Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Abstract

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 alterations in cyclic GMP.Materials and methods. Methylene blue (MB, 2 mg/kg/min, guanylate cyclase inhibitor) was infused into the left anterior descending coronary artery in 5 control, 5 left ventricular hypertrophy (LVH), and 5 LVH pacing-induced failure dogs. Regional myocardial work was calculated as the integrated product of force and segment shortening and regional myocardial O2 consumption (VO2) from coronary blood flow and O2 extraction measurements. Cyclic GMP was determined by radioimmunoassay.Results. MB increased regional work (635 ± 169 vs 1649 ± 500, 781 ± 184 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 O2/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 pmol/g). LVH dogs had elevated baseline cyclic GMP (5875 ± 949) compared to 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 (3670 ± 640).Conclusions. We conclude that the myocardial function, VO2 and cyclic GMP responses to methylene blue are diminished in the transition from hypertrophy to cardiac failure.