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

用~(31)P-核磁共振技术研究了异丙肾上腺素、β-受体阻滞剂心得安、吲哚洛尔和塞利洛尔、6-羟基多巴胺和利血平对缺血早期心肌细胞内pH下降的影响。普萘洛尔对pH下降的抑制作用与剂量相关。而这种抑制作用与抑制该化合物所产生的心肌能量消耗密切相关。因此，内源性CA参与缺血早期pH下降的观点是不成立的。2)长时间缺血期间能量代谢的变化。核磁共振研究显示，在缺血诱导后90min左右出现了一个新的无机磷(PI)峰，该峰由于细胞内空间的酸化而发生了上移。该峰值增加了…随着缺血的进展，与原始PI峰值降低相关的大小增加。这些发现表明，细胞数量的增加严重受损，以至于细胞内液和胞外液之间的质子浓度梯度几乎消失。因此，该峰值可作为不可逆性缺血损伤发展程度的量度。3)缺血时细胞内Na~+的变化。在移动剂存在的情况下，细胞内钠峰在缺血诱导后不久与细胞外钠峰分离，并随着缺血的进展分两个阶段增大。第一阶段对应于细胞内pH的下降，归因于pH下降导致Na-H交换的加速；第二阶段与细胞内PI和心室舒张压的显着升高同时发生，表明不可逆性缺血损伤的开始。较少

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