Panagiotopoulos S, Nayler W G
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
J Cardiovasc Pharmacol. 1987 Dec;10(6):683-91. doi: 10.1097/00005344-198712000-00012.
The excessive gain in Ca2+ that occurs when hearts are reperfused after prolonged periods of ischemia contributes to cell death and tissue necrosis. The following experiments were undertaken to determine whether nicotine, in a concentration equivalent to the peak concentration present in plasma after cigarette smoke inhalation, alters reperfusion-induced Ca2+ gain in isolated rat hearts. Nicotine (0.15 microgram/ml) failed to increase tissue Ca2+ during aerobic perfusion but increased Ca2+ gain during reperfusion after 30 (p less than 0.02) or 60 (p less than 0.02) min of normothermic ischemia. The increase of Ca2+ gain was independent of a nicotine-induced release of norepinephrine (NE) or an altered "reflow area", heart rate, force of contraction, or end-diastolic resting tension. Pretreatment for 3 days with anipamil (20 mg/kg), a long-acting calcium channel blocker, attenuated the reperfusion-induced Ca2+ gain after 30 min of global ischemia, and reduced (p less than 0.001) the nicotine-induced exacerbation of that gain, without altering tissue ATP or creatine phosphate (CP). Verapamil (1 X 10(-6) M) reduced (p less than 0.02) the nicotine-induced exacerbation of Ca2+ gain caused by reperfusion after 30 min of ischemia.
在长时间缺血后心脏再灌注时出现的钙离子过度增加会导致细胞死亡和组织坏死。进行了以下实验，以确定尼古丁在相当于吸入香烟烟雾后血浆中存在的峰值浓度时，是否会改变离体大鼠心脏再灌注诱导的钙离子增加。尼古丁（0.15微克/毫升）在有氧灌注期间未能增加组织钙离子，但在常温缺血30（p＜0.02）或60（p＜0.02）分钟后的再灌注期间增加了钙离子增加量。钙离子增加量的增加与尼古丁诱导的去甲肾上腺素（NE）释放、改变的“再灌注区域”、心率、收缩力或舒张末期静息张力无关。用长效钙通道阻滞剂阿尼帕米（20毫克/千克）预处理3天，可减轻全脑缺血30分钟后再灌注诱导的钙离子增加，并减少（p＜0.001）尼古丁诱导的该增加量的加剧，而不改变组织ATP或磷酸肌酸（CP）。维拉帕米（1×10⁻⁶M）减少了（p＜0.02）尼古丁诱导的缺血30分钟后再灌注引起的钙离子增加量的加剧。
