes) (P<0.05), 57% of Mid-dose AL (2 ± 1 episodes) (P<0.05), and 67% of High-dose AL treated rats (6 ± 3 episodes). VF occurred in 75% of saline controls (4 ± 3 episodes), 100% of Adeno-only (3 ± 2 episodes), 33% Lido-only (2 ± 1 episodes) of rats tested. There was no deaths and no VF in the Low-Dose AL and Mid-dose AL treated rats during ischemia, and only one rat treated with High-dose AL experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats, but only reached significance in the Mid-dose treatment (Saline controls 61 ± 5% vs 38 ± 6%) (P<0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window by ensuring better electrical and metabolic matching in ischemic and non-ischemic regions of the heart.

Key words: adenosine, ischemia, lidocaine, ventricular arrhythmias, infarction, K-ATP channel, Na-channel, sudden death, heart