INCREASED RESPONSIVENESS OF LEFT-VENTRICULAR APICAL MYOCARDIUM TO ADRENERGIC STIMULI

Objective: The aim was to determine whether left ventricular apical myocardium has mechanisms to compensate for sparse sympathetic innervation. Methods: Contractile and metabolic responses to various adrenergic stimuli and beta adrenergic receptor density were compared between left ventricular basal and apical regions in 26 anaesthetised mongrel dogs, weight 12-28 kg. Results: Regional contractile changes in response to graded cardiac sympathetic nerve stimulation were compared among three basal (anterior, middle, and posterior) regions, and between basal middle and apical regions. There were significant differences in contractile changes among the three basal regions with distinct regions of innervation from right and/or left sided sympathetic ganglia, but not between apical and basal regions. Constant infusion of noradrenaline (0.2-0.4 mug.kg-1.min-1 produced a greater response in normalised end systolic length in the apical myocardium than in the basal region, at 9.86(SEM 0.06) mm v 10.14(0.04) mm (n=5, p<0.025), and a greater increase in tissue cyclic AMP: 1.04(0.20) v 0.60(0.08) pmol.mg-1 (n=5, p<0.05). Giving a forskolin derivative (30 mug.kg-1. n=5) produced a greater increase in cyclic AMP in the apical region than in the basal region: 1.26(0.18) v 0.88(0.19) pmol.mg-1 (p<0.02). beta Adrenergic receptor density in the apical region was greater than in the basal region: 455(45) v 341(35) fmol.mg-1 protein (n=5, p<0.05). Conclusions: Greater beta adrenergic receptor density and/or increased myocardial responsiveness to adenylate stimulation in apical myocardium compensates, at least in part, for its sparse sympathetic innervation.