The role of phospholipase in the genesis of reperfusion arrhythmia.
To clarify the mechanism of reperfusion arrhythmia, the following experiments were performed. In vivo study: Using anesthetized mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and the ligation was released. The dogs were divided into two groups depending on whether the pretreatment was with saline or coenzyme Q10 (CoQ10), 15 mg/kg, before the ligation, i.e., the control and the CoQ10 groups. Each group was further divided into two subgroups depending on the presence or the absence of reperfusion arrhythmia. Reperfusion arrhythmia was observed in 12 out of 38 dogs in the control, whereas in the CoQ10 group none developed arrhythmia. Nine species of free fatty acids (FFA) were detected in the plasma membrane in each group. In the dogs in the control group with arrhythmia, all species of detected FFA increased, and phospholipid content in plasma membrane decreased. These changes were not observed in the dogs without arrhythmia in both the control and the CoQ10 groups. In vitro study: Incubation of myocardial plasma membrane with phospholipase (PLase) A2 increased only unsaturated FFA, while PLase C increased all detected FFA. Premedication with CoQ10 prevented the increase in FFA caused by PLases. Perfusion with PLase A2 or C altered membrane action potential. Premedication with CoQ10 also prevented changes in membrane action potential. PLase liberates fatty acids from phospholipids, and CoQ10 is known to protect the membrane phospholipids from the attack of PLase. These facts and results suggest that activation of PLase associated with coronary reperfusion is closely related to the development of reperfusion arrhythmia.
M
M
Ajioka
S
S
Nagai
K
K
Ogawa
T
T
Satake
S
S
Sugiyama
T
T
Ozawa
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000201:enzymology*; D005117:Cardiac Complexes, Premature / Q000201:enzymology; D002462:Cell Membrane / Q000201:enzymology; D003067:Coenzymes; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000201:enzymology*; D004285:Dogs; D004562:Electrocardiography; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000201:enzymology
D003067:Coenzymes; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D014451:Ubiquinone; D010740:Phospholipases; C024989:coenzyme Q10