Tricarboxylic acid cycle activity in postischemic rat hearts

Area of Science:

• Cardiovascular Physiology
• Metabolic Biochemistry
• Cardiac Electrophysiology

Background:

• Myocardial contractile function and tricarboxylic acid (TCA) cycle activity are linked in healthy hearts.
• The relationship between TCA cycle activity and contractile function during post-ischemic reperfusion is not well understood.
• Contractility is often reduced after ischemia and reperfusion.

Purpose of the Study:

• To investigate the hypothesis that oxidative TCA cycle flux is reduced in reperfused myocardium with persistent contractile dysfunction.
• To determine if TCA cycle activity can explain reduced cardiac contractility after ischemia.

Main Methods:

• Isolated rat hearts were subjected to ischemia and reperfusion.
• TCA cycle flux was measured using 13C-labeled substrate infusion and 13C nuclear magnetic resonance spectroscopy.
• Analysis involved assessing sequential myocardial glutamate labeling over time.

Main Results:

• Total TCA cycle flux was not reduced but increased in hearts reperfused after brief ischemia (17-20 minutes) compared to pressure-matched controls.
• Hearts reperfused after longer ischemia (40-45 minutes) showed no detectable TCA cycle activity and lacked contractile recovery.
• Significant contractile dysfunction persisted despite increased TCA cycle flux after brief ischemia.

Conclusions:

• TCA cycle activity is not persistently decreased in dysfunctional reperfused myocardium after a brief ischemic episode.
• Reduced TCA cycle function does not account for the reduced contractile function observed after short-term ischemia and reperfusion.
• Other mechanisms likely contribute to post-ischemic contractile dysfunction.