ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND BETA-ADRENOCEPTOR BLOCKADE REGRESS ESTABLISHED VENTRICULAR REMODELING IN A CANINE MODEL OF DISCRETE MYOCARDIAL DAMAGE

Objectives. This study was designed to assess the effect of angiotensi n converting enzyme inhibition and beta-adrenoreceptor blockade on est ablished ventricular remodeling. Background. Angiotensin converting en zyme inhibitor therapy attenuates the development of ventricular remod eling when given shortly after myocardial infarction. However, regress ion of established ventricular remodeling after infarction has receive d little attention. Methods. The relative effects of angiotensin conve rting enzyme inhibitor therapy and beta-adrenoceptor blockade on estab lished ventricular remodeling were assessed in a canine model characte rized by increased left ventricular mass and chamber dilation as a res ult of localized myocardial necrosis produced by transmyocardial direc t current shock Dogs were randomly assigned to 3 months of therapy wit h captopril (25 mg twice daily, n = 7) or metoprolol (100 mg twice dai ly, n = 7) or to a control group with no intervention (n = 6), 11 +/- 4 (mean +/- SD) months after acute myocardial damage. Results. Compare d with the control group, dogs in both the captopril and metoprolol gr oups had reduced left ventricular mass as measured by magnetic resonan ce imaging (-8.1 +/- 3.8 vs. 1.7 +/- 2.8 g, p = 0.003 and -9.6 +/- 5.6 vs. 1.7 +/- 2.8 g, p = 0.001), respectively. Captopril and metoprolol also produced a reduction in left ventricular end diastolic volume (- 7.6 +/- 6.0 and -6.0 +/- 5.8 ml, respectively) compared with the contr ol value (-1.6 +/- 3.8 ml) (p = 0.14 [NS]). Both agents reduced mean a rterial pressure but had disparate effects on pulmonary wedge pressure and right atrial pressure. There was no significant correlation betwe en change in ventricular mass or volume and change in any measured hem odynamic or neurohormonal variable. Conclusions. These data suggest th at pharmacologic intervention with angiotensin-converting enzyme inhib ition or beta-adrenoceptor blockade can result in regression of establ ished ventricular remodeling. The mechanism of this response will requ ire further study, but these data did not support a close association between regression of remodeling and hemodynamic unloading of the vent ricle or systemic neuroendocrine factors.