Adams H R, Parker J L, Mathew B P
J Pharmacol Exp Ther. 1977 Apr;201(1):171-83.
The influence of ketamine on the inotropic and chronotropic responsiveness of heart muscle was examined in spontaneously beating right atrial preparations and in electrically driven left atrial preparations of guinea pigs. Ketamine (2.63 X 10(-5) to 4.2 X 10(-4) M) decreased heart rate of right atria and decreased contractile tension and its maximum rate of increase in both right and left atrial preparations (right atria greater than left atria). Ketamine did not prevent the heart rate increase produced by norepinephrine (NE; 1 X 10(-8) to 1 X 10(-4) M) in right atria; however, the maximum heart rate was consistently lower in ketamine-treated than in control muscles even after exposure to NE. Although contractile tension was decreased by ketamine, the maximum inotropic response to NE was consistently greater in ketamine-treated atria than in control atria. An inhibitor of the slow Ca++ current in heart muscle, D600, depressed the contractile effects of NE but did not prevent the positive inotropic interaction of ketamine and NE. Ketamine similarly enhanced the inotropic responses to norepinephrine (1 X 10(-6) M), epinephrine (1 X 10(-6) M), isoproterenol (1 X 10(-7) M) and dibutyryl cyclic adenosine 3':5'-monophosphate (AMP; 4 X 10(-3) M) in left atria electrically paced at a constant frequency of contraction of 1 Hz; however, ketamine inhibited the positive inotropic response to increased frequency of stimulation (0.1-3.0 Hz) and to ouabain (3 X 10(-7) M). These findings demonstrate that ketamine can exert a selective positive inotropic influence in heart muscle independent of heart rate or direct or reflexogenic autonomic nervous system changes, and suggest that this activity could in some way be associated with an alteration of the intracellular disposition of cyclic AMP.
在豚鼠自搏性右心房标本和电驱动的左心房标本中，研究了氯胺酮对心肌变力性和变时性反应的影响。氯胺酮（2.63×10⁻⁵至4.2×10⁻⁴M）可降低右心房的心率，并降低右心房和左心房标本的收缩张力及其最大上升速率（右心房大于左心房）。氯胺酮不能阻止去甲肾上腺素（NE；1×10⁻⁸至1×10⁻⁴M）引起的右心房心率增加；然而，即使在暴露于NE后，氯胺酮处理组的最大心率始终低于对照组肌肉。尽管氯胺酮可降低收缩张力，但氯胺酮处理的心房对NE的最大变力反应始终大于对照组心房。心肌慢钙电流抑制剂D600可抑制NE的收缩作用，但不能阻止氯胺酮与NE的正性变力相互作用。氯胺酮同样增强了对去甲肾上腺素（1×10⁻⁶M）、肾上腺素（1×10⁻⁶M）、异丙肾上腺素（1×10⁻⁷M）和二丁酰环磷腺苷（AMP；4×10⁻³M）的变力反应，这些反应发生在以1Hz恒定收缩频率进行电起搏的左心房中；然而，氯胺酮抑制了对刺激频率增加（0.1 - 3.0Hz）和哇巴因（3×10⁻⁷M）的正性变力反应。这些发现表明，氯胺酮可在心肌中发挥选择性正性变力作用，而与心率或直接或反射性自主神经系统变化无关，并提示这种活性可能在某种程度上与环磷腺苷细胞内分布的改变有关。
