Ventricle-specific metabolic differences in the newborn piglet myocardium in vivo and during arrested global ischemia
Danny Quaglietta1, Michael P Belanger, Carin Wittnich
1Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Insights
Newborn hearts show distinct metabolic differences between the left and right ventricles. The left ventricle has higher glycogen but experiences greater energy depletion and byproduct buildup during ischemia, potentially explaining its increased dysfunction.
Area of Science:
- Cardiovascular Physiology
- Neonatal Metabolism
- Ischemic Heart Disease
Background:
- Ventricular dysfunction is more pronounced in the left ventricle (LV) than the right ventricle (RV) in infants post-surgery with induced ischemia.
- Metabolic variations between ventricles may influence their response to ischemia and subsequent functional recovery.
Purpose of the Study:
- To investigate ventricle-specific metabolic differences in the newborn piglet heart at baseline and during ischemia.
- To understand how these metabolic differences contribute to differential ventricular dysfunction.
Main Methods:
- Assessed baseline (working) and ischemic (arrested) metabolic enzyme activities (citrate synthase, hydroxyacyl-CoA dehydrogenase, creatine kinase, phosphofructokinase) and glycogen reserves in LV and RV.
- Measured levels of ATP, lactate, and hydrogen ions in both ventricles during an ischemic period.
Main Results:
- Baseline: LV had lower citrate synthase and hydroxyacyl-CoA dehydrogenase activities but higher creatine kinase, phosphofructokinase activities, and glycogen reserves compared to RV.
- Ischemia: LV showed significantly lower ATP and higher lactate and hydrogen ion accumulation than RV, persisting throughout the ischemic period.
- Glycogen utilization was 58% lower in the LV than RV after 45 minutes of ischemia.
Conclusions:
- The newborn LV exhibits a higher glycolytic capacity, leading to increased anaerobic end-product accumulation and reduced energy levels during ischemia.
- These metabolic characteristics may explain the observed greater LV dysfunction compared to RV in neonates following ischemic events.
Abstract:
Ventricular dysfunction is reported greater in the left (LV) versus right ventricle (RV) in infants following surgically induced ischemia. Ventricle-specific differences in baseline metabolism may alter response to ischemia thus affecting postischemic functional recovery. This study identifies ventricle-specific metabolic differences in the newborn (piglet) heart at baseline (working) and during ischemia (arrested). Baseline LV citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HAD) activities were 15% and 18% lower (p < 0.02), whereas creatine kinase (CK) and phosphofructokinase (PFK) activities were 40% and 23% higher (p < 0.04) than the RV. Baseline LV glycogen reserves were also 55% higher (p = 0.004). By 15 min of ischemia, LV ATP was 20% lower (p < 0.05), lactate was 51% higher (p = 0.001), and hydrogen ions (H) were 43% higher (p = 0.03) compared with the RV. These differences persisted for the entire ischemic period (p < 0.02). After 45 min of ischemia, the LV used 58% less (p < 0.05) glycogen than the RV. These findings demonstrate that the enhanced glycolytic capacity of the newborn LV was accompanied by greater anaerobic end-product accumulation and lower energy levels during ischemia. This profile may offer one explanation for greater LV-dysfunction relative to the RV in children following ischemia.
