Effects of thromboxane A2 synthetase inhibitor (CV-4151) on reperfused skeletal muscle in rats.
To clarify the role of thromboxane A2 synthetase inhibitor (CV-4151) in the ischemia-reperfusion injury, the effect of CV-4151 was investigated in the gastrocnemius muscles of female Lewis rats. All tissues except femoral vessels were transected at the midthigh level and 4 h of ischemia was induced by vascular clamping of the femoral artery and vein, followed by 1 h of reperfusion. The sham group (n = 8) underwent the operation without ischemia-reperfusion; the control group (n = 8) with ischemia-reperfusion, and the CV-4151 group (n = 8) was pretreated with CV-4151 20 mg/kg. Skeletal muscle blood flow was measured by a hydrogen gas clearance method; the blood flow restored fully in the CV-4151 group, while it remained significantly low in the control group after 1 h of reperfusion (p < 0.05). Tissue levels of adenosine triphosphate (ATP) and creatine phosphate (PCR) were measured after 1 h of reperfusion; ATP decreased to 25% of nonischemic values in the control group. In contrast, premedication with CV-4151 significantly improved the recovery of ATP (p < 0.01). PCR showed the same tendency as ATP; CV-4151 also improved the recovery of PCR significantly (p < 0.05), but CV-4151 did not prevent the production of lipid peroxides. Serum thromboxane B2 was determined by radioimmunoassay; in the sham and the CV-4151 group the level was significantly lower than in the control group (p < 0.05). was significantly lower than in the control group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Sasaki
Y
Y
Department of Orthopedic Surgery, School of Medicine, University of Nagoya, Japan.
Ishiguro
N
N
Miura
T
T
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D007511:Ischemia / Q000503:physiopathology; D008054:Lipid Peroxides / Q000378:metabolism; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow; D015424:Reperfusion; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000227:Adenine Nucleotides; D005229:Fatty Acids, Monounsaturated; D008054:Lipid Peroxides; D011725:Pyridines; D010725:Phosphocreatine; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D013930:Thromboxane-A Synthase; C045446:isbogrel