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Local inotropic stimulation by methylene blue does not improve mechanical dysfunction due to myocardial stunning
1Department of Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
Abstract:
We tested the hypothesis that reduction of intramyocardial cyclic guanosine monophosphate (GMP) by methylene blue (MB) would improve mechanical dysfunction in stunned myocardium. Regional stunning was produced in nine open-chest anesthetized dogs by a 12-min left anterior descending coronary artery (LAD) occlusion. MB was infused into the LAD during reperfusion (1 mg/kg per min). Stunning reduced LAD force development, introduced a significant time delay between the onset of force and shortening (delay) and caused significant systolic bulging to occur. Stunning reduced systolic regional work (the integrated product of force and segment shortening during systole), but did not significantly alter regional oxygen consumption or cyclic GMP levels. MB decreased cyclic GMP (1.8 +/- 0.2 to 0.9 +/- 0.1 pmol/g) and increased peak force (36 +/- 5 to 55 +/- 10 g). However, MB increased delay (93.9 +/- 18.4 to 233 +/- 19 ms) and systolic bulging (5.9 +/- 2.1% to 9.3 +/- 2.8%) and further reduced systolic regional work (control; 4204 +/- 933 g x mm/min; stunned: 2191 +/- 542 g x mm/min; MB: 1153 +/- 516 g x mm/min). MB increased regional myocardial oxygen consumption (7.4 +/- 1.0 to 15.6 +/- 2.7 ml O2/min per 100 g). These results suggest that depressed contractility, while present in myocardial stunning, is not the primary cause of mechanical dysfunction.
Insights
Methylene blue (MB) did not improve mechanical dysfunction in stunned myocardium. Reducing cyclic guanosine monophosphate (GMP) with MB worsened systolic bulging and reduced regional work, suggesting impaired contractility isn't the main issue in myocardial stunning.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Myocardial stunning, a transient mechanical dysfunction post-ischemia, is a significant clinical concern.
- The role of cyclic guanosine monophosphate (cGMP) in myocardial stunning remains incompletely understood.
- Methylene blue (MB) is known to inhibit guanylate cyclase, reducing cGMP levels.
Purpose of the Study:
- To investigate the effect of reducing intramyocardial cyclic guanosine monophosphate (cGMP) using methylene blue (MB) on mechanical dysfunction in stunned myocardium.
- To determine if cGMP reduction can ameliorate the impaired contractility and regional work observed in myocardial stunning.
Main Methods:
- Regional myocardial stunning was induced in anesthetized dogs via left anterior descending coronary artery (LAD) occlusion.
- Methylene blue (MB) was infused into the LAD during the reperfusion phase.
- Measurements included regional force development, time delay between force and shortening, systolic bulging, regional work, and myocardial oxygen consumption.
Main Results:
- Stunning reduced systolic regional work and force development, and increased delay and systolic bulging.
- Methylene blue (MB) significantly decreased intramyocardial cyclic guanosine monophosphate (cGMP) levels.
- Despite cGMP reduction, MB worsened systolic bulging and regional work, and increased myocardial oxygen consumption.
Conclusions:
- Reduction of intramyocardial cGMP by methylene blue (MB) does not improve, and may worsen, mechanical dysfunction in stunned myocardium.
- The findings suggest that impaired contractility is not the primary driver of mechanical dysfunction in myocardial stunning.
- Further research is needed to elucidate the precise mechanisms underlying myocardial stunning and identify effective therapeutic targets.