Caffeine effects on heart muscle energetics: species differences

The effects of caffeine (1mM) on energy expenditure and mechanical parameters in rat and toad perfused heart ventricles were examined at various stimulation frequencies. While in rat muscles caffeine significantly depressed developed tension and maximal rates of contraction and relaxation at all frequencies tested, in toad ventricle a slight positive inotropic effect was observed. Even though caffeine did not alter total contraction time in both preparations, in the rat ventricle the last part of relaxation was prolonged. In rat ventricle in the presence of caffeine, the ratios between active heat production per beat and either developed tension or tension time integral increased at all frequencies tested (+303 +/- 47 microJ.mN-1 x g-1 and +1.21 +/- 0.13 mJ.mN-1 x s-1 x g-1 respectively) indicating a decrease in contractile economy. In toad ventricle no changes on these ratios were observed. The fact that only in rat ventricle caffeine decreased muscle economy suggests that caffeine affects a system that is active in rat ventricle but it is not operative in toad ventricle. This gives support to the hypothesis that if in rat ventricle SR-Ca pump (1 ATP hydrolyzed/2 Ca transported) is inhibited by caffeine cytosolic Ca would have to be removed by alternative mechanisms such as Na-Ca exchanger or sarcolemmal Ca pump both with a higher rate of ATP hydrolysis (1 ATP hydrolyzed/Ca transported) with the consequent decrease in muscle economy. Resting heat production was increased by caffeine in both preparations and the magnitude of the increment (+3.0 +/- 0.6 mW.g-1 and +0.75 +/- 0.21 mW.g-1 for rat and toad ventricle respectively) also correlates with the different degree of SR activity in both species

Caffeine influence on the dependence of myocardial response to extracellular calcium

En la aurícula izquierda aislada de rata, el aumento de la concentración extracellular de Ca ... induce un aumento de la tensión desarrollada hasta un máximo de 5.1 ñ 0.5 mN. El desarrollo de tensión como función de la [Ca] fue evaluado por un análisis de Hill, del que se obtuvo un K0,5 = 0.79 (0.55-1.13) mmol. l**-1 y un coeficiente de Hill n= 1.70 (1.46-1.94). La cafeína (1 mmol. 1**-1) disminuyó la fuerza máxima inducida por el aumento de la [Ca] a 3.2 ñ 0.3 mN (p<0.05). El análisis de Hill mostró que tanto el K0.5=0.22 (0.14-0.34) mmol. 1**-1 como el coeficiente de Hill n= 1.21 (0.86-1.56) mmol45 l**l habían disminuído en presencia de cafeína. El eflujo de Ca (realizado a una [Ca] de 1.3 mmol. l**l) disminuyó en presencia de cafeína en alrededor de un 27% (0.38 micronmolgm peso húmedo**l). La disminución del coeficiente de Hill observado en presencia de cafeína sugiere la desaparición de un compartimiento o de un proceso cooperativo. Los experimentos de eflujo de **45Ca sugieren la existencia de un compartimiento que tendría cuatro veces la cantidad de Ca requerida para una contracción máxima y que puede ser deplecionado por la cafeína. En ausencia de este compartimiento (i.e., en presencia de cafeína), las fuentes remanentes de Ca poderían proveer suficiente calcio como para desarrollar más del 70% de la actividad contráctil máxima