Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We assessed the effect of polyethylene glycol conjugated superoxide dismutase (PEG-SOD) on myocardial stunning in the rabbit heart in which xanthine oxidase level is extremely low. 2. In open-chest anaesthetized rabbits, the left marginal branch of the coronary artery was occluded for 10 min and then reperfused for 30 min. A group of rabbits (PEG-SOD group) received 1000 units/kg of PED-SOD and another group (control group) was given saline 15 min before the coronary occlusion. 3. Regional systolic thickening fraction (TF) was similarly reduced to approximately -25% of baseline value during ischaemia in both groups. However recovery of TF after reperfusion was significantly better in the PEG-SOD group (n = 9) and TF at 30 min after reperfusion was 70.1 +/- 3.9% of baseline value compared with 44.9 +/- 3.4% in the control group (n = 9; P less than 0.05). Rate-pressure products, left ventricular pressure, and LV dP/dt max were not significantly different between the PEG-SOD treated and untreated control rabbits at any time during the experiment. PEG-SOD did not modify the regional myocardial blood flow (coloured microsphere method) during ischaemia/reperfusion, which was assessed by using separate groups of rabbits. 4. These findings indicate that oxygen free radicals are important in the pathogenesis of myocardial stunning in xanthine oxidase deficient hearts.
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PMID:Superoxide dismutase attenuated post-ischaemic contractile dysfunction in a myocardial xanthine oxidase deficient species. 155 25

In a recent overview on stunning, Bolli listed the three pillars on which theories on stunning rest: its causation by oxygen radicals, the amplification of damage by Ca2+ overload, and the resulting excitation contraction uncoupling. Our own experiments with SOD and catalase do not convince us that stunning is caused by free radicals, because we and others were unable to show improvement. An important pathway of radical generation, i.e., xanthine oxidase, does not exist in the hearts of several families of mammals, but stunning can of course be produced in these species. We agree with Bolli that stunning represents a disturbance of electromechanical coupling, but we acknowledge the controversy that exists with regard to the subcellular seat of the defect. Our results would support hypotheses that pinpoint the defect to the sarcoplasmic reticulum. However, the possibility of multiple defects should also be considered: Our finding of altered Ca2+ ATPase expression and Kusuoka's finding of altered myofibrillar Ca2+ sensitivity are not necessarily mutually exclusive but may be complementary, or may represent different stages of ischemic damage. Our finding of decreased myosin expression may help to explain the long persistence of the contractile defect. From the available evidence, the hypothetial possibility evolves that stunning is not just an injury, but rather the unmasking of a regulatory mechanism to protect the heart against premature or further damage. The observation that coronary occlusion causes both stunning and preconditioning by a parallel, and not by a sequential, mechanism and that a multitude of genes alter their expression in order to protect the myocyte argue for a regulatory change.
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PMID:Molecular mechanisms in "stunned" myocardium. 175 39

It has been reported that agents having the ability to scavenge oxygen-derived free radicals reduce the severity of ventricular arrhythmias that occur after brief coronary occlusion and reperfusion. Superoxide dismutase plus catalase (SOD + CAT) or placebo was administered in a blinded randomized fashion prior to coronary occlusion in rats (n = 25 each group) undergoing a 5-min left coronary occlusion followed by 15 min of reperfusion. During reperfusion, ventricular tachycardia (VT) developed in 96% of animals in both groups. Reperfusion ventricular fibrillation (VF) developed in 60% of the placebo group vs 56% in the SOD + CAT group (p = 1.0). Irreversible VF occurred in 40% of the placebo group vs 20% in the SOD + CAT group (p = 0.22). Atrioventricular block occurred in 12% of placebo and 4% of SOD + CAT animals (p = 0.61). There were no significant difference between groups in duration of VT (85 +/- 15 s (mean +/- SEM) placebo vs 81 +/- 14 s SOD + CAT, p = 0.81), total duration of VT plus VF (391 +/- 76 s placebo vs 256 +/- 64 SOD + CAT, p = 0.45) or numbers of single ventricular ectopic beats (65 +/- 15 placebo vs 97 +/- 18 SOD + CAT, p = 0.18). Heart rate at reperfusion was slightly higher in control than SOD + CAT animals (340 +/- 33 vs 319 +/- 32, p = 0.02). Risk zone size, determined by Monastral blue injection, was equal in both groups (34 +/- 2% of ventricular mass). The occurrence of reperfusion VF in this model could not be predicted by heart rate at reperfusion (331 +/- 33 VF animlas vs 328 +/- 36 no VF, p = 0.77), or by risk zone size (34 +/- 2%, VF and no VF groups).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of significant effects of superoxide dismutase and catalase on development of reperfusion arrhythmias. 187 67

We tested whether recombinant human superoxide dismutase conjugated to polyethylene glycol (PEG-SOD) to prolong its plasma retention time could limit myocardial infarct size in an ischemia-reperfusion model in the rabbit. One group of animals received 1000 units/kg of PEG-SOD as an intravenous bolus 15 min before coronary occlusion. A second group received saline only and served as controls. Under pentobarbital anesthesia, a left coronary branch was occluded for 30 min and then reperfused. The surgical wounds were repaired and the animals were allowed to recover. Seventy-two hours after the coronary occlusion, the heart was excised and the size of the area at risk (ischemic vascular bed) was assessed with fluorescent particles and the infarct size was determined by histology (Hematoxylin-eosin, Azan stain). Infarct size as a percentage of the area at risk was similar between the groups, 46.5 + 2.7 in the PEG-SOD group (n = 8) and 48.9 + 3.1 in the control group (n = 8). There were no significant differences between the groups indicating that PEG-SOD did not limit infarct size in this model.
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PMID:Superoxide dismutase conjugated to polyethylene glycol fails to limit myocardial infarct size after 30 min ischemia followed by 72 h of reperfusion in the rabbit. 206 22

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

Disagreement regarding the cardioprotective role of superoxide dismutase may relate to the use of different durations for induction of ischemic injury and reperfusion. The present study employed superoxide dismutase conjugated to polyethylene glycol (PEG-SOD), which has a half-life greater than 30 hours. Two protocols differing in the mode of administration and the duration of the reperfusion interval were used. Dogs were subjected to occlusion of the circumflex coronary artery for 90 minutes, then reperfused for 6 hours (Protocol A) or 4 days (Protocol B). The dogs received either polyethylene glycol conjugated to albumin (PEG-ALB) or PEG-SOD (1,000 U/kg). In Protocol A, treatment was administered starting 15 minutes before coronary occlusion and continued for 2 hours, terminating 15 minutes after reperfusion. Infarct size was determined 6 hours later. In Protocol B, the conjugated proteins were given 15 minutes before reperfusion and ended simultaneously with reperfusion. Infarct size was measured after 4 days. Infarct size (percentage of area at risk) in control (n = 9) and treated (n = 9) dogs in Protocol A differed between groups: 46.7 +/- 3.5% versus 28.3 +/- 2.9%, respectively (p less than or equal to 0.005); risk regions did not differ: 42.8 +/- 1.5% versus 43.8 +/- 2.1%, respectively. Myocardial salvage also was observed in Protocol B. Infarct size in control (n = 13) and treated (n = 13) groups was 44.2 +/- 2.6% versus 29.2 +/- 1.6%, respectively (p less than or equal to 0.005), with risk regions being 44.4 +/- 1.4% versus 46.0 +/- 1.6% (p = NS). Hemodynamic variables did not differ during the period of coronary artery occlusion. The respective collateral blood flows to the inner two thirds of the ischemic myocardium determined 60 minutes after occlusion were 0.05 +/- 0.01 ml/min/g and 0.06 +/- 0.04 ml/min/g (p = 0.806) for the PEG-ALB and PEG-SOD treated groups, respectively. Infarct size was related inversely to collateral blood flow in the PEG-ALB treated group. This relation shifted downward (analysis of covariance, p = 0.017). Plasma SOD activity in Protocols A sustained for 6 hours. Significant enzymatic activity was present after 4 days in Protocol B. Previous negative studies with native SOD may be related to the short half-life of its free-radical scavenging capacity, which compromises the chances of observing a protective effect after 4 days of reperfusion. The present results support our previous observations, as well as those of other investigators, demonstrating that superoxide dismutase can reduce that component of myocardial injury associated with reperfusion.
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PMID:Superoxide dismutase conjugated to polyethylene glycol provides sustained protection against myocardial ischemia/reperfusion injury in canine heart. 318 Mar 57

Oxygen-derived free radicals (O-2 and .OH) have been implicated in myocardial injury associated with coronary artery occlusion followed by reperfusion. While these cytotoxic oxygen species are predominantly produced upon reintroduction of molecular oxygen to previously ischemic tissue, they may also be generated throughout coronary occlusion in species (such as dog and man) in which native collateral vessels permit residual blood flow into the ischemic bed. To test this theory, 20 anesthetized, open-chest dogs underwent 6 h of permanent left anterior descending coronary artery occlusion: ten dogs were treated with the potent free radical scavenging enzymes superoxide dismutase (SOD: 5 mg/kg per hour) plus catalase (5 mg/kg per hour), while the remaining ten animals received saline. Infusion of drug or saline solution was begun 15 min prior to occlusion, and maintained throughout occlusion. Infusion of SOD + catalase did not significantly affect the extent of the area at risk of infarction (19.5 +/- 1.8% vs 24.0 +/- 1.4% of the left ventricle for the treated vs control group; P = NS), did not reduce myocardial oxygen demand (heart rate and arterial pressures were comparable for both groups), and did not alter collateral blood flow to the ischemic myocardium. However, mean infarct size in dogs treated with SOD + catalase (39.6 +/- 6.6% of the area at risk; 8.4 +/- 2.1% of the left ventricle) was significantly smaller than that observed in the saline controls (73.0 +/- 6.3% of the area at risk, P less than 0.01; 19.8 +/- 2.2% of the left ventricle, P less than 0.01). Thus, infusion of SOD + catalase prior to and during 6 h of coronary occlusion significantly reduced infarct size assessed at 6 h postocclusion. To determine whether this reduction in infarct size represented long-term salvage of ischemic myocardium, an additional 14 dogs (seven treated and seven controls) underwent the same procedure as described above; in this case the artery was reperfused after the 6-hour occlusion period, infusion of the SOD + catalase or saline solution stopped at 5-10 min postreperfusion, and the hearts examined at 30-48 h postocclusion. In contrast to the results at 6 h postocclusion, the necrosis at 30-48 h postocclusion was large, confluent and transmural in all dogs (infarct size = 21.2 +/- 2.5% vs 22.7 +/- 4.4% of the left ventricle for treated vs controls; P = NS). These results suggest that infusion of SOD + catalase in this model may delay, but not prevent, the development of ischemic necrosis.
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PMID:Effect of oxygen-derived free radical scavengers on infarct size following six hours of permanent coronary artery occlusion: salvage or delay of myocyte necrosis? 360 42

Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.
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PMID:Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs. 395 34

In order to clarify the time course of superoxide generation in situ during ischemia and reperfusion in the rabbit heart, we used a method of enhanced chemiluminescence (CL) with 2-methyl-6-[p-methoxyphenyl]-3, 7-dihydroimidazo [1, 2-alpha]pyrazin-3-one (MCLA) as a specific probe for detecting superoxide radicals. The surface of the rabbit heart was exposed to a photomultiplier tube in a light-proof box. We introduced a reversible snare occluder into the box to continuously observe the light emission. An ischemia-reperfusion group (I/R, n = 7) was subjected to 30 mins of coronary occlusion, followed by 90 mins of reperfusion. We performed the same procedure (except for coronary occlusion) in the sham-operated group (n = 4). Another group of rabbits (n = 4) subjected to I/R received superoxide dismutase (SOD: 20 mg/kg, i.v.) during reperfusion to observe the CL response. In the I/R-group, the increase in CL began at 13 +/- 2 (mean +/- SEM) mins and peaked at 52 +/- 12 mins of reperfusion. CL in the I/R-group gradually increased from 818 +/- 350 counts/10 secs in the preischemic period to 1077 +/- 401 counts/10 secs during reperfusion (p < 0.01). In contrast, there was no increase in CL in the sham-operated group. The administration of SOD briefly attenuated CL by 24.1 +/- 6.8% for a period of 24.3 +/- 6.8 mins. The superoxide generation in situ in the ischemic rabbit heart appears to increase gradually and persists for a period following reperfusion.
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PMID:Continuous detection of superoxide in situ during ischemia and reperfusion in the rabbit heart. 918 85

Previous studies in conscious pigs have demonstrated that a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles renders the heart relatively resistant to myocardial stunning 24 h later [late preconditioning (PC) against stunning] by an unknown mechanism. Since oxygen radicals contribute importantly to myocardial stunning and since antioxidant enzymes have been reported to be upregulated 24 h after PC in dogs and rabbits, we tested the hypothesis that late PC against stunning is related to an increase in endogenous antioxidant defenses. Chronically instrumented conscious pigs underwent a sequence of ten 2-min coronary occlusion/2-min reperfusion cycles (preconditioned group, n = 11) or received no intervention (control group, n = 5). Twenty-four hours later, pigs were killed and the myocardial levels of Mn superoxide dismutase (SOD), Cu-Zn SOD, catalase, glutathione (GSH) peroxidase, GSH reductase, GSH, GSH disulfide, alpha-tocopherol, and ascorbate were measured. There were no differences in any of the enzymatic or nonenzymatic antioxidants between the ischemic and nonischemic regions in the preconditioned group or between the control and the preconditioned group. Thus, when a marked protection against stunning was present (24 h after PC), no alteration in antioxidant defenses was observed. These results indicate that, in conscious pigs, late PC against myocardial stunning is not mediated by increased endogenous antioxidant defenses, thereby refuting one of the major current hypotheses regarding this phenomenon.
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PMID:Late preconditioning against stunning is not mediated by increased antioxidant defenses in conscious pigs. 936 27


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