DIFFERENCES IN ISCHEMIA TOLERANCE BETWEEN HYPERTROPHIED HEARTS OF ADULT AND AGED SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The aim was to examine differences between the postischaemic functional and biochemical recovery of adult and aged hypertrophied hearts. Methods: Isolated hypertrophied hearts of adult and aged spontaneously hypertensive rats (SHR(adult); SHR(aged)) and normal hearts of age matched Wistar-Kyoto rats (WKY(adult); WKY(aged)) were perfused in an ejecting heart preparation. Haemodynamic function was monitored before and after 45 min of ischaemia. Coronary effluent samples and tissue biopsies were taken for biochemical analysis. Results: After ischaemia, in SHR(adult) and WKY(adult) the maximum positive first derivative of the left ventricular pressure (dP/dt(max)) was restored to 105% and 97% respectively of the preischaemic values. Left ventricular developed pressure recovered to 80% (SHR(adult)) and 97% (WKY(adult)), while cardiac output reached 71% (SHR(adult)) and 99% (WKY(adult)) of preischaemic levels. In SHR(aged) and WKY(aged) the dP/dt(max) recovered to 26% and 60% respectively (both p<0.05 compared to the preischaemic values). The left ventricular developed pressure recovered to 36% in SHR(aged) and to 73% in WKY(aged) (both p<0.05), while cardiac output was restored to 6% in SHR(aged) and 38% in WKY(aged) (both p<0.05). Throughout reperfusion, left ventricular end diastolic pressure remained significantly elevated in SHR(aged), and was associated with a prominent subendocardial underperfusion, suggesting an impaired diastolic functional recovery. Overall haemodynamic recovery was significantly better in the WKY(aged) than in the SHR(aged). The preischaemic total adenine nucleotides content was comparable in all groups, but creatine phosphate levels were significantly lower in both aged groups than in adult groups. In all but the WKY(adult), the total adenine nucleotides were depressed upon reperfusion, while creatine phosphate normalised, except in SHR(aged). SHR(aged) lost more lactate dehydrogenase and tended to lose more xanthine and uric acid than other groups. Conclusions: The aged hypertrophied heart shows a higher vulnerability to ischaemic damage than the adult hypertrophied heart. This phenomenon is associated with subendocardial underperfusion, increased membrane damage and inadequate recovery of creatine phosphate levels.