Direct recording of EDP-EDV relationship in isolated rat left ventricle: effect of diastolic crossbridge formation

Objective: The aim was to investigate whether the end diastolic pressure - end diastolic volume (EDP-EDV) relationship of the left ventricle can be influenced by calcium dependent elements, especially at low values of end diastolic pressure. Methods: Isolated rat hearts were perfused in a modified Langendorff perfusion system. The EDP-EDV relationship of the left ventricle was investigated. Pressure was recorded with a microtip pressure catheter and volume with a microconductance catheter. Crossbridge cycling was affected by adding calcium antagonists (verapamil, diltiazem, nifedipine at 2.10−7 M) or by adding the Mg-ATPase blocker BDM (2,3-butanedione-2-monoxime, 10−3 M) to the perfusate. Results: The above drugs had a negative inotropic effect in systole. At EDP = 0 after stimulation the active isovolumetric pressure was zero. In diastole, BDM shifted the EDP-EDV relationship to slightly smaller EDVs. A decrease of about 5% in the EDV was found at lower EDP values. Ca2+ antagonists increased the EDV up to 40-80% at low EDP values. At higher EDP values only a small increase of EDV (about 10%) was found after verapamil perfusion. The results obtained are interpreted in terms of a three step crossbridge model. Conclusions: At low EDP, diastolic volume is dependent upon weakly bound crossbridges as a function of the [Ca2+] in the cardiac cell. Cardiovascular Research 1994; 28 :715-719