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)

Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of perfused rat hearts was photographed to provide a two-dimensional recording of NADH levels. Sodium Amytal inhibition of NADH oxidation resulted in a homogeneous increase in NADH fluorescence, while lowering perfusion pressure from 55 to 10 torr caused a heterogeneous increase in NADH fluorescence, reflecting the heterogeneous oxygen delivery at this low pressure. Local ischemia resulted in a well-defined region of high NADH fluorescence that corresponded to the region of ischemic inslut. The sharp transition between the ischemic and normoxic areas demonstrated that the hypoxic interface separating the two areas must be quite small.
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PMID:Ischemic areas in perfused rat hearts: measurement by NADH fluorescence photography. 18 43

It has not previously been possible to study the in vitro effects of reperfusion on severely injured isolated perfused hearts because of the development of the no-reflow phenomenon, concomitant with the onset of irreversible myocardial cell injury. A new model of ischemic injury which utilizes an intraventricular balloon to allow uniform reperfusion of irreversibly damaged hearts is described. The effects of reperfusion were studied in Langendorff perfused rat hearts after no-flow ischemia for 60 and 150 minutes at 37 C. Uniform reflow was facilitated by maintaining the left ventricle at an isovolumic diastolic volume with a balloon during ischemia and removal of the balloon prior to reflow. Reperfusion was with 1) anoxic media, 2) oxygenated media, 3) oxygenated media in the presence of the mitochondrial inhibitor Amytal, or 4) an initial anoxic reperfusion followed by oxygenated media. Injury was monitored by the assay of released creatine kinase (CK) and myoglobin (Myo), by light-microscopic estimates of the percent of cells containing contraction bands, and by ultrastructural changes. CK and Myo were released with anoxic reperfusion, but larger releases occurred with oxygenated reperfusion. Amytal inhibited the oxygen but not the nitrogen component of release. Contraction bands occurred following oxygenated, but not anoxic, reperfusions and were inhibited by Amytal. Following an initial anoxic reperfusion, oxygen caused additional CK and Myo release and produced an increase in the percent of cells with contraction bands, compared with that with oxygen alone. The response of cells to injury was heterogeneous, and the hearts contained cells with a spectrum of ultrastructural changes. Anoxic reperfusion was associated with cellular swelling and oxygenated reperfusion with contraction band necrosis.
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PMID:Effects of anoxic or oxygenated reperfusion in globally ischemic, isovolumic, perfused rat hearts. 401 39

Previous in vitro studies have shown that isolated mitochondria can generate oxygen radicals. However, whether a similar phenomenon can also occur in intact organs is unknown. In the present study, we tested the hypothesis that resumption of mitochondrial respiration upon reperfusion might be a mechanism of oxygen radical formation in postischemic hearts, and that treatment with inhibitors of mitochondrial respiration might prevent this phenomenon. Three groups of Langendorff-perfused rabbit hearts were subjected to 30 min of global ischemia at 37 degrees C, followed by reflow. Throughout ischemia and early reperfusion the hearts received, respectively: (a) 5 mM KCl (controls), (b) 5 mM sodium amobarbital (Amytal, which blocks mitochondrial respiration at Site I, at the level of NADH dehydrogenase), and (c) 5 mM potassium cyanide (to block mitochondrial respiration distally, at the level of cytochrome c oxidase). The hearts were then processed to directly evaluate oxygen radical generation by electron paramagnetic resonance spectroscopy, or to measure oxygen radical-induced membrane lipid peroxidation by malonyl dialdehyde (MDA) content of subcellular fractions. Severity of ischemia, as assessed by 31P-nuclear magnetic resonance measurements of cardiac ATP, phosphocreatine, and pH, was similar in all groups. Oxygen-centered free radical concentration averaged 3.84 +/- 0.54 microM in reperfused control hearts, and it was significantly reduced by Amytal treatment (1.98 +/- 0.26; p < 0.05), but not by KCN (2.58 +/- 0.96 microM; p = not significant (NS)), consistent with oxygen radicals being formed in the mitochondrial respiratory chain at Site I. Membrane lipid peroxidation of reperfused hearts was also reduced by treatment with Amytal, but not with KCN. MDA content of the mitochondrial fraction averaged 0.75 +/- 0.06 nM/mg protein in controls, 0.72 +/- 0.06 in KCN-treated hearts, and 0.54 +/- 0.05 in Amytal-treated hearts (p < 0.05 versus both groups). Similarly, MDA content of lysosomal membrane fraction was 0.64 +/- 0.09 nM/mg protein in controls, 0.79 +/- 0.15 in KCN-treated hearts, and 0.43 +/- 0.06 in Amytal-treated hearts (p < 0.05 versus both groups). Since the effects of Amytal are known to be reversible, in a second series of experiments we investigated whether transient mitochondrial inhibition during the initial 10 min of reperfusion was also associated with beneficial effects on subsequent recovery of cardiac function after wash-out of the drug. At the end of the experiment, recovery of left ventricular end-diastolic and of developed pressure was significantly greater in those hearts that had been treated with Amytal during ischemia and early reflow, as compared to untreated hearts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. 839 7

The present study was performed to test whether the ischemic preconditioning could reduce mitochondrial O2.- production and prevent mitochondrial respiratory impairment upon reperfusion of ischemic hearts. The isolated perfused rat hearts were subjected to 30 min of global ischemia and 20 min of reperfusion. Ischemic preconditioning was performed, involving three 5-min periods of ischemia, each followed by a 5-min reperfusion just before a sustained ischemia. Ischemic preconditioning improved the post-ischemic cardiac function and reduced LDH release and malondialdehyde production upon reperfusion. 02.- generation of mitochondria isolated from the preconditioned hearts was significantly lower than that of mitochondria from the non-preconditioned hearts, and none of the activities of mitochondrial antioxidant enzymes (SOD, catalase, glutathione peroxidase) was altered as a consequence of the ischemic preconditioning alone. The impairment of mitochondrial state 3 respiration induced by ischemia and reperfusion was prevented by ischemic preconditioning. Amytal, a reversible respiratory chain blocker suppressing 02.- production in mitochondria, prevented the ischemia/reperfusion injury. The cardioprotective effect of Amytal could not be distinguished from that of ischemic preconditioning. These results suggest that the cardioprotective effect of ischemic preconditioning against the ischemia/reperfusion injury is attributed partly to the reduction of mitochondrial oxygen radical generation and prevention of the respiratory impairment during ischemia and reperfusion.
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PMID:Ischemic preconditioning reduces Op6 generation and prevents respiratory impairment in the mitochondria of post-ischemic reperfused heart of rat. 918 64

Mitochondria alteration is an early event in ischemia-induced damage, and its prevention improves tissue survival upon reperfusion. Adenine translocase and complex I activities are rapidly affected by ischemia. Ginkgo biloba extract demonstrates anti-ischemic properties attributable to the terpenoid fraction, mainly due to the presence of bilobalide. The mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated. Mitochondria isolated from rats treated with bilobalide (2 to 8 mg/kg) showed a dose-dependent increase in the respiratory control ratio, due to a lower oxygen consumption during state 4. Bilobalide also decreased the sensitivity of oxygen consumption to inhibition of complex I by Amytal or to inhibition of complex III by antimycin A or myxothiazol. There was no protection of complexes IV and V. It also increased the activity of complex I but not of adenine translocase. Similar effects were also obtained in vitro when control mitochondria were preincubated for 1 hr with 0.8 microg/mL bilobalide. Treatment of the rats with 8 mg/kg bilobalide also prevented the ischemia-induced decrease in state 3 of the mitochondrial respiration and thus the decrease in RCR. The protective effect of bilobalide on cellular ATP content observed under ischemic conditions can be correlated with the above observations. By protecting complex I and III activities, bilobalide allows mitochondria to maintain their respiratory activity under ischemic conditions as long as some oxygen is present, thus delaying the onset of ischemia-induced damage. This mechanism provides a possible explanation for the anti-ischemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions.
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PMID:Protection of mitochondrial respiration activity by bilobalide. 1040 24

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

Cardiac ischemia damages the mitochondrial electron transport chain. Irreversible blockade of electron transport at complex I by rotenone decreases ischemic damage to cardiac mitochondria by decreasing the loss of cytochrome c and preserving respiration through cytochrome oxidase. Therapeutic intervention to protect myocardium during ischemia and reperfusion requires the use of a reversible inhibitor that allows resumption of oxidative metabolism during reperfusion. Amobarbital is a reversible inhibitor at the rotenone site of complex I. We asked whether amobarbital administered immediately before ischemia protected respiratory function. Isolated rat hearts were perfused for 15 min followed by 25-min global ischemia at 37 degrees C. Amobarbital-treated hearts received drug for 1 min before ischemia. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after ischemia, and oxidative phosphorylation was measured. Amobarbital protected oxidative phosphorylation, including through cytochrome oxidase, in both SSM and IFM in a dose-dependent manner, with an optimal dose of 2 to 2.5 mM. Amobarbital also preserved cytochrome c content in both SSM and IFM. Thus, reversible blockade of the electron transport chain during ischemia protects mitochondrial respiration.
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PMID:Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria. 1617 99

Cardiac mitochondria sustain damage during ischemia and reperfusion, contributing to cell death. The reversible blockade of electron transport during ischemia with amobarbital, an inhibitor at the rotenone site of complex I, protects mitochondria against ischemic damage. Amobarbital treatment immediately before ischemia was used to test the hypothesis that damage to mitochondrial respiration occurs mainly during ischemia and that protection of mitochondria during ischemia leads to decreased cardiac injury with reperfusion. Langendorff-perfused Fischer-344 rat hearts were treated with amobarbital (2.5 mM) or vehicle for 1 min immediately before 25 min of global ischemia. Both groups were reperfused for 30 min without additional treatment. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after reperfusion. Ischemia and reperfusion decreased state 3 and increased state 4 respiration rate in both SSM and IFM. Amobarbital treatment protected oxidative phosphorylation measured following reperfusion and improved the coupling of respiration. Cytochrome c content measured in SSM and IFM following reperfusion decreased in untreated, but not in amobarbital-treated, hearts. H(2)O(2) release from SSM and IFM isolated from amobarbital-treated hearts during reperfusion was markedly decreased. Amobarbital treatment before ischemia improved recovery of contractile function (percentage of preischemic developed pressure: untreated 51 +/- 4%, n = 12; amobarbital 70 +/- 4%, n = 11, p < 0.01) and substantially reduced infarct size (untreated 32 +/- 2%, n = 7; amobarbital 13 +/- 2%, n = 7, p < 0.01). Thus, mitochondrial damage occurs mainly during ischemia rather than during reperfusion. Reperfusion in the setting of preserved mitochondrial respiratory function attenuates the mitochondrial release of reactive oxygen species, enhances contractile recovery, and decreases myocardial infarct size.
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PMID:Reversible blockade of electron transport during ischemia protects mitochondria and decreases myocardial injury following reperfusion. 1699 May 10

The goal of endovascular neurosurgery is to occlude aneurysms and arteriovenous malformations (AVMs) or to reduce the vascular supply to hypervascularized tumors, while preserving function in the normal neural tissue. However, the intra-arterial injection of embolizing materials into the cerebral or spinal circulation exposes to the risk of ischemic complications. Under general anesthesia, unless a wake-up test is performed, the only way to assess the functional integrity of sensory and motor pathways is to use neurophysiological monitoring. Somatosensory (SEPs) and muscle motor evoked potentials (mMEPs) can be used in combination with pharmacological provocative tests (PTs) to predict the effects of embolization. Amytal blocks neuronal activity, while lidocaine blocks axonal conduction. Therefore, a positive Amytal or lidocaine test (i.e. more than 50% decrease in SEP amplitude and/or mMEP disappearance) indicates that the vessel distal to the tip of the microcatheter supplies the functional gray or white matter of the spinal-cord respectively and cannot be embolized. Brain and spinal-cord vascularization and hemodynamics are extremely complex and even more unpredictable in the presence of a vascular malformation, but using a combined SEPs, MEPs and PTs protocol, morbidity related to endovascular procedures is very low. Given the high sensitivity of peripheral recordings to spinal-cord ischemia, experimental and clinical studies support the concept that whenever the mechanism of spinal-cord injury is purely ischemic, recording mMEPs may suffice. Reports on the use of PTs and neurophysiological monitoring during embolization of brain AVMs in critical areas are more anecdotal and mainly limited to the use of short-acting barbiturates. Our preliminary experience using lidocaine and combining SEP and mMEP monitoring is encouraging, since no false negative results were observed. Finally, if the sensitivity of this method is very high, its specificity has not been tested because embolization is abandoned whenever PTs are consistently positive. Accordingly, the possibility of false positive results cannot be excluded.
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PMID:Neuroprotective role of neurophysiological monitoring during endovascular procedures in the brain and spinal cord. 1808 97

Mitochondrial dysfunction contributes to myocardial injury during ischemia and reperfusion. Ischemia damages the mitochondrial electron transport chain. Therapeutic intervention during early reperfusion decreases cardiac injury, which suggests that myocardial injury can be attenuated even though mitochondria were already damaged during the preceding ischemia. Our previous study shows that amobarbital given only before ischemia prevents ischemic damage to the electron transport chain and decreases infarct size measured during reperfusion in Langendorff-perfused Fischer 344 rat hearts. In the current study, amobarbital was given at the onset of reperfusion to test whether the blockade of proximal electron transport only during early reperfusion can decrease myocardial injury. Amobarbital administrated during early reperfusion decreased infarct size compared with untreated hearts, which suggests that the modulation of electron transport during early reperfusion attenuates myocardial injury. The increased generation of reactive oxygen species (ROS) contributes to injury. We tested whether the blockade of proximal electron transport prevents ROS release from the mitochondria that sustained ischemic damage. The blockade of the proximal electron transport chain at complex I attenuates maximal ROS generation from ischemia-damaged mitochondria. Thus, the modulation of oxidative function during reperfusion provides a translationally relevant opportunity to prevent a portion of the mitochondrial-dependent injury. The cardiac protection by amobarbital given during reperfusion may result from decreased ROS generation from the electron transport chain.
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PMID:Reversible blockade of electron transport with amobarbital at the onset of reperfusion attenuates cardiac injury. 1937 83


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