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Biomedical subjects

A L Shug

Publications and source records attributed to A L Shug.

At least 73 records · Page 4Linked to original sources
PubMed1975

Acyl-CoA inhibition of adenine nucleotide translocation in ischemic myocardium.

The translocation of adenine nucleotides across the inner mitochondrial membrane and the tissue concentration of long-chain acyl-CoA esters were studied in dog heart after experimental myocardial ischemia. Ligation of the anterior coronary artery initiated events leading to an early decrease in adenine nucleotide translocase activity. A reciprocal increase in the concentration of heart tissue long-chain acyl-CoA esters was also observed. Adjacent nonischemic tissue showed changes intermediate between that of ischemic and normal heart tissue. It is postulated that a decrease in fatty acid oxidation after myocardial ischemia would lead to an accumulation of long-chain acyl-CoA esters, which in turn would inhibit adenine nucleotide translocation. The net result would be a lowering of the energy charge of the cell, adversely affecting muscle contraction and electrical conduction.

Acetyl Coenzyme A↗
PubMed1975

Role of adenine nucleotide translocase in metabolic change caused by ischemia.

Inhibition of adenine nucleotide translocase by elevated levels of long chain acyl-CoA esters has been shown to occur during the onset of ischemia in experiments conducted on dogs. Other findings indicate that, as a consequence of translocase inhibition, the production of mitochondrial creatine phosphate was abolished and, in this manner, respiration was slowed to state 4 or an ischemic-like condition. A variety of biochemical, hemodynamic, and ultrastructural evidence further suggest that this inhibition of adenine nucleotide transport in and out of the heart mitochondria may be the initial and key disturbance which "triggers" the more drastic metabolic changes known to occur as the degree of ischemia becomes more severe. The mitochondrial "damage" caused by long chain acyl-CoA ester inhibition of adenine nucleotide translocase appears to be reversible by carnitine.

Adenosine Diphosphate↗
PubMed1975

Inhibited adenine nucleotide translocation in mitochondria isolated from ishcemic myocardium.

Experiments conducted in healthy mongrel dogs indicate that acyl-CoA levels are raised and adenine nucleotide translocase is inhibited during ischemia. The biochemical findings are accompanied by ultrastructural evidence of myocardial cell damage. These results raise the possibility that the inhibition of adenine nucleotide translocase may be a key disturbance in cellular metabolism.

Animals↗
PubMed1970

Antimycin A: stimulation of cell division and protein synthesis in Tetrahymena pyriformis.

Addition of antimycin A to a culture of Tetrahymena pyriformis caused an increase in cell division and protein synthesis in this ciliated protozoan. The antimycin effect is a function of the time of exposure to the antibiotic as well as of the age of the culture. A large accumulation of endoplasmic reticulum, reflecting increased protein synthesis, was visualized by electron microscopy in cells stimulated by the antimycin A.

Antimycin A↗
PubMedDate not supplied

Effects of POCA on metabolism and function in the ischemic rat heart.

Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) inhibits carnitine palmityltransferase I and fatty acid oxidation. The effects of POCA on cardiac function and on tissue levels of carnitine and coenzyme A esters were studied in the isolated rat heart subjected to 90 minutes of ischemia with and without 15 minutes of reperfusion. The perfusion medium contained 1.2 mM palmitate and 5.5 mM glucose plus or minus 0.5 mM POCA. This compound prevented accumulation of long-chain acylcarnitine and coenzyme A esters during ischemia and significantly improved the recovery of cardiac output after ischemia and reperfusion. Short-chain acylcarnitine levels were increased during ischemia by POCA. No effects were noted on tissue ATP and lactate levels. POCA may protect the ischemic heart by preventing accumulation of these toxic metabolites and by stimulating glucose utilization during ischemia.

Acyl Coenzyme A↗
PubMedDate not supplied

Mitochondrial damage during myocardial ischemia.

The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in whole tissue. Adenine nucleotide translocator (ANT) was severely inhibited and seemed to be a sensitive indicator of a lesion of the inner mitochondrial membrane. Postischemic reperfusion led to a slight loss of adenine and pyridine nucleotides from the reversibly damaged subepicardium and to an enormous loss from the irreversibly damaged subendocardium. The washout of nucleotides from irreversibly damaged areas caused the negative para-Nitro Blue Tetrazolium ( pNBT ) staining of the infarcted tissue. Diagnosis of cell death with pNBT failed after the occlusion period without reflow because pyridine, although lost from the mitochondria, was still present in the tissue. In reversibly injured areas, mitochondrial function and ultrastructure were restored after reperfusion, although a significant nucleotide loss was found in the tissue. These studies suggest that mitochondrial ultrastructure and function may play a key role in cellular viability during recovery from ischemia.

Adenine Nucleotides↗
PubMedDate not supplied

Metabolic and physiological differences between zero-flow and low-flow myocardial ischemia: effects of L-acetylcarnitine.

The metabolic and physiologic differences between low-flow and zero-flow ischemia of varying duration were compared in the isolated perfused rat heart. Hearts subjected to 60 and 90 minutes of zero-flow ischemia recovered less cardiac work than hearts subjected to low-flow ischemia. Low-flow ischemia caused a build-up of both myocardial long-chain acyl coenzyme A and acyl carnitine esters, while zero-flow ischemia produced no change in long-chain acyl carnitine and only a transient increase in long-chain acyl coenzyme A. High energy phosphate depletion was greater in zero-flow ischemia. Perfusion with excess free fatty acids decreased the recovery of cardiac work after low-flow ischemia but had no effect after repeated episodes of zero-flow ischemia. L-Acetylcarnitine improved the recovery of cardiac work after low-flow ischemia in hearts perfused with 0.4 and 1.2 mM palmitate. With zero-flow ischemia, L-acetylcarnitine had no effect on the recovery of cardiac work in hearts perfused with 0.4 mM palmitate and a slight but statistically significant effect with 1.2 mM palmitate. Possible protective mechanisms of L-acetylcarnitine against ischemic damage are discussed.

Acetyl Coenzyme A↗
PubMedDate not supplied

Effects of carnitine on the ischemic arrested heart.

We investigated the effect of L-carnitine on the recovery of cardiac function after ischemic arrest in the perfused rat heart. L-carnitine was added to a cardioplegic solution, both as a free base and hydrochloride. The addition of L-carnitine as a free base to the solution had no effect on recovery of cardiac function. When L-carnitine HCl was added to the cardioplegic solution, it was necessary to adjust the pH of the solution to 7.4. The hearts arrested with this solution showed a greater incidence of reperfusion dysrhythmias than those in the control or the free base solution, but the overall recovery of cardiac function was the same as control. The hydrochloride of L-carnitine is strongly acidic, and these findings indicate that either the free base or a properly buffered solution must be used to study effects of carnitine upon cardiac function.

Animals↗