Differences in ischaemia 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 (SHRadult; SHRaged) and normal hearts of age matched Wistar-Kyoto rats (WKYadult; WKYaged) 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 SHRadult and WKYadult the maximum positive first derivative of the left ventricular pressure (dP/dtmax) was restored to 105% and 97% respectively of the preischaemic values. Left ventricular developed pressure recovered to 80% (SHRadult) and 97% (WKYadult), while cardiac output reached 71% (SHRadult) and 99% (WKYadult) of preischaemic levels. In SHRaged and WKYaged the dP/dtmax recovered to 26% and 60% respectively (both p < 0.05 compared to the preischaemic values). The left ventricular developed pressure recovered to 36% in SHRaged and to 73% in WKYaged (both p < 0.05), while cardiac output was restored to 6% in SHRaged and 38% in WKYaged (both p < 0.05). Throughout reperfusion, left ventricular end diastolic pressure remained significantly elevated in SHRaged, and was associated with a prominent subendocardial underperfusion, suggesting an impaired diastolic functional recovery. Overall haemodynamic recovery was significantly better in the WKYaged than in the SHRaged. 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 WKYadult, the total adenine nucleotides were depressed upon reperfusion, while creatine phosphate normalised, except in SHRaged. SHRaged 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.
Snoeckx
L H
LH
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
van der Vusse
G J
GJ
Coumans
W A
WA
Willemsen
P H
PH
Reneman
R S
RS
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate