White M, Wiechmann R J, Roden R L, Hagan M B, Wollmering M M, Port J D, Hammond E, Abraham W T, Wolfel E E, Lindenfeld J
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.
Circulation. 1995 Oct 15;92(8):2183-9. doi: 10.1161/01.cir.92.8.2183.
Ten percent to 20% of potential cardiac donors with brain injury and no previous cardiac history have myocardial dysfunction. We assessed components of the beta-receptor-G-protein-adenylyl cyclase complex as well as the contractile response in 10 explanted acutely failing human hearts (donor heart dysfunction [DHD]) and compared the results with 13 age-matched nonfailing (NF) organ donor controls.
As measured by echocardiography, all DHD hearts exhibited a decreased shortening fraction (16 +/- 2%, mean +/- SEM). Although total and subpopulation beta-receptor densities measured by [125I]iodocyanopindolol (ICYP) were similar in the DHD and NF groups, DHD hearts exhibited a 30% decrease in maximum isoproterenol-stimulated adenylyl cyclase activity and a 50% decrease in the maximal response to zinterol. DHD hearts also exhibited decreases in adenylyl cyclase maximal stimulation by forskolin (211 +/- 25 [DHD] versus 295 +/- 23 [NF] pmol cAMP.min-1.mg-1, P < .05) and 5'-guanylylimidodiphosphate (12.5 +/- 1.8 [DHD] versus 19.6 +/- 3.2 [NF] pmol cAMP.min-1.mg-1, P < .05), but there was no significant decrease in adenylyl cyclase stimulation by Mn2+, a direct activator of adenylyl cyclase. Right ventricular trabeculae removed from DHD hearts exhibited a profound decrease in the contractile response to isoproterenol (8.7 +/- 1 [DHD] versus 22 +/- 2 [NF] mN, P < .001) as well as reduced calcium responses (7.2 +/- 1.6 [DHD] versus 14 +/- 3 [NF] mN, P = .03). Morphological examination of two hearts revealed some ultrastructural evidence suggestive of catecholamine-mediated injury, but there was no difference in tissue creatine kinase activity between the two groups.
Compared with NF hearts, DHD hearts exhibit marked uncoupling of beta 1- and beta 2-adrenergic receptors from adenylyl cyclase and contractile response stimulation as well as decreased intrinsic systolic function. Thus, acute myocardial dysfunction accompanying brain injury is characterized by marked alterations in beta-adrenergic signal transduction as well as changes in the contractile apparatus, and this profile is markedly different from what occurs in the chronically failing human heart.
10%至20%有脑损伤且既往无心脏病史的潜在心脏供体存在心肌功能障碍。我们评估了10例急性衰竭的人心脏（供体心脏功能障碍[DHD]）中β受体 - G蛋白 - 腺苷酸环化酶复合物的组成部分以及收缩反应，并将结果与13例年龄匹配的非衰竭（NF）器官供体对照进行比较。
通过超声心动图测量，所有DHD心脏的缩短分数均降低（16±2%，平均值±标准误）。尽管通过[125I]碘氰吲哚洛尔（ICYP）测量的总β受体密度和亚群β受体密度在DHD组和NF组中相似，但DHD心脏在最大异丙肾上腺素刺激的腺苷酸环化酶活性方面降低了30%，对齐特罗尔的最大反应降低了50%。DHD心脏对福斯高林（211±25[DHD]对295±23[NF] pmol cAMP·min-1·mg-1，P<.05）和5'-鸟苷酰亚胺二磷酸（12.5±1.8[DHD]对19.6±3.2[NF] pmol cAMP·min-1·mg-1，P<.05）刺激的腺苷酸环化酶最大刺激也降低，但腺苷酸环化酶的直接激活剂Mn2+刺激的腺苷酸环化酶无显著降低。从DHD心脏取出的右心室小梁对异丙肾上腺素的收缩反应显著降低（8.7±1[DHD]对22±2[NF] mN，P<.001）以及钙反应降低（7.2±1.6[DHD]对14±3[NF] mN，P =.03）。对两颗心脏的形态学检查显示一些超微结构证据提示儿茶酚胺介导的损伤，但两组之间组织肌酸激酶活性无差异。
与NF心脏相比，DHD心脏表现出β1和β2肾上腺素能受体与腺苷酸环化酶以及收缩反应刺激的明显解偶联，以及内在收缩功能降低。因此，伴随脑损伤的急性心肌功能障碍的特征是β肾上腺素能信号转导的明显改变以及收缩装置的变化，并且这种情况与慢性衰竭的人心脏明显不同。
