Pacing-induced cardiac failure of hypertrophic hearts: effects of cyclic GMP reduction
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Published on: February 17, 2018
1Department of Surgery, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08903, USA.
Insights
Cardiac failure in hypertrophic hearts reduces responses to guanylate cyclase inhibition. Methylene blue
Area of Science:
- Cardiovascular Physiology
- Cardiac Metabolism
- Guanylate Cyclase Signaling
Background:
- Pacing-induced cardiac failure in hypertrophic hearts may alter functional and metabolic responses.
- Guanylate cyclase inhibition is a potential therapeutic target in heart conditions.
Purpose of the Study:
- To investigate the impact of pacing-induced cardiac failure on hypertrophic hearts' responses to guanylate cyclase inhibition.
- To examine the role of cyclic guanosine monophosphate (cGMP) in these responses.
Main Methods:
- Infusion of methylene blue (MB), a guanylate cyclase inhibitor, into the coronary artery of control, left ventricular hypertrophy (LVH), and LVH with pacing-induced failure dogs.
- Measurement of regional myocardial work and oxygen consumption (VO(2)).
- Quantification of cyclic guanosine monophosphate (cGMP) levels via radioimmunoassay.
Main Results:
- Methylene blue increased myocardial work and VO(2) in control and LVH dogs, but not in failure dogs.
- Methylene blue decreased cGMP in control dogs.
- Both LVH and failure dogs had elevated baseline cGMP, but only LVH dogs showed a decrease in response to MB; failure dogs did not respond.
Conclusions:
- Myocardial function, oxygen consumption, and cGMP responses to methylene blue are diminished in the transition from cardiac hypertrophy to failure.
- These findings suggest impaired guanylate cyclase signaling in advanced heart failure.
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 O(2) consumption (VO(2)) 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 +/- 184 vs 1569 +/- 203 g * mm/min) and VO(2) (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 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, VO(2) and cyclic GMP responses to methylene blue are diminished in the transition from hypertrophy to cardiac failure.
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