Lin C I, Vassalle M
Int J Cardiol. 1983 Jul;3(4):421-34. doi: 10.1016/0167-5273(83)90113-4.
The inotropic effects of caffeine (1-3 mM) were studied in the presence and absence of strophanthidin in canine Purkinje fibers perfused in vitro. Caffeine (1 mM) induced a similar initial increase in contractile force in different calcium solutions (+22, +23 and +24% in 0.54, 2.7 and 8.1 mM calcium, respectively) and when propranolol (3.4 X 10(-6) M) was present. Also, caffeine increased contractile force in high potassium (16.2 mM) at a time when the slow action potentials were unaltered. After the increase, 1 mM caffeine decreased force by about 50%, and the decrease was larger when caffeine (3 mM) or [Ca]0 (8.1 mM) was higher. In the presence of caffeine, strophanthidin (3 X 10(-7)-1 X 10(-6) M) increased force (+302%) if caffeine (0.3 mM) and Ca concentrations (0.54 mM) were low. If either caffeine or calcium was increased, strophanthidin had no effect or decreased force. Strophanthidin alone increased force and then decreased it; caffeine increased force in the first stage and decreased it during the second stage. The positive inotropic effect (+224%) of low sodium (78.4 mM versus 149.4 mM in Tyrode solution) was also abolished by caffeine (-24%). In ventricular muscle fibers, caffeine increased force more (+59%) and reduced force less in the presence of strophanthidin. The results indicate that caffeine increases force initially by releasing calcium from intracellular stores. The caffeine-induced decline in force is modulated by calcium in that it is exaggerated by agents or procedures which increase cellular calcium (strophanthidin, high calcium, low sodium solutions) and is reversed in a low calcium solution.
在体外灌注的犬浦肯野纤维中，研究了咖啡因（1 - 3 mM）在存在和不存在毒毛花苷的情况下的变力作用。咖啡因（1 mM）在不同钙溶液（分别在0.54、2.7和8.1 mM钙中收缩力初始增加相似，分别为+22%、+23%和+24%）以及存在普萘洛尔（3.4×10⁻⁶ M）时，诱导收缩力有相似的初始增加。此外，在高钾（16.2 mM）时，当慢动作电位未改变时，咖啡因增加了收缩力。增加后，1 mM咖啡因使力降低约50%，当咖啡因（3 mM）或[Ca]₀（8.1 mM）更高时，降低幅度更大。在存在咖啡因的情况下，如果咖啡因（0.3 mM）和钙浓度（0.54 mM）较低，毒毛花苷（3×10⁻⁷ - 1×10⁻⁶ M）会增加力（+302%）。如果咖啡因或钙增加，毒毛花苷则无作用或使力降低。单独使用毒毛花苷会先增加力然后降低力；咖啡因在第一阶段增加力，在第二阶段降低力。低钠（78.4 mM与Tyrode溶液中的149.4 mM相比）的正性变力作用（+224%）也被咖啡因（-24%）消除。在心室肌纤维中，在存在毒毛花苷的情况下，咖啡因增加力更多（+59%）且降低力更少。结果表明，咖啡因最初通过从细胞内储存中释放钙来增加力。咖啡因诱导的力下降受钙调节，因为它会被增加细胞钙的试剂或操作（毒毛花苷、高钙、低钠溶液）夸大，并在低钙溶液中逆转。
