Myocardial beta-adrenoceptor changes in heart failure: concomitant reduction in beta,- and beta2-adrenoceptor function related to the degree of heart failure in patients with mitral valve disease

Brodde, Otto‐Erich; Zerkowski, Hans‐Reinhard; Doetsch, N.; Motomura, Shigeru; Khamssi, Massud; Michel, Martin C.

doi:10.1016/0735-1097(89)90181-2

Cited by 142 publications

(40 citation statements)

References 31 publications

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“…Studies in human hearts have shown a reduction in the number of 3-adrenergic receptors ( 12-17), particularly of the f3I subtype ( 1 1, 12, 17), from the left ventricle of failing hearts. Recently, considerable attention has been directed to the pacing-induced heart failure model (8,9), in that it exhibits many features common to human heart failure, e.g., the changes in 0-adrenergic receptor signaling in this model approximate those in human studies (12)(13)(14)(15)(16)(17). The majority of these studies as well as all of the studies using human myocardium have focused on later stages in the disease process, after congestive heart failure has been established for some time.…”

Section: Discussionmentioning

confidence: 99%

“…Myocardial /-adrenergic receptor density has been demonstrated to be increased (5, 6), unchanged (7), or decreased (8)(9)(10)(11) in experimental animals with heart failure. and others (15)(16)(17) have consistently shown a reduction in the number of 3-adrenergic receptors, particularly of the A, subtype ( 1 1, 12, 17), in the left ventricle of failing human hearts. Most prior studies have exam-ined the advanced or terminal stages of heart failure, or examined a single component of the d receptor-GTP-stimulatory protein (Gj) '-adenylyl cyclase pathway, leaving an incomplete picture as to the development of the abnormalities in 3-adrenergic signal transduction.…”

Section: Introductionmentioning

confidence: 99%

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Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure.

Kiuchi¹,

et al. 1993

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The development of pacing-induced heart failure was studied in chronically instrumented, conscious dogs paced at a rate of 240 beats/min for 1 d (n = 6), 1 wk (n = 6), and 3-4 wk (n = 7). Left ventricular (LV) dP/dt was decreased (P < 0.0125) at 1 d, LV end-diastolic pressure and heart rate were increased (P < 0.0125) at I wk, but clinical signs of heart failure were only observed after 3-4 wk of pacing. Plasma norepinephrine rose (P < 0.0125) after 1 d of pacing, whereas LV norepinephrine was reduced (P < 0.0125 ) only after 3-4 wk of pacing. Both the fraction of fl-adrenergic receptors binding agonist with high affinity and adenylyl cyclase activity decreased (P < 0.0125) after 1 d of pacing. Total ,6-adrenergic receptor density was not changed at any time point, but 6,1-adrenergic receptor density was decreased (P < 0.0125) after 1 wk. The functional activity of the guanine nucleotide binding protein, G5, was not reduced, but the Gia2 isoform of the a subunit of the GTP-inhibitory protein rose after 34 wk of pacing. Thus, myocardial fl-adrenergic signal transduction undergoes change shortly (1 d) after the initiation of pacing, before heart failure develops. The mechanism of /3-adrenergic receptor dysfunction in pacing-induced heart failure is characterized initially by elevated plasma levels of catecholamines, uncoupling of fl-adrenergic receptors, and a defect in the adenylyl cyclase catalytic unit. Selective down-regulation of fll-adrenergic receptors, increases in G,62, and decreases in myocardial catecholamine levels occur as later events. (J. Clin. Invest. 1993. 91:907-914.) Key words: adenylyl cyclase . fll-adrenergic receptors* fl2-adrenergic receptors congestive heart failure * norepinephrine

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure.

Kiuchi¹,

et al. 1993

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“…In a study by Bernardi et al,15 an increase in the PEP/LVET ratio was observed in both pate in the cardiac contractile responses. 37,38 The structure of the b-adrenergic receptor has recently been elucidated. alcoholic and nonalcoholic cirrhotic patients, and no significant difference in the magnitude of the cardiac abnormalities The cardiac b-adrenoceptor is, like other G-protein (guanosine triphosphate-binding protein)-coupled receptors, comwas found between the two groups.…”

Section: Cardiac Histology In Cirrhosismentioning

confidence: 99%

Cirrhotic cardiomyopathy: Getting to the heart of the matter

1996

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can lead to liver dysfunction and damage. How unexpected In cirrhosis, cardiac contractile function has been exand gratifying, therefore, to find a voice as eloquent as the tensively documented to be abnormal. At baseline, carlate Chilean Nobel laureate's to not only extoll the many diac output is increased, and this is one of the charactervirtues of the liver, but also remind us that sometimes the istics of hyperdynamic circulation. However, when liver takes precedence over the heart, i.e., that liver failure cirrhotic patients are challenged by pharmacological or can also lead to cardiac dysfunction. physiological stress, ventricular hyporesponsiveness is It has been known for more than four decades that hepatic revealed. Similar patterns have been noted in cirrhotic cirrhosis is associated with a host of cardiovascular abnoranimal models. This phenomenon has been termed ''cirmalities. The initial studies in the early 1950s documented rhotic cardiomyopathy.'' Although alcohol abuse may the existence of hyperdynamic circulation in cirrhosis, manicontribute to some cases of cirrhotic cardiomyopathy, it has been clearly documented to occur even in the ab-fested by increased cardiac output and reduced systemic vassence of alcohol ingestion. Diminished myocardial b-ad-cular resistance. This latter phenomenon, the peripheral varenergic receptor signal transduction function, possibly sodilatation, continues to fascinate investigators even up to caused by a persistent elevation in norepinephrine con-the present, and recent studies have examined the possible tent, has been shown to play an important role. Alter-role of nitric oxide and other endothelium-dependent factors ation in cardiac plasma membrane properties due to im-in mediating the vasodilatation. The heart itself was not expaired lipid metabolism is also crucial. Other possible amined until about three decades ago, and around that time pathogenic factors are reviewed, including accumula-studies of cardiac contractile function in patients with alcotion of cardiodepressant substances caused by hepato-holic-induced liver disease started consistently showing that cellular insufficiency, and ventricular overload sec-despite the increased baseline cardiac output, when ventricuondary to increased blood volume and hyperdynamic lar contractile responses were tested under conditions of circulation. Because the cardiac reserve function is bor-pharmacological or physiological stress, the heart behaved derline in patients with cirrhosis, cardiovascular status abnormally in a blunted manner. For many years, this was should be carefully monitored, especially when patients ascribed to the well-known direct toxic effects of alcohol on undergo stresses such as liver transplantation or porto-cardiac muscle, i.e., as a manifestation of latent or subclinical systemic shunting procedures. (HEPATOLOGY 1996;24: alcoholic cardiomyopathy, and relegated to the scientific 451-459.)backwaters as a clinically insignificant curiosity. However, recently several studies have emerged in both ...

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“…[3][4][5][6][7][8] The response of failing myocytes to increasing beating rates is also abnormal. 9 In the normal heart, contraction rate and magnitude increase with beating rate (often termed a positive force-frequency relationship), whereas in the failing myocardium, contractions decrease over the same range of frequencies.…”

Section: See P 2297mentioning

confidence: 99%

Myocyte Recovery After Mechanical Circulatory Support in Humans With End-Stage Heart Failure

et al. 1998

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Background-The failing myocardium is characterized by decreased force production, slowed relaxation, and depressed responses to ␤-adrenergic stimulation. In some heart failure patients, heart function is so poor that a left ventricular assist device (LVAD) is inserted as a bridge to transplantation. In the present research, we investigated whether circulatory support with an LVAD influenced the functional properties of myocytes from the failing heart. Methods and Results-Myocytes were isolated from human explanted failing hearts (HF-myocytes) and failing hearts with antecedent LVAD support (HF-LVAD-myocytes). Studies of myocyte function indicated that the magnitude of contraction was greater (9.6Ϯ0.7% versus 6.9Ϯ0.5% shortening), the time to peak contraction was significantly abbreviated (0.37Ϯ0.01 versus 0.75Ϯ0.04 seconds), and the time to 50% relaxation was reduced (0.55Ϯ0.02 versus 1.45Ϯ0.11 seconds) in the HF-LVAD-myocytes compared with the HF-myocytes (PϽ0.05). The HF-LVAD-myocytes had larger contractions than the HF-myocytes at all frequencies of stimulation tested. The negative force-frequency relationship of the HF-myocytes was improved in HF-LVAD-myocytes but was not reversed. Responses to ␤-adrenergic stimulation (by isoproterenol) were greater in HF-LVAD-myocytes versus HF-myocytes. Conclusions-The results of the study strongly support the idea that circulatory support with an LVAD improves myocyte contractile properties and increases ␤-adrenergic responsiveness. (Circulation. 1998;97:2316-2322.)

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Myocardial beta-adrenoceptor changes in heart failure: concomitant reduction in beta,- and beta2-adrenoceptor function related to the degree of heart failure in patients with mitral valve disease

Cited by 142 publications

References 31 publications

Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure.

Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure.

Cirrhotic cardiomyopathy: Getting to the heart of the matter

Myocyte Recovery After Mechanical Circulatory Support in Humans With End-Stage Heart Failure

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