Bonazzola P, Ponce-Hornos J E, Márquez M T
Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Acta Physiol Pharmacol Ther Latinoam. 1992;42(3):155-70.
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.
在不同刺激频率下,研究了咖啡因(1毫摩尔)对大鼠和蟾蜍离体灌流心室的能量消耗及力学参数的影响。在大鼠肌肉中,咖啡因在所有测试频率下均显著降低了张力的产生以及收缩和舒张的最大速率;而在蟾蜍心室中,观察到了轻微的正性肌力作用。尽管咖啡因在两种标本中均未改变总收缩时间,但在大鼠心室中,舒张的最后阶段延长。在存在咖啡因的大鼠心室中,在所有测试频率下,每搏主动产热与张力产生或张力时间积分的比值均增加(分别为+303±47微焦·毫牛⁻¹·克⁻¹和+1.21±0.13毫焦·毫牛⁻¹·秒⁻¹·克⁻¹),表明收缩经济性降低。在蟾蜍心室中,这些比值未观察到变化。仅在大鼠心室中咖啡因降低肌肉经济性这一事实表明,咖啡因影响了在大鼠心室中活跃但在蟾蜍心室中不起作用的一个系统。这支持了以下假设:如果在大鼠心室中,咖啡因抑制了肌浆网钙泵(每水解1分子ATP转运2个钙),那么胞质钙将不得不通过诸如钠钙交换体或肌膜钙泵等替代机制来清除,而这两种机制的ATP水解速率都更高(每转运1个钙水解1分子ATP),从而导致肌肉经济性降低。两种标本中咖啡因均增加了静息产热,且增加幅度(大鼠心室为+3.0±0.6毫瓦·克⁻¹,蟾蜍心室为+0.75±0.21毫瓦·克⁻¹)也与两种动物不同程度的肌浆网活性相关。