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

Cardiac dysrhythmias are common during anesthesia and surgery. An important precipitating factor of clinically relevant arrhythmias is the introoperative use of epinephrine. Bradykinin acts as an endogenous cardioprotective substance because it suppresses ventricular dysrhythmias induced by ischemia. In this study, we investigated whether bradykinin has a protective effect, preventing the development of dysrhythmias after epinephrine infusion in rats. Because kinins are potent stimulators of the release of nitric oxide and prostaglandins from the endothelium, we investigated whether the protective effect of bradykinin is mediated by these 2 autacoids. Male Sprague-Dawley rats anesthetized with sodium pentobarbital had catheters placed into a carotid artery and both jugular veins. Arterial blood pressure and lead II of the electrocardiogram (ECG) were continuously monitored and recorded. After a steady state was achieved, 1 mg/kg enalapril, an inhibitor of angiotensin I-converting enzyme/kininase II, was given intravenously to all groups except the one treated with losartan. Bradykinin was infused at the initial rate of 0.5 microg/kg per min. Cardiac arrhythmia was induced with 7.5 microg/kg epinephrine intravenously. Dysrhythmia was assessed by counting the number of premature ventricular contractions (PVCs), runs of ventricular tachycardia (V Tach), and missing beats during the first minute after epinephrine. In untreated, control rats, epinephrine caused 10.8 +/- 2.7 PVCs, 0.8 +/- 0.2 runs of V tach, and 11.6 +/- 7.4 missing beats/min. In rats pretreated with bradykinin, the same dose of epinephrine elicited 1.2 +/- 0.5 PVCs, no runs of V tach, and 0.4 +/- 0.4 missing beats/min. This beneficial effect of bradykinin was partially reversed by N-nitro-L-arginine methyl ester (L-NAME) or indomethacin, and completely by L-NAME plus indomethacin or icatibant, but it was not affected by des-Arg9[Leu8]-bradykinin. We conclude that bradykinin, acting on the B2 receptor, attenuates epinephrine-induced dysrhythmia via a mechanism that involves the release of NO and prostaglandins. Although the mechanism is not clear, NO and prostaglandins may prevent epinephrine-induced dysrhythmia and protect the myocardium via a direct action on cardiac neurons.
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PMID:Attenuation of epinephrine-induced dysrhythmias by bradykinin: role of nitric oxide and prostaglandins. 929 70

This study was undertaken to clarify factors other than nitric oxide involved in reactive hyperemia after a short (30 sec) and a long (300 sec) coronary global no-flow ischemia in isolated rat hearts perfused at a constant pressure (90 mmHg) with special focuses on the contribution of various K channels including large and small conductance Ca-activated K (KCa) channels as well as ATP-sensitive K (KATP) channels. Reactive hyperemia was induced following 30 sec and 300 sec of no-flow ischemia of the heart. Coronary reactive hyperemia was observed even after the inhibition of nitric oxide synthase by N(omega)-nitro-L-arginine methylester (L-NAME). Selected K channel blockers, none of which affected the basal flow, were used to evaluate contribution of K channels to this L-NAME-resistant reactive hyperemia. After 30-sec ischemia, tetraethylammonium (TEA: a non-selective K channel blocker), glibenclamide (Gli: a KATP channel blocker) and alpha,beta-methylene adenosine 5'-diphosphonate (AOPCP: an inhibitor of ecto 5'-nucleotidase) all suppressed both peak flow/basal flow (%PF) and repayment of flow debt (%RFD). After 300-sec ischemia, TEA and charybdotoxin (ChTX: a large conductance KCa channel blocker) decreased %PF and %RFD; AOPCP decreased both %RFD and duration, 4-aminopyridine (a voltage-dependent K channel blocker) decreased only duration. Neither apamin (a small conductance KCa channel blocker) nor indomethacin (a cyclooxygenase inhibitor) affected the both types of reactive hyperemia. These findings suggest that opening of KATP channel contributes to coronary vasodilation in reactive hyperemia after short 30-sec ischemia, and that opening of KCa, but not KATP, channel contributes to it after long 300-sec ischemia. These results also suggest that adenosine may partly be involved in both types of reactive hyperemia.
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PMID:Types of potassium channels involved in coronary reactive hyperemia depend on duration of preceding ischemia in rat hearts. 929 38

We used an experimental model of the perfused isolated rabbit tibia to investigate the vasodilatation produced by nitric oxide in the circulation of bone. Tibiae were perfused at a constant flow rate while the perfusion pressure was monitored continuously. Perfusion pressure was raised by the addition of noradrenaline to the perfusate, and dose responses were measured for bolus doses of acetylcholine and sodium nitroprusside. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, was then added to the perfusate at a concentration of 10(-4) M, and the dose responses to acetylcholine and sodium nitroprusside were repeated. Measurements were performed on groups of bones after 0, 6, 12, and 24 hours of normothermic ischemia (n 5, 4, 6, and 9, respectively). Both acetylcholine and sodium nitroprusside produced significant vasodilatation after 0 and 6 hours' ischemia, but no significant response was observed after 12 or 24 hours of ischemia. The vasodilatation produced by acetylcholine was significantly attenuated when L-NAME was added to the perfusate, but the vasodilatation produced by sodium nitroprusside remained unchanged. These findings confirm endothelial production of NO by stimulation of muscarinic receptors on the endothelial cells in bone and indicate that vasodilatation via the L-arginine/NO pathway remains viable for 6 hours after normothermic ischemia.
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PMID:Endothelium-dependent vasodilatation produced by the L-arginine/nitric oxide pathway in normal and ischemic bone. 931 41

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.
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PMID:Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury. 931 83

Effects of a novel zinc compound polaprezinc [N-(3-aminopropionyl)-L-histidinatozinc] and sucralfate on the mucosal ulcerogenic responses induced by monochloramine (NH2Cl) were examined in rat stomachs. Oral administration of NH2Cl (>60 mM) produced severe lesions in unanesthetized rat stomachs, with concomitant increase of lipid peroxidation. These lesions were aggravated by sensory deafferentation but not affected by pretreatment with indomethacin or L-NAME. The mucosal ulcerogenic response to NH2Cl was significantly inhibited by oral pretreatment with either dmPGE2 (10 microg/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg), the NO donor. Gastric lesions induced by NH2Cl were also inhibited by prior oral administration of polaprezinc (3-30 mg/kg) as well as sucralfate (30 and 100 mg/kg). The protective effect of polaprezinc was not affected by any pretreatments such as indomethacin, L-NAME, or sensory deafferentation, while that of sucralfate was significantly mitigated in the presence of either indomethacin or L-NAME. On the other hand, mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery, followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were also attenuated by prior application of polaprezinc, while dmPGE2 and sucralfate prevented such lesions without affecting the reduced PD response. These results suggest that: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa, (2) both polaprezinc and sucralfate protect the stomach against injury caused by NH2Cl, and (3) the mechanisms underlying the protective action of sucralfate may be partly mediated by both endogenous PGs and NO but may be different from those of polaprezinc.
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PMID:Mucosal ulcerogenic action of monochloramine in rat stomachs: effects of polaprezinc and sucralfate. 936 51

The relative importance of hemodynamic factors in the pathogenesis of thrombotic or embolic stroke is unclear. Of particular therapeutic interest are those substances that facilitate vasodilation and the clearance of platelet aggregates in the compromised microvasculature. A likely contributor to these functions is nitric oxide because it is known to inhibit platelet aggregability and promote vascular relaxation. To investigate the involvement of nitric oxide in the hemodynamic changes after experimental ischemia, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was studied. CCAT is a rat model of unilateral carotid artery stenosis and platelet embolization to the brain. This study characterized the acute hemodynamic consequences of CCAT and the resultant pattern of platelet deposits with and without nitric oxide synthase inhibition by nitro-L-arginine methyl ester (L-NAME). In addition, the subacute local cerebral blood flow changes were studied at 24 hours. Right CCAT was produced in 30 male Wistar rats injected with (111)In-labeled platelets. Between 5 and 15 minutes after thrombosis, rats were treated with either 15 mg/kg of L-NAME (intravenously) or saline vehicle. Hemodynamic changes were studied 30 to 45 minutes after thrombosis using [14C]iodoantipyrine autoradiography. Eight coronal levels were analyzed, and cortical and subcortical regions of interest were defined. Significant increases were observed in total platelets in the ipsilateral hemisphere after L-NAME treatment, and in the distribution of platelets in the anterior frontal and occipital cortices with nitric oxide synthase inhibition, encompassing the anterior and posterior border zone areas of the ipsilateral cortex. Otherwise, foci of labeled platelets were detected throughout the ipsilateral and contralateral hemispheres. Mean local cerebral blood flow images (n = 5) revealed a moderate bilateral global reduction in flow acutely, which normalized in the untreated thrombosed group by 24 hours. In contrast, the L-NAME-treated groups (sham and experimental) had lasting, widespread reductions in flow of approximately 25%. Pairwise comparisons between groups showed that CCAT/L-NAME was significantly different from shams in the corpus callosum and different from L-NAME shams in the internal capsule (P < 0.05) These hemodynamic and platelet accumulation changes may partially account for the aggravation of cognitive and sensorimotor deficits previously reported in this model of thromboembolic stroke.
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PMID:The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke. 939 Jun 50

Nitric oxide (NO) under basal conditions is an important regulator of vascular tone. Under ischemic conditions, however, NO can combine with superoxide anion to produce the damaging hydroxyl free radical. The current project observes the effect of inhibiting NO production (L-Nitro-amino-methyl-arginine, L-NAME) on flaps rendered ischemic by secondary (2 degrees) venous obstruction. Eighty rats had 3 x 6 cm skin flaps based on the epigastric vessels. Primary (1 degree) ischemia was produced by arteriovenous occlusion for 2 hours; (2 degrees) venous ischemia was induced by clamping the vein, alone for either 3 or 5 hours. Thirty minutes prior to 2 degrees ischemia, rats received either L-NAME (30 mg/kg) or saline buffer. Flap survival was assessed 7 days later and Chi-square analysis was used. At 3 hours of ischemia, treatment improved survival from 55% to 85% (P < 0.05). Treatment also improved survival at 5 hours of ischemia from 5% to 35% (P < 0.04). Although under resting conditions, NO is a potent vasodilator, during 2 degrees venous obstruction it may contribute to flap necrosis.
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PMID:Secondary ischemic tolerance improved by administration of L-NAME in rat flaps. 939 60

The involvement of nitric oxide (NO) in the development of ischemic cytotoxic edema was investigated by inhibiting nitric oxide synthase (NOS) activity with N omega-nitro-L-arginine (NLA). Bilateral carotid artery occlusion (15 min) alone or with release (15 and 60 min) served as a model for edema induction. NLA, N omega-nitro-D-arginine methyl ester (D-NAME) or Ringer's solution were administered 4 hr prior to ischemia or sham operation. Treatment with a stable nitroxide radical, 4-hydroxy-2,2, 6,6-tetramethylpiperidine-L-oxyl (TPL), was used to assess free radical involvement in edema. Accumulation of tissue water was evaluated by measuring specific gravity (SG) of brain cortex and histological examination. There was a greater reduction of cortical SG in early reperfusion (15 min) and a lesser decrease in SG (60 min later) in NLA-than in D-NAME- or Ringer's-treated gerbils. The NLA effect was confirmed by histological examination of the brain tissue. TPL treatment (pre- and postischemic) ameliorated the formation of edema to the same degree as NLA. The findings indicate a biphasic NLA modulation of cytotoxic edema most likely mediated through absence or presence of NO-derived free radicals.
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PMID:The effect of nitric oxide inhibition on ischemic brain edema. 941 22

Nitric oxide (NO), identified as the mediator of endothelium-dependent relaxation of vascular smooth muscle, is known to cause a number of inflammatory conditions, especially in ischemia/reperfusion injury. This experimental study, using a rabbit epigastric island flap, was designed to investigate whether skin flap ischemia followed by reperfusion-influenced serum NO and c-GMP concentrations in the flap. In addition, we also investigated the premedicated effects of the NO synthase inhibitor and heparin on serum NO and c-GMP concentrations in skin flap ischemia/reperfusion. Serum NO concentration after 15, 30, 45, and 60 minutes of ischemia followed by reperfusion significantly increased compared with that in nonischemic control and elevated flaps. On the contrary, serum NO concentration was suppressed in L-NAME or aminoguanidine pretreated animals with ischemic group. Administration of heparin increased the serum NO concentration in elevated flaps, but suppressed it in ischemic flaps followed by reperfusion. The changes in serum c-GMP and NO concentrations were related in all of the experimental groups. These results suggest that NO may be derived from vascular endothelial cells and dilate peripheral vessels in compensation for ischemia.
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PMID:Physiological roles of endothelium-derived nitric oxide in the epigastric island flaps of rabbits. 941 20

The effect of N omega-nitro-L-arginine methyl ester (L-NAME) on ischemic neuronal damage was studied in a rat model of permanent focal cerebral ischemia in terms of ipsilateral and contralateral cortical and cerebellar tissue lipid peroxides. Forty-five male Swiss Albino rats were assigned to one of four groups; sham operated as control, subjected to right middle cerebral artery occlusion or injection of L-NAME (10 mg/kg i.p.) either 30 min before or just after right middle cerebral artery occlusion. Changes in lipid peroxides were expressed as nanomoles of malondialdehyde and conjugated diene per milligram of protein. Malondialdehyde values following 60 min of ischemia relative to contralateral cortex and conjugated diene levels in 0, 10 and 60 min of ischemia were found to be higher in ipsilateral cortex than in contralateral cortex. On the other hand, contralateral cerebellar malondialdehyde levels after 0 and 60 min of ischemia and conjugated diene levels after 0, 10 and 60 min of ischemia were higher than those in ipsilateral cerebellum. Pharmacological inhibition of nitric oxide synthase by L-NAME before or just after permanent middle cerebral artery occlusion significantly decreased the malondialdehyde and conjugated diene levels in both the cortex and the cerebellum. No significant differences were found in malondialdehyde values between rats that had been pre- and post-treated with L-NAME, but conjugated diene levels in the post-treated group seemed to be significantly lower than those in the pretreated group. On the whole, these results suggest that malondialdehyde and conjugated diene represent early biochemical markers of lipid peroxidation in ischemic tissues, reflecting the radical-mediated tissue damage.
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PMID:Inhibitory role of N omega-nitro-L-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, on brain malondialdehyde and conjugated diene levels during focal cerebral ischemia in rats. 946 54


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