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

Neutrophil infiltration of the myocardium is an important component of such diverse disease entities as myocarditis, ischemia, and ischemia-reperfusion injury. We have hypothesized that activated neutrophils are capable of disrupting myocardial function via an oxygen free-radical mechanism. Human neutrophils activated with phorbol myristate acetate disrupted calcium transport by canine cardiac sarcoplasmic reticulum, and this process was inhibited by a combination of superoxide dismutase and catalase. In addition, the activated neutrophil system was also inhibited by the combination of cyclooxygenase inhibitors (ibuprofen and indomethacin) and catalase and accelerated by MK-447. These results incriminate both hydrogen peroxide and the hydroxyl radical as mediators of neutrophil-induced myocardial dysfunction. A test of this hypothesis in vivo was performed by neutrophil-depleting dogs with anti-canine leukocyte antisera prior to coronary artery ligation. Following 6 hr of reperfusion, there was a 43% reduction in infarct size compared to non-immune-sera-injected animals. We conclude that oxygen free radicals generated by neutrophils are capable of inducing significant myocardial injury and play an important role in the pathophysiology of ischemia reperfusion injury.
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PMID:Identification of hydrogen peroxide and hydroxyl radicals as mediators of leukocyte-induced myocardial dysfunction. Limitation of infarct size with neutrophil inhibition and depletion. 298 4

The article deals with the effect of permanent, temporal and total myocardial ischemia on the oxidation of acetate, hexanoate, palmitoylcarnitine and palmitoyl-CoA in isolated rabbit heart mitochondria. All the three models of ischemia in different experimental situations demonstrated a similar degree of fatty acid oxidation suppression independent of the length of acyl residue, the suppression being the greatest during the first hours and in total ischemia. Both in the control and in ischemia, respiratory activity was at its highest level with acetate, decreasing in the order above. Thus, the rate of Krebs' cycle reactions and of respiratory chain does not limit medium- and long-chain fatty acid oxidation. It is nevertheless established that suppression of their oxidation in ischemia is completely determined by the decrease of cytochrome S and of endogenous substrate intermediates of Krebs' cycle in the mitochondria; decreased adenine nucleotide and carnitine-palmitoyl-transferase transport (other authors' data) is not critical, at least in early ischemia (0.5 h). Ischemic mitochondria are characterized by incomplete palmitoylcarnitine oxidation.
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PMID:[Mechanism of ischemic disorders of fatty acid oxidation in heart mitochondria]. 298 85

The antiarrhythmic efficacy of 17 beta-amino- and 17 beta-amino-16 alpha-hydroxyestratrien-3-ols and 3-acetates (group 1) was compared with the efficacy of corresponding 3-[2-hydroxy-3-(isopropylamino)propyl] and 3-[2-hydroxy-3-(tert-butylamino)propyl] ethers (group II), substituents which are usually associated with beta-adrenoceptor blocking activity. Group I compounds exerted potent antiarrhythmic activity against both aconitine-induced arrhythmias in mice and ischemia-induced arrhythmias in rats and reduced the maximum following frequency of isolated guinea pig atria. Electrophysiological studies indicated that their mechanism of action is due to an ability to reduce the fast inward sodium current in cardiac cells (class I antiarrhythmic action). Group II compounds were inactive in the aconitine and atrial tests and electrophysiological studies confirmed that they were devoid of class I activity. However, these compounds, like both class I antiarrhythmic and beta-adrenoceptor blocking drugs, were active against ischemia-induced arrhythmias. Group II compounds, unlike group I compounds, exerted nonspecific beta-adrenoceptor blocking actions, which may account for their activity in the rat test. It was concluded that introduction of the 3-substituted ether group did not confer any advantage over the parent 3-ol or 3-acetate compounds.
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PMID:Antiarrhythmic activity of 17 beta-aminoestratrienes. Comparison of 3-ols and 3-acetates with the corresponding 3-(3-amino-2-hydroxypropyl) ethers. 300 68

The antiarrhythmic and antifibrillatory effects of flecainide acetate during the early postinfarction period were evaluated in a conscious canine model of sudden cardiac death. Ventricular tachycardia remained inducible early after infarction in eight of nine dogs receiving an intravenous loading dose of flecainide (2.0 mg/kg body weight) and seven of eight dogs receiving saline vehicle. In both the drug and vehicle groups, there was no significant change in the ventricular refractory period or in the cycle length of the induced ventricular tachycardia. With a maintenance intravenous infusion of flecainide, 1.0 mg/kg per h for 4 hours, the subsequent occurrence of acute posterolateral ischemia resulted in the development of ventricular fibrillation and sudden death in seven of eight flecainide-treated and eight of eight vehicle-treated dogs. Seven additional postinfarction dogs with noninducible tachycardia during pretreatment programmed stimulation, and thereby considered to be at "low risk" for the development of ischemic ventricular fibrillation, were also given flecainide in an intravenous loading and maintenance dosing regimen. The subsequent occurrence of posterolateral ischemia resulted in the development of ventricular fibrillation in three of these seven dogs. These findings suggest that flecainide acetate may not possess pharmacologic properties useful in managing ventricular tachycardia or in preventing ischemic ventricular fibrillation in the presence of recent myocardial damage.
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PMID:Effect of flecainide acetate on prevention of electrical induction of ventricular tachycardia and occurrence of ischemic ventricular fibrillation during the early postmyocardial infarction period: evaluation in a conscious canine model of sudden death. 310 May 99

Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man. Results of initial experiments with carbon-14-labeled acetate (14C-acetate) indicated that the steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8 +/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of 14C-acetate, assessed from the rate of efflux of 14CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p less than .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 14CO2. Clearance of 11C-acetate, measured externally with gamma probes in normal and ischemic myocardium, correlated closely with clearance of 14C-acetate measured directly in the effluent (r = .99, p less than .001) and with overall myocardial oxygen consumption (r = .95, p less than .001). Accumulation and clearance of 11C-acetate from human myocardium with PET demonstrated kinetics comparable to those seen with radiolabeled acetate in vitro. Thus externally detectable clearance of 11C-acetate provides a quantitative index of myocardial oxidative metabolism despite variation in the patterns of intermediary metabolism that confounds interpretation of results with conventionally used tracers such as glucose and fatty acid.
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PMID:Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. 311 65

The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.
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PMID:Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction. 311 99

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

The effects of vitamin E on compression injury of the spinal cord associated with ischemia were studied in rats. Growing rats were divided into two groups and given diet containing 2 IU/100 g (group C) or 50 IU/100 g (group E) of alpha-tocopherol acetate from 8-10 weeks before experiments. The motor disturbance induced by spinal cord injury was greatly reduced by vitamin E-supplementation. After injury, the value of TBA-reactive substances (TBARS) was immediately increased and the level of alpha-tocopherol was correspondingly decreased in the spinal cord. A higher level of TBARS was observed in the proximal region than in the injured region of the spinal cord. The high level persisted for 24 hrs in group C, but decreased within 1 hr in group E. Pathological examination of the spinal cord revealed less damage, such as bleeding and edema, in group E than in group C.
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PMID:[An experimental study on preventive effect of vitamin E in spinal cord injury]. 323 95

The myocardial energy requirements of the noradrenergic nerve terminal to retain its transmitter during acute myocardial ischemia were examined in the isolated perfused rat heart. In hearts perfused with glucose as exogenous substrate no increased release of noradrenaline (NA) could be detected during ischemia. In contrast, an increased efflux of NA was seen from glucose-perfused hearts when the glycolytic pathway was inhibited with 0.5 mM iodacetic acid. Accordingly, induction of ischemia in glycogen-depleted hearts (in the absence of exogenous substrate) or in hearts perfused with either lactate, pyruvate or acetate was also associated with a marked efflux of NA. However, no efflux was detected from glycogen-depleted hearts when glucose was present during the ischemic period. Uncoupling of oxidative metabolism with 0.1 mM 2.4-dinitrophenol did not cause any increased loss of NA during ischemia. In conclusion, these results demonstrate that severe restriction in coronary flow is accompanied by increased release of myocardial NA. Furthermore, maintainance of anaerobic glycolysis is of crucial importance for retention of the noradrenergic transmitter during ischemic conditions.
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PMID:A crucial role of ongoing anaerobic glycolysis in attenuating acute ischemia-induced release of myocardial noradrenaline. 339 56

The present study was performed in order to examine some of the characteristics of the local impulse-independent release of noradrenaline (NA) seen in acute myocardial ischemia. Experiments were carried out mainly in isolated perfused rat hearts submitted to either global coronary flow reduction or ligation of the left coronary artery. An increased efflux of NA, with a concomitant reduction in the tissue content of NA, was observed during reperfusion after only 7.5 min of coronary artery occlusion. Under conditions of global flow reduction, increased amounts of NA appeared in the venous effluent after 10-15 min of ischemia. The NA efflux progressively increased with the duration of ischemia. The maximal efflux of NA was observed during the first min of reperfusion, after which the efflux declined rapidly. Partial reduction or omission of calcium from the perfusion medium, anoxic reperfusion or presence of verapamil did not attenuate the efflux of NA and its metabolites during ischemia and/or reperfusion. Presence of desipramine, an inhibitor of the carrier-mediated transport of catecholamines, markedly reduced the ischemia-induced release of NA and simultaneously attenuated the efflux of NA metabolites. Maintenance of anaerobic glycolysis was of crucial importance for the retention of NA during ischemia. No sign of enhanced NA efflux was observed during ischemia in hearts perfused with exogenous glucose, or in hearts in which the oxidative phosphorylation was inhibited. Induction of ischemia in hearts perfused with lactate, pyruvate or acetate as exogenous substrate, in hearts in which the glycolytic pathway was inhibited, or in hearts depleted from their glycogen stores was associated with an increased efflux of NA. Depletion of myocardial NA stores with alpha-methyl-meta-tyrosine (alpha-MmT) caused a significant reduction in both the incidence of ventricular fibrillation and the mortality rate after left coronary artery ligation in anesthetized rats. The alpha-MmT pretreatment did not reduce arterial blood pressure, heart rate, myocardial energy charge or glycogen levels. It is concluded that acute myocardial ischemia is associated with an increased local release of NA, and that this release may play an important role in the genesis of early ischemic arrhythmias. An important part of the ischemia-induced release of NA is, in all probability, mediated by a carrier-mediated transport mechanism, and inhibition of this mechanism may be a specific approach to attenuate the NA release and thus minimizing its detrimental consequences.
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PMID:Mechanisms of local noradrenaline release in acute myocardial ischemia. 347 26


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