benzofurans and 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)

Topics: Animals; Benzofurans; Coronary Disease; Dogs; Female; Heart; Hyperemia; Male; Myocardial Reperfusion; Myocardium; Peroxidase; Thromboxane A2; Thromboxane-A Synthase

The effects of imidazole and U-63557A (Upjohn), inhibitors of thromboxane synthesis, on food-induced changes in intestinal blood flow and oxygen uptake were determined in the jejunum of anesthetized dogs. Intra-arterial (5.0 mg/min ia) infusions of imidazole had no effect on the postprandial intestinal hyperemia but significantly potentiated food-induced increases in oxygen uptake via enhanced oxygen extraction. Furthermore, imidazole had no effect on intestinal glucose absorption. The selective thromboxane synthesis inhibitor U-63557A (5 mg/kg iv) also enhanced oxygen uptake during nutrient absorption and had no effect on the hyperemia or glucose absorption. Our study indicates that inhibition of thromboxane synthesis has no effect on either resting intestinal blood flow or postprandial intestinal hyperemia but significantly enhances postprandial oxygen extraction and uptake. The potentiation of the food-induced increases in oxygen uptake by imidazole and U-63557A appears not to be related to glucose absorption. Endogenous thromboxane therefore appears to inhibit oxygen uptake more than blood flow, and yet does not affect glucose absorption during nutrient absorption.

Topics: Animals; Benzofurans; Blood Pressure; Dogs; Female; Food; Glucose; Hyperemia; Imidazoles; Injections, Intra-Arterial; Intestinal Absorption; Intestines; Jejunum; Male; Oxygen Consumption; Regional Blood Flow; Thromboxane-A Synthase