흰쥐의 실험적 대동맥 축착에서 허혈손상에 대한 Angiotensin Converting Enzyme Inhibitor의 심근 보호효과에 관한 연구 = Protective Effects of Angiotensin Converting Enzyme Inhibitor on Ischemic Injury in Experimental Aortic Coarctation in the Rat

다국어 초록 (Multilingual Abstract)

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 known to reduce ACE activity and angiotensin Ⅱ generation.
The purpose of this study was to compare the degree of ischemic injury and cardiac hypertrophy in sham-operated rats, abdominal aorta-constricted rats not receiving enalapril and abdominal aorta-constricted rats receiving enalapril.
Aoritic coarctation was induced in Sprague-Dawley rats by tying a silk ligature around both the aorta and a 2-gauge piece of needle tubing; the tubing was then removed and the rats were allowed to grow for the next 3 weeks. Sham operation consisted of a laparotomy and exposure of the abdominal aorta. This study investigated 3 different groups; group 1(sham 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/dt_max were calculated. Creatine kinase activity and pH in the coronary effluent collected at 0, 10, and 30 minutes after reperfusion were measured. heart weihgts were measured. Extent of infarction was determined by staining in tetrazolium salt and % infarcted area/area at risk was calculated.
The following results were obtained.
1) Left ventricular developed pressure recovery rate showed no significant differences between ENAL＋COA and COA.
2) The recovery of left ventricular dP/dt_max 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.