Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The detailed antiischemic pharmacology of the potassium channel activator cromakalim was determined in isolated globally ischemic rat hearts and a canine model of coronary occlusion and reperfusion. Cromakalim significantly improved reperfusion function in rat hearts starting at a concentration of 1 microM; this effect peaked at 7 microM. No cardiodepressant effects were observed in nonischemic tissue with cromakalim until a concentration of 100 microM was achieved, and this effect was reversed by glyburide. The antiischemic effect of 7 microM cromakalim was also completely reversed by glyburide and the novel ATP-sensitive potassium channel blocker sodium 5-hydroxydecanoate (5-HD). Glyburide did not reverse the antiischemic effects of 1 microM diltiazem. Cromakalim not only improved reperfusion contractile function in rat hearts, but improved the functional reserve and efficiency of O2 utilization. In anesthetized dogs, intracoronary cromakalim (0.1 micrograms/kg/min given throughout ischemia and reperfusion) significantly reduced infarct size in hearts subjected to 90-min coronary occlusion and 5-h reperfusion. Along with this reduced infarct size, the frequency of ectopic beats and the proportion of animals fibrillating during reperfusion were significantly reduced by cromakalim. In isolated globally ischemic and reperfused rat hearts, cromakalim was significantly profibrillatory. Thus, cromakalim is significantly cardioprotective, and may have the propensity for profibrillatory activity, although this is not true under all conditions.
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PMID:Pharmacologic profile of cromakalim in the treatment of myocardial ischemia in isolated rat hearts and anesthetized dogs. 170 76

The direct myocardial protective effects of intracoronary infusions of cromakalim and pinacidil were determined in an anesthetized canine model of coronary occlusion and reperfusion. The left circumflex coronary artery was occluded for 90 minutes and reperfused for 5 hours, at which time the infarct size was determined. Cromakalim (0.1 micrograms/kg/min) or pinacidil (0.09 micrograms/kg/min) were infused into the left circumflex coronary artery starting 10 minutes preischemia. Cromakalim significantly reduced infarct size as a percent of the left ventricular area at risk (25 +/- 5%) compared with vehicle controls (55 +/- 7%). Pinacidil did not reduce infarct size at an equimolar dose, but at the higher dose also significantly reduced infarct size. Collateral blood flow was not significantly altered by either drug, though reperfusion flow was significantly higher in cromakalim-treated animals, particularly in the subepicardial region. When the same dose of cromakalim was given starting 2 minutes before the initiation of reperfusion, no significant beneficial effect of cromakalim was observed. In another study, isolated buffer-perfused rat hearts were subjected to 25 minutes of global ischemia and 30 minutes of reperfusion. These hearts were treated with 7 microM cromakalim, either starting 10 minutes before ischemia or only during reperfusion, and its effect on reperfusion function and LDH release were determined. Cromakalim pretreatment (both when given throughout the experiment and when not present in the reperfusion buffer) resulted in significant improvements in the reperfusion function. Reperfusion contracture and LDH were also significantly reduced with this treatment. When given only during reperfusion, cromakalim did not reduce the severity of ischemia when compared with vehicle controls. Thus, both cromakalim and pinacidil reduce ischemic/reperfusion injury, though the timing of treatment may be important.
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PMID:The protective effects of cromakalim and pinacidil on reperfusion function and infarct size in isolated perfused rat hearts and anesthetized dogs. 228 30

We endeavored to determine if the enhanced shortening of the myocardial action potential duration (APD) during ischemia can be dissociated from the cardioprotective effects of the adenosine triphosphate (ATP) sensitive potassium channel (KATP) opener cromakalim. To establish if there is a relationship between APD shortening and the cardioprotective effect of cromakalim, we determined the effect of a dose of the delayed rectifier (IKr) blocker dofetilide (which abolishes the APD shortening effect of cromakalim) on the cardioprotective activity of cromakalim. Cromakalim was infused at a previously determined cardioprotective dose (10 micrograms/kg + 0.3 micrograms/kg/min infusion i.c.), and we determined the effect of 1 mg/kg (followed by a 0.01 mg/kg/min i.v. infusion) dofetilide alone and in combination with cromakalim on APD shortening and infarct size (90-min coronary occlusion and 5-h reperfusion) in anesthetized dogs. Dofetilide completely abolished the APD shortening effects of cromakalim during ischemia such that APD was similar to preischemic values. Cromakalim only shortened the APD during ischemia, although this effect was attenuated late into ischemia. Cromakalim significantly reduced infarct size (40% reduction from vehicle group value), whereas dofetilide alone had no effect. Dofetilide, at a dose that prevented the cromakalim-induced shortening of APD in ischemic tissue, did not attenuate the cardioprotective effects of cromakalim. No differences in collateral blood flow for any of the groups were observed. Dofetilide did cause a slight bradycardia, but this effect is unlikely to affect the interpretation of the results. These data suggest that APD shortening observed with the KATP opener cromakalim is not correlated with its cardioprotective effects.
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PMID:Cardioprotection with the KATP opener cromakalim is not correlated with ischemic myocardial action potential duration. 756 56

We have previously reported that cromakalim and U-89232 reduce infarct size in a rabbit model of myocardial ischemia. Because U-89232 appeared to lack activity in the vasculature, we tested its reversibility with glibenclamide. Twenty-eight ketamine-xylazine anesthetized open-chest, New Zealand White rabbits were instrumented for regional coronary occlusion and reperfusion. Study animals received either cromakalim, U-89232 or vehicle. In some animals, glibenclamide was administered. All animals were then subjected to ischemia (30 min) and reperfusion (120 min), and necrosis was determined using tetrazolium. With comparable hemodynamics and myocardium at risk, infarct size in control animals was 35.5 +/- 4.6% of risk region, and was not different from glibenclamide-treated animals (37.7 +/- 5.8%). Cromakalim alone has been shown to be protective, however when combined with glibenclamide necrosis amounted to 35.1 +/- 3.8% of the risk region (p = NS vs. control). In contrast, U-89232 was protective in the presence of glibenclamide (17.2 +/- 4.9% of the risk region). We conclude that U-89232 produces myoprotection independent of K-ATP channel inhibition, indicating that this compound possesses novel anti-ischemic characteristics.
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PMID:Cardioprotection with U-89232 is not reversible with glibenclamide: evidence of a novel anti-ischemic agent derived from cromakalim. 797 26

The effect of the timing of treatment with the ATP-regulated potassium channel agonist BMS-180448 was evaluated in isolated rat heart and ferret models of ischemia and reperfusion. In rat hearts, 10 microM BMS-180448, given before and after global ischemia as well as only during reflow, improved reperfusion contractile function and attenuated lactic dehydrogenase release, although reperfusion-only treatment was less effective. Cromakalim (10 microM) and bimakalim (10 microM) treatment before and after global ischemia afforded a degree of protection similar to that of BMS-180448, although they were not cardioprotective when given only during reperfusion. Pre- and post-treatment cardioprotection were abolished by glyburide. Ischemia/reperfusion significantly increased cytosolic calcium concentration ([Ca++]i) and BMS-180448 given only during reperfusion attenuated this change. In anesthetized ferrets, BMS-180448 (2 mg/kg) or vehicle was infused i.v. during a 40-min interval beginning 1) 10 min before coronary occlusion, 2) at the 45th min of ischemia or 3) at the 5th min of reperfusion. Preocclusion administration of BMS-180448 was associated with a 35% reduction in infarct damage from that recorded in vehicle-treated control ferrets. Drug administered at the midpoint of ischemia reduced infarct size approximately 44%, whereas delaying BMS-180448 infusion until the 5th min of reperfusion reduced, but still provided a significant (17%) level of salvage. The favorable effects of BMS-180448 in the ferret were not associated with changes in either collateral blood flow or peripheral hemodynamics. Thus BMS-180448 shows some protective effects when given only during reperfusion. Cromakalim and bimakalim did not exert similar actions and the difference may be secondary to the faster penetration of BMS-180448.
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PMID:Effect of timing of treatment of the glyburide-reversible cardioprotective activity of BMS-180448. 910 76