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

BACKGROUND AND PURPOSE

Left ventricular dysfunction following myocardial infarction is the most important predictor of adverse prognosis. Novel treatment options in infarction require an appropriate experimental model with a standardized, hemodynamically relevant myocardial injury. We evaluated a cryoinjury model in rodents that allows quantitative analysis of systolic and diastolic dysfunction.

METHODS

Anesthetized, orally intubated, and ventilated Lewis rats (n = 12) underwent sternotomy. Myocardial necrosis was induced by use of a standardized 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 120. Average heart weight of cryoinjured animals significantly exceeded that of controls. Left ventricular systolic pressure and systolic, diastolic, and mean aortic pressures were lower 4 months after cryoinjury, whereas left ventricular end-diastolic pressure was significantly increased. Cryoinjured animals had reduced aortic blood flow, as well as impaired maximal left ventricular dP/dt during aortic occlusion and aortic occlusion-provoked peak systolic pressure. Analysis of maximal rates of isovolumic pressure decrease revealed significant reduction in peak negative dP/dt in cryoinjured animals. Finally, time constants of isovolumic pressure decline were significantly prolonged in cryoinjured animals.

CONCLUSION

Standardized cryothermia induces a myocardial lesion that results in highly reproducible impairment of left ventricular performance 120 days after cryothermia. The model is ideally suited to test novel therapeutic strategies for myocardial dysfunction.