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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bretylium tosylate and bethanidine sulfate were studied in two models of experimental myocardial ischemia. In anesthetized dogs, left anterior descending coronary artery occlusion during rapid atrial pacing (180-200 min-1) produced ventricular tachycardia and fibrillation within 5 min in 9 of 11 dogs studied. In all cases, arrhythmias were preceded by and appeared to be temporally related to progressive fractionation and delay of electrograms recorded from the ischemic zone. In four dogs, bretylium (10 mg/kg) did not alter the time course of electrogram changes nor the time to onset of arrhythmia. However, in five dogs bethanidine (10 mg/kg) markedly exacerbated conduction changes in the ischemic zone and decreased the time to onset of ventricular arrhythmias (173 +/- 35 vs. 262 +/- 34 s control, mean +/- SEM, p less than 0.05). Bethanidine administration also facilitated ischemia-induced ventricular tachycardia and fibrillation in two dogs that did not exhibit ischemia-induced arrhythmias before receiving the drug. In isolated perfused rabbit hearts, global ischemia produced conduction slowing, depolarization of resting membrane potential, and decreases in amplitude and Vmax that were reproducible in serial 10 min ischemic episodes. Bretylium (10 mg/L) did not affect these parameters under either perfused or ischemic conditions. Although bethanidine (10 mg/L) also did not affect these parameters during perfusion, conduction slowing and depression of Vmax during ischemia were accelerated without affecting the time course of change in resting membrane potential. Both bretylium and bethanidine prolonged action potential duration under perfused conditions, but after 10 min of ischemia this effect was no longer evident. The results demonstrate that differences in the electrophysiologic effects of bretylium and bethanidine are markedly accentuated in the setting of acute ischemia. Although both these agents have been demonstrated to have antifibrillatory effects in other experimental settings, under the conditions of this study, bretylium failed to protect against ischemia-induced arrhythmias and acute bethanidine administration produced a proarrhythmic effect in association with an exacerbation of ischemia-induced conduction changes.
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PMID:Ischemia-induced conduction delay and ventricular arrhythmias: comparative electropharmacology of bethanidine sulfate and bretylium tosylate. 247 95

Whether and how lidocaine reduced infarct size in a canine model of ischemia and reperfusion was investigated. Twenty dogs underwent a 90-min left anterior descending artery ligation and 300 min of reperfusion. Infarct size was measured by triphenyl tetrazolium chloride and the region at risk by 99Tc-labeled albumin microspheres injected during ischemia. In 10 dogs, lidocaine (70 micrograms/kg/min i.v.) was infused 90 min prior to and during ischemia and reperfusion, while 10 dogs were untreated. The ratio of infarct to risk area was 35.2 +/- 3.4% (SEM) in lidocaine dogs vs. 48.5 +/- 5.3% in untreated dogs (p less than 0.05). Lidocaine did not reduce neutrophil accumulation in ischemic and reperfused myocardium at 5 h of reperfusion, inhibit stimulated neutrophil superoxide production, or scavenge superoxide in vitro. However, during early reperfusion, lidocaine reduced coronary sinus levels of a lipid peroxidation product (conjugated dienes). Thus, clinically relevant lidocaine infusion rates reduced myocardial infarct size when given prior to and during ischemia and reperfusion. This protective effect may be due to lidocaine's membrane stabilizing effects, which could have protected the myocardial cell membrane from lipid peroxidation.
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PMID:Lidocaine reduces canine infarct size and decreases release of a lipid peroxidation product. 248 84

The effect of hypocapnia on autoregulation of cerebral blood flow (CBF) and the lower limit of autoregulation (LLA) was determined in dogs anesthetized with nitrous oxide (66%) and halothane (0.2%, end-expired concentration). CBF and cerebral vascular resistance (CVR) were determined during both normocapnia and hypocapnia (PaCO2 21-22 mmHg) at control cerebral perfusion pressure (CPP) and after reducing CPP (by hemorrhage) to 80%, 60%, 50%, and 40% of control. At control CPP hypocapnia decreased CBF from 75 +/- 5 to 48 +/- 3 ml.100 g-1.min-1 (mean +/- SEM, P less than 0.05). During both normocapnia and hypocapnia CVR decreased and CBF did not change as CPP was reduced to 60% of control. When CPP was reduced to 50% or 40% of control, CVR remained decreased and CBF fell sharply. The LLA during hypocapnia, 61 +/- 2% of control CPP, was not different than that during normocapnia, 59 +/- 3% of control CPP. Below the LLA the CBF-CPP slopes differed from zero but did not differ between hypocapnia and normocapnia. Hypocapnia does not produce a substantial shift of the LLA, and over the range of CPP values studied here, autoregulatory cerebral vasodilation only partially abolishes hypocapnia-induced cerebral vasoconstriction. The results suggest that when cerebral autoregulation is intact and in the absence of cerebrovascular disease, hypocapnia does not reduce global CBF to a level that is likely to produce ischemia and remains a useful therapeutic treatment so long as CPP remains above the LLA.
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PMID:Autoregulation of cerebral blood flow during normocapnia and hypocapnia in dogs. 249 10

The purpose of our study was to examine whether cyclooxygenase and lipoxygenase inhibitors ameliorate delayed neuronal death in the hippocampal CA1 sector in Mongolian gerbils after 5 minutes of forebrain ischemia. Gerbils were injected intraperitoneally with cyclooxygenase inhibitors piroxicam and flurbiprofen or with lipoxygenase inhibitors AA-861 and BW-755C. Seven days after ischemic insult, the animals were perfusion-fixed, and the neuronal density in the hippocampal CA1 sector was estimated. The average neuronal density in unoperated normal gerbils was 247 +/- 9/mm (mean +/- SEM). In ischemic gerbils with vehicle administration, the average neuronal densities were 13 +/- 2, 14 +/- 2, 13 +/- 2, and 13 +/- 1 for piroxicam, flurbiprofen, AA-861, and BW-755C, respectively. The average neuronal densities in ischemic gerbils treated with 1.5 and 10 mg/kg piroxicam and 1.5 and 10 mg/kg flurbiprofen were 13 +/- 2, 194 +/- 9, 19 +/- 5, and 143 +/- 12, respectively. In ischemic gerbils treated with 15 and 100 mg/kg AA-861 and 30 mg/kg BW-755C, the average neuronal densities were 12 +/- 1, 13 +/- 1, and 14 +/- 2, respectively. At their higher doses, both piroxicam and flurbiprofen significantly (p less than 0.01) ameliorated delayed neuronal death in the hippocampal CA1 sector. Our results suggest that cyclooxygenase products play an important role in the development of delayed neuronal injury after cerebral ischemia.
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PMID:Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus. 250 15

The purpose of this study was to investigate the electrophysiology of acute ischemia in hypertrophic as compared with nonhypertrophic myocardium. Left circumflex coronary artery occlusion was produced in anesthetized open chest dogs. Of 40 dogs studied, 22 were normotensive and 18 had chronic hypertension produced by a single kidney renal clamp procedure. Recordings of electrograms and extrastimulus testing were performed in endocardial and epicardial sites in both normal and ischemically damaged zones documented by triphenyltetrazolium chloride. In the hypertrophy group, there was greater endocardial to epicardial conduction delay in ischemic zones, mean +/- SEM 57 +/- 4 ms versus 31 +/- 2 ms in the normotensive group (p less than 0.05). Also, sustained monomorphic ventricular tachycardia was inducible in seven of eight dogs with hypertrophy and in none of eight normotensive dogs surviving to 3 h. Entrainment and several observations during induction were consistent with reentrant ventricular tachycardia. To exclude hypertension alone as an etiology of tachycardia, five normotensive dogs without inducible monomorphic tachycardia remained unchanged during hypertension produced with low doses of phenylephrine or descending aortic occlusion. Thus, the electrophysiologic response to ischemia is altered in hypertrophied myocardium, which predisposes to rapid sustained monomorphic ventricular tachycardia.
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PMID:Chronic hypertension and left ventricular hypertrophy facilitate induction of sustained ventricular tachycardia in dogs 3 hours after left circumflex coronary artery occlusion. 253 Feb 62

Leukotriene (LT) E4, an important LT metabolite appearing in urine, can be rapidly separated from normal and pathological urines by automated reversed-phase HPLC after a simple sample-processing. The recoveries of LTE4 afforded by this system (86.4 +/- 6.5%, mean +/- SEM for 60 ng/L, 85.4 +/- 0.3% for 200 ng/L) are superior to those obtained by a manual extraction method. Consistency of results is similar. Highly reproducible retention times combined with a radioimmunoassay allow one to identify (based on co-elution) and quantify as little as 8 ng/L LTE4 in a 10-mL urine sample. LTE4 concentrations in urine from healthy persons approach this value (17 +/- 5 ng/L), whereas samples from patients with cardiac ischemia show a wider range of concentrations (8 to 388 ng/L), up to 50 times the detection limit. Thus this method is applicable to the noninvasive investigation of leukotriene involvement in a wide range of ischemic, inflammatory, and hypersensitive conditions.
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PMID:Measurement of urinary leukotrienes by reversed-phase liquid chromatography and radioimmunoassay. 253 86

Changes in the sinusoids of rat livers stored in cold (2 degrees C) Euro-Collins solution for various periods were observed using combined scanning (SEM) and transmission electron microscopy (TEM). The sinusoidal endothelial cells were vulnerable to cold ischemia. Fenestrations of the endothelial cells were enlarged and became mesh-like after a 4-h preservation period. Following 8 h storage the sieve plates and cytoplasmic processes of the endothelial cells were destroyed and there was a tendency for the perikaryon to desquamate. Blebs derived from hepatocytes were seen after 4 h and these increased in number and size with prolonged preservation. Although the sinusoids were filled with blebs after 24 h preservation. no irreversible ultrastructural damage in the parenchymal cells was observed. Within 12 h storage, the liver had a mosaic pattern after perfusion fixation indicating uneven fixation and profound circulatory disturbance. These results suggest that endothelial cell destruction and/or numerous blebs may have unfavorable effects on the microcirculation of the transplanted liver after prolonged preservation.
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PMID:Ultrastructural changes in rat liver sinusoids during storage in cold Euro-Collins solution. 257 3

Recent studies suggest the norepinephrine (NE) may play a regulatory role in neuronal cell death in the hippocampus after transient ischemia. However, ischemia-induced changes in extracellular NE release have not been demonstrated. In the present study, we utilized the microdialysis technique to measure extracellular NE levels in the hippocampus before, during, and after 20 min of global ischemia induced by two-vessel occlusion combined with systemic hypotension in the rat. Stable basal concentrations of extracellular NE were detected in three consecutive samples collected prior to ischemia (1.86 +/- 1.21 pmol/ml of perfusate mean +/- SEM). During ischemia, NE levels increased to 30.1 +/- 5.5 pmol/ml, representing an 18-fold increase. The levels gradually returned to baseline by 40 min of reperfusion. These results are the first to demonstrate that acute and massive extracellular release of NE occurs in the hippocampus during ischemia and early recirculation. These results support the hypothesis that the activation of the noradrenergic system may play a significant role in modulating the development of ischemic neuronal damage.
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PMID:Direct evidence for acute and massive norepinephrine release in the hippocampus during transient ischemia. 258 78

On-line conjunctival oxygen tension (PcjO2) and cerebral cortical oxygen tension (PcxO2) were measured simultaneously using polarographic oxygen sensors during hemorrhagic hypotension in dogs. Mean arterial pressure (MAP) decreased from a control value of 119 +/- 7 to 52 +/- 1 (SEM) mmHg during initial bleeding of 30 minutes, and then this level of MAP was maintained for another 150min by adjusting the height of the reservoir. During the early phase of arterial hypotension, PcjO2 fell sharply, and this was accompanied by a parallel decrease of carotid artery blood flow and cardiac output, whereas PcxO2 remained unaffected with this level of hypovolemic hypotension which was possibly due to the cerebral tissue autoregulatory mechanism. Thus, it was demonstrated that despite the anatomical similarity and proximity of their blood supply, the conjunctival tissue responded differently to the intracranial cerebral tissues when compared during hemorrhagic hypotension. The study also suggests that monitoring the PcjO2 during surgery may be a useful monitoring tool in detecting early signs of tissue ischemia and hypoxia during hypovolemic shock.
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PMID:[Changes in canine conjunctival and cerebral oxygen tension during hemorrhagic hypotension]. 258 11

Exogenous adenosine has been shown to have potent electrophysiologic effects and antiarrhythmic properties within the atrioventricular (AV) node. Endogenous adenosine, a nucleoside with an increased release signaled by ischemia and hypoxia, is not believed to exert significant effects during homeostatic conditions. Recent experimental evidence suggests, however, that under normoxic conditions, the amount of adenosine released may be sufficient to mediate some of its physiologic effects. This study was designed to test the hypothesis that in humans the electrophysiologic effects of endogenously released adenosine on AV nodal conduction can be demonstrated under normoxic conditions by inhibiting uptake and degradation of the nucleoside. In the first protocol, the effects of intravenous dipyridamole (0.56 mg/kg bolus i.v., 5 micrograms/kg/minute infusion), a nucleoside-transport blocker that elevates endogenous plasma levels of adenosine, on AV nodal conduction were evaluated in seven patients. At a constant atrial paced cycle length, dipyridamole increased the AH interval from 110 +/- 19 to 164 +/- 26 msec, p = 0.002 (+/- SEM). Aminophylline (5.6 mg/kg i.v.), a competitive antagonist of adenosine, completely reversed the effects of dipyridamole on AV nodal conduction. Similarly, dipyridamole increased the cycle length at which pacing-induced AV nodal Wenckebach occurred, from 348 +/- 31 (control) to 388 +/- 33 msec (dipyridamole) (p = 0.002). In a second protocol, the effects of intravenous dipyridamole were evaluated in another group of six patients who had supraventricular tachycardia (SVT) in which the AV node was part of the reentrant circuit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine. 259 20


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