Karmazyn M, Tani M, Neely J R
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania.
Cardiovasc Res. 1993 Mar;27(3):396-402. doi: 10.1093/cvr/27.3.396.
The aim was to examine the effect on cardiac function, energy metabolism, and calcium uptake of either prostaglandin I2 (PGI2, prostacyclin) or prostaglandin F2 alpha (both 28.6 nM) on the response of isolated rat hearts to 25 min of total global ischaemia with or without 30 min reperfusion.
Rat hearts were perfused by the Langendorff method and function assessed by left ventricular pressure. Energy metabolites were measured using enzymatic techniques and 45Ca2+ uptake determined by radioisotopic analysis.
Although there was no effect of either prostaglandin on contractile depression during ischaemia, both compounds accelerated the onset of and increased the magnitude of ischaemic contracture. High energy phosphate content at the end of the ischaemic period was not affected by prostaglandin treatment; however, tissue lactate levels were increased by PGI2 as was tissue calcium content. Under control conditions mean recovery of left ventricular developed pressure ranged from 66% to 83%. In the presence of PGI2 and PGF2 alpha, recovery of developed pressure was reduced to 20% and 38% of preischaemic values, respectively. The reduced recovery in developed pressure was accompanied by an approximately threefold increase in diastolic pressure (p < 0.05). The depression of functional recovery in reperfused hearts treated with prostaglandins was associated with various disturbances of cellular metabolism including depressed ATP and creatine phosphate content and increased tissue lactate and calcium following 30 min of reperfusion. A significant correlation was found between the changes in developed pressure and diastolic pressure during reperfusion and the reduction in ATP and creatine phosphate repletion. The deficit in recovery of ventricular function also correlated significantly with increased lactate and calcium accumulation in the reperfused heart.
Low concentrations of PGI2 and PGF2 alpha can depress contractile recovery of the globally ischaemic heart through a mechanism associated with altered cellular energy metabolism and increased calcium accumulation.
研究前列腺素I2（PGI2，前列环素）或前列腺素F2α（均为28.6 nM）对离体大鼠心脏在25分钟全心缺血（有无30分钟再灌注）反应时心脏功能、能量代谢及钙摄取的影响。
采用Langendorff法灌注大鼠心脏，通过左心室压力评估心脏功能。使用酶促技术测量能量代谢产物，通过放射性同位素分析测定45Ca2+摄取量。
尽管两种前列腺素对缺血期间的收缩抑制均无影响，但两种化合物均加速了缺血性挛缩的发生并增加了其程度。缺血期末的高能磷酸含量不受前列腺素处理的影响；然而，PGI2使组织乳酸水平升高，组织钙含量也升高。在对照条件下，左心室舒张末压的平均恢复率为66%至83%。在存在PGI2和PGF2α的情况下，舒张末压的恢复分别降至缺血前值的20%和38%。舒张末压恢复降低伴随着舒张压大约增加三倍（p < 0.05）。用前列腺素处理的再灌注心脏功能恢复的抑制与细胞代谢的各种紊乱有关，包括再灌注30分钟后ATP和磷酸肌酸含量降低以及组织乳酸和钙增加。再灌注期间舒张末压和舒张压的变化与ATP和磷酸肌酸补充减少之间存在显著相关性。心室功能恢复的不足也与再灌注心脏中乳酸和钙积累增加显著相关。
低浓度的PGI2和PGF2α可通过与细胞能量代谢改变和钙积累增加相关的机制抑制全心缺血心脏的收缩恢复。
