Model of Chronic Systolic and Diastolic Dysfunction after Cryothermia-induced Myocardial Necrosis in Rats
Abstract: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°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.
Document Type: Research Article
Publication date: 2000-08-01
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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