Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects 400 million people worldwide and is the most common enzyme deficiency. Heart failure increases myocardial [NADPH] and NADPH-dependent reactive oxygen species (ROS). G6PD activity controls cytoplasmic [NADPH], thus suppression of G6PD activity may decrease NADPH-dependent ROS. On the other hand, NADPH also fuels the antioxidant glutathione system. Therefore we determined the effect of G6PD deficiency on heart failure after myocardial infarction.Methods
WT and G6PD deficient (G6PDX) mice were subjected to Sham (n = 10/group) surgery or permanent LAD occlusion (n = 19 WT and n=28 G6PDX surviving the duration of the study) for12 weeks.Results
sham G6PDX mice had a 53% reduction in myocardial G6PD activity. No differences were observed in Survival or body mass. Infarction increased heart mass and LV dilation in G6PDX mice compared to WT mice (Figure). Infarction also decreased ejection fraction and dp/dt min, and increased LV end diastolic pressure and MPI, indicative of systolic and diastolic dysfunction, but there was no effect of G6PD deficiency on any functional parameter. Further, G6PD activity was increased by infarction in WT mice. Mitochondrial oxidative enzyme activities (citrate synthase, medium chain acyl-CoA dehydrogenase & aconitase) were decreased after infarction in both WT & G6PDX mice, with no differences between WT & G6PDX mice.Conclusions
The results indicate that G6PD deficiency worsened LV dilation in response to myocardial infarction, but did not affect systolic or diastolic function or oxidative enzyme capacity. The effects of G6PD deficiency on development and progression of heart failure in patients should be assessed.