Ventricular aneurysm formation is a critical complication of myocardial infarction (MI) and markedly increases post-MI mortality. However, relatively little research has been done on basic factors influencing aneurysm formation. I would like to extend my work on post-MI healing following coronary artery occlusion and reperfusion in the rabbit by studying the elongation and thinning of different types of acute infarcts and chronic post-MI scars exposed to increased loading conditions. The time of coronary artery perfusion can be varied to simulate clinical reperfusion and to produce infarcts and scars differing in transmural extent of necrosis, histologic composition, scar strength, and collagen crosslink content. The following infarct scar types can be reliably produced: a) subendocardial and transmural, b) reperfused mixed fibrous-myocyte, c) reperfused fibrous and d) nonreperfused fibrous. A reperfused fibrous scar has been shown to have a reduced collagen crosslink density. The influence of these factors, and infarct and scar age, on elongation and thinning will be assessed by an in vivo method, utilizing aortic valvular insufficiency (AI) imposed on the different types of infarcts at different times during healing (1 day, 1 week, 3 weeks post-MI) to determine infarct resistance to aneurysm. The minimum and maximum duration of AI producing a significant aneurysmal expansion in the infarcts will be determined. Following these studies, two interventions: 1) Ibuprofen, an anti-inflammatory agent known to reduce infarct size, and 2) Vitamin C, a co-factor in collagen formation will be given along with AI to determine their influence along with reperfusion on aneurysm formation. The incidence and size of in vivo aneurysm will be measured from infarct or scar dimensions in post-mortem infarcted hearts fixed at physiologic intra-LV pressure. Any aneurysmal expansion will be correlated to the degree of LV wall stress directly obtained by the Law of LaPlace from measurements of LV pressure, wall thickness and LV radius in the infarcted area and to the degree of aortic insufficiency as measured by changes in aortic pulse pressure and by angiographic and echocardiographic (Doppler) techniques. Aneurysmal expansion will also be related to the hydroxyproline content and histologic analysis of the different infarct types. The results from these studies should provide new information about the influence of reperfusion of post-MI aneurysm formation in relation to wall stress.
| Connelly, C M; Ngoy, S; Schoen, F J et al. (1992) Biomechanical properties of reperfused transmural myocardial infarcts in rabbits during the first week after infarction. Implications for left ventricular rupture. Circ Res 71:401-13 |
| Knowlton, A A; Connelly, C M; Romo, G M et al. (1992) Rapid expression of fibronectin in the rabbit heart after myocardial infarction with and without reperfusion. J Clin Invest 89:1060-8 |
| Connelly, C M; McLaughlin, R J; Vogel, W M et al. (1991) Reversible and irreversible elongation of ischemic, infarcted, and healed myocardium in response to increases in preload and afterload. Circulation 84:387-99 |
