Effect of enalapril on ventricular remodeling and function during healing after anterior myocardial infarction in the dog.
BACKGROUND
Ventricular remodeling after myocardial infarction involves changes in ventricular size, shape, structure, and matrix that impact on function. Prolonged angiotensin-converting enzyme inhibition after infarction with captopril reduces ventricular enlargement and improves clinical outcome, but whether enalapril produces similar benefits is controversial.


RESULTS
The effect of enalapril during healing between 1 day and 6 weeks after myocardial infarction on in vivo changes in ventricular size, shape, mass, and function (asynergy, or akinesis and dyskinesis, and ejection fraction), as determined by serial two-dimensional echocardiography, hemodynamics, postmortem topography (planimetered short- and long-axis ventricular contours), and collagen content (determined by levels of hydroxyproline, a marker for collagen), was measured in 25 instrumented dogs. The dogs were randomized 1 day after left anterior descending coronary artery ligation to a control group (no treatment) and a group receiving oral enalapril (2.5 mg BID). Compared with no treatment, enalapril produced a sustained lowering of left atrial pressure but no difference in heart rate and mean blood pressure over the 6 weeks. Also compared with no treatment, enalapril modified in vivo remodeling parameters between 1 day and 6 weeks, with less elongation of the asynergy-containing segment, a lower expansion index (ratio of endocardial lengths of infarct to non-infarct-containing segments demarcated by papillary muscle landmarks), less scar wall thinning, a lower thinning ratio (ratio of average thickness of infarcted wall to average thickness of the normal wall), smaller ventricular volume, less regional bulging and aneurysm frequency, prevention of the increase in ventricular mass, less total extent of asynergy, and higher volume ejection fraction. At postmortem examination, scar mass was similar in the two groups, but topographic maps with enalapril revealed less infarct bulging, flatter infarct scars, and less noninfarct wall thickness. In addition, postmortem collagen content was similar in noninfarct zones of the two groups but lower in infarct zones of the dogs given enalapril.


CONCLUSIONS
Prolonged enalapril therapy, in a dose that did not lower blood pressure, during healing after anterior infarction produced prolonged reduction of left ventricular preload in dogs. This diastolic unloading was associated with limitation of remodeling parameters (infarct expansion and thinning, progressive ventricular dilation and hypertrophy, and regional bulging), less total asynergy, and improved left ventricular ejection fraction. Although angiotensin-converting enzyme inhibition was associated with lower collagen content in the infarct area and altered scar topography, these effects did not impact negatively on overall remodeling and function.
Jugdutt
B I
BI
Department of Medicine, University of Alberta, Edmonton, Canada.
Khan
M I
MI
Jugdutt
S J
SJ
Blinston
G E
GE
D000450:Aldosterone / Q000097:blood; D000818:Animals; D003094:Collagen / Q000032:analysis; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D012083:Renin / Q000097:blood; D016276:Ventricular Function / Q000187:drug effects*
D000450:Aldosterone; D004656:Enalapril; D003094:Collagen; D012083:Renin