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

The effects of nitroprusside and cyanide on myocardial relaxation were studied during hypoxia and reoxygenation of isolated rat papillary muscle, and during segmental ischemia and reperfusion in the intact dog heart. Nitroprusside did not affect isolated muscle performance before or during hypoxia. During reoxygenation of hypoxic muscles, the tension prolongation phenomenon (which characterizes abnormal or prolonged relaxation) was only slightly attenuated by the addition of nitroprusside to the muscle bath; in contrast, cyanide (at concentrations that did not prevent the return of tension) abolished tension prolongation during reoxygenation. During reperfusion of ischemic segments in intact hearts, the prolongation of segment tension was not affected by systemic administration of nitroprusside, but was abolished by intracoronary cyanide. Attenuation of the tension prolongation phenomenon by nitroprusside in the isolated muscle may be due to the liberation of cyanide. Inasmuch as nitroprusside did not affect the tension prolongation phenomenon in the intact heart, it is unlikely that the influence of this drug on left ventricular diastolic compliance is mediated through an alteration in the tension prolongation phenomenon.
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PMID:Myocardial relaxation. I. Effect of nitroprusside on the tension prolongation phenomenon. 46 11

The protective effects of the PGI2 analogue, OP-2507 against hypoxic tissue injury were investigated in a 60-70 min acute hemorrhagic shock model in 29 rats. To assess the metabolic recovery of mitochondria after tissue injury induced by hemorrhagic hypotension with a mean arterial pressure of 30 mmHg, we have non-invasively monitored changes in the brain tissue parameters of cyt. aa3 redox state, blood oxygenation and relative blood volume by spectrophotometry through the closed skull and intact skin. Pretreatment with 0.1 mg/Kg s.c. of OP-2507 at 30-40 min before induction of shock was performed on 14 rats (OP-treated group). The remaining 15 rats were used as a control (control group). There was a consistent prolongation of survival time and a significant improvement in survival rate after reinfusion of the shed blood in the OP-treated group. In this group there was a rapid and complete reoxidation of cyt. aa3 with a mean overshoot of 9 +/- 5.5% above the baseline value after reinfusion. On the other hand, in the control group the extent of reoxidation was significantly lower, with a minimal 11 +/- 3.2% below the base line. In order to evaluate the mechanisms involved 10 mg of NaCN i.v. was administered to the living rats at 60-70 min after reinfusion of the blood in both groups. In the OP-treated group, brain Hb saturation increased up to 20% above the pre-cyanide infusion level. However in the control group there was a non-significant increase in the Hb oxygenation level. These observation indicate that in the OP-treated group oxygen consumption by mitochondria is significantly higher than that in the control group. Thus, enhanced oxygen utilization could lead to the active restoration of injured tissue by promoting oxidative phosphorylation. Under these experimental conditions the oxidative response of cyt. aa3 is concluded to correlate closely with the prognosis of shock animals in both groups. These results indicate the potential usefulness of OP-2507 in protecting the brain and other organs from oxygen insufficiency as a result of tissue ischemia and anoxia.
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PMID:Protective effects of a PGI2 analogue OP-2507 on hemorrhagic shock in rats--with an evaluation of the metabolic recovery using near-infrared optical monitoring. 131 77

The association between cigarette smoking and delayed wound healing is well recognized in clinical practice, although extensive controlled studies have yet to be performed. The documented effects of the toxic constituents of cigarette smoke--particularly nicotine, carbon monoxide, and hydrogen cyanide--suggest potential mechanisms by which smoking may undermine expeditious wound repair. Nicotine is a vasoconstrictor that reduces nutritional blood flow to the skin, resulting in tissue ischemia and impaired healing of injured tissue. Nicotine also increases platelet adhesiveness, raising the risk of thrombotic microvascular occlusion and tissue ischemia. In addition, proliferation of red blood cells, fibroblasts, and macrophages is reduced by nicotine. Carbon monoxide diminishes oxygen transport and metabolism, whereas hydrogen cyanide inhibits the enzyme systems necessary for oxidative metabolism and oxygen transport at the cellular level. Slower healing has been observed clinically in smokers with wounds resulting from trauma, disease, or surgical procedures. The reduced capacity for wound repair is a particular concern in patients undergoing plastic or reconstructive surgery. Compared with nonsmokers, smokers have a higher incidence of unsatisfactory healing after face-lift surgery, as well as a greater degree of complications following breast surgery. Smokers should be advised to stop smoking prior to elective surgery or when recovering from wounds resulting from trauma, disease, or emergent surgery.
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PMID:Smoking and wound healing. 132 8

Na(+)-Ca2+ exchange has been shown to contribute to reperfusion- and reoxygenation-induced cellular Ca2+ loading and damage in the heart. Despite the fact that both [Na+]i and [Ca2+]i have been documented to rise during ischemia and hypoxia, it remains unclear whether the rise in [Ca2+]i occurring during hypoxia is linked to the rise in [Na+]i via Na(+)-Ca2+ exchange before reoxygenation and how this relates to cellular injury. Single electrically stimulated (0.2 Hz) adult rat cardiac myocytes loaded with Na(+)-sensitive benzofuran isophthalate (SBFI), the new fluorescent probe, were exposed to glucose-free hypoxia (PO2 less than 0.02 mm Hg), and SBFI fluorescence was monitored to index changes in [Na+]i. Parallel experiments were performed with indo-1-loaded cells to index [Ca2+]i. The SBFI fluorescence ratio (excitation, 350/380 nm) rose significantly during hypoxia after the onset of ATP-depletion contracture, consistent with a rise in [Na+]i. At reoxygenation, the ratio fell rapidly toward baseline levels. The indo-1 fluorescence ratio (emission, 410/490 nm) also rose only after the onset of rigor contracture and then often showed a secondary rise early after reoxygenation at a time when [Na+]i fell. The increase in both [Na+]i and [Ca2+]i, seen during hypoxia, could be markedly reduced by performing experiments in Na(+)-free buffer. These experiments suggested that hypoxic Ca2+ loading is linked to a rise in Na+i via Na(+)-Ca2+ exchange. To show that Na(+)-Ca2+ exchange activity was not fully inhibited by profound intracellular ATP depletion, cells were exposed to cyanide, and then buffer Na+ was abruptly removed after contracture occurred. The sudden removal of buffer Na+ would be expected to stimulate cell Ca2+ entry via Na(+)-Ca2+ exchange. A large rapid rise in the indo-1 fluorescence ratio ensued, which was consistent with abrupt cell Ca2+ loading via the exchanger. The effect of reducing hypoxic buffer [Na+] on cell morphology after reoxygenation was examined. Ninety-five percent of cells studied in a normal Na(+)-containing buffer (144 mM NaCl, n = 38) and reoxygenated 30 minutes after the onset of hypoxic rigor underwent hypercontracture. Only 12% of cells studied in Na(+)-free buffer (144 mM choline chloride, n = 17) hypercontracted at reoxygenation (p less than 0.05). Myocytes were also exposed to hypoxia in the presence of R 56865, a compound that blocks noninactivating components of the Na+ current. R 56865 blunted the rise in [Na+]i typically seen after the onset of rigor, suggesting that Na+ entry may occur, in part, through voltage-gated Na+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dependence of hypoxic cellular calcium loading on Na(+)-Ca2+ exchange. 132 32

It has been shown in vitro that dihydrolipoate (DL-6,8-dithioloctanoic acid) has antioxidant activity against microsomal lipid peroxidation. We tested dihydrolipoate for its neuroprotective activity using models of hypoxic and excitotoxic neuronal damage in vitro and rodent models of cerebral ischemia in vivo. In vitro, neuronal damage was induced in primary neuronal cultures derived form 7-day-old chick embryo telencephalon by adding either 1 mM cyanide or 1 mM glutamate to the cultures. Cyanide-exposed and dihydrolipoate-treated (10(-9)-10(-7) M) cultures showed an increased protein and ATP content compared with controls. The glutamate-exposed cultures treated with dihydrolipoate (10(-7)-10(-5) M) showed a decreased number of damaged neurons. In vivo, dihydrolipoate treatment (50 and 100 mg/kg) reduced brain infarction after permanent middle cerebral artery occlusion in mice and rats. Dihydrolipoate treatment (50 and 100 mg/kg) could not ameliorate neuronal damage in the rat hippocampus or cortex caused by 10 min of forebrain ischemia. A comparable neuroprotection was obtained by using dimethylthiourea, both in vitro (10(-7) and 10(-6) M) and at a dose of 750 mg/kg in the focal ischemia models. Lipoate, the oxidized form of dihydrolipoate, failed to reduce neuronal injury in any model tested. We conclude that dihydrolipoate, similarly to dimethylthiourea, is able to protect neurons against ischemic damage by diminishing the accumulation of reactive oxygen species within the cerebral tissue.
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PMID:Dihydrolipoate reduces neuronal injury after cerebral ischemia. 134 59

Glucocorticoids potentiate injury to the rodent hippocampus following a variety of metabolic insults, including hypoxia/ischemia, both in vitro and in vivo. We have examined whether corticosterone (CORT), the principal glucocorticoid in the rat, could exacerbate hypoxic energy failure in cultured hippocampal astrocytes. Exposure to 6 h of atmospheric hypoxia (100% N2) or to 30 min of cyanide did not cause any detectable cell injury, although moderate astrocyte damage did occur alter 6 h of hypoxia in the absence of glucose. Both cyanide and hypoxia significantly reduced astrocyte ATP content, a decline that was further reduced when glucose was omitted. A 30 min exposure to 100 microM glutamate elevated ATP content under normoxic conditions but enhanced the cyanide-induced loss of ATP. A 24 h pre-treatment with CORT did not influence normoxic ATP levels but potentiated the loss of ATP following both cyanide and hypoxia. CORT also exacerbated the loss of ATP seen after combined exposure to cyanide and glutamate, as well as that following cyanide + 0 mM glucose. These results indicate that both CORT and glutamate can potentiate hypoxia-induced energy failure in hippocampal astrocytes, albeit by different mechanisms.
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PMID:Corticosterone accelerates hypoxia- and cyanide-induced ATP loss in cultured hippocampal astrocytes. 135 86

Microinjections of cyanide (300 pmol) into the cardiovascular portion of the rostral ventrolateral reticular nucleus (RVL) of anesthetized rats (paralyzed and ventilated) produced a pressor response (26.5 +/- 1.6 mmHg, n = 7) and a transient depression of phrenic nerve discharge (90 +/- 8%, n = 5). Microiontophoretic applications of cyanide (less than or equal to 100 nA, 5-40 s) excited the RVL-spinal sympathoexcitatory neurons (31 out of 31). The response was dose dependent, reversible, independent of the baroreflex input to these neurons, and different from the responses of units with spontaneous discharge synchronized with the lung inflation or with unidentified function. The cyanide-induced excitation of the RVL-spinal sympathoexcitatory neurons was reversibly abolished by CO2+, applied iontophoretically at a dose at which the baroreflex inhibition of these neurons was not markedly affected whereas iontophoretic applications of kynurenic acid, a glutamate receptor antagonist, did not alter the response of the RVL-spinal sympathoexcitatory neurons to cyanide. It was concluded that cyanide induces a rapid Ca(2+)-dependent response of the RVL-spinal sympathoexcitatory neurons, which may underlie the cellular mechanism of these neurons in responding to ischemia-hypoxia.
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PMID:Cyanide excites medullary sympathoexcitatory neurons in rats. 153 25

Verapamil has beneficial effects on ischemic myocardium, including reduction in electrophysiological derangements, prevention of intracellular K+ loss, and preservation of high-energy phosphates, but the mechanisms underlying these actions are not clear. Recent studies have demonstrated a role of ATP-regulated K+ (KATP) current in action potential shortening and K+ loss during ischemia and metabolic inhibition. Therefore, we studied the effects of verapamil on KATP current in feline ventricular myocytes to test the hypothesis that the drug prevents ischemic electrophysiological disturbances by affecting the KATP channel. Membrane potentials and currents were recorded using standard patch-clamp techniques. During 15-minute superfusion with 1 mM CN-, action potential duration measured at 90% repolarization was reduced from 259 +/- 12 to 98 +/- 15 msec (62% reduction) in the absence of verapamil and from 266 +/- 11 to 183 +/- 16 msec (31% reduction) in the presence of 2 microM verapamil (p less than 0.01). In inside-out membrane patches, the KATP current, activated in the absence of ATP, was significantly suppressed by intracellular application of 2 microM verapamil, but the single-channel conductance was not changed. Verapamil did not change the mean open and closed times of the channel within bursts (e.g., the mean open time was 1.92 +/- 0.18 and 1.82 +/- 0.21 msec in the absence and presence of 2 microM verapamil, respectively), but it shortened the mean lifetime of bursts from 41.1 +/- 3.5 to 24.9 +/- 2.8 msec (p less than 0.01) and prolonged the closed time between bursts from 39.4 +/- 4.6 to 78.5 +/- 5.1 msec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Verapamil diminishes action potential changes during metabolic inhibition by blocking ATP-regulated potassium currents. 160 69

Although findings from several reports suggest that nonreentrant or focal mechanisms contribute to the genesis of arrhythmias during early ischemia, the contribution of triggered activity arising from early or delayed afterdepolarizations has not been resolved. We have previously demonstrated that beta- but not alpha-adrenergic stimulation induces afterdepolarizations and triggered activity in isolated normoxic myocytes. In the present study, the influence of the extent of cellular derangements as well as increases in [K+]o on alpha- and beta-adrenergic-mediated afterdepolarizations and triggered activity was evaluated. Adult canine myocytes were exposed to one of the following experimental conditions with simultaneous intracellular transmembrane action potential recordings: 1) low PO2 (less than 10 mm Hg, obtained using a specially designed hypoxic chamber) and low (6.8) pH; 2) low PO2, low pH, and high extracellular potassium ([K+]o) (10 mM); or 3) severe metabolic inhibition with cyanide (10(-6) M). Cells from each group were superfused with either the alpha-agonist phenylephrine (10(-5) or 10(-7) M, with 10(-5) M nadolol) or the beta-agonist isoproterenol (10(-6) M). Moderate changes in the action potentials were observed under conditions 1 and 2 (moderate hypoxia), whereas marked but reversible changes were observed with cyanide (severe metabolic inhibition). During moderate hypoxia in normal [K+]o, delayed afterdepolarizations or triggered activity were elicited by both alpha- (12 of 13 cells) and beta-adrenergic (five of five cells) stimulation. Increasing [K+]o during moderate hypoxia completely abolished the afterdepolarizations induced by alpha-adrenergic stimulation and prevented the occurrence of triggered activity. In contrast, the influence of beta-adrenergic stimulation was only attenuated by an increase in [K+]o. Exposure to cyanide completely prevented the induction of afterdepolarizations and triggered activity by both alpha- and beta-adrenergic stimulation. Our findings indicate that moderate hypoxia in normal [K+]o is associated with the development of adrenergic-mediated afterdepolarizations and triggered activity. In contrast, accumulation of [K+]o or severe impairment of cellular metabolism is accompanied by inhibition of adrenergic-mediated afterdepolarizations and triggered activity.
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PMID:Influence of hypoxia on adrenergic modulation of triggered activity in isolated adult canine myocytes. 167 Jun 27

Several studies have demonstrated that focal mechanisms contribute to arrhythmogenesis during acute myocardial ischemia in vivo. However, the biochemical derangements during ischemia may either potentiate or depress the electrophysiological mechanisms leading to focal arrhythmias. In the study presented here we have characterized the consequences of various levels of cellular depression and of alterations in the extracellular environment on the development of early (EADs) and delayed (DADs) afterdepolarizations induced by catecholamines. Adult canine myocytes were exposed to: normoxia; hypoxia (pO2 less than 10 mmHg); hypoxia + high K+ or cyanide infusion. Early and delayed afterdepolarizations were induced by alpha or beta adrenergic stimulation in the different experimental conditions by infusing isoproterenol (10(-8)-10(-6) M) or phenylephrine (10(-7)-10(-5) M) + the betablocker nadolol. Hypoxia did not modify EADs or DADs induced by beta stimulation and potentiated DADs induced by alpha stimulation; hypoxia + high K+ blunted DADs induced by both types of stimulation and cyanide infusion completely prevented and suppressed them. Thus, triggered arrhythmias dependent upon adrenergic stimulation can either be potentiated or inhibited by the biochemical derangements of acute ischemia. Focal arrhythmias are more likely to occur in the borderline ischemic cells where cellular depression and extracellular K+ accumulation are less marked.
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PMID:[Variations in arrhythmogenic response to catecholamines in acute myocardial ischemia]. 191 17


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