Improvement of myocardial ischemic dysfunction with dichloroacetic acid: experimental study by repeated ischemia in dogs.
We investigated metabolic factors related to the recovery of myocardial function during ischemia and after reperfusion using dichloroacetic acid (DCA) in canine models with repeated 10-min regional ischemia and reperfusion. Administration of 100 mg/kg DCA, which activates pyruvate dehydrogenase, improved regional wall motion significantly as compared with the nontreated controls (p < 0.05). The mechanism was studied by determining changes in myocardial levels of pH, glucose, lactate, and nonesterified fatty acids (NEFA). Glucose extraction was increased significantly during ischemia and reperfusion by the pretreatment of DCA (p < 0.01). the calculated contribution of glucose to myocardial oxidative metabolism during ischemia and reperfusion was greater than that of NEFA and lactate in case of DCA treatment. The uptake of [99mTc]pyrophosphate (PYP), which reflects myocardial injury, was also significantly suppressed by DCA (p < 0.01). pH was not affected by an infusion of DCA. These findings suggest that the activation of glucose metabolism by DCA, which is impaired and reduced during ischemia and reperfusion, may be responsible for the improved myocardial function after reperfusion.
Okuda
K
K
Department of Internal Medicine, Kyoto University Hospital, Japan.
Nohara
R
R
Fujita
M
M
Tamaki
N
N
Konishi
J
J
Sasayama
S
S
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D017202:Myocardial Ischemia / Q000378:metabolism*; D017682:Myocardial Stunning / Q000378:metabolism; D016698:Technetium Tc 99m Pyrophosphate
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D019344:Lactic Acid; D016698:Technetium Tc 99m Pyrophosphate; D003999:Dichloroacetic Acid; D005947:Glucose; D002118:Calcium