Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diastolic pressure-volume curve shifts upward during demand ischemia, most likely because of changes in Ca2+ dynamics within the sarcomere. It is possible that agents that affect Na+/Ca2+ exchange, such as lidocaine, a class 1b-type Na+-channel blocker that decreases intracellular Na+, could affect the diastolic pressure-volume relationship because of indirect effects on intracellular Ca2+. Lidocaine is a drug widely used to treat arrhythmias in patients with myocardial ischemia. We studied the effects of lidocaine on diastolic dysfunction associated with demand ischemia. We compared diastolic (as represented by the shift in the diastolic pressure-volume relationship) and systolic function during demand ischemia before and after lidocaine injection. We created demand ischemia in pigs before and after administering lidocaine (5 mg/kg) in eight open-pericardium anesthetized pigs. Demand ischemia was induced by constricting the left anterior descending coronary artery and then pacing at 1.5-1.8 times the baseline heart rate for 1.5-3 min. Hemodynamics were recorded during baseline, demand ischemia, baseline after lidocaine injection, and demand ischemia after lidocaine. Lidocaine did not affect systolic function or the time constant of isovolumic relaxation, but it increased the upward shift of the diastolic pressure-volume curve during demand ischemia compared with the increase that occurred before lidocaine was administered. This result suggests that lidocaine could aggravate diastolic dysfunction in patients with ischemic heart disease.
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PMID:Effect of lidocaine on left ventricular pressure-volume curves during demand ischemia in pigs. 984 37

The effect of warm ischemia on lidocaine-metabolizing activity was examined in vivo. Total liver ischemia was produced for 1 hr in Sprague-Dawley rats by clamping the portal vein and hepatic artery at the hilum. Livers were then reperfused, and liver microsomes were prepared before and 0, 2, 6, and 24 hr, and 3, 6, and 10 days after reperfusion. Microsomal lidocaine-metabolizing activity and cytochrome P-450 content were examined. Lidocaine N-deethylase activity was decreased from 2.25 +/- 0.33 to 0.97 +/- 0.21 nmol/mg protein/min (mean +/- SD) 24 hr after reperfusion. This inhibition was prolonged, and activity gradually recovered after 10 days. The cytochrome P-450 content showed the same tendency. On the other hand, serum levels of alanine aminotransferase increased significantly 2 hr after reperfusion and returned to control levels 3 days after reperfusion. Liver blood flow recovered rapidly after unclamping and reached baseline levels within 6 hr. Our results suggest that after warm ischemia, prolonged hepatic dysfunction in drug metabolism, which cannot be detected by evaluating serum enzymes or liver blood flow, exists at the microsomal level.
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PMID:Lidocaine-metabolizing activity after warm ischemia and reperfusion of the rat liver in vivo. 1059 3

Lidocaine is a widely used local anesthetic agent. The aim of this work was to study the action of lidocaine on human red blood cells exposed to an oxidative stress in vitro. Blood was obtained from healthy volunteers. After separation from plasma, the erythrocytes were suspended in phosphate buffer. Oxidative stress was induced by incubation with a free radical generator, the 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Erythrocytes were incubated with or without lidocaine at two concentrations (36.93 and 73.85 microM) and with or without AAPH (20 mM). Electron paramagnetic resonance (EPR) spectroscopy was performed to identify the free radical species generated by AAPH using the spin trap 5-5'-dimethyl-L-pyroline-N-oxide (DMPO). Different sets of experiments were run. Potassium efflux was measured by flame photometry in each group at time 0 min and every 30 min of the experiment for 2 h. Hemolysis was studied by the Drabkin method at increasing concentrations of AAPH (20, 50, and 100 mM) and with or without lidocaine (36.93 microM). The oxygen radical absorbance capacity (ORAC) was measured by using allophycocyanin (APC) as a fluorescent indicator protein, and the antioxidant capacity of lidocaine (36.93 microM) was studied by the analysis of fluorescence of the APC. AAPH was shown to produce alkoxyl free radicals. Oxidative stress induced a marked increase in the potassium efflux and the hemolysis that was AAPH dose-dependent. Lidocaine inhibited the potassium efflux and delayed the occurrence of hemolysis. Lidocaine did not show any antioxidant properties for the free radical species generated by AAPH. In this model, lidocaine protects erythrocytes against oxidative stress. This effect is not explained by a free radical scavenging property. The results may be of great interest in clinical practice such as intravenous regional anesthesia or the prevention of ischemia-reperfusion injury.
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PMID:Lidocaine inhibits potassium efflux and hemolysis in erythrocytes during oxidative stress in vitro. 1112 Mar 81

The endovascular treatment of spinal vascular malformations places the spinal cord at risk for ischemia. When these procedures are performed using general anesthesia, the neurophysiological monitoring methods currently available provide the only means by which to assess the functional integrity of sensory and motor pathways. Neurophysiological monitoring allows a warning for the neuroradiologist of impending irreversible neurological damage so that action may be taken for the prompt restoration of adequate spinal cord perfusion. Muscle motor evoked potentials (mMEPs) better reflect spinal cord perfusion in the anterior spinal artery territory than do somatosensory evoked potentials (SEPs), although their use during spinal endovascular procedures remains anecdotal in the literature. In the study reported here we assessed: (1) the feasibility of intraoperative neurophysiological monitoring, (2) the role of provocative tests with Amytal and Xylocaine, and (3) the specific but complementary role played by SEPs and mMEPs, during endovascular embolization of spinal vascular malformations and tumors. The results suggest that: (1) neurophysiological monitoring is feasible during most endovascular procedures in the spine and spinal cord under general anesthesia, (2) provocative tests enhance the safety of the procedure, (3) mMEPs are more feasible than SEPs and more sensitive than SEPs to provocative tests. We strongly suggest the use of multimodal neurophysiological monitoring and provocative tests during the endovascular treatment of spinal and spinal cord vascular lesions.
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PMID:Neuroprotective role of neurophysiological monitoring during endovascular procedures in the spinal cord. 1146 64

Paraplegia secondary to spinal cord ischemia is a devastating complication in operations on the descending and thoracoabdominal aorta. We hypothesized that the tolerance of the spinal cord to an ischemic insult could be improved by means of regional administration of lidocaine. Thirty-one New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by the placement of clamps both below the left renal vein and above the aortic bifurcation. The animals were divided into 5 groups. Aortic occlusion time was 20 minutes in Group 1 and 30 minutes in all other groups. Groups 1 and 2 functioned as controls. Lidocaine (Group 5) or normal saline solution (Group 3) was infused into the isolated aortic segment after cross-clamping. Group 4 animals received 20% mannitol regionally, before and after reperfusion. Postoperatively, rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 20 minutes of aortic occlusion did not produce any neurologic deficit (Group 1: 0/4 injured), while 30 minutes of occlusion resulted in more consistent injury (Group 2: 6/8 injured). Animals that received normal saline (Group 3) or mannitol (Group 4) regionally showed 80% neurologic injury (4/5). Animals treated with the regional lidocaine infusion (Group 5) showed much better neurologic outcomes (7/9 normal: 78%). This superiority of Group 5 over Groups 2, 3, and 4 was significant (P <0.02). We conclude that regional administration of lidocaine reduced neurologic injury secondary to spinal cord ischemia and reperfusion after aortic occlusion in the rabbit model.
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PMID:Regional lidocaine infusion reduces postischemic spinal cord injury in rabbits. 1167 49

Off-pump coronary artery bypass grafting (OPCABG) has recently gained popularity. During OPCABG, patients remain vulnerable to ischemic-reperfusion injury due to a temporary coronary occlusion without any active cardioprotection. Some strategies such as ischemic preconditioning (IP) and an intracoronary shunt have been applied with a view to minimizing the effects of ischemia, but the effects of these strategies remain controversial. This study was carried out to investigate the protective effect of lidocaine against myocardial ischemic-reperfusion injury. Twenty-one pigs were assigned to three groups, each consisting of seven pigs. In the control group, using a left internal thoracic artery (LITA) bypass circuit, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by two hours of reperfusion. In the IP group, five min of occlusion followed by 15 min of reperfusion was performed. In the lidocaine group, 2 mg/kg of lidocaine was administered directly into the LAD just before the LAD occlusion. Infarct size expressed as a percentage of the area at risk was significantly smaller in the lidocaine group (2.7+/-4.2%) than in the control group (79.9+/-6.0%, p<0.001) or the IP group (57.0+/-25.9%, p<0.001). Lidocaine exhibited a potent myocardial protective effect in the present OPCABG model.
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PMID:Myocardial protective effect of lidocaine during experimental off-pump coronary artery bypass grafting. 1266 28

A 52-year-old man had loss of vision and black discoloration of the lids of the right eye after a retrobulbar injection of 3 mL lidocaine hydrochloride 2% (Xylocaine). Examination of the right eye revealed no light perception with extensive necrosis of the lids. Anterior segment examination revealed conjunctival pallor, corneal edema, and necrosis of the sclera. This is a previously unreported complication of retrobulbar anesthesia comprising ophthalmic artery occlusion with scleral melt, ocular ischemia, and eyelid necrosis.
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PMID:Necrosis of the eyelids and sclera after retrobulbar anesthesia. 1268 60

Peripheral nerve injury secondary to injection of therapeutic agents is well-documented. Until recently, the precise mechanism of injury has been obscure; even today, the treatment of these nerve injection injuries remains controversial. The aim of this study was to determine the involvement of ischemia-reperfusion injury in the development of peripheral nerve injection injury. Wistar rats were randomized into three groups. Sciatic nerve was used as the standardized nerve injection injury model. Two commonly used agents, lidocaine HCl 1 percent and phenol 5 percent, were tested for their comparative effects on the sciatic nerve. Lidocaine and phenol were injected into the sciatic nerves of the rats in Groups 1 and 2, respectively. Physiologic saline was used in the controls (Group 3). All the agents were injected intrafascicularly. The effects of nerve injection injury were assessed by measuring thiobarbituric acid reactive substance (TBARS) levels and obtaining walking-track analyses (WTA). Nerve injection caused significant increases in TBARS levels, which were correlated with the severity of the injury. The TBARS levels were related to the severity of injury caused by the tested agents; TBARS levels in phenol-injected nerves were significantly higher than those of lidocaine-injected nerves. Patterns of alterations in TBARS levels also paralleled the changes in print-length factor. Injection of lidocaine and phenol resulted in near-normal walking tracks at 8 and 12 weeks, respectively, while saline injection caused only transient impairment in walking tracks. These findings indicate that reactive oxygen species are involved in the pathogenesis of experimental peripheral nerve injection injury. Indices of free oxygen radical damage correlate with the progression of functional alterations after nerve injection injury.
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PMID:Free radical-induced damage in experimental peripheral nerve injection injury. 1451 34

It has been suggested that class I antiarrhythmic drugs and ischemia can widen the QT interval in the Langendorff-perfused rat heart preparation as a consequence of slowed ventricular conduction. If this were so, it would undermine the clinical relevance of the preparation and its effectiveness as an antiarrhythmic bioassay. To test this, the authors determined whether three different class I drugs could prolong QT in the preparation and whether this effect was augmented by ischemia and elevation of the potassium (K+) content of the perfusion solution. Baseline drug-free QT intervals correlated inversely with the K+ content (3 microM vs. 5 mM). QT intervals widened during the first 3-5 minutes of ischemia (P < 0.05), then returned gradually to baseline. Lidocaine (3.88 microM and 12.93 microM) had no effect on the QT interval before or during ischemia, whereas quinidine (7.90 microM but not 0.79 microM) and flecainide (1.48 microM but not 0.74 microM) caused QT widening before and during ischemia (P < 0.05). Elevating perfusion solution K+ content from 3 microM to 5 mM reduced the QT-widening effects of quinidine and flecainide (P < 0.05). Because lidocaine, a relatively selective sodium (Na+) channel blocker, failed to widen QT interval whereas quinidine and flecainide (combined Na+ and K+ channel blockers) did so, and because K+ elevation reduced rather than potentiated the drug-induced QT widening, it is unlikely that Na+ channel blockade and conduction slowing play any role in ischemia- or class I drug-induced QT widening in this model.
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PMID:Does QT widening in the Langendorff-perfused rat heart represent the effect of repolarization delay or conduction slowing? 1457 9

Lidocaine is a local anesthetic and antiarrhythmic agent. Although clinical and experimental studies have shown that an antiarrhythmic dose of lidocaine can protect the brain from ischemic damage, the underlying mechanisms are unknown. In the present study, we examined whether lidocaine inhibits neuronal apoptosis in the penumbra in a rat model of transient focal cerebral ischemia. Male Wistar rats underwent a 90-min temporary occlusion of middle cerebral artery. Lidocaine was given as an i.v. bolus (1.5 mg/kg) followed by an i.v. infusion (2 mg/kg/h) for 180 min, starting 30 min before ischemia. Rats were killed and brain samples were collected at 4 and 24 h after ischemia. Apoptotic changes were evaluated by immunohistochemistry for cytochrome c release and caspase-3 activation and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for DNA fragmentation. Cytochrome c release and caspase-3 activation were detected at 4 and 24 h after ischemia and DNA fragmentation was detected at 24 h. Double-labeling with NeuN, a neuronal marker, demonstrated that cytochrome c, caspase-3, and TUNEL were confined to neurons. Lidocaine reduced cytochrome c release and caspase-3 activation in the penumbra at 4 h and diminished DNA fragmentation in the penumbra at 24 h. Lidocaine treatment improved early electrophysiological recovery and reduced the size of the cortical infarct at 24 h, but had no significant effect on cerebral blood flow in either the penumbra or core during ischemia. These findings suggest that lidocaine attenuates apoptosis in the penumbra after transient focal cerebral ischemia. The infarct-reducing effects of lidocaine may be due, in part, to the inhibition of apoptotic cell death in the penumbra.
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PMID:Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. 1509 83


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