EFFECT OF CYCLIC-GMP REDUCTION ON REGIONAL MYOCARDIAL MECHANICS AND METABOLISM IN EXPERIMENTAL LEFT-VENTRICULAR HYPERTROPHY

We tested the hypotheses that decreased myocardial cyclic GMP levels p roduced by intracoronary injection of methylene blue would increase lo cal myocardial work and O-2 consumption while decreasing intracellular cyclic GMP and that the relation between work, O-2 consumption, and c yclic GMP may be altered in left ventricular hypertrophy (LVH) produce d by aortic valve plication. In 8 control and 8 LVH open-chest anesthe tized dogs, 1 mg/kg/min methylene blue was infused into the left anter ior descending coronary artery (LAD); the circumflex region (CFX) serv ed as control area. Regional work was calculated as the integrated pro duct of force (miniature transducer) and segment shortening (sonomicro metry). Regional myocardial O-2 consumption was calculated from flow m easurements (radioactive microspheres), and regional O-2 saturations ( microspectrophotometry). A radioimmunoassay was used to determine intr acellular level of cyclic GMP in the myocardium. Global hemodynamics a nd blood gases were unchanged by methylene blue in both control and LV H animals. Intracoronary methylene blue increased regional work from 7 62 +/- 129 to 1,451 +/- 307 g . mm/min in controls and from 912 +/- 17 3 to 1581 +/- 253 g . mmimin in the LVH groups. No significant changes in CFX regional work were observed. Regional blood flow, O-2 extracti on, and O-2 consumption remained unchanged after injection of methylen e blue in both control and LVH animals. The basal levels of cyclic GMP in the LVH group were fivefold higher than that in controls. In both groups, cyclic GMP levels were significantly decreased by methylene bl ue and to a greater extent in the LVH animals (from 6.16 +/- 1.2 to 3. 34 +/- 0.44 pmol/g) than in the control animals (from 1.32 +/- 0.20 to 1.09 +/- 0.19 pmol/g). Therefore, intracoronary methylene blue increa sed regional myocardial work equally in control and LVH hearts without affecting regional metabolism (i.e., increased efficiency). For the s ame increased mechanical function, the hypertrophic myocardium exhibit ed a greater reduction in cyclic GMP pool size.