Beneficial effects of therapy on the progression of structural remodeling during healing after reperfused and nonreperfused myocardial infarction: different effects on different parameters.
BACKGROUND
Structural left ventricular remodeling after myocardial infarction is a complex process with several pathophysiologic descriptors that can be modified by pharmacotherapy. However, the possibility that different classes of antiremodeling agents might exert different effects on different remodeling parameters after reperfused and nonreperfused myocardial infarction has not been systematically studied.


RESULTS
We measured detailed left ventricular remodeling parameters in vivo (echocardiograms) repeatedly over 6 weeks and ex vivo (planimetry) at 6 weeks after myocardial infarction in 36 dogs randomized (factorial design) after reperfused or nonreperfused myocardial infarction to 6 weeks of twice daily oral therapy with the calcium channel blocker amlodipine (5 mg), the angiotensin-converting enzyme inhibitor enalapril (5 mg) or placebo, and 18 matching sham or control animals. Compared to placebo and control groups over 6 weeks, both agents reduced left ventricular loading and limited overall remodeling in both reperfused and nonreperfused groups, but there were pertinent differences. Enalapril limited the increase in left ventricular asynergy in the reperfused group. Both enalapril and amlodipine limited infarct zone thinning in the nonreperfused groups but increased infarct zone thinning in the reperfused groups, despite preserved infarct zone collagen with amlodipine. Enalapril decreased left ventricular diastolic volume and mass more than amlodipine in the reperfused group and increased left ventricular ejection fraction in the nonreperfused group. Both agents limited regional and global shape deformation in reperfused and non-reperfused groups. Diastolic wall stress in the infarct zone decreased with amlodipine, and increased with enalapril and reperfusion.


CONCLUSIONS
Different antiremodeling therapies may exert different effects on different remodeling parameters during healing after reperfused myocardial infarction. Significant interactions occur during reperfusion. More than one variable may be needed for the comprehensive assessment of the antiremodeling efficacy of different therapies.
Jugdutt
Bodh I
BI
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Menon
Vijayan
V
D017311:Amlodipine / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002306:Cardiac Volume / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D017311:Amlodipine; D004656:Enalapril; D003094:Collagen