In isolated animal heart models, higher extracellular calcium increases the additive inotropic effect of theophylline and isoproterenol but decreases overall myocardial responsiveness.
Should not inform clinical calcium management with theophylline-isoproterenol; leaves open translation to human myocardium.
At diff erent extracellular calcium concentrations, the positive inotropic eff ect of isoproterenol and isoproterenol in combination with theophylline, a phosphodiesterase inhibitor have been evaluated in the isolated frog heart and the isolated guinea pig left atria to investigate whether extracellular calcium produces any eff ect on the additive eff ect of the theophylline on the cardiac response to catecholamine. Cumulative dose response study of isoproterenol and isoproterenol in presence of theophylline at diff erent extracellular calcium concentration was performed. Th e study revealed an increase in additive eff ect of theophylline on the cardiac response to catecholamine with increase in extracellular calcium concentration, but increase in extracellular calcium concentration decreased the myocardial responsiveness to additive eff ect of theophylline and isoproterenol combination. Th e mechanism of positive inotropic eff ect of isoproterenol and in combination with theophylline involves increase in intracellular CAMP by diff erent pathways and extracellular calcium produces positive inotropic eff ect by initiating the interaction between the contractile proteins actin and myosin.The study revealed that an increase in the concentration of extracellular calcium increased the additive eff ect of theophylline and isoproterenol combination, but a decrease in the myocardial responsiveness was observed.
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Shamkuwar et al. (2008) studied this question.
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