Beneficial effects of lidocaine and disopyramide on oxygen-deficiency-induced contractile failure and metabolic disturbance in isolated rabbit hearts.
The purpose of the present study was to determine whether antiarrhythmic agents, lidocaine and disopyramide, which reveal a membrane stabilizing action, may exert a beneficial effect on posthypoxic recovery of cardiac function and metabolism. Rabbit hearts were perfused for 20 min under hypoxic conditions, followed by 45-min reoxygenation. Hypoxic insults induced cessation of cardiac contractile force, rise in resting tension, depletion of myocardial high-energy phosphates, accumulation of tissue calcium and release of creatine kinase and ATP metabolites such as adenosine, inosine and hypoxanthine. These alterations were not returned to the initial levels upon reoxygenation. Administration of either 69 microM lidocaine or 55 microM disopyramide after the onset of oxygen deficiency (between 8th and 20th min of the hypoxia) resulted in a significant suppression of hypoxia-induced rise in resting tension, tissue calcium accumulation and release of creatine kinase and ATP metabolites, whereas hypoxia-induced decline in cardiac contractile force and depletion of myocardial high-energy phosphates were not affected by the treatment. The latter two variables were improved markedly during 45-min reoxygenation when the heart had been treated with the agents. The improvement was accompanied by a suppression of the release of creatine kinase and ATP metabolites and the tissue calcium accumulation. The results suggest that lidocaine and disopyramide are beneficial for posthypoxic recovery of cardiac function and metabolism.
Takeo
S
S
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuyama University, Japan.
Tanonaka
K
K
Shimizu
K
K
Hirai
K
K
Miyake
K
K
Minematsu
R
R
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000032:analysis; D002118:Calcium / Q000032:analysis; D002463:Cell Membrane Permeability / Q000187:drug effects; D003402:Creatine Kinase / Q000032:analysis; D004206:Disopyramide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen; D010725:Phosphocreatine / Q000032:analysis; D011817:Rabbits
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D008012:Lidocaine; D003402:Creatine Kinase; D004206:Disopyramide; D010100:Oxygen; D002118:Calcium