Lymphocyte G proteins reflect response to treatment in congestive heart failure

Evelyn M. Horn, Marrick L. Kukin, Gerald W. Neuberg, Rochelle L. Goldsmith, Moira McCarty, Mary Gratch, Norma Medina, Madeline Yushak, Milton Packer, John P. Bilezikian

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Abstract

Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in G or an increase in G is associated with a decrease in adenylyl cylase activity. The current study assessed G proteins in response to treatment with direct-acting vasodilators and correlated changes in lymphocyte β-adrenergic receptor components with changes in hemodynamic variables. Twenty-three patients with severe chronic congestive heart failure (New York Heart Association functional classes III and IV) were studied. Patients were grouped as responders (n = 10) or nonresponders (n = 13) on the basis of clinical assessment of functional status from questionnaires. Therapy was associated with an increase in cardiac index, a decrease in mean arterial pressure, and a decrease in systemic vascular resistance in all patients. Left ventricular filling pressure significantly decreased in responders (26 ± 2 mm to 13 ± 3 mm, p < 0.05) but did not change significantly in nonresponders. Similarly, mean right atrial pressure significantly decreased in responders (11 ± 2 mm Hg to 4 ± 1 mm Hg, p < 0.05) but did not change in nonresponders. Plasma norepinephrine increased significantly only in nonresponders (679 ± 100 pg/ml to 1233 ± 201 pg/ml, p < 0.05). Whereas lymphocyte β-adrenergic receptor density and Gs did not significantly change, Gi increased after treatment only in the nonresponder group (23 ± 5 to 51 ± 11 fmol/mg, p < 0.05). A poor response to direct-acting vasodilators can be distinguished by reactive increases in plasma norepinephrine and lymphocyte Gi in the absence of a decrease in either left- or right-sided filling pressures.

Original languageEnglish (US)
Pages (from-to)98-106
Number of pages9
JournalAmerican heart journal
Volume129
Issue number1
DOIs
StatePublished - Jan 1995

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Horn, E. M., Kukin, M. L., Neuberg, G. W., Goldsmith, R. L., McCarty, M., Gratch, M., Medina, N., Yushak, M., Packer, M., & Bilezikian, J. P. (1995). Lymphocyte G proteins reflect response to treatment in congestive heart failure. American heart journal, 129(1), 98-106. https://doi.org/10.1016/0002-8703(95)90049-7