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

药物对缺血性心功能、心肌能量代谢及离子通透性变化的影响——核磁共振波谱（NMR）研究9

• 批准号: 60480126
• 负责人: IMAI Shoichi
• 金额: $ 3.97万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480126/
• 关键词: Myocardial ischemia; intracellular pH; <beta>-blockers; 6-OH dopamine; reserpine; ^<31>P-NMR; ^<23>Na-NMR; ^<23>Na-NMR; 【^(31)P】-NMR; 【^(23)Na】-NMR; 摘出心灌流標本; ATP; 無機リン; Dy【(TTHA)^(3-)】; 心室拡張終期圧

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

在离体大鼠离体心脏灌流标本上，用~ 1 P-NMR研究了异丙肾上腺素、β-<beta>受体阻滞剂（心得安、吲哚洛尔和塞利洛尔）、6-OH多巴胺和利血平对缺血早期心肌细胞内pH下降的影响<31>。只有普萘洛尔产生了剂量相关的抑制pH值下降。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，在缺血早期，内源性CA参与pH下降的观点没有得到证实。2）缺血延长期间能量代谢的变化。<31>P-NMR研究揭示了在诱导缺血后约90分钟出现新的无机磷酸盐（Pi）峰，其低场至原始细胞内Pi峰，所述原始细胞内Pi峰由于细胞内空间的酸化而经历了高场移位。该峰值增加 ...更多信息 随着缺血的进展，其大小艾德减小，与原始Pi峰的降低相关。这些发现表明，细胞数量的增加，如此严重的损害，质子的浓度梯度之间的内和细胞外液室几乎消失。因此，该峰值可用于衡量不可逆缺血性损伤的发展程度。3）缺血期间细胞内Na^+的变化。在位移试剂的存在下，细胞内的Na峰被检测到诱导缺血后不久从细胞外的一个解离，并成为更大的两个阶段，缺血进展。第一阶段对应于细胞内pH的下降，归因于由于pH的下降而导致的Na-H交换的加速。第二阶段与ATP几乎完全耗尽和细胞内Pi和心室舒张压的显著升高同时发生，并被用来表示不可逆的缺血性损伤的开始。少

项目成果

Ochi, S.: Jap. J. Pharmac.40. 73p (1986)

Ochi, S.：日本。

Ochi,S.: "Effect of <beta>-blocking agents on the fall of pH in the early phase of ischemia in the isolated perfused rat heart." Jap. J. Pharmac.40. 73- (1986)

Ochi,S.：“β-阻断剂对离体灌注大鼠心脏缺血早期阶段 pH 值下降的影响。”

Nakazawa, M.: Jap. J. Pharmac.43. 13P (1987)

中泽 M.：日本。

Ishibashi,T.: "Changes in myocardial energy metabolism and Na^+ permeability produced by a long ischemia as studied by ^<31>P-NMR and ^<23>Na-NMR." J. Mol. Cell. Cardiol.20(Suppl.I). 45- (1988)

Ishibashi,T.：“通过 31 P-NMR 和 23 Na-NMR 研究，长期缺血引起的心肌能量代谢和 Na 渗透性的变化。”

Nakazawa,M.: "The ischemic derangements of myocardial energy mebolism assessed by phosphorus nuclear magnetic resonance (^<31>P-NMR)." Jap. J. Pharmaco.43. 13 (1987)

Nakazawa,M.：“通过磷核磁共振（^ 31 P-NMR）评估心肌能量代谢的缺血性紊乱。”