A load-independent in vivo model for evaluating therapeutic interventions in injured myocardium

Abstract

Although cardiomyocyte damage is normally irreversible, gene therapy and somatic cell transfer offer potential for improving function in damaged regions of the heart. However, in ischemic models of injury, variability in depth, size, and location of damage compromises statistical evaluation of in vivo function. We have adapted cryoablation to create a reproducible, posterior, transmural lesion within rabbit myocardium in which small changes in function are measurable in vivo. Before and at 2 and 6 wk postinjury, in vivo left ventricular intracavitary pressure and myocardial segment length were measured. Regional indexes of performance, segmental stroke work (SW), and percent systolic shortening (SS) were significantly decreased ( P < 0.001) postcryoinjury as was the slope ( M w) of the linear preload recruitable SW relationship between SW and end-diastolic segment length ( P = 0.0001). Decreased SW, SS, and M w correlated with wall thinning, loss of myocytes, presence of fibroblasts, and transmural scar formation. Reproducible changes in regional myocardial performance in vivo postcryoinjury suggest that this is a reasonable model for evaluating novel therapies for cardiovascular disease.