Pacing-induced cardiac failure of hypertrophic hearts: Effects of cyclic GMP reduction

Background We tested the hypothesis that pacing-induced cardiac failure of hypertrophic hearts would reduce the functional and metabolic responses of these hearts to guanylate cyclase inhibition and this was associated with a lterations in cyclic GMP. Materials and methods. Methylene blue (MB, 2 mg/kg/min, guanylate cyclase i nhibitor) was infused into the left anterior descending coronary artery in 5 control, 5 left ventricular hypertrophy (LVH), and 5 LVH pacing-induced f ailure dogs. Regional myocardial work was calculated as the integrated prod uct of force and segment shortening and regional myocardial O-2 consumption (VO2) from coronary blood flow and O-2 extraction measurements. Cyclic GMP was determined by radioimmunoassay. Results. MB increased regional work (635 +/- 169 vs 1649 +/- 500, 781 +/- 1 84 vs 1569 +/- 203 g * mm/min) and VO2 (8.3 +/- 1.4 vs 10.9 +/- 1.4, 7.3 +/ - 0.7 vs 9.1 +/- 0.7 ml O-2/min/100 g) in both control and LVH dogs but not in failure dogs (536 +/- 234 vs 623 +/- 193, 3.6 +/- 1.1 vs 4.7 +/- 1.9). MB also decreased cyclic GMP in control dogs (1170 +/- 142 vs 812 +/- 105 p mol/g). LVH dogs had elevated baseline cyclic GMP (5875 +/- 949) compared t o control dogs but also demonstrated decreased cyclic GMP in response to MB (2820 +/- 372). In failure dogs, basal cyclic GMP was also elevated (4650 +/- 613) compared to control dogs but there was a lack of response to MB (3 670 +/- 640). Conclusions. We conclude that the myocardial function, VO2 and cyclic GMP r esponses to methylene blue are diminished in the transition from hypertroph y to cardiac failure. (C) 1999Academic Press.