Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation...

Area of Science:

• Cardiovascular Physiology
• Cellular Acid-Base Balance
• Myocardial Ischemia Research

Background:

• Myocardial cell pH regulation is critical for cardiac function.
• Ischemia significantly alters intracellular pH, impacting cardiac performance.
• The therapeutic potential of correcting intracellular acidosis during ischemia is under investigation.

Purpose of the Study:

• To measure myocardial cell pH using 5,5-dimethyl-2,4-oxazolidinedione (DMO) in a canine model of myocardial ischemia.
• To investigate the effects of alkali administration (sodium carbonate) on intracellular acidosis and cardiac function during ischemia.
• To assess the impact of alkali treatment on hemodynamic parameters, electrocardiographic changes, and ionic shifts in ischemic myocardium.

Main Methods:

• Transient indicator dilution technique with DMO and other indicators injected into the left anterior descending coronary artery.
• Blood sampling from the great cardiac vein to calculate DMO distribution and cell-to-plasma pH.
• Induction of myocardial ischemia via balloon catheter, followed by infusions of sodium carbonate or saline solution.

Main Results:

• Normal myocardial cell pH averaged 6.94; ischemia decreased cell pH to 6.59 within 1 hour.
• Sodium carbonate infusion diminished intracellular acidosis and improved hemodynamic parameters, including reduced left ventricular end-diastolic pressure and increased stroke volume.
• Alkali treatment led to improved ventricular wall motion, reduced S-T segment elevations, and mitigated cellular ion shifts (reduced Na+ gain, K+ loss).

Conclusions:

• Myocardial ischemia causes significant intracellular acidosis, which can be attenuated by sodium carbonate.
• Correction of intracellular acidosis improves cardiac function and reduces ischemic myocardial injury markers.
• Alkali therapy holds promise for managing myocardial ischemia by preserving cellular integrity and enhancing ventricular performance.