UMLS:C0022116 - FACTA Search

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

The relationships among intracellular Na concentration ([Na+]i), intracellular pH, [ATP], and contracture during global ischemia were studied in isolated, perfused rat hearts. Intracellular Na was monitored by 23Na nuclear magnetic resonance (NMR) spectroscopy using thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonate) (TmDOTP5-) as the paramagnetic shift reagent. High-energy phosphates and pH were monitored under the same conditions using 31P-NMR spectroscopy. Lidocaine (130 microM), a class IB fast Na channel blocker known to protect ischemic myocardium, prolonged the time to contracture in both unpaced and paced hearts (240 beats/min). After 10 min of global ischemia in paced hearts, [Na+]i was lower in the lidocaine-treated group compared with untreated hearts. The addition of lidocaine also significantly attenuated the depletion of ATP as well as development of intracellular acidosis. At the time of contracture, however, there was no difference in [Na+]i or pH between the two groups. Interestingly, the effect of lidocaine on Na+i accumulation during ischemia was manifested during the first 5-10 min of ischemia, while its effect on pH occurred after 9 min. This finding suggests that a mechanism other than the Na-H exchanger may play a role in the accumulation of Na+i early in the course of ischemia.
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PMID:Effect of lidocaine on contracture, intracellular sodium, and pH in ischemic rat hearts. 832 18

A case can be made for the participation of polymorphonuclears (PMN) in the initiation and propagation of venous thrombosis. In animal models leukocytes adhered to areas of veins that serve as sites for initiation of thrombi in patients. In addition, PMN are found in white layers of thrombin where they may interact with platelets to attract more of each. This would add bulk and promote coagulation so that red layers are formed. Lidocaine and one of its derivatives inhibited leukocyte adhesion to veins in dogs and lidocaine reduced the incidence of deep venous thrombosis (DVT) in patients after hip replacement, suggesting but not proving that inhibition of PMN adhesion might have contributed. A new approach for preventing PMN contribution to DVT is suggested by recent studies which identified three families of adhesive receptors (integrins, intercellular adhesion molecules and selectins) on endothelium, leukocytes and platelets. Monoclonal antibodies against beta 2-integrins on leukocytes reduced leukocyte adhesion, emigration and PMN-dependent tissue injury in infection, inflammation and ischemia-reperfusion injury in animals. Selectins bind to specific carbohydrate ligands containing sialylated Lewis X, suggesting that relatively small analogues might inhibit PMN adhesion. Both platelets and PMN adhere to polymerizing fibrin through undefined mechanisms. Inhibition of this process might inhibit the buildup of white layers of thrombi.
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PMID:Neutrophils and deep venous thrombosis. 849 64

1. Lidocaine has been extensively investigated as a potential neuroprotective drug against ischemia-induced neurodegeneration without reaching any satisfactory conclusion. 2. The present work evaluates the effect of lidocaine -17 microM- on the hypoxia-induced release of tritiated D-aspartate from rat striatal slices in superfusion. 3. Hypoxia resulted in a significant increase in the amount of D-aspartate released from striatal slices preloaded with the tritiated excitatory amino acid analog. 4. The addition of lidocaine to the superfusion solution resulted in a drastic reduction in the amount of D-aspartate release evoked by hypoxia, rendering it close to normal values.
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PMID:Lidocaine reduces the hypoxia-induced release of an excitatory amino acid analog from rat striatal slices in superfusion. 853 30

The effect of lidocaine on brain lipid peroxidation, as reflected by jugular vein malondialdehyde concentrations, and of polymorphonuclear leukocyte activation in peripheral venous blood samples following transient global cerebral ischemia, were studied. In normothermic dogs subjected to a 10 min elevation of cerebrospinal fluid pressure and a subsequent 60 min reperfusion, the malondialdehyde concentration during the first 3 min of reperfusion increased significantly (p < 0.05) in the jugular vein. Lidocaine (10 mg/kg, i.v.), administered 10 min before ischemia, not only prevented the elevation of the malondialdehyde concentrations during ischemia, but also provoked a significant transient decrease 10 min after the start of reperfusion. A 10 min ischemia and a 60 min reperfusion caused no significant changes in the polymorphonuclear leukocyte radical production, neither following ischemia nor after addition of lidocaine. These results suggest that lidocaine exerts a scavenging action on free radical processes but that it has no direct effect on the polymorphonuclear leukocyte activation in the early phase of reperfusion following ischemia.
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PMID:Effects of lidocaine on cerebral lipid peroxidation and neutrophil activation following complete compression ischemia. 893 28

To further elucidate the role of the Na+ channel in the ischemic accumulation of intracellular Na+ (Na+i), 200 microM lidocaine was included in the perfusate for 5 min prior to 30 min of ischemia in isolated rat hearts paced at 5 Hz. Na+i and high-energy phosphates were measured, using 23Na-NMR with the shift reagent TmDOTP5- and 31P-NMR, respectively. Control values of phosphocreatine (PCr) and ATP were 14.1 +/- 1.5 mM and 7.7 +/- 0.7 mM, respectively (all data: mean +/- S.D.). During lidocaine perfusion the rate pressure product (RPP) decreased by approximately 50% and Na+i declined from 11.5 +/- 1.5 mM to 9.8 +/- 2.1 mM. During ischemia Na+i in lidocaine hearts rose to 17.9 +/- 2.5 mM v 28.4 +/- 1.7 mM in control hearts (P<0.05). In hearts in which extracellular Ca2+ was lowered prior to ischemia to reach a similar RPP decrease as in lidocaine hearts, Na+i rose to 26.3 +/- 3.0 mM during ischemia (P<0.05 v lidocaine, N.S. v control). Lidocaine did not affect the decline of PCr during ischemia (to 0.5 +/- 0.5 v 0.7 +/- 0.8 mM in lidocaine and control hearts, respectively) but significantly attenuated the initial decrease of pH(i) (6.06 +/- 0.07 v 5.76 +/- 0.04 after 20 min, P<0.01), attenuated the initial decline of ATP (3.3 +/- 1.3 v 1.5 +/- 0.9 mM after 20 min, P<0.05) and delayed the time to onset of contracture. However, at the end of ischemia pH(i) (5.73 +/- 0.04 and 5.78 +/- 0.05) and ATP (1.2 +/- 0.6 and 0.9 +/- 0.8 mM) were not significantly different. At 30 min of reperfusion Na+i was 14.9 +/- 2.6 mM in lidocaine hearts v 20.0 +/- 3.1 mM in controls. PCr (9.6 +/- 2.3 v 4.9 +/- 0.9 mM, P<0.05) and ATP (3.0 +/- 0.6 v 1.8 +/- 0.6 mM) recovered better in lidocaine hearts. Furthermore, developed and end-diastolic pressure recovered better in lidocaine hearts. In conclusion, Na+ influx during ischemia occurs, at least partly, via the Na+ channels, and blocking this channel during ischemia improves post-ischemic functional and metabolic recovery.
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PMID:The role of the Na+ channel in the accumulation of intracellular Na+ during myocardial ischemia: consequences for post-ischemic recovery. 904 24

Myocardial reperfusion is associated with increased influx of activated neutrophils and intracellular accumulation of sodium in the ischemic zone. Lidocaine is a sodium channel blocker that also inhibits several neutrophil functions. We investigated the effect of lidocaine on infarct size in rabbits undergoing 30 minutes of ischemia and 48 hours of reperfusion. Animals randomly received lidocaine (10 mg/kg, n = 11) or saline (n = 11) during occlusion. The area of necrosis (AN) was measured histologically and expressed as a percentage of the area at risk (AR). Myocardial oxygen consumption and the perfusion bed at risk were similar in the two groups. Lidocaine reduced infarct size compared with control (AN/AR = 30% +/- 4% vs 61% +/- 5%, respectively; p = 0.0001). This reduction was associated with a significant decrease in neutrophil infiltration and in the degree of hemorrhage in the reperfused myocardium. Lidocaine also significantly inhibited superoxide anion production by rabbit and human neutrophils in whole blood. Therefore, lidocaine treatment results in a significant reduction in infarct size in the rabbit model, partly through reduction of neutrophil-mediated injury to viable cells, suggesting that lidocaine may be useful to enhance myocardial salvage in patients undergoing pharmacologic or mechanical reperfusion.
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PMID:Reduction of myocardial infarct size in rabbits and inhibition of activation of rabbit and human neutrophils by lidocaine. 906 Aug

Although the monoethylglycinexylidide (MEGX) test defined as a single determination of MEGX plasma concentration after lidocaine injection has been proposed as a liver function test, some discrepancies appeared in assessing the quality of liver donor for transplantation as well as the severity of liver disease. The present study used a severe ischemia-reperfusion liver injury (IRI) in rat to evaluate the various factors able to influence the level of MEGX. The metabolism of lidocaine was studied on microsomes isolated from intact rats and from rats submitted to this liver injury. A significant reduction of the various pathways transforming lidocaine but also MEGX was demonstrated. Lidocaine inhibited the MEGX transformation both in intact and injured liver microsomes. In vivo, plasma MEGX concentrations, determined by high-performance liquid chromatography (HPLC), were lower in IRI than in controls up to 80 minutes after lidocaine injection but not later. By contrast, using the usual commercial fluorescence polarization immunoassay (FPIA), MEGX concentrations were paradoxically higher in IRI than in controls. Moreover, MEGX values obtained using FPIA were threefold higher in controls and ninefold higher in IRI than with HPLC. It was shown that these differences were related to the detection by FPIA of free and mainly of conjugated hydroxy-MEGX that accumulated in plasma from rats submitted to an IRI. These data emphasize the complexity of factors influencing the appearance and disappearance of MEGX because of delayed MEGX formation with liver injury but also to inhibition of its further metabolization. The choice of the sampling time for MEGX determination is critical and has to be optimized in every type of liver injury. Moreover, a specific technique, such as HPLC, will avoid cross-reactivity with other metabolites, which may be particularly abundant when the biliary excretion is impaired.
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PMID:The monoethylglycinexylidide test does not correctly evaluate lidocaine metabolism after ischemic liver injury in the rat. 979 37

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.
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PMID:Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery. 938 59

The aims of this study were to establish a working rabbit heart model of regional myocardial ischaemia in which electrophysiologic parameters and arrhythmogenesis could be correlated and to explore the mechanisms underlying the antiarrhythmic activity of lignocaine. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated hearts paced at 3.3 Hz. The hearts were treated before and throughout 30 min of ischaemia and 15 min of reperfusion with a vehicle or 20 microM lignocaine. In both groups, ischaemia produced a similar shortening in MAPD90. Lignocaine decreased ERP shortening during ischaemia from -56+/-4 to -32+/-6 ms. An ischaemia-induced increase in conduction delay was greater in the lignocaine than the control group (49+/-7 vs. 11+/-2 ms). Ischaemia-induced dispersion of repolarisation was reduced by lignocaine from 66+/-4 to 32+/-7 ms, and dispersion of refractoriness was decreased from 57+/-6 to 16+/-3 ms. Lignocaine decreased inducibility of ventricular fibrillation (VF) during ischaemia from 86 to 25%. We conclude that, in this model, the antiarrhythmic activity of lignocaine during regional ischaemia is associated with an increase in ischaemia-induced conduction delay and reduced dispersion of repolarisation and refractoriness.
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PMID:Effects of lignocaine on dispersion of repolarisation and refractoriness in a working rabbit heart model of regional myocardial ischaemia. 947 67

Flap ischemia is often encountered during pedicled and free tissue transfer. In this study, the vascular effects of varying doses of lidocaine, papaverine, and a combination of the two agents were evaluated and compared in an in vitro and in vivo model in the rabbit carotid artery. In the in vitro study, 14 rings from the rabbit carotid artery were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7-4.2 grams. Their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 microM), and a dose response curve was established by adding cumulatively either lidocaine (to 7 arterial rings) or papaverine (to 7 arterial rings) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 30 animals using 9-0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride and served as the control. The other side was treated blindly, during and after the anastomoses, with a topical application of 1 ml of either lidocaine 2% (n = 5), lidocaine 20% (n = 5), papaverine (30 mg/ml, n = 5), lidocaine 2% combined with papaverine (30 mg/ml, n = 5), or lidocaine 20% combined with papaverine (30 mg/ml, n = 5). For 30-60 minutes after the procedure, blood flow changes in the vessels were continuously monitored with a transonic doppler applied to both carotid arteries. The 20% lidocaine group was flushed with saline at the end of the first hour and monitored for an additional 60 minutes. Papaverine elicited a concentration-dependent relaxation of norepinephrine precontracted carotid artery rings in vitro. Lidocaine elicited a biphasic response, with low concentrations (10(-6)-10(-4) M) increasing the norepinephrine-induced contraction and high concentrations (10(-4)-10(-2) M) relieving this contraction. Microsurgical anastomosis produced a significant decrease of blood flow through the rabbit carotid artery as measured by the transonic doppler. Drug application did not alter the systemic blood pressure of the animals. Topical application of lidocaine 2% did not significantly change the blood flow after microvascular anastomosis. Topical application of lidocaine 20%, papaverine (30 mg/ml), or lidocaine (2% or 20%) combined with papaverine significantly increased the blood flow in the rabbit carotid artery. In the lidocaine 20% group, the blood flow remained significantly increased after the drug was flushed with heparinized saline solution. These results demonstrate that topical lidocaine 20%, papaverine, and lidocaine 2% or 20% combined with papaverine significantly increase blood flow in the rabbit carotid artery after microvascular anastomosis. The data confirm the use of papaverine and lidocaine 20%, alone or in combination, as spasmolytics during clinical microsurgery. This suggests that lidocaine 2% alone is not the ideal drug to relieve vascular constriction, and further studies on the clinical use of low concentrations of topical lidocaine in microsurgery is warranted.
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PMID:Drug-induced vasodilation: in vitro and in vivo study on the effects of lidocaine and papaverine on rabbit carotid artery. 967 23

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