Possible roles of cardiac chymase after myocardial infarction in hamster hearts

The significance of cardiac chymase after myocardial infarction (MI) was ev aluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after M I, tissues were removed for measurements of angiotensin-converting enzyme ( ACE) and chymase activities. The mean infarct size 3 days after left corona ry artery ligation was 47.3 +/- 5.9% of the left ventricle circumference. T he ratio of left ventricle weight to body weight was significantly increase d from 3 days after MI. The level of plasma renin activity in the MI hamste rs was significantly increased at the early phase of MI (1 - 3 days), while no significant changes in plasma ACE activity were observed. The ACE activ ity in the infarcted left ventricle was significantly increased starting fr om 3 days after MI and this increase was sustained up to 28 days. The chyma se activity in the infarcted left ventricle was significantly increased sta rting from 1 day after MI and this increase was sustained up to 56 days. Th e number of chymase-positive mast cells in the infarcted left ventricle was significantly higher than in the sham group 3 and 7 days after operation. Treatment with an angiotensin (Ang) II type 1 receptor antagonist (candesar tan cilexetil, 10 mg/kg per day) starting 3 days before the induction of MI significantly reduced the mortality rate during 14 days of observation fol lowing MI, whereas treatment with an ACE inhibitor (lisinopril, 20 mg/kg pe r day) did not. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development, left ventricular systolic pres sure and end-diastolic pressure, mean arterial blood pressure) was observed by the treatment with candesartan cilexetil, but not with lisinopril, 3 an d 14 days after MI. These results suggested that Ang LI produced by chymase may participate in the pathophysiologic state after MI in hamsters.