Stunned myocardium and cellular damage in patients undergoing valvular cardiac surgery and pretreated with captopril.

BACKGROUND

Following extracorporeal cardiac surgery, transient myocardial dysfunction (stunning) and cellular damage may develop in relation, among other mechanisms, to the production of free radicals (FR) during reperfusion. The purpose of this study is to evaluate whether captopril (CTP), an angiotensin converting enzyme inhibitor with a thiolic group, which has been shown to be useful as an antioxidant agent both in in vitro and in vivo studies, can prevent emergence of those problems when used as pretreatment within 24 hours in patients undergoing valvular cardiac surgery.

EXPERIMENTAL DESIGN

prospective and randomized study. Comparison of data pre-ischemic (pre-aortic clamping) and post-reperfusion (post-cardiac rewarming) was performed. Ejection fraction was compared pre-surgery, after surgery and after 3 months.

SETTING

cardiology and cardiovascular surgery services in a general hospital.

PATIENTS OR PARTICIPANTS

thirty patients who had to undergo valvular replacement surgery were randomly allocated to two similar groups, one group pretreated with captopril (CTP group, n = 15) and the other group without it (CON group, n = 15). Exclusion criteria (left ventricular ejection fraction <40%, evidence of angiographic coronary disease or prior myocardial infarction and peroperative myocardial infarction).

INTERVENTION

in CTP group, the dose of captopril administered was 12.5 mg every 8 hours orally, from 24 hours before.

MEASURES

using electron microscopy of myocardial biopsies taken prior to aortic clamping and post-reperfusion, a semi-quantitative analysis was performed on the degree of myocytic damage (MD), mitochondrial swelling (MS), sarcoplasmic reticulum swelling (SRS) and content in glycogen granules (GLY). Left ventricular ejection fraction was evaluated isotopically at three timepoints, preoperatively (EF1), at 2-3 days (EF2) and at 3 months (EF3). Also, analytical data were collected from the coronary sinus to determine creatine phosphokinase (CPK) and activity of the angiotensin converting enzyme (ACE).

RESULTS

We noted that, in general, cellular damage resulting from valvular surgery is low, the degree of MS and SRS being lower in the CTP group. In the CTP group, however, there is a stunning phenomenon (EF1: 54.9+/-6.9%; EF2: 50.8+/-8.5%; EF3: 57.7+/-7.7%) which does not occur in the CON group (EF1: 58.0+/-8.3%; EF2: 60.8+/-10.9%; EF3: 63.0+/-9.3%).

CONCLUSIONS

We conclude that the cellular damage caused during valvular replacement surgery is small, and emphasize that pretreatment with CTP further minimizes both MS and SRS; however, for reasons as yet unknown, CTP pretreatment may induce myocardial stunning, an indication that at these low rates of cellular damage, CTP has no beneficial effect, either because it is ineffective as an antioxidant agent or because FR formation has little repercussion in human beings, pointing out to the likely existence of other mechanisms that may induce an appearance of postsurgical myocardial stunning.