Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myocardial ischemia leads to a rapid increase of cardiac beta-adrenergic receptors in plasma membranes despite the release of large and desensitizing amounts of endogenous catecholamines. Part of this increase has been shown to occur at the expense of intracellular receptors. To investigate whether an additional expressional regulation of beta-adrenergic receptors due to an increase of mRNA levels is involved, the mRNA levels specific for beta 1- and beta 2-adrenergic receptors were determined after various periods of global ischemia in isolated perfused rat hearts. The subtype-specific quantification of mRNA for beta 1- and beta 2-adrenergic receptors was determined using reverse-transcription followed by PCR (RT-PCR) and RNA protection assays. RT-PCR resulted in single amplification products of the expected sizes (159 bp for beta 1-adrenergic receptors and 240 bp for beta 2-adrenergic receptors). The specificity of these amplification products was confirmed by specific restriction digests. Southern blot hybridizations with internal oligonucleotides and sequencing using the dideoxy chain termination method. For quantification purposes, the mRNAs of housekeeping gene GAPDH and of cardiac alpha-actin were determined as internal standards. Additionally, cRNAs specific for beta 1- and beta 2-adrenergic receptors were used as external standards. Brief periods of global ischemia induced a rapid increase in the steady state level of mRNA for beta 1-adrenergic receptors. There was a statistically significant rise already after 15 min by 57% compared to controls. After 30 min of ischemia the mRNA levels had almost doubled. After 60 min of ischemia, the mRNA levels specific for beta 1-adrenergic receptors tended to decrease, but remained significantly above normoxic controls. In contrast, the mRNA levels specific for beta 2-adrenergic receptors remained constant up to 60 min of global myocardial ischemia. To investigate, whether agonist occupancy of the receptors may contribute to this regulation, the effect of preperfusion with the beta-blocker alprenolol was determined. Contrary to expectation, beta-blockade did not influence the ischemia-induced increase of mRNA levels specific for beta 1-adrenergic receptors. These data demonstrate for the first time, that acute myocardial ischemia induces a rapid, and subtype-selective regulation of mRNA levels for beta 1-adrenergic receptors. However, occupation or activation of beta-adrenergic receptors by an agonist is not involved in this newly characterized regulation of mRNA for beta 1-adrenergic receptors in acute myocardial ischemia.
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PMID:Regulation of beta-adrenergic receptors in acute myocardial ischemia: subtype-selective increase of mRNA specific for beta 1-adrenergic receptors. 776 Mar 63

Acute myocardial ischemia and reperfusion injury of rats were produced by ligating the left coronary artery for 15 min and reopening. The myocardial calcium contents were increased from 3.53 +/- 0.58 mumol/g dry wt in sham operation group to 6.02 +/- 1.19 mumol/g dry wt with reducing SOD/MDA ratio and showing ventricular extrasystole (VE), ventricular tachycardia (VT), and ventricular fibrillation (VF). Sinomenine (Sin) and verapamil (Ver) infusion 15 min before ischemia attenuated the elevated calcium contents to the level of the sham operation group, increased SOD/MDA ratio, and produced antagonistic effects on VE, VT, VF. These improvements indicated that Sin, similar to Ver, prevented myocardial injury by lowering intracellular Ca2+ accumulation.
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PMID:[Prevention of sinomenine on isolated rat myocardial reperfusion injury]. 801 64

Acute myocardial ischemia and reperfusion in 49 young pigs were produced by balloon occlusion of the left anterior descending coronary artery. Alternations of ST segment and T wave (STTA) were detected in 33 pigs during ischemia. They started at 30 seconds to 14 minutes (mean 5.4 +/- 4.1 minutes) after occlusion and maintained for 4.0 +/- 3.4 minutes. The start and end of STTA might be gradual or abrupt. Abrupt STTA provoked by ventricular premature beat (VPB), and might be reset by VPB and short run of non-sustained repetitive ventricular firing. In leads V1 and V4 simultaneously recorded, STTA showed concordant in most cases and the discordant alternation was transient STTA was a significant discriminator in identifying cases in whom ventricular fibrillation or tachcardia was inducible in acute myocardial ischemia (P < 0.01). We conclude that STTA may provide a non-invasion measure of cardiac electrical stability during acute myocardial ischemia.
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PMID:[Alternation of ST segment and T wave in experimental acute myocardial ischemia]. 839 16

Short periods of ischemia render the myocardium more resistant to a subsequent prolonged coronary occlusion resulting in a reduction of infarct size. This cardioprotective mechanism has been called ischemic preconditioning. Acute myocardial ischemia results in a rapid decline of high energy phosphates. After short periods of ischemia the high energy phosphate levels are better preserved and the increase of lactate is slower during the prolonged subsequent ischemia in the preconditioned group compared to control. The duration of ischemia needed for induction of the protective effect is 2.5 min in dogs and 20 min in our swine model. In porcine myocardium the protection is lost about 1 h after induction and a renewal is not possible at that time, but is 24 h later. For rabbits or dogs, but not in pigs, a late protection 24 h after induction or preconditioning has been shown ("second window of protection"). Adenosine or adenosine A1 receptor agonists, muscarinic M2 receptor agonists, alpha 1-receptor agonists and bradykinin B2 receptor agonists as well as opening of the K+ATP-channel substitute for ischemia in the induction of protection. Activation of protein kinase C results in protection in rats and rabbits, but not in dogs or pigs. Inhibition of protein kinase C translocation or kinase activity results in a loss of the protection induced by preceding ischemia. After blockade of the K+ATP-channel the protection induced by adenosine A1 receptor activation is lost. Therefore opening of the K+ATP-channel is a prerequisite for induction of the protective effect. Inhibition of the inhibitory G-protein by pertussis toxin has been shown to result in a loss of protection, therefore the Gi-protein seems to be involved in the evolution of protection. In humans during coronary angioplasty anginal pain and lactate production during a second balloon occlusion is diminished without any change in the regional myocardial perfusion. This adaptation is inhibited by blockade of the K+ATP-channel or of the adenosine A1 receptor. Intermittent cross-clamping before a longer occlusion during open-heart surgery results in a better preservation of high energy phosphates compared to controls without preceding short ischemia. These observations support the hypothesis that ischemic preconditioning also occurs in humans. Angina pectoris preceding the myocardial infarction may have preconditioned the human heart against the subsequent myocardial infarction, but studies concerning the influence of angina pectoris on short-term outcome after thrombolysis are conflicting. In the future, ischemic preconditioning or preconditioning with drugs may prolong the duration of ischemia tolerated without necrosis and improve the prognosis of patients by reducing the infarct size.
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PMID:-Myocardial protection by preconditioning. Experimental and clinical significance-. 865 Sep 86

Acute myocardial ischemia initiates a cascade of cellular events that lead to irreversible injury. We previously described the transient nature of heat-shock induced cardioprotection; treatment with a catalase inhibitor abolished the cytoprotective actions without affecting expression levels of HSP71. Repeated, transient ischemic episodes augment the ischemic tolerance of affected myocardium but the fundamental cytoprotective mechanism(s) for both "early" and "delayed" preconditioning remains unclear. Increased cellular induction of protooncogenes, heat shock genes, and downstream effector proteins might play critical roles in the cytoprotection afforded by delayed preconditioning. We measured c-fos, c-jun, c-myc, and hsp70 induction in preconditioned (2 x 5-min ischemia/10-min reperfusion) and control rabbit hearts that either underwent 30- or 120-min coronary occlusion and 60-min reperfusion, or did not undergo subsequent sustained ischemia; the latter hearts were allowed to recover for 0, 1, 3, 6, 24, 48, 72, or 96 hours. Both c-fos and c-jun in ischemic tissue were strongly induced by ischemia-reperfusion injury and preconditioning pretreatment. However, expression levels diminished significantly by 1-h reperfusion and remained depressed during the 96-h recovery period. Hsp70 (inducible) mRNA expression levels were highest primarily in ischemic myocardium after 6-h recovery post-preconditioning; Hsp70 levels in ischemic myocardium were slightly stronger after 48-h recovery but subsequently diminished to barely detectable levels by 96-h post-preconditioning. Induction of c-fos and c-jun preceded that of Hsp70. These findings support the concept that upregulation of immediate early genes and heat shock genes plays an important role in myocardial adaptation to acute ischemic stress.
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PMID:Cardiac adaptation to ischemia-reperfusion injury. 1041 23

To understand better the pathophysiological roles of the vagal efferent system in ischemic heart diseases, we examined endogenous acetylcholine (ACh) release in the myocardium in vivo. Acute myocardial ischemia was induced in anesthetized cats by a 60-min occlusion of the left anterior descending coronary artery (LAD). We implanted dialysis probes in the left ventricular free wall and measured the dialysate ACh concentration using liquid chromatography. In the ischemic region, the ACh level increased from 0.68+/-0.12 to 12.3+/-3.3 n M (mean+/-S.E., P<0.01) by LAD occlusion. Bilateral vagotomy did not inhibit ischemia-induced ACh release (20.3+/-6.4 n M). In vagotomized animals, inhibition of the N-type Ca(2+)channel by intravenous administration of omega-conotoxin GVIA (10microg/kg) also failed to suppress ACh release (15.9+/-2.0 n M). However, the inhibition of intracellular Ca(2+)mobilization by local administration of 3,4,5-trimethoxybenzoic acid 8-(dietyl amino)-octyl ester (1 m M) suppressed ACh release (4.4+/-0.8 n M, P<0.05 compared with no pharmacological intervention). In the non-ischemic region, the ACh level increased from 1.9+/-0.4 to 6. 0+/-1.0 n M (P<0.05) by LAD occlusion, which was completely abolished by vagotomy. We concluded that ACh release in the ischemic region was mainly attributed to a local release mechanism, whereas that in the non-ischemic region depended on the presence of intact vagal activity. The local release mechanism would depend on intracellular Ca(2+)mobilization but not on N-type Ca(2+)channel opening.
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PMID:Differential acetylcholine release mechanisms in the ischemic and non-ischemic myocardium. 1073 40

Acute myocardial ischemia was induced by occluding the LAD in Clawn miniature pigs. Eight pigs (group 1) were subjected to 6 h ischemia and nine pigs (group 2) were subjected to 20 min ischemia, followed by reperfusion for 340 min. Three animals of the group 1 died due to ventricular fibrillation after occlusion and in group 2, four animals died due to the arrhythmia after reperfusion. Though the ischemic area of group 2 (15.6% of the ventricle) was narrower than that of group 1 (21.7%), the survival rate was lower. We supposed that ischemia-reperfusion injuries were strongly connected with the hemodynamics of group 2. Clawn miniature pigs are useful experimental animals for myocardial ischemic researches.
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PMID:The hemodynamic effects of acute myocardial ischemia and reperfusion in Clawn miniature pigs. 1456 10

Acute myocardial ischemia is a critical adverse effect potentially occurring during cardiac procedures. A peptide inhibitor of the beta-adrenergic receptor kinase (betaARK1), betaARKct, has been successful in rescuing chronic myocardial ischemia. The present study focused on the effects of adenoviral-mediated betaARKct (Adv-betaARKct) delivery on left ventricle (LV) dysfunction induced by acute coronary occlusion. Rabbits received intracoronary delivery of phosphate-buffered saline (PBS) (n=9) or 5x10(11) viral particles of betaARKct (n=8). A loose prolene 5-0 Potz-loop suture was placed around the circumflex coronary artery (LCx) with both ends buried under the skin. Four days later, the suture was retrieved and pulled to occlude the LCx. Ischemia was confirmed by immediate ECG changes. LV function was continuously recorded for 45 min. Contractility (LVdP/dtmax), relaxation (LVdP/dtmin) and end diastolic pressure (EDP) were less impaired in the betaARKct group as compared to PBS (P<0.05, two-way ANOVA). betaAR density was higher in the ischemic area of the LV in the betaARKct group (betaARKct: 71.9+/-4.6 fmol/mg protein, PBS: 54.5+/-4.0 fmol/mg protein, P<0.05). Adenylyl cyclase activity was also improved basally and in response to betaAR stimulation. betaARK1 activation was less in the betaARKct group (P<0.05). Therefore, inhibition of myocardial betaARK1 may represent a new strategy to prevent LV dysfunction induced by acute coronary ischemia.
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PMID:Acute ischemic cardiac dysfunction is attenuated via gene transfer of a peptide inhibitor of the beta-adrenergic receptor kinase (betaARK1). 1588 Apr 49

Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and reperfusion. We implanted a dialysis probe into the left ventricular myocardial free wall and measured dialysate catecholamines levels in anesthetized rabbits. Dialysate catecholamine levels served as an index of myocardial interstitial catecholamine levels. We introduced myocardial ischemia by 60 min occlusion of the main coronary artery. The ischemia-induced dialysate catecholamines levels were compared with and without the pretreatment with entacapone (COMT inhibitor, 10 mg/kg, i.p.). Acute myocardial ischemia progressively increased dialysate catecholamine levels. Acute myocardial ischemia increased dialysate norepinephrine (NE) levels (20,453+/-7186 pg/ml), epinephrine (EPI) levels (1724+/-706 pg/ml), and dopamine (DA) levels (1807+/-800 pg/ml) at the last 15 min of coronary occlusion. Inhibition of COMT activity by entacapone augmented the ischemia-induced NE levels (54,306+/-6618 pg/ml), EPI levels (2681+/-567 pg/ml), and DA (3551+/-710 pg/ml) levels at the last 15 min of coronary occlusion. Myocardial ischemia evoked NE, EPI, and DA accumulation in the myocardial interstitial space. The inhibition of COMT activity augmented these increments in NE, EPI, and DA. These data suggest that cardiac COMT activity influences on the removal of accumulated catecholamine during myocardial ischemia.
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PMID:Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia. 1602 27

Many experimental studies have pointed out the controversy involving the arrhythmogenic effects of potassium channel openers (KCOs) in ischemia. KCOs activate the ATP-sensitive potassium current [IK(ATP)], resulting in action potential duration (APD) shortening, especially under pathological conditions such as ischemia. Acute myocardial ischemia leads to electrophysiological inhomogeneities in APD, conduction velocity, and refractoriness, which provide the substrate for reentry initiation and maintenance and may lead to malignant arrhythmias. The aim of this work is to analyze the effect of the KCO pinacidil on vulnerability to reentry during acute regional ischemia using computer simulations. We use a two-dimensional virtual heart tissue with implementation of acute regional ischemia conditions. Membrane kinetics are represented by a modified version of Luo-Rudy (phase II) action potential model that incorporates the effect of pinacidil on IK(ATP). The vulnerable window (VW) for reentry is quantified for different doses of pinacidil. Our results show that for doses below 3 micromol/l the VW widens with increasing pinacidil concentration, whereas for higher doses of pinacidil the VW decreases, becoming zero for concentrations above 10 micromol/l. The ionic mechanisms involved in this behavior are explored. This study demonstrates that the effect of pinacidil on arrhythmogenesis is strongly dose-dependent, and that high doses of pinacidil exert a strong antiarrhythmic effect.
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PMID:Effects of pinacidil on reentrant arrhythmias generated during acute regional ischemia: a simulation study. 1606 May 29


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