Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: Reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptors

Baumann, Gert; Rieß, Gotthard; Erhardt, W.; Felix, Stephan B.; Ludwig, Liesel; Blümel, G.; Blömer, H

doi:10.1016/0002-8703(81)90223-4

Cited by 75 publications

(24 citation statements)

References 31 publications

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“…There is, however, evidence to suggest that the increase in sympathetic tone persists (3)(4)(5). Thus, when hypoxemia is prolonged, the benefits of increased sympathetic stimulation may be outweighed by its deleterious cellular, metabolic, and circulatory effects (2,(6)(7)(8). One potential cellular-level consequence of chronic sympathetic stimulation is a down-regulation of the ,B-adrenergic receptor/adenylate cyclase system, as occurs in patients with heart failure secondary to cardiomyopathy (9,10).…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of right and left ventricular beta-adrenergic receptors in newborn lambs with experimental cyanotic heart disease.

Bernstein¹,

Voss²,

Huang³

et al. 1990

J. Clin. Invest.

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To determine whether chronic hypoxemia secondary to an intracardiac right-to-left shunt alters regulation of the myocardial 63-adrenergic receptor/adenylate cyclase system, we produced chronic hypoxemia in nine newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 wk. Eight lambs served as normoxemic controls. 13-receptor density (B.) and ligand affinity (KD) were determined with the radioligand '2"5iiodocyanopindolol and adenylate cyclase activity determined during stimulation with isoproterenol, sodium fluoride (NaF), and forskolin. During chronic hypoxemia, B.. decreased 45% (hypoxemic, 180.6±31.5 vs. control, 330.5±60.1 fmol/mg) in the left ventricle (exposed to hypoxemia alone) but was unchanged in the right ventricle (exposed to hypoxemia and pressure overload). KD was not different from control in either ventricle. Left ventricular isoproterenolstimulated adenylate cyclase activity was decreased by 39% (30.0±4.3% increase vs. 44.1±9.5% increase) whereas right ventricular adenylate cyclase activity was unchanged. Stimulation of adenylate cyclase with NaF or forskolin was not different from control in either ventricle. Circulating epinephrine was increased fourfold whereas circulating and myocardial norepinephrine were unchanged. These data demonstrate a downregulation of the left ventricular ,6-adrenergic receptor/adenylate cyclase system during chronic hypoxernia secondary to an intracardiac right-to-left shunt. (J. Clin. Invest. 1990. 85:68-74.) cyanotic heart disease -hypoxemia* myocardial fl-adrenergic receptor regulation

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Section: Introductionmentioning

confidence: 99%

Differential regulation of right and left ventricular beta-adrenergic receptors in newborn lambs with experimental cyanotic heart disease.

Bernstein¹,

Voss²,

Huang³

et al. 1990

J. Clin. Invest.

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“…Ejection fraction in patients often spontaneously improves during the first 2 weeks postinfarction, independent of specific therapy.28,31 Early in acute infarction, plasma catecholamine levels increase markedly,34-36 but this is followed by down-regulation of ,Breceptors resulting in a blunted response to inotropic stimulation during recovery. 37 In animal studies, acute protein synthesis is preferentially shifted toward increased mitochondria and other elements necessary for contractile function,29 and, days to weeks later, shifts to enhanced production of myofilaments.30 Thus, recovery from an acute myocardial infarction is facilitated by multiple mechanisms that are different in the acute and chronic phase. Hypertrophy of the noninfarcted myocardium appears to be an important chronic factor leading to improved rest and exercise left ventricu-lar function, but which probably has little or no role as an early adaptation to the myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.

et al. 1989

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Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20

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“…In ischemic myocardial tissue, Devos et al demonstrated that the concentration of isoproterenol required for half-maximal adenylate cyclase activation was identical in control and ischemic tissues and that the ischemic area demonstrated a marked increase in the number of low-affinity sites as measured by isoproterenol competition curves compared with control nonischemic myocardium (29 Effects of 13-adrenergic blockade. Previous studies of the 13-receptor after chronic 13-adrenergic blockade have yielded conflicting results, both increases in receptor density (38)(39)(40)(41)(42)(43)(44) or no change having been reported (45)(46)(47)(48)(49)(50) (52). However, none of these studies examined 1-adrenergic receptor density or affinity in the presence of acute myocardial ischemia in 13-blocked preparations.…”

Section: Discussionmentioning

confidence: 99%

Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.

Karliner¹,

Stevens²,

Honbo³

et al. 1989

J. Clin. Invest.

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We ligated the left anterior descending coronary artery for 1 or 2 h in 31 purebred beagles. We did not detect any changes in ,8-adrenergic receptor density or affinity when normal and ischemic zones were compared, either in the subendocardium or in the subepicardium. In the ischemic zones, there was a significant decline in all measures of adenylate cyclase activity, including activity mediated by the ,-adrenergic receptor. By contrast, after chronic fl-adrenergic blockade (1.5 mg/kg propranolol i.v. twice daily for 7 d), there was an increase in adenylate cyclase activity stimulated by (-)-isoproterenol relative to adenylate cyclase activity stimulated by guanyl-5'imidodiphosphate (GppNHp) in both normal and ischemic tissue, suggesting that one effect of chronic ,B blockade may be to enchance coupling between the stimulatory guanine nucleotide regulatory protein (Gs) and the fl-adrenergic receptor, despite a reduction in the number or function of Gs units. Chronic ,B blockade also led to up regulation of ,-adrenergic receptor density in subepicardial regions. After 20 min of reperfusion following 2 h of ischemia, adenylate cyclase activity tended to return to control levels, particularly in the subepicardium, where (-)-isoproterenol-stimulated adenylate cyclase activity was not different from normal myocardium. We conclude that chronic f-adrenergic blockade may have beneficial effects during prolonged episodes of myocardial ischemia by preserving signal transduction mediated by the ,-adrenergic receptor.

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Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: Reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptors

Cited by 75 publications

References 31 publications

Differential regulation of right and left ventricular beta-adrenergic receptors in newborn lambs with experimental cyanotic heart disease.

Differential regulation of right and left ventricular beta-adrenergic receptors in newborn lambs with experimental cyanotic heart disease.

Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.

Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.

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