Abstract
To investigate the mechanisms of altered myocardial diastolic stiffness and relaxation induced by myocardial oxygen deficit, we compared the hemodynamic effects of low flow ischemia (myocardial infarction model) and hypoxia in which the coronary flow was not reduced (angina pectoris model) in isolated retrograde perfused rabbit hearts. A 15-min hypoxia induced a significant increase in the left ventricular end diastolic pressure (LVEDP 10±3 to 21±7 mmHg, p<0.05), Po(-1±6 to 12±5 mmHg, p<0.01) and TB(41±8 to 54±10 ms, p<0.05), where Po and TB are the asymptote and the time constant of the isovolumetric left ventricular pressure decline (P=Po+A·e-t/TB), respectively. There was a close linear correlation between the delta Po and delta LVEDP (t=0.98, p<0.01), and between delta TB and delta LVEDP (r=0.73, p<0.05). Low flow ischemia increased Po (0±4 to 2±3 mmHg, p<0.05) and TB (43±4 to 50±11 mmHg, NS). When DPI 201-106, a cardiotonic agent, was given to the hypoxia moded by increasing the Ca++ sensitivity of contractile proteins, further increases were observed in LVEDP (to 258 mmHg, p<0.05) and Po (to 157 mmHg, p<0.05). DPI also increased LVEDP (72 to 94 mmHg, NS) and Po(to 44 mmHg, p<0.05) in the ischemia model, However, TB was not altered by DPI. Conclusions: 1) Po reflects the LVEDP, 2) The discrepancies between the changes of T and Po induced by DPI indicate different mechanisms underlying changes in LV diastolic stiffness and relaxation. 3) Both hypoxia and ischemia induced abnormalities in myocardial diastolic stiffness and relaxation.
