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

The purpose of this study was to examine the use of hypothermia to protect skeletal muscle from the effects of 4 hr of tourniquet ischemia. Muscle recovery was investigated at 6 weeks. Four hours of tourniquet ischemia was induced in two groups (n = 8 per group) of male, Wistar rats (344 +/- 15 g). In the ischemia-only group (IO), the ischemic leg was exposed to room temperature. In the ischemic-hypothermic group (IH), the ischemic leg was cooled to 5-8 degrees C throughout the ischemic period. The contralateral leg served as control. After 6 weeks, the isometric contractile function of the gastrocnemii of both the ischemic and nonischemic legs was determined. Following the functional assessment, the soleus and plantaris muscles were removed and weighed, and biopsies were taken for muscle fiber composition, mean fiber area, and myosin heavy chains (MHC) analysis. Differences between groups (P < 0.05) were determined using ANOVA. Muscle wet weight, tetanic forces, fiber area, fiber type, and MHC composition of IH group were the same as the control group. Yet, twitch tension and relaxation time were lower and longer in the IH group than control group. The tetanic force at 100 Hz of the IH group (12.62 +/- 0.73 N/g) was significantly greater than that of the IO group (2.12 +/- 0.84 N/g). The type 1 muscle fiber areas of plantaris in the IH (1.84 +/- 0.04 x 1000 microns 2) were significantly greater than those of the IO group (1.56 +/- 0.42 x 1000 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skeletal muscle form and function after 4 hr ischemia-hypothermia. 793 25

It is hypothesized that because of its potential to increase coronary flow and simultaneously decrease myocardial performance and O2 consumption, midazolam would minimize regional metabolic impairment during myocardial ischemia. Therefore, the hemodynamic and regional metabolic effects of systemic midazolam administration were compared during moderate and severe constrictions of the left anterior descending artery (LADa) to nontreated but ischemic animals in a canine model of acute coronary occlusion. In 16 anesthetized, ventilated, surgically prepared, and catheterized dogs, resting flow in the LADa was decreased by 50% and 75% for 15 minutes with 1 hour of normal flow in between. By arbitrary assignment, 7 dogs received midazolam (0.3 mg/kg and then 0.05 mg/kg/min) before thoracotomy. In all dogs, heart rate, electrocardiogram, LADa flow, left ventricular (LV) first time-derivative, and aortic, pulmonary artery, LADa, and LV pressures were measured continuously. Before and during constrictions, cardiac output by thermodilution and regional myocardial blood flow by microspheres were measured and blood was sampled for analysis. Data (mean +/- SEM) were compared within and between groups using ANOVA. Before placement of the LADa ligature, midazolam decreased heart rate and mean aortic pressure. Before ischemia, heart rate and LADa pressure were lower with midazolam than without it, but baseline metabolic variables were similar between the two groups (except for O2 consumption in the ischemic zone, which was lower with midazolam than without it). During 75% constriction with midazolam, LV end-diastolic pressure, coronary resistance, and ischemic zone O2 consumption were lower than without midazolam. Ischemic zone O2 delivery/consumption ratio was higher.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Midazolam's effects on myocardial load and coronary perfusion: reduced regional O2 consumption and lactate production during ischemia in dogs. 806 Dec 64

Transforming growth factor-beta 1 (TGF-beta 1) has been shown to be an injury-related peptide growth factor within the mammalian central nervous system. We tested whether TGF-beta 1 has the capacity to protect rat neocortical neurons against excitotoxic damage in vitro and mouse neocortex against ischemic injury in vivo. After 14 days in vitro, cultured neurons from rat cerebral cortex were exposed to 1 mM L-glutamate in serum-free culture medium. The cultures received TGF-beta 1 immediately after the addition of glutamate. Eighteen hours later, the cell viability of the cultures was determined using trypan blue exclusion. TGF-beta 1 (1-10 ng/ml) significantly reduced the excitotoxic neuronal damage in a concentration-dependent manner. In vivo, male NMRI mice were subjected to a permanent occlusion of the left middle cerebral artery by microbipolar electrocoagulation. After 48 h, the animals received a transcardiac injection of carbon black. The area of ischemia (devoid of carbon) was restricted to the neocortex and its size was determined planimetrically by means of an image-analyzing system. The treatment with TGF-beta 1 (1 microgram/kg i.c.v.) at 6, 4, or 2 h prior to vessel occlusion reduced the area of ischemia by 5.3, 10.0, and 9.6%, respectively. The effect of the treatment with TGF-beta 1 was statistically significant (p < 0.05 by two-way ANOVA). The present in vitro and in vivo data suggest that TGF-beta 1 has the capacity to diminish the deleterious consequences of an excitotoxic or ischemic insult.
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PMID:Transforming growth factor-beta 1 prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse neocortex from ischemic injury in vivo. 809 19

This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Sixteen isolated rabbit hearts were subjected to 120 minutes of mildly hypothermic (34 degrees C) cardioplegic arrest with multi-dose, modified St. Thomas' cardioplegia. Following ischemia, hearts were reperfused with either a physiologic salt solution (PSS) as controls, (CON, N = 10), or PSS containing DCA (DCA, N = 6) at a concentration of 1 mmol/L. Functional and metabolic indices were determined at baseline and at 15, 30, and 45 minutes of reperfusion. Results were analyzed using analysis of variance (ANOVA, Sheffe F test) and significance was defined as P < 0.05. Functional recovery was significantly better in hearts reperfused with DCA. Developed pressure (DP) recovered to 62 +/- 4% of baseline in DCA hearts, compared to 37 +/- 8% in CON hearts. Recovery of dP/dt was also improved in DCA versus CON hearts (67 +/- 5 v 43 +/- 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO2) was increased in the DCA versus CON hearts (71 +/- 10% of baseline, v 51 +/- 19%). Diastolic compliance during reperfusion was improved in those hearts receiving DCA, as was myocardial mechanical use efficiency (DP/MVO2). Correction of myocardial tissue pH to baseline values was similar in both groups, indicating that the beneficial effect on functional recovery seen with DCA was not solely related to amelioration of acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dichloroacetate enhances myocardial functional and metabolic recovery following global ischemia. 820 12

This study determined the variation among individuals in ATP use during contraction and ATP synthesis after stimulation in a human limb muscle. Muscle energetics were evaluated using a metabolic stress test that separates ATP utilization from synthesis by 31P NMR spectroscopy. Epicutaneous supramaximal twitch stimulation (1 Hz) of the median and ulnar nerves was applied in combination with ischemia of the finger and wrist flexors in eight normal subjects. The linear creatine phosphate (PCr) breakdown during ischemic stimulation defined ATP use (delta PCr per twitch or approximately P/twitch) and was highly reproducible as shown by the relative standard deviation [(standard deviation/mean) x 100] of 11% in three repeated measures. The time constant of the monoexponential PCr change during aerobic recovery represented ATP synthesis rate and also showed a low relative standard deviation (9%). Individuals were found to differ significantly in both mean approximately P/twitch (PCr breakdown rates, 0.29-0.45% PCr per sec or % PCr per twitch; ANOVA, p < 0.001) and in mean recovery time constants (41-74 sec; ANOVA, P < 0.001). This range of approximately P/twitch corresponded with the range of fiber types reported for a flexor muscle. In addition, approximately P/twitch was negatively correlated with a metabolite marker of slow-twitch fiber composition (Pi/ATP). The nearly 2-fold range of recovery time constants agreed with the range of mitochondrial volume densities found in human muscle biopsies. These results indicate that both components involved in the muscle energy balance--oxidative capacity and contractile costs--vary among individuals in human muscle and can be measured noninvasively by 31 P NMR.
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PMID:Individual variation in contractile cost and recovery in a human skeletal muscle. 834 62

Recent findings indicate that ischemia/reperfusion (IR) is associated with phospholipase C (PLC)-induced inositol 1,4,5-triphosphate production, as well as abnormal sarcoplasmic reticulum (SR) Ca2+ release. Therefore, we hypothesized that increased SR Ca2+ release may contribute to Ca2+ overload and myocardial stunning. Neomycin (NEO) was used to inhibit PLC, and sodium dantrolene (DAN) was used to inhibit myocardial SR Ca2+ release. The purposes of this study were (1) to determine if PLC inhibition would reduce IR-induced ventricular dysfunction, (2) to examine ventricular function during inhibition of SR Ca2+ release prior to ischemia, and (3) to examine the influence of SR Ca2+ release inhibition on post-IR ventricular function. Left ventricular developed pressure (DP) and +/- dP/dt of isolated crystalloid perfused rat heart (Langendorff apparatus) paced at 350 bpm were compared before and after global IR (38 degrees C, 20 min I, 40 min R) to assess functional recovery. PLC was inhibited with NEO (10 microM x 5 min prior to ischemia), and SR Ca2+ release was retarded with DAN (12.5 microM) in 0.05% DMSO (vehicle) infused for 3 min via the aortic cannula 13 min prior to ischemia. No effect on DP was observed during NEO or DAN infusion. NEO and DAN pretreatment each improved recovery of DP (% recovery +/- SEM) following IR: control, 46.5 +/- 5.1%; NEO + IR, 71.0 +/- 6.3%,* vehicle + IR, 44.4 +/- 2.9%; DAN + IR, 71.0 +/- 4.7%, *, # (*P < 0.05 vs control IR, #P < 0.05 vs vehicle + IR, ANOVA, Scheffe F test, n = 5 all groups). We conclude that SR Ca2+ release during IR contributes to myocardial stunning.
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PMID:Inhibition of sarcoplasmic reticulum calcium release reduces myocardial stunning. 836 Nov 66

Bowel mucosal ischemia may be related to the development of systemic sepsis. Traditional indices of oxygen metabolism are flow-weighted averages which do not reflect tissue-specific oxygen concentration. We undertook this study to examine the relationship between systemic oxygen delivery (DO2) and tissue oxygen tension (TPO2) in hypovolemic shock. A modified Wiggers model was used to produce hypotension in five swine. TPO2 was measured continuously with fluorescence-quenching 1-mm probes placed in the submucosa of the terminal ileum and subcutaneously in an axillary fold. Shock was maintained for 1 hr, followed by resuscitation. Cardiac output, systemic and pulmonary arterial pressures, and arterial and mixed venous blood gases were measured every 15 min. Data were analyzed by nonparametric ANOVA and rank coefficients, with logarithmic curve fitting and linear regression. DO2 decreased with phlebotomy (P < 0.003) as did skin TPO2 (P < 0.001) and bowel TPO2 (P < 0.0004). Skin and bowel TPO2 varied with DO2 and each other (P < 0.05). TPO2 remained low throughout the shock period and returned to or exceeded baseline levels with resuscitation (P < 0.05). The following were concluded: (1) Hypovolemic shock produces a significant and rapid decrease in subcutaneous and bowel TPO2 with concomitant change in DO2. (2) The degree of bowel ischemia, clinically inaccessible for quantitation, is paralleled by subcutaneous TPO2. (3) TPO2 provides information about oxygen availability in shock and resuscitation not available from traditional parameters of oxygen transport.
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PMID:Tissue oxygenation in hypovolemic shock. 841 20

Intestinal ischemia is considered a major factor in the development of necrotizing enterocolitis (NEC). Despite this, the majority of affected infants lack documentation of clinical events associated with obvious gut hypoperfusion. Recent evidence in adults suggests that endotoxin may impair flow in the microcirculation through alterations in erythrocyte deformability. As the gut serves as a semipermeable reservoir of endotoxin in the stressed neonate, such localized activity may result in intestinal ischemia at the microcirculatory level through alterations in the red cell membrane. This study evaluates the role of endotoxin on neonatal erythrocyte membrane viscosity. Paired anticoagulated whole blood specimens were obtained from the umbilical cord of 10 neonates at delivery. Samples were incubated with either 2 micrograms/mL of E coli endotoxin (LPS) or an equal volume of saline (control). Following incubation, erythrocytes were isolated, washed, and incorporated with the fluorescent membrane probe TMA-DPH. Membrane viscosity was assessed by spectroscopic analysis of the fluorescent emissions induced by excitation of the probe at 365 nm. Results were calculated as anisotropy and analyzed for differences by ANOVA. Endotoxin resulted in a significant increase in red cell membrane viscosity as compared to control (LPS 291.2 +/- 5.1 v Control 271.7 +/- 3.3, P < .01). As the effects of endotoxin are known to be primarily the result of white blood cell (WBC) activation, this study was repeated in an additional 10 neonates in whom WBCs were removed prior to endotoxin/saline incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of endotoxin on the neonatal erythrocyte. 846 42

This report describes the results of 96 infrainguinal endovascular revascularization procedures performed in 86 patients with limb-threatening ischemia over a 3-year period. There were 41 women and 45 men (mean age 72.9 +/- 11.9 years) including 47 patients (51.1%) with diabetes and 13 (15.1%) with renal insufficiency. All patients had severe ischemia characterized by rest pain (18.8%), ulceration (12.5%), or gangrene (68.8%). Twelve procedures were carried out in association with conventional surgical reconstruction and in eight patients with mixed ulcers a venous procedure was performed during the same session. A total of 143 arterial lesions were treated including 61 occlusions (mean length 5.9 +/- 3.5 cm) and 82 stenoses (mean length 4.6 +/- 3 cm). The following techniques were used: transluminal angioplasty in 99 cases, laser in five cases, Rotablator in 24 cases, and aspiration thrombectomy in 15 cases. Nine patients (10.5%) died in the hospital. Initial failure was observed in 32 patients, of whom 18 underwent subsequent surgical revascularization and 14 required amputation of the extremity within 2 months. Analysis of variance was used to assess the following 12 risk factors for initial failure of endovascular revascularization: sex, age, diabetes, renal insufficiency, associated surgery, treatment of multiple lesions, artery treated, type of lesion, length of lesion, quality of runoff, use of an atherotome, and stent placement. Results showed a significant correlation between initial failure and both quality of runoff (12.9% in patients with two or more patent leg arteries vs. 36.5% in patients with one or fewer patent leg arteries; p < 0.05) and type of lesion (14.5% for stenosis vs. 45.9% for occlusion). Mean follow-up was 9.98 +/- 9.9 months and 4.7% of patients were lost. Restenosis was observed during follow-up of 16 of the 74 initially successful procedures. ANOVA was used to assess the same 12 risk factors for restenosis. Results showed a significant correlation between restenosis and both sex (10.8% in women vs. 32.4% in men; p < 0.05) and age (8% for patients > 80 years of age vs. 28.6% for patients < 80 years; p < 0.05). Primary patency, secondary patency and limb salvage rates calculated according to the actuarial method were 65%, 75%, and 84%, respectively, at 6 months and 47%, 67%, and 81%, respectively, at 1 year. Limb salvage rates for the endoluminal techniques used in this study were satisfactory, especially in elderly patients with either segmental lesions or contraindications for distal bypass.
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PMID:Outcome of infrainguinal endovascular revascularization procedures for limb-threatening ischemia. 868 6

Eicosanoids play an important role in mediating deleterious effects following skeletal muscle ischemia-reperfusion injury. It has previously been shown that oxygenated perfluorocarbon emulsion (O2 Fluosol-DA 20%) decreases the amount of muscle necrosis and neutrophil sequestration when given during the reperfusion phase following skeletal muscle ischemia. As thromboxane is known to alter the endothelial cytoskeleton, thereby favoring diapedesis of neutrophils, the effects of O2 Fluosol-DA 20% on thromboxane release in a canine gracilis muscle model were investigated. The gracilis muscle on one randomly selected side of 14 adult mongrel dogs (body-weight 22-26 kg) was subjected to 6 h of normothermic ischemia followed by 48 h of normothermic reperfusion. The control group (n = 7) underwent ischemia-reperfusion, but without any pharmacological intervention. The Fluosol group (n = 7) were infused with O2 Fluosol-DA 20% (4.3(0.2) ml O2/100 ml) at 12 ml/min for 40 min via the gracilis artery following the ischemic period. Thromboxane B2 levels were measured from blood samples obtained at pre-ischemia, and at 1 h and 48 h of reperfusion. The gracilis muscles were harvested at the end of the experiment and extent of muscle necrosis quantitated by serial transections, nitroblue tetrazolium staining and computed planimetry. The mean(s.e.m.) muscle necrosis in the control group (59(6)%) was significantly higher than in the Fluosol group (22(5)%, P < 0.05, t-test). Thromboxane levels (pg/ml) in the control group at 1 h of reperfusion were significantly higher than the pre-ischemic and 48-h reperfusion levels (7286(1383) versus 1336(592) and 2314(1297), P < 0.05 by ANOVA and Student-Newman-Keuls test). The thromboxane level in the Fluosol group at 1 h reperfusion was significantly lower than the control group (2700(556) and 7286(1383) pg/ml, respectively; P < 0.05, t-test). In contrast, there was no statistically significant difference between thromboxane levels in the Fluosol group at 1 h reperfusion compared with levels at pre-ischemia and 48 h reperfusion (2700(556) versus 1336(592) and 1400(474). Thus, perfluorocarbons are effective in decreasing skeletal muscle necrosis, probably by maintaining the endothelial integrity and preventing vasospasm, secondary to their inhibitory effect on thromboxane release. Perfluorocarbons may also minimize some of the deleterious pulmonary effects known to be caused by increased levels of eicosanoids during reperfusion.
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PMID:Perfluorocarbon emulsion prevents eicoasanoid release in skeletal muscle ischemia and reperfusion. 878 46


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