DECREASED MYOFILAMENT RESPONSIVENESS IN MYOCARDIAL STUNNING FOLLOWS TRANSIENT CALCIUM OVERLOAD DURING ISCHEMIA AND REPERFUSION

被引:124
作者
CARROZZA, JP
BENTIVEGNA, LA
WILLIAMS, CP
KUNTZ, RE
GROSSMAN, W
MORGAN, JP
机构
[1] HARVARD UNIV,BETH ISRAEL HOSP,CHARLES A DANA INST,BOSTON,MA 02215
[2] HARVARD UNIV,BETH ISRAEL HOSP,HARVARD THORNDIKE LAB,BOSTON,MA 02215
关键词
CALCIUM; AEQUORIN; ISCHEMIA; REPERFUSION; STUNNING;
D O I
10.1161/01.RES.71.6.1334
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The purpose of this study was to test the hypothesis that abnormal intracellular calcium handling characterizes myocardial stunning. Isolated, isovolumic, buffer-perfused ferret hearts were loaded with the bioluminescent calcium indicator aequorin for simultaneous measurement of individual calcium transients and left ventricular pressure. After 15 minutes of global ischemia and 20 minutes of reperfusion, left ventricular developed pressure was significantly reduced (75 +/- 7 versus 93 +/- 6 mm Hg, p<0.05). During ischemia, [Ca2+]i levels were significantly elevated compared with preischemic levels, both during systole (138 +/- 0.31 versus 0.88 +/- 0.2 muM, p<0.05) and end diastole (0.85 +/- 0.16 versus 0.38 +/- 0.13 muM, p<0.05). Early during reperfusion, [Ca2+]i was also significantly elevated during systole (1.63 +/- 0.44 versus 0.88 +/- 0.20 muM, p<0.05) and end diastole (0.75 +/- 0.15 versus 0.38 +/- 0.13 muM, p<0.05). After 20 minutes of reperfusion, myocardial stunning occurred, but [Ca2+]i was not significantly different from preischemic levels. Thus, myocardial stunning does not result from decreased levels of activator calcium. The force-pCa relation generated by the stunned hearts was shifted downward compared with that generated by the control hearts, consistent with a decrease in maximum calcium-activated force (F(max)). At steady state during tetanus, the decrease in F(max) was confirmed, but there was no significant difference in the slope of the force-pCa relation of the stunned hearts versus controls. Thus, we conclude that stunned myocardium is characterized by decreased F(max) without desensitization of the myofilaments to [Ca2+]i. Elevations of [Ca2+]i during ischemia and reperfusion precede myocardial stunning and may relate to its pathogenesis.
引用
收藏
页码:1334 / 1340
页数:7
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