TxA2 inhibition and ischemia-induced loss of myocardial function and reactive hyperemia.
To determine the contribution of thromboxane (Tx) A2 release in reperfusion injury, 17 dogs were subjected to total coronary occlusion for 1 h and reperfusion for 1 h. Eleven dogs were treated with saline, and six were treated with selective TxA2 synthetase inhibitor U63,557A (5 mg/kg iv) 30 min before coronary artery occlusion. In all saline-treated dogs, peak reactive hyperemia after 10-s total coronary artery occlusion was diminished (P less than 0.01) after reperfusion. Myocardial segmental shortening was also reduced (9.8 +/- 1.9 to -6.7 +/- 2.0%, P less than 0.01) in the reperfused region. Reperfusion was associated with 737 +/- 343 premature ventricular contractions (PVCs) per hour. Histology revealed extensive myocardial infiltration and capillary plugging by leukocytes in the reperfused region. Myeloperoxidase, an index of leukocyte infiltration, was also increased (P less than 0.02) in the reperfused region. In the U63,557A-treated animals, serum and plasma TxB2 levels were markedly (P less than 0.02) reduced. Decrease in myocardial shortening fraction was less in U63,557A- than in saline-treated animals (P less than 0.05). The frequency of reperfusion PVCs was also significantly reduced (10 +/- 5 PVCs/h, P less than 0.02 compared with saline-treated dogs). However, peak reactive hyperemia was reduced similar to that in saline-treated dogs. Myocardial infiltration and capillary plugging by leukocytes in the reperfused regions was also similar in the U63,557A- and saline-treated dogs. These results indicate that treatment with U63,557A decreases reperfusion arrhythmias and preserves myocardial function. However, coronary reperfusion-induced deterioration in reactive hyperemia is not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Mehta
J L
JL
Veterans Administration Medical Center, Gainesville, Florida.
Nichols
W W
WW
Schofield
R
R
Donnelly
W H
WH
Chandna
V K
VK
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D003327:Coronary Disease / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006940:Hyperemia / Q000209:etiology*; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001572:Benzofurans; D013928:Thromboxane A2; D009195:Peroxidase; D013930:Thromboxane-A Synthase; C039936:furegrelate