In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 92, No. 8 ( 1995-10-15), p. 2183-2189
Abstract:
Background Ten percent to 20% of potential cardiac donors with brain injury and no previous cardiac history have myocardial dysfunction. We assessed components of the β-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. Methods and Results As measured by echocardiography, all DHD hearts exhibited a decreased shortening fraction (16±2%, mean±SEM). Although total and subpopulation β-receptor densities measured by [ 125 I]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 Mn 2+ , 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. Conclusions Compared with NF hearts, DHD hearts exhibit marked uncoupling of β 1 - and β 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 β-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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.92.8.2183
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1995
detail.hit.zdb_id:
1466401-X
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