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

The disease state of myocardial ischemia results from a hypoperfusion-induced insufficiency of heart-muscle oxidative metabolism due to inadequate coronary circulation. Myocardial ischemia is an important, lifespan-limiting medical problem and a major economic health-care concern. Reperfusion, although avidly pursued in the clinic as essential to the ultimate survival of acutely ischemic heart muscle, may itself carry an injury component. Cardiac reperfusion injury appears to reflect, at least in part, an oxidant burden established upon reoxygenation of ischemic myocardium. Laboratory evidence demonstrates that oxidative stress to the heart-muscle cell (cardiomyocyte) can elicit the three known types of ischemia-reperfusion injury that directly affect the myocardium: arrhythmia, stunning, and infarction. The limited clinical occurrence of serious reperfusion arrhythmias has restricted the importance of antioxidants as antiarrhythmic agents against this form of myocardial ischemia-reperfusion damage. Despite the utmost clinical significance of lethal cardiomyocyte injury as a negative prognostic indicator for the ischemic heart-disease patient, inconsistent results of antioxidant interventions in reducing infarct size have somewhat tempered interest in antioxidant infarct trials. By contrast, the negative clinical consequences of stunning may indeed be preventable by utilizing antioxidants to help restore postischemic cardiac pump function. Several as yet unanswered questions remain regarding oxidative stress in the reperfused heart, its significance to cardiomyocyte damage, and its ability to elicit specific postischemic myocardial derangements. Targeted mechanistic studies are required to address these questions and to define the pathogenic role of oxidative stress (and, hence, the therapeutic potential of antioxidant intervention) in myocardial ischemia-reperfusion injury. The overall aim of current research in this area is to enable the cardiac surgeon/cardiologist to advance beyond the largely palliative drugs now available for management of the coronary heart-disease patient and attack directly the pathogenic determinants of heart-muscle ischemia-reperfusion injury. Optimal use of antioxidants may help address this important medical need.
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PMID:Ischemic heart disease and antioxidants: mechanistic aspects of oxidative injury and its prevention. 774 81

Coronary vascular adaptations to exercise training have been extensively studied at the microscopic level in animals and correlated with direct and indirect measurements of myocardial blood flow in patients with coronary artery disease. Animals have permitted more extensive study. These findings have generally supported an increased blood flow to the myocardium with exercise training. However, consistent positive structural and functional adaptations to training have not been observed in large animals. Clinical studies have been limited by methodological problems related to techniques for detecting ischemia and measuring myocardial blood flow and the variability in exercise stimulus. Well-established ischemia and high-intensity, long-duration training were the factors that promoted vascular growth in exercising patients with coronary artery disease. Animals studies also have demonstrated the necessity for myocardial ischemia to be present to induce coronary collateral development with exercise training. Optimal promoters of vascular growth in patients with coronary disease may consist of pharmacological interventions combined with exercise training.
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PMID:Clinical significance of coronary vascular adaptations to exercise training. 779 69

Previous studies have demonstrated a role for both tumor necrosis factor (TNF) and reactive oxygen intermediates (ROI) in hepatic ischemia/reperfusion (I/R) injury. Biologically active TNF was present in liver homogenates in ischemic and nonischemic lobes after 2 h of ischemia but without reperfusion. Using an in situ liver perfusion model, we measured ROI, TNF, and hepatic enzymes in the effluent after 2 h of ischemia. Increased reduction of ferricytochrome C was observed in the hepatic effluent, indicative of the formation of ROI. Treatment of animals with TNF neutralizing antisera significantly reduced both ROI and aspartate aminotransferase (AST). Animals treated with superoxide dismutase (SOD), or SOD + catalase (CAT) had greater TNF in the hepatic effluent compared with I/R alone; however, SOD or SOD + CAT did not cause additional release of AST.SOD + CAT plus anti-TNF serum resulted in significant protection compared with SOD + CAT plus control serum. Reperfusion of ischemic liver with 4 mM H2O2 increased both TNF and AST. Optimal protection of hepatocellular injury from reperfusion injury is achieved with a combination of antioxidants and inhibition of TNF.
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PMID:Hepatic ischemia/reperfusion injury: importance of oxidant/tumor necrosis factor interactions. 781 Jun 59

Optimal methods of myocardial preservation remain controversial in the neonate. This study compared prolonged hypothermic storage of neonatal hearts with modified University of Wisconsin solution (group I) with a solution formulated to promote anaerobic glycolysis by providing proton buffering with histidine (100 mmol/L) and exogenous glucose and insulin (group II). Hearts from piglets aged 3 to 5 days were given a single dose of either solution (n = 6 each), subjected to 20 hours of global ischemia at 4 degrees C, and reperfused with an erythrocyte-enhanced perfusate in an isovolumic Langendorff preparation. After 1 hour of reperfusion, in comparison with hearts preserved with University of Wisconsin solution, those in group II demonstrated (mean +/- standard error of the mean) greater left ventricular developed pressure (101 +/- 7 versus 62 +/- 9 mm Hg, p < 0.01) and the first derivative of left ventricular pressure (816 +/- 23 versus 614 +/- 69 mm Hg.sec-1, p < 0.05). Diastolic indices were reduced to a similar degree in the two groups. Myocardial oxygen consumption was significantly greater (38.8 +/- 2.4 versus 11.8 +/- 2.4 microliters oxygen.min.g-1, p < 0.01) in group II hearts. Group I hearts vasoconstricted (6% increase in coronary vascular resistance) in response to an intracoronary infusion of acetylcholine (20 nmol.min-1); in contrast, acetylcholine produced coronary dilation in group II hearts (5% decrease in coronary resistance, p < 0.02) that was similar to that observed in nonischemic control hearts. These results demonstrate enhanced preservation of myocardial contractility, oxidative metabolism, and vascular function in neonatal hearts provided by a solution designed to buffer protons and promote anaerobic glycolysis during ischemia.
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PMID:Prolonged neonatal myocardial preservation with a highly buffered low-calcium solution. 793 15

Because many infants who require cardiac operation have cyanotic heart disease, we determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is optimal to protect the immature rabbit heart hypoxemic from birth during subsequent ischemia. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting chronically hypoxemic (PaO2 = 34 +/- 11 mmHg, SaO2 = 63% +/- 3%) versus normoxemic (PaO2 = 76 +/- 11 mmHg, SaO2 = 92% +/- 3%) immature hearts (7 to 12 days old) during ischemia. Hearts (n = 6 per group) underwent aerobic 'working' perfusion with Krebs bicarbonate buffer and cardiac function was measured. The hearts were then arrested with a 3 minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or modified St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile was observed for recovery of postischemic aortic flow but not for postischemic creatine kinase leakage, with improved protection occurring at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.4 mmol/L, which was significantly better than with hypothermia alone or standard St. Thomas' II solution. We conclude that the existing calcium concentration of St. Thomas' II solution is responsible, in part, for its inadequate protection of immature myocardium hypoxemic from birth during ischemia.
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PMID:Calcium and cardioplegic protection of the ischemic immature heart: impact of hypoxemia from birth. 794 63

One of the rarer anatomic variants is persistent sciatic artery. Only 93 cases have been reported since the first description of this anomaly. The earlier reports were mainly pathologic descriptions, whereas the more recent have been clinically oriented. There is a slight male predominance, and the average age of presentation is 49 years old (range 6 months to 85 years). The majority of patients have symptoms of a mass, ischemia, or gluteal pain. There is no preference for the right or left side, and one in four patients has both legs affected. In this anomaly the sciatic vessel acts as the principal blood supply to the lower limb. One half of all patients develop aneurysms that are characteristically located caudal to the sciatic notch as opposed to gluteal aneurysms that are cephalad to this landmark. Various methods (some now obsolete) have been tried to treat these aneurysms, but the best results were obtained through aneurysm ablation and vascular reconstruction. Arterial bypasses succeeded when used for ischemic complications of persistent sciatic artery. Optimal management of this condition requires prompt recognition, an understanding of the developmental anatomy, exclusion and bypass of aneurysms, appropriate vascular intervention for ischemic sequelae, and close observation of asymptomatic individuals.
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PMID:Persistent sciatic artery: collective review and management. 831 97

Hypothermic alkaline pharmacologic cardioplegia used in pediatric cardiac surgery may be less than satisfactory despite its benefits in adults. We determined whether the pH (7.8) of standard St. Thomas' II cardioplegic solution contributes to inadequate protection of the ischemic immature heart and whether the effect is age-related. Modified hypothermic St. Thomas' II solution (pH range, 4.8 to 8.8) was compared with hypothermic bicarbonate buffer alone (pH 7.25) in protecting the ischemic immature (7 to 10 days old) and mature (12 months old) rabbit heart. Isolated hearts (n = 6 per group) were perfused with bicarbonate buffer, and aortic flow was measured before hypothermic (14 degrees C) ischemia (immature hearts: 4 hours; mature hearts: 3 hours). Hearts were reperfused, and enzyme leakage and recovery of function were measured. In the immature heart, a bell-shaped dose-response profile was observed for pH and recovery of aortic flow but not for postischemic creatine kinase leakage. Optimal recovery of aortic flow (98% +/- 3%) occurred at pH 6.8, which was greater than protection with hypothermia alone (82% +/- 4%; p < 0.05) and standard St. Thomas' II solution (72% +/- 2%; p < 0.05). In the mature heart, a bell-shaped dose-response curve existed for recovery of aortic flow and a U-shaped curve existed for creatine kinase leakage. Again, optimal recovery of aortic flow (84% +/- 5%), which was superior to that with standard St. Thomas' II solution (60% +/- 8%; p < 0.05), and minimal enzyme leakage also occurred at pH 6.8, as did the least enzyme leakage (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age and protection of the ischemic myocardium: is alkaline cardioplegia appropriate? 845 42

Several forms of cardiac adaptation to stress are known, differing in the evoking stress, in the time needed for adaptation and in the duration of the protective effect. A delayed adaptation produced a late appearing, prolonged protection against consequences of ischemia, such as early morphological changes, early and late postocclusion and reperfusion arrhythmias due to coronary artery occlusion or ouabain intoxication. Delayed adaptation was evoked by ischemic stress (repeated brief periods of rapid cardiac pacing or brief coronary occlusions) or by drugs (prostaglandin I2 and its stable derivatives). The protection produced by delayed adaptation proved to be time- and dose-dependent. Optimal effects appeared 24 to 48 h after treatment with an optimal dose of 50 microg/kg 7-oxo-prostacyclin or 10 microg/kg Iloprost. It is suggested that the mechanism of delayed cardioprotection is based on the fact that the stress-evoking adaptation stimulates the adenylate-cyclase/cyclic adenosine monophosphate (cAMP) system; the resulting elevation of cardiac cAMP level triggers the induction of some key enzymes such as Na/K-ATPase and phosphodiesterase (PDE) isoforms I and IV. Increased amount and activity of Na/K-ATPase accounts for preservation of normal membrane function and moderation of ischemic loss of potassium, and accumulation of sodium and calcium in the myocardium, as well as for reduced ouabain toxicity. The detrimental consequences of heavy stress-induced accumulation of cAMP in the heart are mitigated by hydrolysis of the latter, carried out by an enhanced amount and activity of PDE isoforms. Response to beta-adrenergic stimuli is also attenuated. In addition, electrophysiological changes such as prolongation of the effective refractory period and of the action potential duration may attenuate arrhythmias due to ischemia and reperfusion.
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PMID:On the mechanism and possible therapeutic application of delayed cardiac adaptation to stress. 860 40

Resuscitative (postinsult) hypothermia is less well studied than protective-preservative (pre- and intra-arrest) hypothermia. The latter is in wide clinical use, particularly for protecting the brain during cardiac surgery. Resuscitative hypothermia was explored in the 1950s and then lay dormant until the 1980s when it was revived. This change occurred through the discoveries of brain damage mitigating effects after cardiac arrest in dogs, and after forebrain ischemia in rats, of mild (34 degrees C) hypothermia (which is safe), and of benefits derived from moderate hypothermia (30 degrees C) after traumatic brain injury or focal brain ischemia in various species. The idea that protection-preservation or resuscitation by hypothermia is mainly explained by its ability to reduce cerebral oxygen demand has been replaced by an increasingly documented synergism of many beneficial mechanisms. Deleterious chemical cascades during and after these insults are suppressed even by mild hypothermia. Prolonged moderate hypothermia carries some risks, e.g., arrhythmias, infection and coagulopathies. These side effects need further study. In global brain ischemia, protective-preservative mild hypothermia provides lasting mitigation of brain damage. Resuscitative mild hypothermia, however, may be beneficial in terms of long-term outcome or may merely delay the inevitable loss of selectively vulnerable neurons. Even if the latter is true, mild hypothermia may extend the therapeutic window for other interventions. This extension of the therapeutic window requires further documentation. After normothermic cardiac arrest of 11 mins in dogs, mild resuscitative hypothermia from 15 mins to 12 hours after reperfusion plus cerebral blood flow promotion normalized functional recovery with the least histologic damage seen thus far. Optimal duration of, and rewarming methods from, resuscitative hypothermia need clarification. The earliest possible induction of mild hypothermia after cardiac arrest seems desirable. Head-neck surface cooling alone is too slow. Among many clinically feasible rapid cooling methods, carotid cold flush and peritoneal cooling look promising. After traumatic brain injury or focal brain ischemia, which seem to still benefit from even later cooling, surface cooling methods may be adequate. Resuscitative hypothermia after cardiac arrest, traumatic brain injury, or focal brain ischemia should be considered for clinical trials.
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PMID:Resuscitative hypothermia. 860 9

Hydrogen peroxide (H2O2) is suspected to be involved in numerous brain pathologies such as neurodegenerative diseases or in acute injury such as ischemia or trauma. In this study, we examined the ability of pyruvate to improve the survival of cultured striatal neurons exposed for 30 min to H2O2, as estimated 24 hr later by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay. Pyruvate strongly protected neurons against both H2O2 added to the external medium and H2O2 endogenously produced through the redox cycling of the experimental quinone menadione. The neuroprotective effect of pyruvate appeared to result rather from the ability of alpha-ketoacids to undergo nonenzymatic decarboxylation in the presence of H2O2 than from an improvement of energy metabolism. Indeed, several other alpha-ketoacids, including alpha-ketobutyrate, which is not an energy substrate, reproduced the neuroprotective effect of pyruvate. In contrast, lactate, a neuronal energy substrate, did not protect neurons from H2O2. Optimal neuroprotection was achieved with relatively low concentrations of pyruvate (</=1 mM), whereas at high concentration (10 mM) pyruvate was ineffective. This paradox could result from the cytosolic acidification induced by the cotransport of pyruvate and protons into neurons. Indeed, cytosolic acidification both enhanced the H2O2-induced neurotoxicity and decreased the rate of pyruvate decarboxylation by H2O2. Together, these results indicate that pyruvate efficiently protects neurons against both exogenous and endogenous H2O2. Its low toxicity and its capacity to cross the blood-brain barrier open a new therapeutic perspective in brain pathologies in which H2O2 is involved.
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PMID:Pyruvate protects neurons against hydrogen peroxide-induced toxicity. 936 52


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