Pressure overload cardiac hypertrophy in response to aortic coarctation would result in cardiac dysfunction and increased ischemic injury. Angiotensin II is known to contribute to the development of cardiac hypertrophy. The enhanced conversion of
angiotensin I to angiotensin II contributes to the enhanced sensitivity of hypertrophied hearts to ischemic injury. Pharmacological interference with angiotensin converting enzyme(ACE) inhibitor(enalapril) has been knwon to reduce ACE activity
and
angiotensin II generation.
The purpose of this study was to compare the degree of ischemic injury and cardiac hypertrophy is sham-operated rats, abdominal aorta-constricted rats not receiving enalapril and abdominal aorta-constricted rats receiving enalapril.
Aortic coarctation was induced in Sprague-Dawley rats by tying a skill ligature around both the aorta and a 20-gauge piece of needle tubing; the tubing was then removed and the rats were allowed to grow for the next 3 weeks. Sham
operationconsisted
of a
laparotomy and exposure of the abdominal aorta. This study investigated 3 different group; group 1(shan operation, SHAM), laparotomy without silk ligature; group 2(abdominal coarctation+enalapril, ENAL+COA), ACE inhibition started 2 days before
induction of abdominal coarctation for additional 3 weeks; group 3(coarctation only, COA), abdominal coarctation without additional intervention. Hearts from each group were isolated, perfused with Tyrode solution by Langendorff method. After
stabilization of baseline hemodynamics, sustained ischemia of 20 minutes followed by 30 minutes reperfusion were performed. Left ventricular function including left ventricular developed pressure(LVEDP), dp/dt, and left ventricular end-diastolic
pressure was simultaneously recorded and recovery rates of LVDP and dP/dtmax were calculated. Creatine kinase activity and pH in the coronary effluent collected at 0, 10, and 30 minutes after reperfusion were measured. Heart weights were
measured.
Extent of infarction was determined by staining in tetrazolium salt and % infarcted area/area at risk was calculated.
@ES The following results were obtained.
@EN 1) Left ventricular developed pressure recovery rate showed no significant differences between ENAL+COA and COA.
2) The recovery of left ventricular dP/dtmax was greater in ENAL+COA than in COA at 5, 20 and 30 minutes.
3) There was no significant difference in left ventricular end-diastolic pressure, creatine kinase leakage, and extracellular pH among experimental groups.
4) Cardiac hypertrophy was prevented in animals fed enalapril maleate(0.2mg/ml) in their drinking water.
5) Extent of infarction was decreased in ENAL+COA than in COA(94.7±9.3% VS 76.1±4.7%, p<0.05). These results suggest that enalapril can prevent cardiac hypertrophy and attenuates ischemic injury in experimental aortic coarctation in the rats.
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