Altered adrenergic receptor density in myocardial hibernation in humans : A possible mechanism of depressed myocardial function

• Published in: Circulation (New York, N.Y.) Vol. 102; no. 21; pp. 2599 - 2606
• Main Authors: SHAN, Kesavan, BICK, Roger J, ZOGHBI, William A, POINDEXTER, Brian J, NAGUEH, Sherif F, SHIMONI, Sarah, VERANI, Mario S, KENG, Felix, REARDON, Michael J, LETSOU, George V, HOWELL, Jimmy F
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 21.11.2000; American Heart Association, Inc
• Subjects: Aged; Biological and medical sciences; Biopsy; Cardiology. Vascular system; Coronary Artery Bypass; Coronary heart disease; Dobutamine; Echocardiography; Female; Fibrosis - pathology; Heart; Heart - diagnostic imaging; Humans; Male; Medical sciences; Middle Aged; Myocardial Contraction - drug effects; Myocardial Stunning - metabolism; Myocardial Stunning - pathology; Myocardium - metabolism; Myocardium - pathology; Radiography; Radionuclide Imaging; Receptors, Adrenergic, alpha - metabolism; Receptors, Adrenergic, beta - metabolism; Recovery of Function; Ventricular Dysfunction, Left - diagnosis; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - surgery; Sonography; Human; Pharmacologic test; Cardiac performance; Echocardiography; Pathophysiology; Contractility; Dobutamine; Cardiovascular disease; Exploration; Coronary heart disease; Myocardial disease; Density; Vascular disease; Ischemia; Hibernation; Myocardium; Adrenergic receptor
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.102.21.2599

Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. alpha- and ss-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compared with normal segments and were most pronounced in those without contractile reserve (P:<0.001). Similar findings were observed if recovery of function or scintigraphic uptake was analyzed as a marker for viability. No significant relation between either ARD or BRD and percent myocardial fibrosis was noted (r=0.37 and -0.39, respectively). Thus, graded and reciprocal changes in alpha- and ss-adrenergic receptor densities occur in viable, hibernating myocardium and may account in part for the observed depression in resting myocardial function and preserved contractile reserve in this entity.