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 cellular and subcellular responses related to the survival or destruction and subsequent regeneration of muscle fibers within the freely grafted extensor digitorum longus muscle of the rat were examined by light and electron microscopy. A small number of fibers at the periphery of the grafts survived the initial ischemia but underwent denervation changes and accumulated lipid deposits. The majority of fibers in the grafts, however, became ischemic and underwent an intrinsic degeneration within 4 hours. Cell-mediated destruction of the degenerating fibers occurred as the grafts became revascularized. The basal laminae and some of the satellite cells were the only elements of the original fibers that persisted. Regeneration began at the periphery of the graft within three days after grafting and reached the center about three days later. After phagocytosis of the original fibers, presumptive myoblasts within the grafts differentiated into myoblasts and myotubes. The formation of myotubes followed a biphasic pattern of development comparable to that of normal fetal muscle. Although most of the myotubes were formed within the basal lamina remaining from the original fiber, there was also evidence for regeneration outside the basal lamina. Myotubes matured into muscle fibers which were essentially normal in apperance when examined up to 180 days after grafting. Some fibers, however, were atrophic, presumably due to a failure to become innervated, and some fibers were joined by myo-myous junctions. Pre-denervated grafts and Marcaine-treated grafts were also examined. There were more surviving fibers in pre-denervated grafts, and cell-mediated destruction of degenerating fibers proceeded more rapidly than in normal grafts. No surviving fibers were found in Marcaine-treated grafts. The changes in these grafts were otherwise similar to normal grafts. A schematic model of the spatial and temporal sequence of degeneration and regeneration within a free muscle graft is presented.
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PMID:Cellular responses to free grafting of the extensor digitorum longus muscle of the rat. 43 49

Bupivacaine was infused intravenously into healthy volunteers to assess its analgesic effect. In a double-blind manner, 11 male subjects received, on separate days, saline solution or 0.1% bupivacaine, at three rates of infusion. Experimental pain was produced by the tourniquet-induced ischemia test. Times to onset of ischemic pain (threshold) and unbearable pain (tolerance) were compared. Venous blood samples were analyzed for levels of bupivacaine and its metabolite, pipecolyxylidine, by gas chromatography. No significant difference in pain threshold or tolerance was found following control and bupivacaine infusion. In the 72-hour postinfusion urine collection period, only 0.7% of the infused dose was recovered as unmetabolized bupivacaine, with 4.8% recovered as pipecolyxylidine. Systemic blood levels of bupivacaine achieved during regional anesthesia did not produce analgesia in this model.
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PMID:Evaluation of the analgesic effect and urinary excretion of systemic bupivacaine in man. 719 9

Myocardial ischemia sensitizes the cardiotoxic effects of bupivacaine, especially the propensity to ventricular fibrillation. To investigate this sensitization and to elucidate its mechanism, the influence of bupivacaine alone, or associated with ischemia, was studied on electrical fibrillation threshold in anesthetized, open chest pigs. Determination of fibrillation threshold was performed with impulses of 100 ms duration at the rate of 180 bpm, in the absence of ischemia and at the end of increasing periods of ischemia (30, 60, 120, 180 s) obtained by complete occlusion of the left anterior descending coronary artery close to its origin. The effect of bupivacaine (1.00 mg/kg initial dose plus 0.04 mg.kg-1.min-1 over 25 min) was compared to the control in the same animals. This effect corresponded to 1.4-1.8 micrograms/mL plasma concentrations likely to be observed in humans after regional anesthesia. Bupivacaine significantly increased the fibrillation threshold before coronary occlusion from approximately 7.0 to 9.5 mA. In contrast, during ischemia the fibrillation threshold was shifted to the left and down, with a hastening of spontaneous fibrillation. Recording of monophasic action potentials in the ischemic area revealed that conduction time was prolonged by more than 100% under the combined influence of ischemia and bupivacaine, whereas the major enhancement of excitability due to ischemia was not attenuated by bupivacine. Therefore, bupivacaine should be used with caution in the condition of ischemia, especially if heart rate is rapid. In the present experiments, tachycardia is another factor in the enhancement of bupivacaine effects on conduction.
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PMID:Bupivacaine hastens the ischemia-induced decrease of the electrical ventricular fibrillation threshold. 789 14

Neuroprotective actions of local anesthetics, bupivacaine and tetracaine, against the irreversible membrane dysfunction induced by in vitro ischemia were investigated. Intracellular recordings were made from hippocampal CA1 neurons in rat brain slice preparations. Oxygen and glucose deprivation (in vitro ischemia) produced a rapid depolarization after approximately 5 min of exposure. When oxygen and glucose were reintroduced, the membrane depolarized further and reached at 0 mV: the membrane showed no functional recovery (irreversible membrane dysfunction). Pretreatment with tetracaine or bupivacaine significantly prolonged the latency of rapid depolarization. Bupivacaine, but not tetracaine, restored the membrane potential after the reintroduction of oxygen and glucose. Tetracaine and bupivacaine depressed both field postsynaptic potentials and presynaptic volleys. The drugs also reduced the dV/dt of Ca(2+)-dependent spikes and the rapid rise of [Ca(2+)](i) induced by in vitro ischemia. Compared with tetracaine, bupivacaine markedly suppressed the resting K(+) conductance and the ATP-sensitive and Ca(2+)-dependent K(+) conductances. Moreover, in the presence of tetraethylammonium (TEA), a majority of CA1 neurons impaled with Cs acetate-filled electrodes showed complete or partial recovery of the membrane potential after reintroducing oxygen and glucose. These results suggest that the neuroprotective action of bupivacaine is mainly due to the suppression of the K(+) conductances.
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PMID:Bupivacaine, but not tetracaine, protects against the in vitro ischemic insult of rat hippocampal CA1 neurons. 1190 Aug 32

Historically, the use of regional anesthetic techniques in patients with preexisting central nervous system (CNS) disorders has been considered relatively contraindicated. The fear of worsening neurologic outcome secondary to mechanical trauma, local anesthetic toxicity, or neural ischemia is commonly reported. We examined the frequency of new or progressive neurologic complications in patients with preexisting CNS disorders who subsequently underwent neuraxial blockade. The medical records of all patients at the Mayo Clinic from the period 1988 to 2000 with a history of a CNS disorder who subsequently received neuraxial anesthesia or analgesia were retrospectively reviewed. One-hundred-thirty-nine (n = 139) patients were identified for study inclusion. Mean patient age was 60 +/- 17 yr. Gender distribution was 86 (62%) males and 53 (38%) females. An established CNS disorder diagnosis was present a mean of 23 +/- 23 yr at the time of surgical anesthesia, with 74 (53%) patients reporting active neurologic symptoms. Spinal anesthesia was performed in 75 (54%) patients, epidural anesthesia or analgesia in 58 (42%) patients, continuous spinal anesthesia in 4 (3%) patients, and a combined spinal-epidural technique in 2 (1%) patients. Bupivacaine was the local anesthetic most commonly used in all techniques. Epinephrine was added to the injectate in 72 (52%) patients. There were 15 (11%) technical complications, with the unintentional elicitation of a paresthesia and traumatic needle placement occurring most frequently. A satisfactory block was reported in 136 (98%) patients. No new or worsening postoperative neurologic deficits occurred when compared to preoperative findings (0.0%; 95% confidence interval, 0.0%-0.3%). We conclude that the risks commonly associated with neuraxial anesthesia and analgesia in patients with preexisting CNS disorders may not be as frequent as once thought and that neuraxial blockade should not be considered an absolute contraindication within this patient population.
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PMID:Neuraxial anesthesia and analgesia in patients with preexisting central nervous system disorders. 1679 Jun 57

The cardiotoxic effects of local anesthetics increase in cardiac ischemia which is characterized by the tissue pH lowering to 6.5 or less. Apart from the cardiac channel blockade, the membrane interaction has been referred to as another mode of their cardiotoxic action. By using biomimetic membranes, we verified the hypothesis that bupivacaine and lidocaine may increasingly interact with cardiac mitochondrial membranes under ischemia-like acidic conditions. Biomimetic membranes were prepared with different phospholipids and cholesterol to be unilamellar vesicles suspended in buffers of pH 7.4, 6.9, 6.4 or 5.9. Bupivacaine and lidocaine were reacted with the membrane preparations at cardiotoxically relevant concentrations and their membrane interactivities were determined by measuring fluorescence polarization. Both drugs interacted with 100 mol% 1,2-dipalmitoylphosphatidylcholine, peripheral nerve cell-mimetic and cardiomyocyte-mimetic membranes to increase membrane fluidity, although lowering the reaction pH from 7.4 to 5.9 decreased their membrane-fluidizing effects. In cardiomyocyte mitochondria-mimetic membranes containing 20 mol% cardiolipin, however, bupivacaine and lidocaine reversely increased their membrane interactivities at pH 5.9-6.4 compared with pH 7.4. Such increases were greater in anionic phospholipid membranes which consisted of substantial amounts of cardiolipin and phosphatidylserine. Positively charged bupivacaine and lidocaine would form ion-pairs with the negatively charged head-groups of anionic phospholipids under acidic conditions, thereby increasing the induced membrane fluidization. The mitochondrial membrane interactions depending on pH lowering may be, at least in part, responsible for local anesthetic cardiotoxicity enhanced in acidosis associated with cardiac ischemia.
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PMID:Cardiotoxic local anesthetics increasingly interact with biomimetic membranes under ischemia-like acidic conditions. 2268 45