Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Reentrant ventricular arrhythmias (RVA) were analyzed in dogs 3--7 days after ligation of the anterior descending coronary artery using averaged "composite" recordings of electrical activity of reentrant pathways (RP) from the epicardial surface of the infarction zone (IZ). Verapamil (V) and D-600 (D) (0.2--0.5 mg/kg i.v.) resulted in slight-to-moderate improvement of conduction in RP with abolition of spontaneous RVA and RVA initiated by premature depolarizations. The effect of V was not blocked by pretreatment with propranolol (0.5 mg/kg i.v.). Using a standard microelectrode technique and strips of epicardial muscle from the IZ, D (0.5--1 X 10(-6) g/ml) slightly improved the upstroke velocity and membrane responses of depressed ischemic cells. In contrast, tetrodotoxin (5 X 10(-7) g/ml) further depressed or abolished action potentials of ischemic cells. We conclude: 1) the moderate antiarrhythmic effect of V and D on RVA is the result of improved conduction in RP; 2) this action is partly explained by improvement of a depressed sodium channel and is not related to catecholamine release; 3) slow-response action potentials play no significant role in the genesis of ischemia-related RVA, which probably results from depression of the fast response.
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PMID:Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel". 45 24

Conduction block is electrophysiologically defined and is shown to be an important pathologic condition encountered in both central and peripheral nervous system disorders. The conduction block is encountered most frequently in peripheral nerve injuries, which are the results of compression and ischemia. It is impossible to study morphologically the particular myelinated fibers showing the conduction block in human cases, but the alterations of myelinated fibers in the experimental models have been studied. The disturbance and/or destruction of the axoglial junction, with or without subsequent paranodal and segmental demyelination, is the major cause of the conduction block and is relatively easily identified morphologically in teased fiber and electron microscopic preparations of myelinated fibers. Following paranodal and segmental demyelination, the compensatory increase of large intramembranous particles, probably corresponding to the sodium channel, may enable the continuous conduction to be successful across the demyelinated axon. The abnormality of the nodal axolemma, dysfunction and/or loss of sodium channels, is another major cause and is not easily proven by light and electron microscopic techniques. Both causes may be concomitant under certain clinical and experimental conditions. Clinical and experimental conditions characterized by the conduction block are also listed.
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PMID:[Morphologic basis of conduction block]. 181 4

The ATP-sensitive potassium channel opener, cromakalim, protects ischemic hearts and its effect can be reversed by glyburide. It is presently unknown if glyburide can abolish the anti-ischemic effects of mechanistically different agents or if blockers of other potassium channels can abolish the protective effects of cromakalim. Thus, the effect of glyburide on previously reported cardioprotective agents was tested in globally ischemic/reperfused isolated rat hearts. Calcium antagonists, sodium channel blockers and calmodulin antagonists were found to significantly improve postischemic contractile function and reduce lactate-dehydrogenase release after 25 min of global ischemia and 30 min of reperfusion. Glyburide did not reverse their cardioprotective effects. 5-(N,N-dimethyl)amiloride, an inhibitor of Na+/H+ exchange, significantly reduced lactatedehydrogenase release without improving postischemic contractile function, and glyburide did not reverse this. The potassium channel opener, cromakalim, protected ischemic rat hearts (improved recovery of contractile function and reduced enzyme release) and this was abolished by glyburide. Charybdotoxin blocks both calcium-activated potassium channels and voltage-gated potassium channels and E-4031 the delayed rectifier potassium channels. Neither was found to effect the action of the potassium channel opener, cromakalim. These data indicate that glyburide is selective in that it only blocks the anti-ischemic effects of potassium channel openers and not other cardioprotective compounds. In addition, cromakalim is unaffected by blockers of other potassium channels, further indicating selectivity of glyburide for ATP-sensitive potassium channels.
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PMID:Effect of potassium channel blockade on the anti-ischemic actions of mechanistically diverse agents. 192 Jan 38

Encainide is a potent sodium channel antagonist. It dissociates slowly from blocked, repolarized channels (time constant of recovery greater than 20 seconds). It markedly slows myocardial and His Purkinje conduction in vitro, in animal models and in humans. In vitro the parent compound and its major metabolites, O-demethyl and 3-methoxy-O-demethyl encainide, have variable effects on action potential duration and refractoriness. In man the parent compound has relatively little effect on refractoriness and QT interval, but its metabolites may increase refractoriness moderately. Encainide has no significant effect on the normal sinoatrial node, and only its metabolites significantly depress atrioventricular nodal conduction and refractoriness. In models of ischemia, all of encainide's actions are more pronounced in ischemic than in normal tissue. Encainide is similar in its basic and clinical electrophysiologic profile to flecainide and lorcainide although its constellation of electrophysiologic properties is unique. It differs from quinidine, procainamide and disopyramide by slowing conduction more and affecting refractoriness less, and by absence of anticholinergic side effects.
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PMID:Basic and clinical cardiac electrophysiology of encainide. 242 30

The oxygen radicals produced by polymorphonuclear neutrophils (PMN) during ischemia and reperfusion play an important role in the development of arrhythmias. We investigated the influence of selected antiarrhythmic drugs on PMN superoxide anion production. Amiodarone, verapamil and propranolol significantly decreased the stimulated superoxide anion production, which may be an additional mechanism of their antiarrhythmic activity. The fast sodium channel inhibitors lidocaine, procainamide and mexiletine affected neither spontaneous nor stimulated superoxide anion production.
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PMID:Effect of selected antiarrhythmic drugs on the superoxide anion production by polymorphonuclear neutrophils in vitro. 255 59

The cardioprotective effect of SUN 1165, a novel sodium channel blocker, was investigated on ischemic myocardium. Nineteen anesthetized dogs were subjected to 2 hours coronary occlusion, and divided into 2 groups. In the control group, physiological saline was infused. In the SUN 1165 group, 2 mg/kg of SUN 1165 was injected intravenously. Two hours after occlusion, heart mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions (RCI and St.III O2) were measured polarographically with succinate as a substrate. Fractionation of myocardial tissue from both non-ischemic and ischemic areas was performed according to the method of Weglicki et al., and the activities of lysosomal enzymes (NAG and beta-gluc) were measured. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 hours occlusion were observed. Administration of SUN 1165 maintained mitochondrial function, and prevented the leakage of lysosomal enzymes caused by ischemia significantly. These results indicated that SUN 1165 has a cardioprotective effect in ischemic heart.
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PMID:The effects of SUN 1165, a novel sodium channel blocker, on ischemia-induced mitochondrial dysfunction and leakage of lysosomal enzymes in canine hearts. 284 30

The class Ic antiarrhythmic agent flecainide has recently become available in this country for management of ventricular arrhythmias. The pharmacologic and electrophysiologic features of this class of drug--marked sodium channel blockade producing inhibition of phase 0 of the myocardial action potential, moderate blockade of slow inward (calcium) channels, and general lack of systemic toxicity--suggest that these agents may exert significant myocardial protective effects. This hypothesis was tested in isolated, perfused rat hearts subjected to 30 minutes of global normothermic ischemia followed by 30 minutes of reperfusion after pretreatment with (1) Krebs-Henseleit buffer (n = 7); (2) Krebs-Henseleit buffer with potassium adjusted to 20.9 mmol/L with potassium chloride (n = 10); and (3) Krebs-Henseleit buffer plus flecainide acetate 50 mg/L (0.12 mmol/L) (n = 11). Severity of ischemic injury was assessed by time to ischemic contracture: 9.9 +/- 1.3 (Krebs-Henseleit buffer), 18.4 +/- 1.1 (potassium chloride), and 25.4 +/- 1.0 (flecainide) minutes (mean +/- standard error of the mean) (p less than 0.05 among all groups). Functional recovery after ischemia and reperfusion was measured by developed pressure (expressed as percent of preischemic control): 19.6 +/- 5.4 (Krebs-Henseleit buffer), 70.8 +/- 3.2 (potassium chloride), and 67.3 +/- 2.7 (flecainide). These results suggest that class Ic agents afford significant myocardial protection from global normothermic ischemia.
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PMID:Myocardial protective effects of the class Ic antiarrhythmic agent flecainide. 311 48

We investigated the effect of the sodium channel blocker, tetrodotoxin, in two animal models of brain pathology. In the first, an acute model, we recorded the interstitial brain potential in the striatum of rats after cardiac arrest. The time of deflection of this potential, an indication of changes in cerebral cation concentrations, was determined in control rats, and in rats pretreated with intrastriatal tetrodotoxin. In control rats a deflection of the brain potential was noted 2 min after cardiac arrest; tetrodotoxin pretreatment delayed this deflection to about 5 min. The second, a survival model, was based on the Levine preparation in rats. A combination of ischemia and hypoxia produced unilateral, cerebral infarcts, which were characterized by a decrease of brain [K+], and by increases of [Ca2+] and [Na+] and thus of the Na+:K+ ratio. Data on the cation shifts, determined by chemical assay methods, were complemented by those of more conventional methods of assessment of brain damage, such as the determination of survival, of Evans blue staining, and of brain water content. Cation shifts could be prevented locally by tetrodotoxin. In conclusion, the drug can, at least partially, prevent the detrimental effects of an ischemic insult. In addition, our results showed that protective effects observed in the acute model may sometimes offer an indication of the effects to be expected in the survival model. Furthermore, the effect of tetrodotoxin on the brain potentials in the acute model showed that its protective action in the survival model may be brought about by delaying cell depolarization and by shortening the actual duration of the depolarized state. We conclude that Na+ influx and, consequently, neurotransmission may play a crucial role in the development of cerebral damage.
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PMID:Cerebral cation shifts in hypoxic-ischemic brain damage are prevented by the sodium channel blocker tetrodotoxin. 333 36

The effects of calcium channel blockers and lidocaine on changes in action potential characteristics and conduction time during exposure to altered Tyrode's solution imitating some of metabolic alterations that occur in acute myocardial ischemia (pO2 less than 50 mmHg, KCl 8 mM, pH 6.80) were examined in the isolated right ventricular epicardium of canine heart. The superfusion with altered Tyrode's solution produced loss of resting membrane potential (RMP), action potential amplitude (APA), action potential duration (APD), and upstroke velocity of action potential (Vmax), and prolonged conduction time (CT). In the presence of lidocaine (5 mg/l), altered Tyrode's solution aggravated the reductions of APA and Vmax, and of the prolongation of CT. On the other hand, in the presence of either verapamil (1 mg/l), diltiazem (3 mg/l), nifedipine (1 mg/l), or Ni2+ (1 mM), the degree of the reductions of APA and Vmax and of the prolongation of CT induced by altered Tyrode's solution was reduced. However, neither lidocaine nor calcium channel blockers affected change in RMP. These results suggest that decreasing calcium influx during ischemia improves depressed sodium channel, and this effect can partly explain the improvement of ischemia-induced conduction delay by calcium channel blockers.
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PMID:[Mechanism of actions involved in improved effects of calcium channel blockers on ischemic myocardial conduction delay]. 666 84

The ability of five agents (dizocilpine [MK-801], 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline [NBQX], enadoline [CI-977], L-nitroarginine methyl ester [L-NAME] and BW 1003c87) with well defined, distinct pharmacological profiles and with established anti-ischemic efficacy, to modify neuronal damage has been examined in a simple in vivo model of glutamate excitotoxicity. Cortical lesions were produced in physiologically-monitored halothane-anesthetised rats by reverse dialysis of glutamate. The volume of the lesion was quantified histologically by image analysis of approximately 20 sections taken at 200 microm intervals throughout the lesion. The AMPA and NMDA receptor antagonists (NBQX and MK-801) and the inhibitor of nitric oxide synthase (L-NAME) significantly reduced the lesion volume by a similar extent (by approximately 30% from vehicle). Two agents (the kappa opioid agonist, CI-977 and the sodium channel blocker, BW 1003c87) which putatively inhibit the release of endogenous glutamate presynaptically, had dissimilar effects on lesion size. CI-977 failed to alter the amount of damage produced by exogenous glutamate, whereas BW 1003c87 reduced the lesion size by approximately 50%. Using this model, the neuroprotective effects of anti-ischemic drugs can be explored in vivo, uncomplicated in contrast to experimental ischemia by reduced oxygen delivery, drug effects on tissue blood flow and compromised energy generation. In consequence, additional mechanistic insight into anti-ischemic drug action in vivo can be obtained.
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PMID:Pharmacological modification of glutamate neurotoxicity in vivo. 750 85


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