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Effect of diltiazem, a calcium antagonist, on myocardial pH in ischemic canine heart
Insights
Diltiazem effectively reduces acid buildup in the heart muscle during ischemia. This study shows diltiazem enhances pH recovery after partial coronary artery occlusion, indicating its potential therapeutic benefit.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
Background:
- Myocardial acidosis is a consequence of reduced coronary blood flow during ischemia.
- Understanding interventions that mitigate acidosis is crucial for managing ischemic heart conditions.
Purpose of the Study:
- To investigate the effect of diltiazem on myocardial acidosis in a canine model of partial coronary occlusion.
- To assess the impact of diltiazem on pH recovery and tissue metabolites during myocardial ischemia.
Main Methods:
- Partial occlusion of the left anterior descending coronary artery in canine hearts to induce ischemia.
- Measurement of myocardial pH using a micro glass pH electrode.
- Intravenous administration of saline, diltiazem, or propranolol post-occlusion.
Main Results:
- Partial occlusion significantly decreased myocardial pH from 7.53 to 6.93.
- Diltiazem (100 µg/kg) administration resulted in a 76% increase in pH recovery, significantly potentiating spontaneous recovery.
- Propranolol also potentiated pH recovery.
- Myocardial acidosis correlated with increased lactate and decreased ATP and creatine phosphate levels.
Conclusions:
- Diltiazem attenuates ischemic myocardial acidosis.
- The drug's effect on pH is linked to alterations in myocardial energy metabolism.
- Diltiazem demonstrates potential as a therapeutic agent for ischemic heart conditions.
Abstract:
The effect of diltiazem on ischemic myocardial acidosis was studied in the canine heart whose left anterior descending coronary artery was partially occluded to reduce coronary flow to about one-third (partial occlusion). Myocardial pH was measured by use of a micro glass pH electrode. The pH decreased from 7.53 to 6.93 by partial occlusion and appeared to reach a steady state within 30 min. Saline or drugs were injected i.v. 30 min after partial occlusion. The decreased pH increased spontaneously by 34% of the total reduction of pH in the next 60 min after saline injection. Diltiazem (100 micrograms/kg) potentiated the increase in pH; the pH increased by 76% 60 min after the injection. Propranolol (1 mg/kg) also potentiated the increase in pH that had been decreased by partial occlusion. The relation between pH decrease and the tissue levels of metabolites was also studied. The reduction of myocardial pH from 7.5 to 6.8 was accompanied by a 2-fold increase in the tissue lactate content and by decreases in the ATP and creatine phosphate contents. There was a significant correlation between the hydrogen ion concentration calculated from the pH and each of the lactate, ATP and creatine phosphate contents. The present study indicates that diltiazem attenuates ischemic myocardial acidosis.