Effects of the prostanoid EP₃‐receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat

Abstract

1 This study investigates the eects of two agonists of the prostanoid EP 3 -receptor (M&B 28767 and GR 63799X) on the infarct size caused by regional myocardial ischaemia and reperfusion in the anaesthetized rat. 2 One hundred and sixty-seven, male Wistar rats were anaesthetized (thiopentone, 120 mg kg 71 , i.p.), ventilated (8 ± 10 ml kg 71 , 70 strokes min 71, inspiratory oxygen concentration: 30%; PEEP: 1 ± 2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. 3 M&B 28767 (0.5 mg kg 71 min 71 , i.v., n=7) or GR 63799X (3 mg kg 71 min 71 , i.v., n=7) caused signi®cant reductions in infarct size from 60+3% (25 min ischaemia and 2 h reperfusion; salinecontrol, n=8) to 39+6 and 38+4% of the area at risk, without causing a signi®cant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenuated the cardioprotective eects of both EP 3 -receptor agonists. The reduction in infarct size aorded by M&B 28767 was also abolished by glibenclamide and the protein kinase C (PKC) inhibitors staurosporine and chelerythrine. 4 Thus, M&B 28767 and GR 63799X reduce myocardial infarct size in the rat by a mechanism(s) which involves the activation of PKC and the opening of ATP-sensitive potassium channels.

Myocardial Angiogenesis Resulting in Functional Communications with the Left Cavity Induced by Intramyocardial High-Frequency Ablation: Histomorphology of Immediate and Long-Term Effects in Pigs

“…In the acute setting, the thermally damaged myocardium showed no structural changes by histology. The border zone between viable and irreversibly damaged myocardium can be delineated by fuchsin staining with high precision [22, 23]. We could confirm the high reproducibility of dimensions of the thermally damaged zone using of the temperature-controlled HF energy application mode, the dimensions of which were comparable to that found in a previous investigation for identical energy delivery [6].…”

Endotoxin Induces a Second Window of Protection in the Rat Heart as Determined by Using p -Nitro-Blue Tetrazolium Staining, Cardiac Troponin T Release, and Histology

“…Previously, we have demonstrated that there is a significant increase in the levels of cTnT in the plasma within 3 hours after regional myocardial ischemia and reperfusion in the rat. 14 In cases of acute myocardial infarction in humans, cTnT levels in serum rise approximately 3 to 4 hours after the occurrence of cardiac symptoms and can remain elevated for up to 14 days. 18 It is interesting to speculate on the prospective mechanisms by which LPS causes a significant reduction in the degree of necrosis as demonstrated in this study.…”

Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia–reperfusion damage

“…At the end of reperfusion, the hearts were cut into small pieces and incubated with p-nitroblue tetrazolium (0.5 mg⅐ml Ϫ1 for 20 min at 37°C). In the presence of intact dehydrogenase enzyme systems (normal myocardium), p-nitroblue tetrazolium forms a dark blue formazan, whereas areas of necrosis lack dehydrogenase activity and therefore do not stain (33,34). Infarct size is expressed as the percentage of the dry weight of the infarcted pieces over the total weight of the heart.…”