TY - JOUR
T1 - Lymphocyte G proteins reflect response to treatment in congestive heart failure
AU - Horn, Evelyn M.
AU - Kukin, Marrick L.
AU - Neuberg, Gerald W.
AU - Goldsmith, Rochelle L.
AU - McCarty, Moira
AU - Gratch, Mary
AU - Medina, Norma
AU - Yushak, Madeline
AU - Packer, Milton
AU - Bilezikian, John P.
N1 - Funding Information:
From the Departments of aMedicine and bpharmacology, College of Physicians and Surgeons, Columbia University, and the bDepartment of Medicine, Mount Sinai School of Medicine. Supported in part by National Institutes of Health grant HL-25055. Dr. Horn was a Physician-Scientist of the American College of Chest Physicians during the time this study was conducted. Received for publication May 9, 1994; accepted June 20, 1994. Reprint requests: Evelyn M. Horn, MD, 177 Fort Washington Ave., Millstein 5-435, New York, NY 10032. Copyright © 1995 by Mosby-Year Book, Inc. 0002-8703/95/$3.00 + 0 4/1/59898
PY - 1995/1
Y1 - 1995/1
N2 - Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in Gsα or an increase in G1α 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.
AB - Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in Gsα or an increase in G1α 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.
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U2 - 10.1016/0002-8703(95)90049-7
DO - 10.1016/0002-8703(95)90049-7
M3 - Article
C2 - 7817932
AN - SCOPUS:0028870098
SN - 0002-8703
VL - 129
SP - 98
EP - 106
JO - American heart journal
JF - American heart journal
IS - 1
ER -