Sensitivity to ischaemic ATP breakdown in different models of cardiac hypertrophy in rats

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 isoproterenol.

Ischaemia was induced in the isolated perfused hearts by a stepwise lowering of the perfusion pressure; at each step the coronary effluent was assessed for the products of ATP breakdown.

Hypertension increased cardiac weight by 35 and 56% after 2.5 and 12 weeks, respectively. Volume overload increased heart weight by 25 and 55% after 1 and 12 weeks, respectively. Minoxidil (for 5 weeks) or isoproterenol (for 1 week) increased cardiac weight by 22 and 16%, respectively. The hearts from 2-K,1C rats started to release ATP catabolites in the coronary effluent at a substantially higher perfusion pressure, and with significantly higher maximal levels, than the control hearts. In contrast, in volume overload cardiac ATP breakdown was similar to that in the controls, and isoproterenol administration caused significantly lower levels of ATP breakdown. At identical flow rates, normalized per gram dry tissue, the purine concentration in the coronary effluent was similar in all of the models of cardiac hypertrophy studied and in the respective controls, and was even lower in the long-term volume-overloaded and isoproterenol-induced hypertrophic hearts.

We conclude that hearts from hypertensive rats are more sensitive to ischaemic ATP breakdown during lowering of perfusion pressure than hearts from volume-overloaded or control rats. This is independent of the duration of the hypertrophic process, and can be explained by a lower coronary flow per gram heart tissue at a given perfusion pressure. This conclusion is strengthened by the observation that hypertrophic hearts from volume-overloaded rats had similar amounts of cardiac hypertrophy to the hearts from the hypertensive rats, without a change in flow, coronary vascular resistance or ischaemic sensitivity, whereas the hearts from isoproterenol-treated rats had lower ischaemic sensitivity and coronary vascular resistance.