Model of chronic systolic and diastolic dysfunction after cryothermia-induced myocardial necrosis in rats

Background and Purpose: Left ventricular dysfunction following myocardial i nfarction is the most important predictor of adverse prognosis. Novel treat ment options in infarction require an appropriate experimental model with a standardized, hemodynamically relevant myocardial injury. We evaluated a c ryoinjury model in rodents that allows quantitative analysis of systolic an d diastolic dysfunction. Methods: Anesthetized, orally intubated, and ventilated Lewis rats (n = 12) underwent sternotomy, Myocardial necrosis was induced by use of a standard ized cryolesion to the obtuse margin of the left ventricle, freezing for 3 minutes to -160 degrees C, Left ventricular performance was analyzed at day 120 after cryoinjury, Sham-operated animals (n = 10) served as controls. Results: Cryoinjured animals behaved normally and gained weight up to day 1 20, Average heart weight of cryoinjured animals significantly exceeded that of controls. Left ventricular systolic pressure and systolic, diastolic, a nd mean aortic pressures were lower 4 months after cryoinjury, whereas left ventricular end-diastolic pressure was significantly increased. Cryoinjure d animals had reduced aortic blood flow, as well as impaired maximal left v entricular dP/dt during aortic occlusion and aortic occlusion-provoked peak systolic pressure. Analysis of maximal rates of isovolumic pressure decrea se revealed significant reduction in peak negative dP/dt in cryoinjured ani mals. Finally, time constants of isovolumic pressure decline were significa ntly prolonged in cryoinjured animals. Conclusion: Standardized cryothermia induces a myocardial lesion that resul ts in highly reproducible impairment of left ventricular performance 120 da ys after cryothermia, The model is ideally suited to test novel therapeutic strategies for myocardial dysfunction.