Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen free radical injury during reperfusion of ischemically stored heart transplants may further impair the ability of the transplanted heart to reuse substrate for recovery. We compared the effects of oxygen free radical scavengers, superoxide dismutase and catalase, either alone or combined with glucose-insulin-potassium, in an improved model of the heterotopically transplanted rat heart. Group 1 hearts (n = 8) received no preservation before transplantation and were transplanted immediately. Hearts in four other groups (n = 8 for each group) underwent cold storage (4 degrees to 6 degrees C) for 3 1/2 hours before transplantation. Five minutes before reperfusion of the transplanted hearts, recipient rats received one of the following intravenous treatments: saline (group 2), glucose-insulin-potassium (group 3), superoxide dismutase/catalase (group 4), and superoxide dismutase/catalase plus glucose-insulin-potassium (group 5). Left ventricular end-diastolic pressure, rate of rise of left ventricular pressure, myocardial blood flow, coronary resistance, and tissue adenosine triphosphate content of the heart transplants were assessed during or at the end of 2 hours of reperfusion. Hearts treated with superoxide dismutase/catalase alone showed improvement of end-diastolic pressure and myocardial blood flow. The use of glucose-insulin-potassium alone did not facilitate the recovery of transplanted hearts. In contrast, the combined use of superoxide dismutase/catalase plus glucose-insulin-potassium resulted in a superior recovery of all functional and hemodynamic parameters. These results indicate that free radical scavengers in the presence of glucose-insulin-potassium significantly improve functional recovery in the setting of heart transplantation.
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PMID:Improved recovery of heart transplants by combined use of oxygen-derived free radical scavengers and energy enhancement. 151 71

In the present investigation, we used electrolysis as a source of oxygen free radicals to test their possible role in norepinephrine release, as well as in the mechanism of cellular injury, cardiac dysfunction and arrhythmias. In the isolated rat heart perfused under constant pressure, according to the Langendorff technique, electrolysis of the Krebs-Henseleit solution (10 mA d.c. current for 1 min) produced myocardial irreversible dysfunction within 5 min. Fifteen minutes after electrolysis, significant falls in the left ventricular pressure (from 87.5 +/- 6.8 to 33.7 +/- 5.2 mmHg), dP/dt max (from 1230 +/- 90 to 375 +/- 59 mmHg/s), heart rate (from 287 +/- 18 to 119 +/- 13.5 beats/min) and coronary flow (from 14.8 +/- 9 to 3.4 +/- 1.7 ml/min) were observed, along with an increase in left ventricular end diastolic pressure from 10 to 50 +/- 3.5 mmHg (n = 8, P less than 0.01). AV conduction block and/or sinus bradycardia were noted in all preparations. An increase in norepinephrine washout from 298.5 +/- 84 at baseline to 610 +/- 110 pg/min/g 5 min after electrolysis was measured (n = 8, P less than 0.05) and a 44.8 +/- 9.2% and 35 +/- 7.5% reduction, respectively in right and left ventricular tissue norepinephrine content was also found at 30 min (n = 5, P less than 0.05). Pretreatment of the hearts 10 min before electrolysis and throughout the experimental period by superoxide dismutase (SOD; 100 U/ml), catalase (150 U/ml), a combination of SOD + catalase or mannitol (50 mM) partially blocked the deleterious effect of free radicals and permitted a functional recovery of 50 to 60%, mannitol being the more potent protective agent. Furthermore, these scavengers also significantly reduced norepinephrine washout.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial dysfunction and norepinephrine release in the isolated rat heart injured by electrolysis-induced oxygen free radicals. 190 7

This study was designed to evaluate the efficacy of superoxide dismutase (SOD) and catalase on ischemic and reperfusion injury in the isolated working rat heart. The temperature and duration of ischemia varied under three conditions: 1) at 37 degrees C for 35 minutes, 2) at 28 degrees C for 120 minutes and 3) at 20 degrees C for 120 minutes. SOD (100 mg/L) and catalase 10 mg/L) were either added to St. Thomas' Hospital cardioplegic solution during ischemia (CP group) or to the reperfusion solution for 10 minutes after reflow (RS group). They were compared with a control group which received no free radical scavengers. The postischemic recovery ratio of cardiac functions were markedly superior to the values of the control group with a significant difference being noted in the CP and RS groups under ischemia at 37 degrees C and 28 degrees C. In the series done at 20 degrees C, a significant improvement was seen in the RS group, and the CP group also showed better functional recovery rates compared with the control group, although the differences were not statistically significant. Thus, SOD and catalase added to the cardioplegic solution or reperfusion fluid demonstrated an excellent protective effect on the myocardium against ischemic or reperfusion injury in both hypothermic ischemia and normothermia.
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PMID:The effect of superoxide dismutase and catalase on myocardial reperfusion injury in the isolated rat heart. 196 Sep

The objective of this study was to determine the effect of oxygen and the oxygen radical-scavenging enzyme catalase on the neonatal rabbit heart exposed to global ischemia. The experiments were performed with an isolated neonatal (7 to 10 days of age) working heart model in which normothermic (37 degrees C) ischemia was produced for 60 minutes. Left ventricular developed pressure, ratio of change of ventricular pressure to change in time, and aortic flow were measured before ischemia and 30 minutes after reperfusing the hearts with physiologic saline solution. In the control group (ischemia only), developed pressure and ratio of change of ventricular pressure to change in time recovered to 27% +/- 3% (mean +/- standard error of the mean) and 24% +/- 7% of baseline; the hearts were incapable of ejecting (aortic flow = 0). Treatment of hearts before and after ischemia with catalase (150 units/ml of perfusate) was studied in a second group (control plus catalase), but functional recovery (developed pressure = 32% +/- 1%; ratio of change of ventricular pressure to change in time = 24% +/- 2%, and aortic flow = 0) was not significantly different from the control group. The effect of washout midway through the ischemic period with a low oxygen (oxygen concentration less than 35 mm Hg) solution was measured in a third group (hypoxic physiologic saline solution). Functional recovery (developed pressure = 13% +/- 3%; ratio of change of ventricular su pressure to change in time = 13% + 2%; aortic flow = 0) was not significantly different from the control and control plus catalase groups. In marked contrast were the effects of washout with an oxygenated (oxygen concentration greater than 500 mm Hg) solution (oxygenated physiologic saline solution) in which functional recovery (developed pressure = 78% +/- 3%; ratio of change of ventricular pressure to change in time = 80% +/- 3%; aortic flow = 39% +/- 9%) was significantly better than in the control, control plus catalase, and hypoxic physiologic saline solution groups. Use of modified St. Thomas' Hospital cardioplegic solution (cardioplegic solution group) during the ischemic period also resulted in substantial functional recovery (developed pressure = 80% +/- 3%; ratio of change of ventricular pressure to change in time = 78% +/- 5%; aortic flow = 64% +/- 7%) that did not differ significantly from that in the oxygenated physiologic saline solution group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recovery of the neonatal heart after normothermic ischemia. Effect of oxygen and catalase. 199 43

The present study was performed to clarify whether the combination of superoxide dismutase (SOD) and catalase (CAT) can reduce Ca2+ overload and improve recovery of function and metabolites during reperfusion in isolated globally ischemic rat hearts. In non-treated hearts, left ventricular developed pressure (LVDP) recovered to only 30% of the preischemic value with elevation of left ventricular end-diastolic pressure (LVEDP) after 30 min of reperfusion following 30 min of global zero-flow ischemia. ATP and CP fell by 40% and 60%, respectively with 13 fold increase in Ca2+ uptake. A combined administration of SOD and CAT at low concentrations improved recovery of function (LVDP to 60%), reduced Ca2+ uptake (10 fold) without any improvement in high energy phosphates. However a combination of SOD and CAT at higher concentrations did not improve, or even deteriorate functional and metabolic recovery with increased Ca2+ overload (12 to 14 fold). These results indicated that the extracellular free radical scavengers, SOD and CAT, had a biphasic effect on reperfusion injury and could be partially beneficial at low concentrations.
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PMID:[Biphasic effects of a combined administration of SOD and CAT on Ca overload and recovery of function and metabolites]. 223 62

The purpose of the present study was to determine whether the combined administration of superoxide dismutase (SOD) and catalase (CAT) or efforts to maintain the glutathione redox pathways with sulfhydryl agents could improve Na+ imbalance, reduce Ca2+ overload, and enhance recovery of function and metabolites upon reperfusion in isolated ischemic rat hearts, presumably by scavenging oxygen free radicals. After a 30-min exposure to zero-flow ischemia, left ventricular developed pressure (LVDP) and heart rate recovered to 31 and 81% of the preischemic value, respectively, ATP fell by approximately 40%, and 45Ca2+ uptake rose from 0.8 to 10.4 mumol/g dry tissue. A combination of SOD and CAT at low concentrations (5 X 10(4) and 7.5 X 10(4) U/l, respectively) had a beneficial effect on recovery of LVDP (to 59%), reperfusion 45Ca2+ uptake (to 7.9 mumol/g dry tissue), and recovery of Na+ imbalance. When sulfhydryl donors, such as glutathione, cysteine, N-acetyl-L-cysteine, or dithiothreitol, were administered 20 min before induction of ischemia, no significant protective effects were observed. These results indicated that the extracellular free radical scavengers, SOD and CAT, could attenuate partially the ionic imbalance in ischemic-reperfused myocardium and result in improved recovery of contractile function. Attempts to enhance the intrinsic scavenging system were not successful, suggesting that this system may not play an important role in disposing of free radicals.
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PMID:Effects of anti-free radical agents on Na+, Ca2+, and function in reperfused rat hearts. 237 99

Eicosanoid metabolism is altered by diabetes. However, postischemic responses of diabetic hearts (DH) to eicosanoids such as prostacyclin are unknown. a prostacyclin analogue iloprost (Ilo) was given to isovolumically beating rat hearts during 20 min of total global ischemia and 30 min of reperfusion. Acute DH (48 h) but not chronic DH (2 mo) had pronounced postischemic dysfunction (developed pressure = 22 +/- 11%), which was completely reversed by 3 X 10(-8) M Ilo (developed pressure = 113 +/- 15%). Ilo also stimulated endogenous prostacyclin release in postischemic control hearts (CH) but not acute or chronic DH. Ilo significantly decreased postischemic recovery in CH (from 67 +/- 11 to 15 +/- 4%), which was partially blocked by the coadministration of the calcium-entry blocker diltiazem or almost completely reversed by the free radical scavengers superoxide dismutase plus catalase (100 U/ml). These data suggest that Ilo may promote functional recovery in DH at concentrations that produce dysfunction in CH. Furthermore, Ilo may induce dysfunction in CH by a calcium ionophoretic action, which appears depressed in diabetes, and by concomitant free radical production (presumably via prostaglandin hydroperoxidases) during Ilo-stimulated endogenous prostacyclin synthesis.
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PMID:Diabetes alters postischemic response to a prostacyclin mimetic. 247 Feb 63

Electron paramagnetic resonance (EPR) spectroscopy was used to investigate whether (i) the free radicals produced in the "stunned" myocardium (myocardium with postischemic contractile dysfunction) are derived from O2, (ii) inhibition of radical reactions improves function, and (iii) i.v. spin traps are effective. Open-chest dogs undergoing a 15-min coronary occlusion received an i.v. infusion of the spin trap, alpha-phenyl N-tert-butylnitrone (PBN) (50 mg/kg). In group I (n = 6), EPR signals characteristic of radical adducts of PBN appeared in the coronary venous blood during ischemia and increased dramatically after reperfusion. In group II (n = 6), which received PBN and i.v. superoxide dismutase (SOD; 16,000 units/kg) plus catalase (12,000 units/kg), myocardial production of PBN adducts was undetectable during ischemia (delta = -100%, P less than 0.01 vs. group I) and markedly inhibited after reperfusion (delta = -86%, P less than 0.001). This effect was seen at all levels of ischemic zone flow but was relatively greater in the low-flow range. In group III (n = 8), the same dosages of SOD and catalase without PBN markedly enhanced contractile recovery (measured as systolic wall thickening) after reperfusion [P less than 0.01 at 3 hr vs. controls (group IV, n = 7)]. Systemic plasma activity of SOD and catalase averaged 127 +/- 24 and 123 +/- 82 units/ml, respectively, 2 min after reperfusion. PBN produced no apparent adverse effects and actually improved postischemic contractile recovery in group I (P less than 0.05 at 3 hr vs. controls). This study shows that (i) SOD and catalase are highly effective in blocking free radical reactions in vivo, (ii) the radicals generated in the "stunned" myocardium are derived from univalent reduction of O2, and (iii) inhibition of radical reactions improves functional recovery. The results provide direct, in vivo evidence to support the hypothesis that reactive oxygen metabolites play a causal role in the myocardial "stunning" seen after brief ischemia.
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PMID:Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. 254 84

The isolated perfused working rat heart model of cardiopulmonary bypass was used to assess whether (a) allopurinol pretreatment enhances resistance to normothermic (30 min) or hypothermic (4 h) ischemia; (b) addition of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to cardioplegic and/or reperfusion solutions are protective; (c) any protective effects are additive. With normothermic ischemia, allopurinol pretreatment improved recovery of aortic flow from its control value of 25 +/- 3% to 48 +/- 6% (P less than 0.05). Similarly, SOD plus CAT used during both ischemia and reperfusion improved recovery of aortic flow from a control value of 28 +/- 4% to 48 +/- 6% (P less than 0.05). However, various combinations of the two types of intervention afforded no additive protection. Under hypothermic (21 degrees C) conditions, allopurinol pretreatment was not effective, whereas SOD and CAT added during ischemia and reperfusion improved recovery of aortic flow from its control value of 53 +/- 4% to 69 +/- 5% (P less than 0.05). This value was similar to allopurinol pretreatment and SOD plus CAT added during ischemia and reperfusion (69 +/- 6%: P less than 0.05). These results provide further evidence that reperfusion-induced free radical formation may adversely affect postischemic recovery of function. The absence of an additive effect suggests a common mechanism of action, which is likely to involve the free radical-generating enzyme xanthine oxidase; however, other mechanisms may exist. Our results further support the use of antifree radical intervention in conjunction with cardioplegia to protect the heart during ischemia and reperfusion.
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PMID:Free radicals and cardioplegia: the absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat. 285 11

In an isolated, normothermic rat heart model (Langendorff, 37 degrees C), dimethylthiourea (DMTU) infusion only during reperfusion reduced both injury and measurable hydrogen peroxide (H2O2) concentrations after global ischemia. Cardiac function was assessed by measurement of ventricular developed pressure (DP). H2O2 was assessed using H2O2 dependent aminotriazole inactivation of myocardial catalase. Depletion of xanthine oxidase by two methods (tungsten or allopurinol inhibition) also improved recovery of function and H2O2 production. The results indicate that XO derived H2O2 contributes to myocardial reperfusion injury.
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PMID:Hydrogen peroxide mediates reperfusion injury in the isolated rat heart. 314 10


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