Tanz R D, Kettelkamp N, Hirshman C A
Agents Actions. 1985 Jul;16(5):415-24. doi: 10.1007/BF01982883.
This study was designed to determine the effects of different calcium concentrations on the perfused isolated guinea-pig heart preparation subjected to cardiac anaphylaxis. Following challenge both physiological and biochemical effects were determined on hearts from guinea-pigs previously sensitized to ovalbumin. Perfusion media containing either 1,2.54 or 5 mM of calcium was used. In comparison to nonsensitized controls challenged to ovalbumin, challenged sensitized hearts (CSH) perfused with 1 mM Ca2+ showed an initial increase in dF/dt, a prolonged rise in H.R. and depressed coronary flow. Raising the calcium concentration to either 2.54 or 5 mM in CSH preparations resulted in a marked increase in the release of lactate dehydrogenase (LDH) into the coronary effluent and depressed coronary flow. Perfusing CSH preparations with increasingly higher calcium concentrations more often produced severe tachyarrhythmias and fibrillation. The highest level of histamine released into the coronary effluent occurred immediately following challenge and then declined exponentially over the next 20 min. Both challenge and the administration of histamine induced an immediate but transient increase in H.R., a rise in dF/dt, and LDH release. The infusion of histamine produced an increase in coronary flow, but on porcine tubular coronary arterial segments only a direct constricting effect was obtained. The prior administration of cimetidine (10(-5) M) attenuated the rise in LDH and dF/dt in CSH and nonsensitized preparations infused with histamine (3 micrograms). However, although cimetidine did not affect the decreased coronary flow in CSH preparations, it initially attenuated the rise in coronary flow in preparations infused with histamine. These results suggest that calcium enhances the likelihood of tachyarrhythmias in cardiac anaphylaxis. The release of LDH in histamine-infused preparations and those CSH preparations perfused with 2.54 and 5 mM calcium-containing media also suggests the possibility that calcium enhances the damaging effects on the myocardial cell in cardiac anaphylaxis.
本研究旨在确定不同钙浓度对经历心脏过敏反应的灌注离体豚鼠心脏标本的影响。在激发后，对先前对卵清蛋白致敏的豚鼠心脏测定其生理和生化效应。使用含有1、2.54或5 mM钙的灌注培养基。与用卵清蛋白激发的未致敏对照相比，用1 mM Ca2+灌注的激发致敏心脏（CSH）显示dF/dt最初增加、心率持续升高以及冠状动脉血流降低。在CSH制剂中将钙浓度提高到2.54或5 mM会导致乳酸脱氢酶（LDH）释放到冠状动脉流出液中显著增加以及冠状动脉血流降低。用越来越高的钙浓度灌注CSH制剂更常产生严重的快速性心律失常和颤动。释放到冠状动脉流出液中的组胺最高水平在激发后立即出现，然后在接下来的20分钟内呈指数下降。激发和组胺给药均引起心率立即但短暂的增加、dF/dt升高以及LDH释放。组胺输注使冠状动脉血流增加，但仅在猪冠状动脉节段上获得直接的收缩效应。预先给予西咪替丁（10(-5) M）可减轻用组胺（3微克）灌注的CSH和未致敏制剂中LDH和dF/dt的升高。然而，尽管西咪替丁不影响CSH制剂中降低的冠状动脉血流，但它最初减弱了用组胺灌注的制剂中冠状动脉血流的升高。这些结果表明钙增加了心脏过敏反应中快速性心律失常的可能性。在用组胺灌注的制剂以及用含2.54和5 mM钙的培养基灌注的CSH制剂中LDH的释放也表明钙可能增加心脏过敏反应中对心肌细胞的损伤作用。
