Intracellular endocardial calcium and myocardial function in rat hearts.

Analyses of [Ca2+]i in the isolated beating rat heart (using Indo-1 dye) demonstrated a direct relationship between developed pressure and each of the following: (a) systolic [Ca2+]i; (b) amplitude of [Ca2+]i transients; and (c) diastolic level of [Ca2+]i. Agents which increased cAMP levels, augmented amplitude of [Ca2+]i transients, and lowered the resting level of [Ca2+]i, thereby shifting the relationship between developed pressure and diastolic as well as systolic [Ca2+]i concentrations towards lower [Ca2+]i levels for comparable peak systolic pressure measurements at constant end-diastolic pressure. Addition of adenosine to the perfusate containing isoproterenol completely prevented any cAMP-induced cytosolic changes. Interventions which altered [Ca2+]i and developed pressure, but did not increase cAMP (e.g., perfusion pressure, extracellular calcium, calcium entry blockers, and alpha agonist), caused an increase in diastolic levels of [Ca2+]i commensurate with the augmentation in developed pressure and amplitude of [Ca2+]i transients. When the diastolic [Ca2+]i rose to 400 nmoles and the cAMP was below 4 nmoles the heart fibrillated. The heart fibrillated at a diastolic [Ca2+]i of 350 nmoles when the cAMP was elevated to 6 nmoles. The diastolic level of [Ca2+]i at which the heart begins to fibrillate is indicative of the effect contraction threshold.