Mechanical abnormalities in the rat ischemic heart failure model which lie downstream to cAMP production.

OBJECTIVE: We previously showed diminished inotropic responses to isoproterenol in uninfarcted posterior papillary muscles of rats with anterior wall infarcts comprising > or = 30% of the left ventricle. We have also shown that this occurs in the absence of beta-receptor downregulation. Our objective was to show a mechanical defect in the rat infarct model which is secondary to cellular defects downstream to cAMP production. METHODS: Sprague-Dawley rats were infarcted via coronary ligation. After 3 weeks, the uninfarcted papillary muscle was placed in a muscle bath and exposed to increasing concentrations of dibutyryl cAMP while contracting isometrically at 28 degrees C. RESULTS: The large infarct group showed evidence of right ventricular hypertrophy which was manifested by an increased right ventricular mass. No differences were found in baseline measurements of developed tension (DT); rate of tension development (dT/dt); rate of relaxation (-dT/dt); time to peak tension (TPT); and relaxation time (t1/2R). When these muscles were stimulated with dibutyryl cAMP, the large infarct group had a reduced inotropic response as measured by +dT/dt and TPT. No consistent abnormalities were noted in relaxation. The findings are similar to those we noted previously with isoproterenol stimulation. CONCLUSION: The impaired response to beta stimulation in uninfarcted myocardium from rats with large myocardial infarctions is due to cellular defects which lie downstream to cAMP production.