Effects of drugs on the ischemic changes in cardiac function, myocardial energy metabolism and ion permeability-A study by nuclear magnetic resonance spectroscopy (NMR)9

内源性儿茶酚胺（CA）在早期缺血pH下降产生中的作用。用^<31>P-NMR研究异丙肾上腺素、< β - >受体阻滞剂（心得安、品多洛尔和塞利洛尔）、6-羟基多巴胺和利血平对大鼠离体灌注心肌早期缺血时细胞内pH下降的影响。只有心得安对pH值下降有剂量相关的抑制作用。然而，这种抑制作用与该化合物对心肌能量消耗的抑制密切相关。因此，内源性CA参与早期缺血时pH下降的观点没有得到证实。2)长时间缺血时能量代谢的变化。P-NMR研究显示，在诱导缺血后约90分钟，出现了一个新的无机磷酸盐（Pi）峰，该峰位于由于细胞内空间酸化而发生上移的原始细胞内Pi峰。随着缺血的进展，Pi峰的大小增加，与原始Pi峰的降低有关。这些发现表明细胞数量的增加是如此严重的受损，以至于细胞内和细胞外液体间的质子浓度梯度几乎消失。因此，峰值可以用来衡量不可逆缺血性损伤的发展程度。3)缺血时细胞内Na^+的变化。在转移试剂的存在下，细胞内钠峰在缺血诱导后很快被检测到与细胞外钠峰分离，并随着缺血的进展在两个阶段变得更大。第一阶段与细胞内pH值下降相对应，归因于pH值下降导致Na-H交换加速；第二阶段与ATP几乎完全耗尽、细胞内Pi和心室舒张压显著升高同时发生，被认为是不可逆缺血性损伤的开始。少

Role played by endogenous catecholamines (CA) in the production of pH fall during early ischemia.Effects of isoproterenol, <beta>-blockers (propranolol, pindolol and celiprolol), 6-OH dopamine and reserpine on the fall of myocardial intracellular pH during early ischemia were studied with ^<31>P-NMR in the isolated perfused rat heart preparations. Only propranolol produced a dose-related inhibition of the pH fall. However, the inhibition was closely related to the suppression of the myocardial energy consumption produced by this compound. Thus, the idea of involvement of the endogenous CA in the pH fall during early ischemia was not substantiated.2) Changes in energy metabolism during a prolonged period of ischemia.^<31>P-NMR studies revealed the appearance of a new inorganic phosphate (Pi) peak around 90 min after induction of ischemia downfield to the original intracellular Pi peak which had undergone an upfield shift due to acidification of the intracellular space. This peak increas … More ed in size as ischemia progressed in association with a decrease in the original Pi peak. These findings indicate the increase in the numbers of cells so severely damaged that the concentration gradient of the proton between the intra- and extracellular fluid compartments almost disappeared. Thus, the peak can be used as a measure of the degree of development of the irreversible ischemic damage.3) Changes in intracellular Na^+ during ischemia. In the presence of a shift reagent the intracellular Na peak was detected soon after induction of ischemia dissociated form the extracellular one, and became greater in two stages as ischemia progressed. The first stage corresponded to the fall of intracellular pH and was ascribed to acceleration of Na-H exchange due to the fall of pH The second stage occurred simultaneous with an almost complete depletion of ATP and a marked rise of the intracellular Pi and the ventricular diastolic pressure and was taken to denote the onset of the irreversible ischemic damage. Less