Key Points
- To investigate the cellular mechanisms linking altered glucose metabolism to impaired calcium handling and contractile dysfunction in immature pressure overload hypertrophied myocardium.
- Assessed myocardial mechanics in 6- to 7-week-old pressure-overloaded rabbit hearts under dobutamine challenge using serial in vivo echocardiography and isolated Langendorff perfusion.
- Quantified cytosolic calcium ([Ca2+]i) dynamics using fluorescence spectroscopy and measured SERCA2 expression via Western immunoblotting.
- Tested the metabolic effects of glycolytic inhibition using 2-deoxy-D-glucose with and without supplemental pyruvate.
- Hypertrophied hearts exhibited elevated systolic and diastolic [Ca2+]i, significantly slower diastolic calcium removal (tauCa), and a blunted functional response to dobutamine stimulation.
- SERCA2 expression increased in early hypertrophy but decreased significantly by 6 weeks of age alongside progressive contractile failure.
- Inhibition of glycolysis or SERCA2 elevated [Ca2+]i and slowed tauCa, whereas pyruvate supplementation completely preserved myocardial contractile function and calcium handling during glycolytic inhibition.
Structured PICO
PPopulation6-7-week-old pressure overload hypertrophied rabbit hearts
IInterventionDobutamine administration and glycolytic inhibition (2-deoxy-D-glucose +/- pyruvate)
OOutcomeMyocardial mechanics, cytosolic Ca2+ ([Ca2+]i), and sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expressionsurrogate
In a rabbit model of pressure overload hypertrophy, impaired glucose metabolism leads to SERCA2 downregulation and abnormal calcium handling, suggesting metabolic modulation as a potential therapeutic target.