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 effect of anesthetics on ischemic myocardium to which blood was supplied by a stenotic coronary artery was investigated in dogs. The ischemia was assessed by regional wall motion (ultrasonic dimension technique) using fractional shortening (FS) [(EDL - ESL)/EDL x 100] and end-systolic pressure-segment length relationships (ESPLR). The latter is considered to be a more load-independent measure of regional myocardial function. Isoflurane and fentanyl were chosen as anesthetics of current interest. On reducing the left circumflex coronary artery (LCX) flow to approximately 50% of its resting value, a decrease in FS and a rightward shift in ESPLR were observed in myocardium perfused by the LCX. Simultaneously, increases in FS were observed in the nonischemic area perfused by the left anterior descending coronary artery (LAD), which was most likely due to the intraventricular unloading effect. No significant changes of ESPLR were observed in the area supplied by LAD. Isoflurane induced a dose-dependent decrease in FS and a rightward shift in ESPLR in the ischemic myocardial segment, whereas fentanyl caused an increase in FS and tended to shift ESPLR leftward in the same area. The results suggest that isoflurane may have deleterious effects on preexisting myocardial ischemia, whereas fentanyl may not when loading conditions are taken into consideration. Fractional shortening and ESPLR seem to provide similar information about regional myocardial function.
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PMID:Effects of isoflurane and fentanyl on ischemic myocardium in dogs: assessment by end-systolic measurements. 186 44

Inosine and adenosine formation was evaluated in different types of rat skeletal muscle during ischemic and non-ischemic contraction. Extensor digitorum longus (EDL, fast) and soleus (slow) muscles were stimulated electrically via the sciatic nerve (5 Hz, 10 min). Under non-ischemic condition, the concentrations of IMP, inosine, adenosine, and hypoxanthine increased in EDL muscles but not in soleus muscles during stimulation. Under ischemic condition, these metabolites increased in both EDL and soleus muscles, although the increases in IMP and inosine were greater in EDL muscles. The increase in inosine had a strong positive correlation with that in IMP in ischemic EDL and soleus muscles, but the ratio, delta inosine/delta IMP was smaller in EDL muscles. The increase in adenosine under ischemic condition was not significantly different between the two muscles. These findings suggest that ischemia enhances degradation of purine nucleotides in contracting fast and slow muscles, and that although the degradation of purine nucleotides to IMP is greater in fast muscles than in slow muscles, the relative degradation rate of IMP to inosine is rather smaller in fast muscles.
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PMID:Inosine and adenosine formation in ischemic and non-ischemic contracting muscles of rats: difference between fast and slow muscles. 317 30

The mechanism of cocaine-induced rhabdomyolysis and/or muscle damage has not been elucidated. To determine if cocaine has a direct effect on muscle, isolated soleus and EDL muscles were incubated in the presence of 1 mM and 0.2 mM cocaine using a pulse and continuous exposure protocol. The release of creatine kinase from the isolated EDL muscle was statistically significant only when muscles were exposed to 1 mM cocaine for a period of 30 minutes. These findings suggest that cocaine-induced creatine kinase release could be mediated by a direct action on the fibers. It is also possible, however, that cocaine-induced muscle damage and creatine kinase release may be mediated via an indirect effect. It is possible that cocaine's vasoconstrictor effects could lead to muscle damage via an ischemia-reperfusion injury leading to free radical formation and lipid peroxidation. This study, therefore, also investigated the possibility that cocaine-induced cytosolic enzyme release may be mediated via the formation of free radicals leading to lipid peroxidation. To test this hypothesis, muscle total glutathione levels, a free radical scavenger, and muscle thiobarbituric acid reactive substances (TBARS), a measurement of lipid peroxidation, were examined following an acute IV cocaine dose in mice. Sedentary BalbC mice were injected with cocaine (40 mg/kg) or normal saline via the tail vein. Creatine kinase levels in serum and total glutathione and TBARS in liver and muscle were determined at 4, 8, and 24 hrs. Serum creatine kinase levels were significantly elevated 5-fold, while TBARS were elevated 100% in the gastrocnemius muscle of cocaine-treated animals at 4 hrs compared to normal saline controls. However, serum creatine kinase levels, total glutathione and TBARS in the gastrocnemius muscle were not statistically different at 8 or 12 hrs; or in the liver and anterior tibialis muscle at 4, 8, or 24 hrs. The present findings suggests that lipid peroxidation may be occurring in skeletal muscle after a single IV cocaine dose in mice.
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PMID:Effects of cocaine on leakage of creatine kinase from skeletal muscle: in vitro and in vivo studies in mice. 756 4

The aim of the present experiment was to determine whether the potassium channel opener 2-(2,2-bis(difluoromethyl)-6-nitro-3,4-dihydro-2H-1, 4-benzoxazine-4-yl)pyridine-N-oxide (ZM260384) was capable of accelerating the decline in skeletal muscle function during restricted blood flow in vivo. Cats (3.0-4.5 kg body weight) were anaesthetized with alphaxalone-alphadalone and breathed spontaneously following tracheotomy. Isometric tension was measured in the extensor digitorum longus-anterior tibialis (EDL-TA) muscle group. Ischaemia was induced by perfusing the hindlimb with the animal's own blood at a rate of 12.5 ml min-1 using a roller pump and stimulating the common peroneal nerve to induce repetitive submaximal tetanic contractions in the EDL-TA. The number of stimulation voltage increments required each minute to maintain a constant level of submaximal mechanical output and the time to exhaustion were used as indices of the rate of tension decline. The rate of tension decline in the ischaemic EDL-TA in the presence of ZM260384 at 3 mg kg-1, a maximally hypotensive dose predicted to be within the dose range required to exert direct effects on skeletal muscle, was measured and compared with the rate of tension decline in the presence of ZM260384 at 0.03 mg kg-1, also maximally hypotensive dose but below the predicted dose range for skeletal muscle effects. The number of voltage increments per minute was 1.93 +/- 0.07 and 1.48 +/- 0.14 (P < 0.05) in the presence of 3 and 0.03 mg kg-1 ZM260384, respectively. Time to exhaustion was 17.5 +/- 4.2 and 7.2 +/- 0.8 min (P < 0.05) in the presence of 3 and 0.03 mg kg-1 ZM260384, respectively. Given that there was no difference between these two groups in any haemodynamic variable measured, the results of the present study suggest that ZM260384 (3 mg kg-1) increases the rate of isometric force loss in ischemic skeletal muscle in vivo.
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PMID:Effect of the potassium channel opener ZM260384 on skeletal muscle function during restricted blood flow in the anaesthetized cat. 902 8

Complete occlusion of blood flow to rat hind limb by tourniquet was used to study the effects of total ischemia for 1, 2, and 3 h on contractile function and metabolic behaviour of two muscles composed predominantly of either fast-twitch (extensor digitorum longus, EDL) or slow-twitch (soleus, SOL) fibres. Percent loss in twitch force (Pt) was greater (p < 0.05) in SOL than EDL during the first 45 min of ischemia. Following 1 h of ischemia, ATP concentration was lower (p < 0.05) than in the contralateral control (20.8 +/- 2.0 vs. 26.4 +/- 1.5 mmol/kg dry weight). Thereafter, the decline in ATP was greater, with approximately 95% depleted by 3 h of ischemia (1.46 +/- 0.46 mmol/kg dry weight). The effect of ischemia on ATP levels in the SOL was similar to ATP levels in the EDL, 1 h of ischemia also resulted in a large decrement in PCr, from 50.1 +/- 2.9 to 11.7 +/- 2.4 mmol/kg dry weight, and a large increase in lactate, from 25.0 +/- 3.0 to 114 +/- 10 mmol/kg dry weight. As ischemia was prolonged, only lactate was increased (p < 0.05) both at 2 h (171 +/- 12 mmol/kg dry weight) and 3 h (208 +/- 5.4 mmol/kg dry weight). Similar trends were found for SOL. By 3 h of ischemia, glycogen was depleted (p < 0.05) by 88% in EDL and 92% in SOL, respectively. These results support the hypothesis that both high energy phosphate transfer and anerobic glycolysis are of major importance in defending ATP hemostasis, particularly during the 1st h of ischemia, and that the resulting metabolic disturbances are responsible for the large fatigability observed. The mechanisms underlying the greater resistance to fatigue observed for the SOL compared with the EDL during the earlier period of ischemia remain uncertain.
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PMID:Metabolic and contractile responses of fast- and slow-twitch rat skeletal muscles to ischemia. 904 44

Skeletal muscle is frequently damaged by ischemia-reperfusion when exposed to direct injury or in the surgical practice. The purpose of the present experiments was to examine how the different types of skeletal muscles (fast & slow) react functionally to one and two hours of ischemia followed by two weeks of reperfusion. The fast-twitch (m. extensor digitorum longus/EDL) and the slow-twitch (m. soleus/SOL) muscle were prepared. They were stimulated, in vivo, either directly or indirectly at different reperfusion times following tourniquet ischemia, and the contraction force (CF) was recorded. CF of the EDL was reduced over 40% and 90% of the control value during the first 24 hours of reperfusion after 1 and 2 hours of ischemia, respectively. It was about 50% at the end of the 2nd week in the one-hour group. CF increased significantly during the second week if ischemia lasted for two hours. Reduction of CF in the SOL muscle was over 50% and 90% following one and two hours of ischemia, respectively. It further decreased in the 1-hour group, and it started to regenerate from the second week after 2 hours of ischemia. It is concluded that 1. two hours of ischemia causes significantly more severe damages in both types of skeletal muscles than one hour. 2. There is a reperfusion injury in both muscles during the first week of reperfusion. 3. The two types of muscles regenerate differently, i.e. the SOL starts to regenerate earlier than the EDL.
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PMID:The functional damages of ischemic/reperfused skeletal muscle. 921 91

Skeletal muscle is frequently damaged by ischemia-reperfusion both caused by direct injury and also by surgery. The purpose of the present experiments was to examine how the different types of skeletal muscles (fast and slow) react functionally and morphologically after 1 and 2 h of ischemia followed by different periods of reperfusion. The fast-twitch (musculus extensor digitorum longus, EDL) and the slow-twitch (musculus soleus, SOL) muscle of Wistar rats were prepared. They were stimulated in vivo, either directly or indirectly at different reperfusion times following tourniquet ischemia, and the contraction force of the muscles was recorded. The morphological changes were examined by light microscopy. At early reperfusion times, the contraction force of the EDL muscle was reduced by 40 and 90% after 1 and 2 h of ischemia, respectively. The contraction force was about 50% at the end of a 2-week reperfusion period in the 1-hour ischemia group and it increased significantly (from 5 to 38%) during the second week if the ischemia lasted for 2 h. Reduction of contraction force in the SOL muscle was over 50 and 90% following 1 and 2 h of ischemia, respectively, and it started to improve from the 2nd week. Morphological changes of the two types of muscle were identical. At early reperfusion times granulocytes were seen in the blood vessels adhering to the endothelium. 24 h later neutrophil granulocytes migrated into the endomysium and thereafter into the perimysium. One week after 1 h of ischemia both muscles showed normal histology. However, the structural regeneration process only started at the end of the 1st week of reperfusion after 2 h of the ischemic damage. The following conclusions can be drawn. (1) There is functional morphological evidence of ischemic and reperfusion injury in both muscles after 24 h and also after 1 week of reperfusion. (2) Functionally, the two types of muscles regenerate differently, i.e. the SOL starts to regenerate earlier than the EDL. (3) Morphologically the two types of muscle show the same reactions. An increase in the time of ischemia from 1 to 2 h delays the regeneration processes.
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PMID:The functional and morphological damage of ischemic reperfused skeletal muscle. 925 97

Phospholipase A2 has been considered to play a role in physiological membrane turnover in cardiac tissue and in the degradation of membrane lipids under pathophysiological conditions, such as ischemia and reperfusion. We report the cloning of a cDNA encoding a member of the Ca2+-dependent, low molecular mass phospholipase A2 (PLA2) present in rat heart. The cDNA predicts a mature protein of 146 amino acid residues including a 21 amino acid sequence at the N-terminal end, which has the features characteristic of eukaryotic secretory signal peptides. The deduced amino acid sequence constitutes an enzyme of the group II class of PLA2s, and resembles PLA2s from other mammalian sources. A Northern blot analysis performed to determine the tissue distribution showed that rat ileum contains the largest amount of the PLA2 transcript among the tissues examined, a weaker signal was present in heart, spleen and soleus muscle, and no signal could be detected in EDL muscle, stomach, liver, kidney, brain and lung. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques indicate the presence of this enzyme in neonatal and adult rat cardiomyocytes and in a cultured rat cardiac fibroblast-like cell line, but not in rat cardiac-derived endothelial cell lines. Transcription levels of rat heart group II PLA2 in isolated neonatal rat cardiomyocytes were found to increase after stimulating the cells with tumor necrosis factor-alpha (TNF-alpha) or the alpha1-adrenergic agonist phenylephrine.
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PMID:Cloning and cellular distribution of a group II phospholipase A2 expressed in the heart. 928 42

Ischemia and denervation of EDL muscle of adult rat induce a large central zone of degeneration surrounded by a thin zone of peripheral surviving muscle fibers. Muscle regeneration is a complex phenomenon in which many agents interact, such as growth factors and heparan sulfate components of the extracellular matrix. We have shown that synthetic polymers, called RGTA (as regenerating agents), which imitate the heparan sulfates, are able to stimulate tissue repair when applied at the site of injury. In crushed muscles, RGTA were found to accelerate both regeneration and reinnervation. In vitro, RGTA act as protectors and potentiators of various heparin binding growth factors (HBGF). It was postulated that in vivo their tissue repair properties were due in part to an increase of bioavailability of endogenously released HBGF. In the present work, we show that ischemic and denervated EDL muscle treated by a unique injection of RGTA differs from the control after 1 wk in several aspects: 1) the epimysial postinflammatory reaction is inhibited and the area of fibrotic tissue among fibers is reduced; 2) the peripheral zone, as measured by the number of intact muscle fibers, was increased by more than twofold; and 3) In the central zone, RGTA enhances the regeneration of the muscle fibers as well as muscle revascularization. These results suggest that RGTA both protects muscle fibers from degeneration and preserves the differentiated state of the surviving fibers. For the first time it is demonstrated that a functionalized polymeric compound can prevent some of the damage resulting from muscle ischemia. RGTA may therefore open a new therapeutic approach for muscle fibrosis and other postischemic muscle pathologies.
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PMID:A substituted dextran enhances muscle fiber survival and regeneration in ischemic and denervated rat EDL muscle. 1009 36

This study tested the hypothesis that regional low-flow ischemia and reperfusion alter myocardial material properties by causing non-elastic deformation. Twenty-two anesthetized, open-chest pigs were studied. Pigs underwent 90 min of regional low-flow ischemia (anterior LV subendocardial blood flow 29+/-7% of baseline) followed by 90 min reperfusion. LV pressure and regional subendocardial segment length were recorded to derive end-diastolic pressure vs segment length (EDP vs EDL) and preload-recruitable stroke work (PRSW) relations. In vivo, non-elastic myocardial deformation was inferred from increases in minimally loaded myocardial dimensions: the EDL at zero EDP (L0) and the EDL at which no regional external work was performed (Lw, the PRSW intercept). In 15 pigs, ultrastructural confirmation of non-elastic deformation was obtained from sarcomere dimensions measured by transmission electron microscopy after in situ perfusion fixation under non-ischemic conditions, after 90 min ischemia, or after 90 min ischemia plus 90 min reperfusion. Ischemia increased L0 and Lw to 1.17+/-0.05 and 1. 13+/-0.04 times baseline, respectively. After reperfusion, L0 and Lw remained increased to 1.09+/-0.03 and 1.15+/-0.02 times baseline (all P<0.05). After reperfusion, PRSW slope was not different from baseline, but regional external work remained depressed (0.38+/-0.03 times baseline) due to the persistent increase in Lw. Neither L0 nor Lw changed in the posterior (non-ischemic) region. In hearts fixed after ischemia or after ischemia plus reperfusion, sarcomere length was significantly greater and transverse distance between thick myofilaments was significantly smaller in the anterior (ischemic) subendocardium than in the posterior (non-ischemic) subendocardium (P<0.01). We conclude that regional low-flow ischemia and reperfusion cause non-elastic deformation of myocardium, manifest in vivo by increased minimally loaded myocardial dimensions (L0 and Lw) and ultrastructurally by increased sarcomere length and decreased transverse interfilament distance. Non-elastic deformation of myocardium may contribute to contractile dysfunction in low-flow ischemia and reperfusion.
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PMID:Non-elastic deformation of myocardium in low-flow ischemia and reperfusion: ultrastructure-function relations. 1033 53


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