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

Background-Alterations in adrenergic receptor densities can potentially con tribute to myocardial dysfunction. Their relevance to myocardial hibernatio n in humans is unknown. Methods and Results-Accordingly, 22 transmural myocardial biopsies were obt ained in 11 patients with ischemic ventricular dysfunction during bypass su rgery, guided by transesophageal echocardiography. Patients underwent dobut amine echocardiography (DE) and rest scintigraphic studies before revascula rization and DE at 3 to 4 months. alpha- and beta -receptor density (ARD an d BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Sever ely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increa se in ARD, a decrease in BRD to a lesser extent, and thus an increase in AR D/BRD ratio were seen in dysfunctional segments with contractile reserve co mpared with normal segments sand were most pronounced in those without cont ractile reserve (P<0.001). Similar findings were observed if recovery of fu nction or scintigraphic uptake was analyzed as a marker for viability. No s ignificant relation between either ARD or:BRD and percent myocardial fibros is was noted (r=0.37 and -0.39, respectively). Conclusions-Thus, graded and reciprocal changes in <alpha>- and beta -adren ergic receptor densities occur in viable, hibernating myocardium and may ac count in part for the observed depression in resting myocardial function an d preserved contractile reserve in this entity.