Cavallini L, Valente M, Rigobello M P
Dipartimento di Chimica Biologica, Universitá di Padova, Italy.
J Mol Cell Cardiol. 1990 Feb;22(2):143-54. doi: 10.1016/0022-2828(90)91111-j.
The recovery of both contractile performance and metabolic response of rat heart following 1 h of ischemia after equilibration with glucose + insulin (glucose-ischemia) or with pyruvate (pyruvate-ischemia), was tested in normoxic reperfusion in the presence of glucose + insulin, pyruvate, lactate or acetate. In glucose-ischemia only the reperfusion with pyruvate results in a complete recovery of the contractile force (left ventricular pressure, LVP) (170%) and good recovery of high energy phosphate compounds. Lower LVP and tissue energy charge were found in glucose reperfusion and even less in lactate and acetate reperfusion. Disappearance of the IMP accumulated during ischemia is evident only in the pyruvate reperfusion indicating a higher metabolic recovery. On the contrary in pyruvate-ischemia all types of reperfusion tested were effective in reactivating the contractile force (although acetate to a lesser extent); the contractile activity was accompanied by a good recovery of phosphocreatine, ATP, energy charge and by the decrease of IMP. Large decreases of adenine nucleotides and NADP and lower decreases of NAD are observed during ischemia/reperfusion in both systems. Pyruvate-ischemia is quite similar to, if not worse than glucose-ischemia, for all the metabolic parameters considered, but not worse for the possibility of recovery. Some specific effect of pyruvate should be exerted during the ischemic phase. The mechanism of pyruvate protection is discussed in relationship to: (i) the possible activation of pyruvate dehydrogenase, (ii) the activation of NADPH-dependent peroxide scavenging systems, (iii) the direct scavenging action of pyruvate on H2O2.
在用葡萄糖+胰岛素(葡萄糖-缺血)或丙酮酸(丙酮酸-缺血)平衡后,对大鼠心脏进行1小时缺血处理,之后在存在葡萄糖+胰岛素、丙酮酸、乳酸或乙酸盐的常氧再灌注条件下,测试其收缩性能和代谢反应的恢复情况。在葡萄糖-缺血中,只有用丙酮酸再灌注能使收缩力(左心室压力,LVP)完全恢复(170%),并使高能磷酸化合物得到良好恢复。在葡萄糖再灌注中LVP和组织能荷较低,而在乳酸和乙酸盐再灌注中更低。缺血期间积累的肌苷酸(IMP)仅在丙酮酸再灌注中明显消失,表明代谢恢复程度更高。相反,在丙酮酸-缺血中,所有测试的再灌注类型都能有效恢复收缩力(尽管乙酸盐的程度较小);收缩活性伴随着磷酸肌酸、三磷酸腺苷(ATP)、能荷的良好恢复以及IMP的减少。在两个系统的缺血/再灌注过程中,均观察到腺嘌呤核苷酸和烟酰胺腺嘌呤二核苷酸磷酸(NADP)大幅下降,而烟酰胺腺嘌呤二核苷酸(NAD)下降幅度较小。就所考虑的所有代谢参数而言,丙酮酸-缺血即使不比葡萄糖-缺血更严重,也与之非常相似,但在恢复可能性方面并不更差。丙酮酸的某些特定作用应在缺血期发挥。本文结合以下方面讨论了丙酮酸的保护机制:(i)丙酮酸脱氢酶可能的激活;(ii)烟酰胺腺嘌呤二核苷酸磷酸(NADPH)依赖性过氧化物清除系统的激活;(iii)丙酮酸对过氧化氢(H2O2)的直接清除作用。