An Experimental Myocardial Infarction Model in the Rat and Its Properties

Abstract

ABSTRACT-The photochemical reaction between rose bengal and light (540 nm) produces thrombotic occlusion in rat coronary artery. We have now developed an experimental myocardial infarction (MI) model by photochemically induced thrombosis (PIT) in rats and investigated the mechanisms responsible for the induction of MI. PIT in the coronary artery induced myocardial ischemia, which was determined by tissue oxygen tension (tpO2), and resulted in MI. Pretreatment with a thromboxane (TX) A2-receptor antagonist, vapiprost, prevented a decrease in myocardial tpO2 and markedly reduced the MI area, although vapiprost inhibited collagen-induced platelet aggregation by 30% ex vivo. An ADP-induced platelet aggregation inhibitor, clopidogrel, also reduced the MI area. In contrast to vapiprost, clopidogrel inhibited collagen-induced platelet aggregation by 90% ex vivo. Pretreatment with a 5-HT2-receptor antagonist, ketanserin, which did not inhibit collagen-induced platelet aggregation ex vivo, prevented the decrease in myocardial tpO2 and reduced the MI area. These results suggest that TXA2, 5-HT and ADP play a role in the induction of MI and that platelet aggregation and other factors induce ischemia in this model. (1), insertion of copper coil into an artery (2) and endothelial injury by electrical current (3). The model is selected for use according to the aim of the study; e.g., ischemia-reperfusion, thrombogenesis or arrhythmias. However, an MI model caused by thrombus in rats has not been reported. Thus, mediators involved in the MI model produced by thrombus in rats remain unclear.Recently, we have reported some photochemically induced thrombosis (PIT) models in rats (4) and guinea pigs (5, 6). In these PIT models, endothelial injury is induced by singlet oxygen generated by a photochemical reaction (7,8). Fukuchi et al. (9) have previously demonstrated that the photochemically induced thrombus in the coronary artery consisted of platelets, and ventricular arrhythmias were induced. Since their model had high mortality within a few hours, they failed to detect MI in rats. Therefore, we attempted to make an MI model by thrombus in the rat coronary artery and investigate representative mediators, thromboxane (TX) A2, 5-HT and ADP, involved in MI using antagonists. MATERIALS AND METHODS Photochemically induced thrombosis (PIT) in rat coronary arteryThirty-four male Sprague-Dawly rats (Charles River Japan, Atsugi) weighing about 400 g were anesthetized by i.p. injection of 50 mg/kg of sodium pentobarbital. The jugular vein was cannulated for rose bengal and drug delivery. Tracheal intubation was performed for artificial respiration. The chest was opened by a left thoracotomy. Transillumination with green light (540 nm) was achieved by use of a xenon lamp with a heat absorbing filter and a green filter (Hamamatsu Photonics, Hamamatsu). The head (3 mm in diameter) of the green light source was fixed 5-mm-apart from the surface of the myocardium between the conoventricular vein and branches of the ventricular cordis magna in...

Influence of Polyunsaturated Fatty Acids on Vasoconstrictions Induced by 8-iso-PGF_2α and 8-iso-PGE₂

“…Administrations of TP receptor antagonists inhibit the vasoconstrictor actions of isoPs, which suggest an activation of either a TP receptor or a TP receptor like isoP receptor [1,2,35]. Although the use of TP-receptor antagonists in experimental studies reduced myocardial infarctions and dysfunctions [36][37][38], similar results of clinical studies, to our knowledge, are yet outstanding. In contrast, the beneficial effects of EPA and DHA had been proven in numerous experimental and clinical studies [10,11,21,22,39].…”

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

“…Contractile synergism between 5-hydroxytryptamine and other vasoconstrictor substances has been observed in a number of peripheral and cerebrovascular blood vessels (19). In some animal coronary artery models (20,21), as well as in human coronary arteries (22,23), a contractile synergistic effect between 5-hydroxytryptamine and U46619 has been demonstrated.…”

Selective Blockade of P2Y12 Receptors by Prasugrel Inhibits Myocardial Infarction Induced by Thrombotic Coronary Artery Occlusion in Rats

“…Several rat models of arterial thrombotic occlusion have been described, 19,25,26 including the photochemical injury model, which has been applied to several arterial beds, namely, the femoral artery, 26 coronary artery, 16 middle cerebral artery, 20 and carotid artery. 27 In this study, we utilized this approach to examine the effects of P2Y 12 inhibition on MI after thrombotic coronary artery occlusion originally described by Hirata et al 16 Prasugrel (3 mg/kg, po) demonstrated near-complete inhibition of P2Y 12 but resulted in an approximately 60% inhibition of infarct size, suggesting only a partial role for P2Y 12 in this thrombotic model of MI.…”

“…Irradiation with green light (F: 3 mm) was achieved by using a xenon lamp (L4887: ;60,000 lx, Hamamatsu Photonics, Hamamatsu). 16 The head of the green light source was fixed under the left atrium, and rose bengal (20 mg/kg) was administered. The green light was applied to an area including the junction of the left circumflex artery and left anterior descending artery for 30 minutes.…”