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)

The effect of graded doses of lidocaine (1.25-10 mg/kg) on endocardial Purkinje and transmural conduction at different heart rates as well as during extrasystolic stimulation was studied in dogs, 30 min after ligation of the anterior descending coronary artery. The drug had no effect on endocardial conduction within the ischemic zone except at the highest dose. Transmural conduction time was increased by ischemia in only 50% of dogs. Transmural conduction time was increased further at high heart rates but not by short coupled extrasystoles. Lidocaine slowed conduction further in the ischemic myocardium by a process that was both rate and interval dependent. "Apparent" supernormal transmural conduction was observed during short coupled extrasystoles but not at fast drive rates. This phenomenon was blocked only by administration of high doses of lidocaine.
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PMID:Effect of lidocaine on ventricular conduction in acutely ischemic dog hearts. 619 Nov 32

Therapeutic modalities for ventricular tachycardia include antiarrhythmic drugs, direct current cardioversion, electrical pacing and surgical intervention. Lidocaine, procainamide and bretylium are all capable of controlling recurrent ventricular tachycardia; bretylium has the advantage of also being antifibrillatory and of raising the threshold for ventricular fibrillation. Lidocaine and bretylium are available only in i.v. form. Procainamide is available in i.v. as well as oral form. Other oral antiarrhythmic agents include quinidine, disopyramide, beta-blockers such as propranolol and verapamil. The latter may be useful in ventricular arrhythmias induced by ischemia; of these, only beta-blockers appear to significantly raise the threshold for ventricular fibrillation. Control of ventricular ectopy does not always preclude ventricular tachycardia and ventricular fibrillation. In treating ventricular tachycardia, bretylium tosylate is generally given 5 to 10 mg/kg i.v. over 10 to 20 minutes. Given too rapidly, it may cause nausea and vomiting. Orthostatic hypotension, a common side effect, generally abates with continued use and may be ameliorated with tricyclic antidepressants such as protriptyline. Significant supine hypotension may be encountered in patients with acute myocardial infarction and may be managed with pressor agents or fluids, or both. The antiarrhythmic efficacy of bretylium was analyzed in 40 patients. Five etiologic groups were defined by cardiac catheterization: 19 patients had atherosclerotic heart disease, 6 had primary myocardial disease, 4 had mitral valve prolapse, 4 had rheumatic heart disease and 7 had miscellaneous or no heart disease. All patients had recurrent ventricular tachycardia (VT); 23 had ventricular fibrillation (VF) as well. Other antiarrhythmic agents had failed in 38 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapy of ventricular tachycardia. 646 97

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thiopental treatment after global brain ischemia in pigtailed monkeys. 669 50

During ischemia, lidocaine or quinidine may prevent arrhythmias by blocking conduction without suppressing abnormal automaticity. The purpose of this study was to determine whether lidocaine or quinidine (5 micrograms/ml) produced Purkinje fiber-papillary muscle block during superfusion in vitro with an altered Tyrode's solution containing some components of ischemia: 6 mM potassium, PO2 less than 40, pH = 6.8. Unbranched canine Purkinje fibers connected to papillary muscle at one end were threaded through a three-chamber bath with Purkinje fiber-papillary muscle in the left chamber and Purkinje fiber alone in the middle and right chambers. Action potentials were recorded using microelectrodes from Purkinje fiber, papillary muscle, and cells at the Purkinje fiber-papillary muscle junction. Purkinje fiber or papillary muscle was stimulated at 1.5-4 Hz. Perfusion of the left chamber with altered Tyrode's solution decreased resting membrane potential, action potential amplitude, and the maximum rate of rise of phase 0 of the action potential of Purkinje fiber, papillary muscle, and junctional cells, and prolonged activation times of junctional cells and papillary muscle; but action potentials propagated from Purkinje fiber to papillary muscle, and from papillary muscle to Purkinje fiber. Lidocaine or quinidine plus altered Tyrode's solution further decreased action potential amplitude and the maximum rate of rise of phase 0 of the action potential of Purkinje fiber, papillary muscle, and junctional cells, and prolonged activation of junctional cells and papillary muscle, inducing bidirectional block only at the Purkinje fiber-papillary muscle junction. Lidocaine or quinidine plus normal Tyrode's solution and each component of altered Tyrode's solution alone did not produce block. Perfusion of the right chamber with 0.25 mM barium induced Purkinje fiber automaticity that: propagated to papillary muscle during perfusion of the left chamber with normal Tyrode's or altered Tyrode's solution; blocked at the Purkinje fiber-papillary muscle junction during perfusion of the left chamber with altered Tyrode's solution plus lidocaine; and was not suppressed during perfusion of the right chamber with lidocaine. Thus, lidocaine or quinidine may produce bidirectional block at Purkinje fiber-papillary muscle junction and interrupt a potential limb of a reentrant circuit without suppressing automatic arrhythmogenic foci.
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PMID:The effects of lidocaine and quinidine on impulse propagation across the canine Purkinje-muscle junction during combined hyperkalemia, hypoxia, and acidosis. 674 28

For the purpose to evaluate the effects of lidocaine on the ventricular arrhythmias occurring as complications of acute myocardial ischemia or infarction, the electrophysiological actions of lidocaine were estimated, as compared with those of procainamide, on the right ventricular papillary muscle of the rabbit heart superfused with hypoxic, hyperkalemic and/or acidic Krebs-Ringer solution. Lidocaine (1 to 5 x 10(-5)M) and procainamide (1.7 to 3.4 x 10(-5)M) depressed the maximum rate of action potential upstroke (Vmax) and prolonged both of the effective refractory period (ERP) and the diastolic interval needed for the premature Vmax to recover to 98% in magnitude of the basic Vmax (98% recovery time) dose-dependently, without decreasing the resting potential. Among the ischemic components, low pH (pH 6.9) and high potassium (10 mM) extracellular environments potentiated the depressant actions of lidocaine in synergic manner, but no significant enhancement of the actions of procainamide were observed under exposure to any components of ischemia. Mechanisms underlying the difference of the depressant actions on ischemic myocardium between lidocaine and procainamide were discussed in the light of recent concepts of actions of local anesthetics, and came to the conclusion that lidocaine is the most preferable antiarrhythmic agent for the management of ventricular arrhythmias during acute ischemia or infarction.
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PMID:The electrophysiological actions of lidocaine on ischemic ventricular muscle as compared with procainamide. 682 74

Studies were undertaken to determine the effects of lidocaine on ischemic myocardium, which was induced by coronary artery constriction in open-chested dogs. A real-time epicardial fluorescent technique to detect in vivo-reduced nicotinamide adenine dinucleotide (NADH) during 60 seconds of ischemia was used. Blood flow of ischemic myocardium was measured by using radioactive microspheres of 9 +/- 1 micrometers (mean +/- SE) and was compared with that of normal myocardium, shown by injection of alpha-zurine blue dye. Lidocaine effectively reduced peak NADH fluorescence by 18.6%, from 93.9 +/- 7.2 to 76.4 +/-4.1 mV (p less than 0.005). Lidocaine delayed the onset of fluorescence (2.2 +/- 0.2 versus 1.3 +/- 0.1 s p less than 0.002) and facilitated the recovery from ischemia (38.4 +/- 2.9 versus 54.8 +/- 2.9 s p less than 0.001). Increase in NADH concentration during ischemia correlated (r=0.76, p less than 0.006) with ischemic fluorescence. These findings were independent of altered hemodynamics or change in myocardial blood flow. Results indicate that lidocaine provides myocardial cellular protection during transient ischemia; there is an altered NADH fluorescent response to coronary artery occlusion.
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PMID:Protective effect of lidocaine during regional myocardial ischemia: an altered pathophysiologic response assessed by NADH fluorescence. 708 50

Effects of Ca++-antagonists on the conduction delay observed in the ischemic myocardium were studied in open-chest anesthetized dogs. Complete occlusion of the left anterior descending coronary artery (LAD) for 5 or 10 min under a constant atrial pacing produced conduction delay in the ischemic zone. Lidocaine which was administered prior to the LD occlusion increased the conduction delay, whereas Ca++-antagonists, verapamil and diltiazem, reduced the ischemia-induced conduction delay. To determine whether the coronary vasodilating action of these Ca++-antagonists can play a role in reducing the ischemia-induced conduction delay by means of increasing the collateral blood flow, the effects of these Ca++-antagonists were compared with those of other coronary vasodilating drugs on the coronary circulation and the ischemia-induced conduction delay. Administration of verapamil, diltiazem, nifedipine, nitroglycerin+phenylephrine and dipyridamole increased both the blood flow of the left circumflex coronary artery and the regional myocardial blood flow at LAD area, whereas nitroglycerin alone decreased and isosorbide dinitrate hardly affected them. Nevertheless, only drugs possessing a slow channel blocking action, i.e. verapamil, diltiazem and a large dose of nifedipine, improved the conduction delay. Effects of verapamil on the conduction delay and potassium efflux induced by global myocardial ischemia were evaluated in isolated Langendorff-perfused rabbit hearts. Perfusion with a modified Tyrode solution containing 10-1000 ng/ml of verapamil prior to 7 min of global ischemia significantly prevented the intramyocardial conduction delay. However, the potassium efflux into the coronary effluents during ischemia and 1 min after reperfusion was not significantly reduced by verapamil. These results indicate that the favorable effect of Ca++-antagonists on the ischemia-induced conduction delay is not associated with the improvement of coronary circulation or the reduction of potassium efflux from the ischemic myocardium.
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PMID:[Underlying mechanism of favorable effect of Ca++-antagonists on conduction delay observed in ischemic myocardium (author's transl)]. 731 55

Antiarrhythmic drugs, such as lidocaine, quinidine, and procainamide, have been shown to be effective against postischemic reperfusion injury in isolated rat lungs. Rat lungs were perfused at a constant flow with Krebs-Henseilet buffer supplemented with 4% bovine serum albumin and ventilated with air containing 5% CO2. The lungs were subjected to ischemia by stopping perfusion and ventilation for 60 min followed by 30 min of reperfusion. Lung injury was determined by measuring the increase in wet-to-dry lung weight ratio, while pulmonary arterial pressure and peak airway pressure were calculated from the pre- and postischemic differences. Lidocaine, quinidine, and procainamide at doses of 5, 10, and 20 mg/kg body weight, respectively, were found to attenuate the postischemic lung injury significantly (p < 0.0001). The formation of cyclooxygenase products, which were elevated during reperfusion, was also significantly (p < 0.0001) inhibited by these drugs. Since these antiarrhythmic agents are found to be powerful scavengers of hydroxyl radicals and can prevent membrane lipid peroxidation, these findings suggest that the antioxidant properties of these drugs may, in part, be responsible for protecting the lungs against reperfusion injury.
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PMID:Amelioration of postischemic reperfusion injury by antiarrhythmic drugs in isolated perfused rat lung. 770 85

One of the goals of our laboratory is to examine how the presence of drugs of abuse will influence traumatic brain injury. Previous studies in our laboratory have shown that cocaine or lidocaine treatment before experimental fluid percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to determine if pretreatment with cocaine or lidocaine is also associated with changes in trauma-induced suppression of reflexes and motor and cognitive dysfunction that occurs following traumatic brain injury (TBI). Twenty-four hours after surgical preparation, rats were randomly assigned to a saline or drug pretreatment group, cocaine (0.5, 2, or 5 mg/kg) or lidocaine (2 mg/kg), which was injected via the tail vein. None of the drug pretreatments worsened injury. Lidocaine and cocaine decreased the duration of suppression of some neurological reflexes and reduced posttraumatic body weight losses. Lidocaine and cocaine both decreased postinjury motor deficits. Lidocaine and cocaine did not affect cognitive function on days 11-15 postinjury. The mechanism by which lidocaine improves acute neurological and motor function following brain injury is unknown, but may involve improved posttraumatic cortical blood flow, as seen in our previous study. Our results, along with other studies showing lidocaine to be neuroprotective in animal models of ischemia, suggest that studies of the effect of posttraumatic administration of lidocaine are warranted.
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PMID:The effect of acute cocaine or lidocaine on behavioral function following fluid percussion brain injury in rats. 778 35

To determine if the previously reported limitation of i.v. lidocaine in facilitating recovery from cerebral ischemia was related to an effect on ischemic depolarization, we recorded cortical DC potential, electrocorticogram (ECoG) or EEG, and evoked potentials in rabbits subjected to either 3 or 5 min of complete ischemia. Three control animals undergoing 3 min of ischemia and all animals subjected to 5 min of ischemia were continuously monitored under anesthesia for 24 h, at which time the brains were processed for neocortical histology. Complete ischemia was produced by occlusion of the basilar artery and cervical collateral vessels followed by transient snare occlusion of the brachiocephalic trunk. In control animals of either ischemic duration, the onset of ischemic depolarization occurred at 102 +/- 5 s (n = 18). In animals receiving 0.2 mg/kg/min lidocaine infusion, the negative DC shift was delayed to 182 +/- 28 s (n = 7) in animals with 3-min ischemia and 195 +/- 15 s (n = 9) in lidocaine animals with 5 min ischemia (p < .01 and p < .0005 respectively, compared to controls of the same ischemic duration). In 3-min ischemia, lidocaine also reduced the amplitude of the DC shift from 8.9 +/- 0.4 mV to 4.6 +/- 1.1 mV (p < .005), whereas in 5-min ischemia there was no significant difference in the amplitude of the shift between lidocaine and control animals (11.1 +/- 1.4 and 12.7 +/- 1.0 mV, respectively). Lidocaine shortened the isoelectric EEG duration and hastened the recovery of evoked potentials in animals with 3-min ischemia; with 5-min ischemia, however, there was no significant difference in the recovery of either type of electrical activity between control and lidocaine-treated animals. Significant correlations were found between the recovery of cortical electrical activity (both spontaneous and evoked) and the amplitude or integral of the ischemic depolarization shift (p < .001 in each case). Postischemic epileptiform bursts accompanied by negative DC shifts occurred in 3/7 controls and 4/7 lidocaine animals after reperfusion for > 12 h following 5-min ischemia. There was no significant difference in the degree of cortical neuronal injury or status spongiosus found between lidocaine and control animals subjected to 5-min ischemia and 24 h reperfusion. Cortical injury in control animals with 3-min ischemia was negligible and not significantly different from sham-operated animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lidocaine delays cortical ischemic depolarization: relationship to electrophysiologic recovery and neuropathology. 801 79


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