Mitsos S E, Jolly S R, Lucchesi B R
Pharmacology. 1985;31(3):121-31. doi: 10.1159/000138107.
The effects of a purine precursor, AICAriboside (5-aminoimidazole-4-carboxamide riboside), on postischemic recovery of myocardial function and adenine nucleotides have been studied in the isolated blood-perfused cat heart. The isolated hearts received either AICAriboside or saline prior to 60 min of global ischemia and during 60 min of subsequent reperfusion. After 60 min of global ischemia and reperfusion, left ventricular function of the AICAriboside-treated hearts approached preischemic values, whereas contractile function of the saline-treated hearts remained depressed. At 60 min postischemia, recovery of left ventricular developed pressure (LVDP) was 62 +/- 10% for the saline-treated hearts as compared to 93 +/- 8% for the AICAriboside-treated hearts. Left ventricular compliance of the saline-treated hearts was decreased slightly at 60 min postischemia. In contrast, left ventricular compliance was increased in the isolated hearts which received AICAriboside. Myocardial ATP concentrations were decreased significantly at 60 min postischemia in both the saline-treated hearts and in the AICAriboside-treated hearts relative to nonischemic hearts. Similarly, total adenine nucleotides (TAN = ATP + ADP + AMP) were decreased significantly in both the saline-treated hearts and AICAriboside-treated hearts relative to nonischemic hearts. The present study demonstrates that AICAriboside protected globally ischemic hearts from the mechanical dysfunction associated with an ischemic insult but did not restore ATP or the total adenine nucleotide pool of the postischemic myocardium.
在离体血液灌注猫心脏中,研究了嘌呤前体5-氨基咪唑-4-甲酰胺核苷(AICA核苷)对心肌功能缺血后恢复及腺嘌呤核苷酸的影响。在60分钟全心缺血前及随后60分钟再灌注期间,离体心脏分别接受AICA核苷或生理盐水处理。全心缺血和再灌注60分钟后,接受AICA核苷处理的心脏左心室功能接近缺血前值,而接受生理盐水处理的心脏收缩功能仍受抑制。缺血60分钟时,接受生理盐水处理的心脏左心室舒张末压(LVDP)恢复率为62±10%,而接受AICA核苷处理的心脏为93±8%。接受生理盐水处理的心脏在缺血60分钟时左心室顺应性略有降低。相比之下,接受AICA核苷的离体心脏左心室顺应性增加。与非缺血心脏相比,接受生理盐水处理的心脏和接受AICA核苷处理的心脏在缺血60分钟时心肌ATP浓度均显著降低。同样,与非缺血心脏相比,接受生理盐水处理的心脏和接受AICA核苷处理的心脏总腺嘌呤核苷酸(TAN = ATP + ADP + AMP)均显著降低。本研究表明,AICA核苷可保护全心缺血心脏免受与缺血损伤相关的机械功能障碍,但不能恢复缺血后心肌的ATP或总腺嘌呤核苷酸池。