SENSITIVITY TO ISCHEMIC ATP BREAKDOWN IN DIFFERENT MODELS OF CARDIAC-HYPERTROPHY IN RATS

Objective: To evaluate the sensitivity to ischaemia of rat hearts made hypertrophic by pressure overload [two-kidney, one clip (2-K,1C) rats ], volume overload (aortocaval arteriovenous shunt), minoxidil or isop roterenol. Methods: Ischaemia was induced in the isolated perfused hea rts by a stepwise lowering of the perfusion pressure; at each step the coronary effluent was assessed for the products of ATP breakdown. Res ults: Hypertension increased cardiac weight by 35 and 56% after 2.5 an d 12 weeks, respectively. Volume overload increased heart weight by 25 and 55% after 1 and 12 weeks, respectively. Minoxidil (for 5 weeks) o r isoproterenol (for 1 week) increased cardiac weight by 22 and 16%, r espectively. The hearts from 2-K,1C rats started to release ATP catabo lites in the coronary effluent at a substantially higher perfusion pre ssure, and with significantly higher maximal levels, than the control hearts. In contrast, in volume overload cardiac ATP breakdown was simi lar to that in the controls, and isoproterenol administration caused s ignificantly lower levels of ATP breakdown. At identical flow rates, n ormalized per gram dry tissue, the purine concentration in the coronar y effluent was similar in all of the models of cardiac hypertrophy stu died and in the respective controls, and was even lower in the long-te rm volume-overloaded and isoproterenol-induced hypertrophic hearts. Co nclusions: We conclude that hearts from hypertensive rats are more sen sitive to ischaemic ATP breakdown during lowering of perfusion pressur e than hearts from volume-overloaded or control rats. This is independ ent of the duration of the hypertrophic process, and can be explained by a lower coronary flow per gram heart tissue at a given perfusion pr essure. This conclusion is strengthened by the observation that hypert rophic hearts from volume-overloaded rats had similar amounts of cardi ac hypertrophy to the hearts from the hypertensive rats, without a cha nge in flow, coronary vascular resistance or ischaemic sensitivity, wh ereas the hearts from isoproterenol-treated rats had lower ischaemic s ensitivity and coronary vascular resistance.