Reduced effect of phenylephrine on regional myocardial function and O₂ consumption in experimental LVH

In a dog model of left ventricular hypertrophy (LVH) created by aortic valve plication, we examined the hypothesis that regional myocardial inotropic and metabolic responses to α-adrenergic stimulation would be diminished due to decreased α-adrenoceptor number. After systemic β- adrenergic blockade, phenylephrine (PE, 5 μg · kg^-1 · min^-1) was infused into the left anterior descending artery in eight LVH and nine control open-chest anesthetized dogs. The circumflex region served as control. In both regions, local segment work was calculated as the integrated products of force (miniature transducer) and segment shortening (ultrasonic crystals). Local myocardial O₂ consumption was calculated from regional blood flow (microspheres) and O₂ saturation (microspectrophotometry). A saturation radioligand binding assay was used to determine adrenoceptor number and affinity. In control animals in the treated region, PE increased work from 815 ± 140 to 1,493 ± 149 g · mm · min^-1. In LVH, work was not significantly altered (688 ± 142 vs. 730 ± 149 g · mm · min^-1). Regional blood flow was elevated in controls (81 ± 10 to 141 ± 24 ml · min^-1 · 100 g^-1) but was not changed in LVH (105 ± 12 vs. 123 ± 18 ml · min^-1 · 100 g^-1). In controls, but not in LVH, myocardial O₂ consumption was almost doubled during PE infusion (6.2 ± 0.9 vs. 12.0 ± 2.1 ml O₂ · min^-1 · 100 g^-1). α-Adrenoceptor number and dissociation constants values were not different between control and LVH (15.7 ± 2.8 vs. 16.4 ± 2.7 fmol/mg protein; 13.2 ± 3.4 vs. 16.9 ± 4.3 nm, respectively). Thus in vivo α-adrenergic stimulation was expressed locally as positive inotropy and elevated oxidative metabolism only in controls but not in LVH. Because receptor number and affinity were not diminished in LVH, decreased inotropy in LVH may stem from impaired production of second messengers or their effects on myocardial function.