REDUCED EFFECT OF PHENYLEPHRINE ON REGIONAL MYOCARDIAL-FUNCTION AND O-2 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 alpha-adrenergic stimulation woul d be diminished due to decreased alpha-adrenoceptor number. After syst emic beta-adrenergic blockade, phenylephrine (PE, 5 mu g . kg(-1). min (-1)) was infused into the left anterior descending artery in eight LV H 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 segmen t shortening (ultrasonic crystals). Local myocardial O-2 consumption w as calculated from regional blood flow (microspheres) and O-2 saturati on (microspectrophotometry). A saturation radioligand binding assay wa s used to determine adrenoceptor number and affinity. In control anima ls 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 O-2 consumption wa s almost doubled during PE infusion (6.2 +/- 0.9 vs. 12.0 +/- 2.1 mi O -2 . min(-1). 100 g(-1)). alpha-Adrenoceptor number and dissociation c onstants 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 alpha-adrenergic stimulation was expresse d 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 impaire d production of second messengers or their effects on myocardial funct ion.