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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentrations of lactate, pyruvate, and adenosine, together with some of their derivatives, were determined in microdialysates from 12 pig hearts, 6 of which were subjected to preconditioning and 40 min of ischemia (index ischemia) and 6 of which were subjected to only 40 min of index ischemia. Two microdialysis probes were inserted in ischemic myocardium. Glyburide (10 mu M) in a modified isotonic Krebs-Ringer phosphate buffer was administered through one of the probes and plain isotonic phosphate buffer was administered through the other. Accordingly, the experimental setup permitted us to study the metabolic effects of glyburide on ischemic myocardium constituting two groups that were either preconditioned or unpreconditioned. The preconditioning effect was validated with area at risk and infarction area measurements in 12 other pigs. We noted no functional differences between the groups. In the unpreconditioned group glyburide infusion resulted in enhanced 60% lactate production during index ischemia. However, preconditioning attenuated the enhancing effect of glyburide on lactate production. The interplay between the effects of glyburide and preconditioning on ischemic myocardium is suggested to be dependent on the different modes of action on the K(+)(ATP) channel.
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PMID:Glyburide enhancement of lactate production in ischemic heart is modified by preconditioning: an in vivo experimental study in pigs by microdialysis technique. 885 30

We investigated the effect of NIP-121, a novel ATP-sensitive K+ channel opener, on myocardial damage during ischemia/reperfusion. The action potential and contractile force of coronary-perfused guinea pig right ventricular walls were recorded. The preparations were subjected to 30-min no-flow ischemia with or without NIP-121 or glibenclamide, followed by 60-min reperfusion. In untreated tissues, decreases in action potential duration (APD) and contractile force and an increase in resting tension were observed during the no-flow period. On reperfusion, transient arrhythmias were observed and resting or contractile force returned to <50% of preischemic values. NIP-121, at 0.3 microM, a concentration showing only a slight negative inotropic effect, caused a faster decrease in APD and contractile force but abolished the increase in resting tension (RT) during the no-flow period. On reperfusion, no arrhythmia was observed in NIP-121-treated preparations, and contractile force recovered to approximately 80% of the preischemic value. Glibenclamide 1 microM attenuated the decrease in APD but affected neither the decrease in contractile force nor the increase in RT during the no-flow period. On reperfusion, the incidence of arrhythmia was increased in glibenclamide-treated preparations, and the recovery of basal tension and contractile force was inhibited: Contractile force recovered to only approximately 15% of the preischemic value. NIP-121 was also shown to attenuate the decrease in tissue ATP during ischemia and reperfusion. We demonstrated that NIP-121 may have protective effects against myocardial injury during ischemia and reperfusion. Activation of ATP-sensitive K+ current may be an adaptive mechanism for cardioprotection under compromised blood flow.
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PMID:Cardioprotective effects of NIP-121, a novel ATP-sensitive potassium channel opener, during ischemia and reperfusion in coronary perfused guinea pig myocardium. 885 40

Blocking of the KATP-channel with glibenclamide has been shown to abolish the infarct-reducing effect of ischemic preconditioning in dog and swine. In the rabbit the results have been divergent purportedly related to anaesthesia. The aim of this study was to investigate the importance of the KATP-channel in a rabbit model where anaesthesia was not a confounding factor. Isolated rabbit hearts perfused with a Krebs-Henseleit bicarbonate buffer were subjected to 30 min regional ischemia by ligating a coronary artery, followed by 120 min reperfusion. The preconditioning protocol was 5 min global ischemia and 10 min reperfusion. Glibenclamide (100 microM) was added to the perfusion solution before the preconditioning ischemia and stopped after 5 min regional ischemia. Infarcts were measured with tetrazolium staining and risk zones with fluorescent microspheres. The main results expressed as percent infarction of the risk zone +/- SEM for the different groups are as follows: control (n = 12) 26.8 +/- 3.2, ischemic preconditioning (IP) (n = 9) 7.3 +/- 1.5, (p < 0.05 vs. control), control + glibenclamide (n = 9) 46.9 +/- 7.3 (p < 0.05 vs. control), IP + glibenclamide (n = 10) 38.3 +/- 6.9 (p < 0.05 vs. IP). These results show that glibenclamide treatment aggravates ischemia. Also, under the influence of glibenclamide ischemic preconditioning was no longer effective in reducing infarct size in the isolated perfused rabbit heart.
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PMID:Blockade of the KATP-channel by glibenclamide aggravates ischemic injury, and counteracts ischemic preconditioning. 892 56

The aim of this study was to assess whether the cardioprotective effect of ischemic preconditioning (IPC) on endothelial function in resistance coronary arteries of the rat involves adenosine and/or activation of ATP-sensitive K+ channels (KATP channels). Isolated rat hearts perfused under constant-flow conditions were exposed to 30 min of partial ischemia (flow rate 1 ml/min) followed by 20 min of reperfusion. Preconditioning was performed with 5 min of ischemia and 10 min of reperfusion before the 30-min ischemia. After the 20-min reperfusion period, coronary arteries were precontracted with U-46619 (0.1 microM), and the coronary response to the endothelium-dependent vasodilator serotonin (5-HT; 10 microM) was compared with that of the endothelium-independent vasodilator sodium nitroprusside (SNP; 3 microM). KATP channels or adenosine receptors were blocked with perfusion of either glibenclamide (0.3 microM) or 8-phenyltheophylline (8-PT; 5 microM), respectively, starting 15 min before IPC or a corresponding sham period. In untreated hearts, ischemia selectively diminished 5-HT-induced vasodilation, compared with sham hearts (without ischemia). The vasodilation by SNP was unaffected after ischemia and reperfusion. Preconditioning in untreated hearts preserved the vasodilation produced by 5-HT. Treatment of hearts with either glibenclamide or 8-PT halved the vasodilation produced by both 5-HT and SNP in sham hearts. Glibenclamide reduced by one-half, whereas 8-PT completely blocked, the protective effect of IPC on endothelium-dependent vasodilation. These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of the rat partially by activation of KATP channels. Adenosine plays a major role in that protection.
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PMID:Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury. 894 94

The effects of berberine on cardiac action potentials were measured in isolated guinea-pig papillary muscles exposed to hypoxia and cromakalim using the standard microelectrode technique. In addition, the patch clamp technique was used to determine the effects of berberine on cromakalim-induced outward currents in isolated ventricular myocytes and on ATP-sensitive K+ (KATP) channels in inside-out membrane patches. Berberine, at 3 microM significantly inhibited, while at 100 microM completely blocked the shortening of action potential duration and effective refractory period induced by hypoxia or cromakalim (100 microM). Under the whole-cell voltage clamp conditions, berberine (3-100 microM) attenuated or even abolished the cromakalim-elicited outward K+ currents. Berberine (3-100 microM) inhibited KATP channel activity in a concentration-dependent fashion in inside-out membrane patches exposed to 0.1 mM ATP. This inhibition appeared to be mainly due to a decrease in the open channel probability without affecting unitary conductance or the time constants for open and closed channel times. Glibenclamide (10 microM) partially blocked the hypoxia-evoked but fully reversed the cromakalim-evoked abbreviation of action potential duration and effective refractory period. Both the whole-cell outward K+ currents induced by cromakalim and the opening of single KATP channels induced by the low intracellular ATP concentration were also completely abolished by 10 microM glibenclamide. We conclude that berberine is a blocker of the cardiac KATP channel. The reported beneficial effect of berberine on ischemia-induced arrhythmias is likely attributed to its inhibition of KATP channel activation and subsequent shortening of action potential duration and effective refractory period during ischemia.
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PMID:Inhibitory effects of berberine on ATP-sensitive K+ channels in cardiac myocytes. 898 2

There has been controversy regarding whether ATP-sensitive potassium channel activation protects hearts through adenosine A1 receptor activation or the converse. We addressed this issue by determining the effect of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) on the cardioprotective activity of the ATP-sensitive potassium channel opener bimakalim. In isolated rat hearts subjected to 25 min of global ischemia and 30 min of reperfusion, bimakalim significantly reduced lactate dehydrogenase release and improved postischemic recovery of contractile function. Bimakalim increased the time to the onset of ischemic contracture (EC25 = 1.2 microM), compared with vehicle, and 10 microM DPCPX had no effect on this protective action (EC25 = 1.1 microM). The 10 microM concentration of DPCPX was sufficient to abolish the bradycardic and cardioprotective effects of the adenosine A1 receptor agonist (R)-(-)-N6-(2-phenylisopropyl)adenosine. DPCPX alone had no effect on the severity of ischemia/reperfusion damage. Glyburide completely abolished the cardioprotective effects of bimakalim. Bimakalim (1 microg/kg, intracoronarily) given over four periods of 5 min, interspersed with 10-min drug-free periods, before a 60-min occlusion and 3-hr reperfusion significantly reduced infarction size in anesthetized dogs (25 +/- 5 and 8 +/- 2% of the left ventricular area at risk for vehicle- and bimakalim-treated groups, respectively). DPCPX had no effect on the infarction-sparing activity of bimakalim (9 +/- 3% of the left ventricular area at risk). The protective effect of bimakalim was not accompanied by marked hemodynamic changes or by changes in regional myocardial blood flow. The results of this study suggest that the cardioprotective effects of ATP-sensitive potassium channel openers are not dependent on adenosine A1 receptor activation in rat or dog models of ischemia.
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PMID:Adenosine A1 receptor blockade does not abolish the cardioprotective effects of the adenosine triphosphate-sensitive potassium channel opener bimakalim. 902 61

The role of adenosine triphosphate-sensitive potassium channels in the adaptive response to demand ischemia was tested in 22 patients treated with placebo or glibenclamide before sequential exercise testing or atrial pacing. Glibenclamide did not affect the improvement in signs of ischemia in both protocols, indicating that opening of these channels is not a mechanism of this adaptive response in humans.
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PMID:Blockade of K(ATP) channels with glibenclamide does not abolish preconditioning during demand ischemia. 902 42

A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: "chemical preconditioning." The amplitude of CA1 population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 +/- 27% (mean +/- SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1-24 h prior to slice preparation (preconditioned slices), psap improved to 90 +/- 15% (p < 0.01). Posthypoxic oxygen free radicals were reduced to 65 +/- 10% (mean +/- SD) of control in preconditioned slices (p < 0.05). Posthypoxic neuronal density improved from 52 +/- 15% (mean +/- SD) in control slices to 97 +/- 23% in preconditioned slices (p < 0.001). Glibenclamide, an antagonist at KATP-channels, partly reversed increased hypoxic tolerance. We conclude that chemical preconditioning induces early-onset long-lasting tolerance against in vitro hypoxia. Ultimately, this strategy may be applicable as a neuroprotective strategy in humans.
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PMID:Increased hypoxic tolerance by chemical inhibition of oxidative phosphorylation: "chemical preconditioning". 911 98

The present study describes the protective effects of the ATP-sensitive K+ (KATP) channel opener Y-26763 ((-)-(3S,4R-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl -2H-1-benzopyran-3-ol), on a model of reversible ischemia/reperfusion injury ('stunned' myocardium). Stunning was caused by 10-min occlusion of the left circumflex coronary artery followed by 3-h reperfusion in pentobarbital anesthetized beagle dogs. This procedure reduced by over 80% myocardial segment function measured by sonomicrometry in control preparations. Y-26763, administered 10 min before the left circumflex coronary artery occlusion, at a dose (3 micrograms/kg, i.v.) lacking significant systemic hemodynamic effects, produced a rapid and marked (80%) recovery of the shortening of the ischemic segment. By contrast, nifedipine (1 microgram/kg plus 0.2 microgram/kg per min, i.v.) did not ameliorate postischemic function. Glibenclamide, administered before Y-26763 at a dose (0.3 mg/kg, i.v.) that did not affect adversely hemodynamics and stunning injury negated the beneficial action of Y-26763. However, glibenclamide failed to do so when administered 2 min before starting reperfusion. The ischemia/reperfusion areas, which were measured by digital image analysis with NIH image software, were similar among experimental groups. Overall, these results indicate that Y-26763 protects the canine myocardium from reversible ischemia/reperfusion injury, probably through activation of myocardial KATP channels which appear to be involved in affording protection during the ischemic insult and not at the reperfusion.
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PMID:Y-26763 protects the canine heart from a stunning injury through opening of the KATP channels. 912 39

Increased tolerance to ischemia exhibited in chronically hypoxia immature rabbit hearts is associated with increased activation of ATP-sensitive potassium (KATP) channels. We determined whether exposure to hypoxia from birth alters the electrophysiological characteristics of Purkinje fibers obtained from rabbits (n = 12/group) which were raised in a normoxic (F O2 = 0.21) or hypoxic (F1O2 = 0.12) environment from birth to 9 days of age and the involvement of the KATP channel. The endocardial surface was exposed and impaled with microelectrodes to record action potential characteristics from Purkinje fibers under control conditions and following exposure to glibenclamide (3 microM). Action potential durations (APD)90 in Purkinje fibers were significantly shorter in hypoxic hearts compared with normoxic controls (110 +/- 5 ms v 121 +/- 4 ms). Glibenclamide increased APD90 in hypoxic hearts (120 +/- 4 ms) to values similar to those observed in normoxic controls (121 +/- 4 ms). Glibenclamide had no effect on APD90 in normoxic hearts. Maximum diastolic potential was more negative in hypoxic hearts and this effect was attenuated by glibenclamide. We conclude that chronic myocardial hypoxia results in a shorter APD as compared with normoxic controls by enhanced activation of KATP channels.
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PMID:KATP channel activation in a rabbit model of chronic myocardial hypoxia. 914 Aug 41


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