RELATIONSHIP BETWEEN CYCLIC-AMP CONTENT, REGIONAL MYOCARDIAL-FUNCTIONAND O-2 CONSUMPTION IN EXPERIMENTAL LEFT-VENTRICULAR HYPERTROPHY - EFFECT OF NEGATIVE INOTROPES

The aim of this study was to examine the hypothesis that negative inot ropic agents that lower myocyte cyclic-AMP by different means would ha ve similar effects on local myocardial segment work and O2 consumption in control hearts, but that this response would differ in left ventri cular hypertrophy (LVH) induced by aortic valve stenosis. Open chest a nesthetized LVH and control dogs were studied before and during esmolo l (100 mug/kg/min) and acetylcholine (100 mug/kg/min) infusion. Region al work was calculated as the integrated product of instantaneous forc e (miniature transducer) and shortening (sonomicrometry) per min. Regi onal O2 consumption was calculated from blood flow (radioactive micros pheres) and O2 saturation of small frozen vessels (microspectrophotome try). Cyclic-AMP level was determined with a competitive binding assay using H-3-cyclic-AMP and was found to be 731 +/- 90 (mean +/- S.D.) p mol/g in control and 711 +/-163 in LVH. There were similar decreases i n cyclic-AMP levels in control hearts with acetylcholine (365 +/- 135) and the beta adrenergic blocker (430 +/- 95). In LVH, esmolol lowered cyclic-AMP (383 +/- 39) but acetylcholine did not (689 +/- 105). In c ontrol animals, regional O2 consumption (7.7 +/- 0.6, 5.6 +/- 0.4 and 5.6 +/- 0.5 ml O2/min/100 g, control, acetylcholine, esmolol, respecti vely) and segment work (878 +/- 82, 546 +/- 80, 627 +/- 66 gmm/min) f ell to similar levels with these agents. Similar decreases were found in LVH with esmolol for O2 consumption (7.1 +/- 1.2, 5.1 +/- 1.0, base line, esmolol) and segment work (895 +/- 140, 427 +/- 65). Acetylcholi ne had no significant effect on segment work (800 +/- 201), but did lo wer regional O2 consumption (4.0 +/- 0.7) in LVH dogs. It is concluded that there is a strong relationship between the level of cyclic-AMP a nd myocardial function and O2 consumption in control hearts. The actio n of acetylcholine is altered in LVH leading to an uncoupling between regional cyclic-AMP, function and metabolism.