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

An experimental model of myocardial ischemia/reperfusion injury was used to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isolated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 microM SC-52608 exhibited a decrease in the release of creatine kinase and intracellular potassium compared to hearts receiving vehicle (control). A progressive increase in left ventricular end-diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in control hearts when compared to hearts treated with SC-52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irreversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 microM SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 protects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed protective effect is most likely related to its ability to scavenge superoxide.
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PMID:Protective effects of the SOD-mimetic SC-52608 against ischemia/reperfusion damage in the rabbit isolated heart. 779 54

The advent of molecular biology techniques has profoundly changed pathophysiological concepts of myocardial hypertrophy and overload-induced heart failure. Heart failure is a consequence of the limits and imperfection of biological adaptation to mechanical overload. Factors including fibrosis, senescence, ischemia, inflammation, catabolism and hormonal response may contribute to myocardial dysfunction. In humans changes in the genes coding for myosin are observed only in the atrial myocardium, in association with diastolic left ventricular function. In most animal species, alteration in proteins involved in intracellular calcium movement and autonomic nervous dysfunction are responsible for both reduction of Vmax and arrhythmias associated with myocardial hypertrophy. Moreover, myocardial fibrosis is a major determinant of enhanced left ventricular stiffness and arrhythmogenicity.
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PMID:[Physiopathology of cardiac insufficiency. Biological factors of adaptation and disadaptation of the heart to chronic mechanical overload]. 787 7

The purpose of this study was to examine the use of hypothermia to protect skeletal muscle from the effects of 4 hr of tourniquet ischemia. Muscle recovery was investigated at 6 weeks. Four hours of tourniquet ischemia was induced in two groups (n = 8 per group) of male, Wistar rats (344 +/- 15 g). In the ischemia-only group (IO), the ischemic leg was exposed to room temperature. In the ischemic-hypothermic group (IH), the ischemic leg was cooled to 5-8 degrees C throughout the ischemic period. The contralateral leg served as control. After 6 weeks, the isometric contractile function of the gastrocnemii of both the ischemic and nonischemic legs was determined. Following the functional assessment, the soleus and plantaris muscles were removed and weighed, and biopsies were taken for muscle fiber composition, mean fiber area, and myosin heavy chains (MHC) analysis. Differences between groups (P < 0.05) were determined using ANOVA. Muscle wet weight, tetanic forces, fiber area, fiber type, and MHC composition of IH group were the same as the control group. Yet, twitch tension and relaxation time were lower and longer in the IH group than control group. The tetanic force at 100 Hz of the IH group (12.62 +/- 0.73 N/g) was significantly greater than that of the IO group (2.12 +/- 0.84 N/g). The type 1 muscle fiber areas of plantaris in the IH (1.84 +/- 0.04 x 1000 microns 2) were significantly greater than those of the IO group (1.56 +/- 0.42 x 1000 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skeletal muscle form and function after 4 hr ischemia-hypothermia. 793 25

To assess the development of oxidative stress in cardiac ischemia/reperfusion, the resulting depletion of plasma ascorbate was monitored by electron spin resonance spectroscopic detection of ascorbyl free radical (AFR) in a homogeneous group of 12 patients undergoing aortic valve replacement. Dimethyl sulfoxide (DMSO) was used as an enhancer and stabilizer for AFR in plasma separated from blood samples collected 15 min before incision, 10 min before aortic declamping, and sequentially during the initial 30 min of reperfusion. Plasma DMSO/AFR levels of patients were found to be significantly lower than in healthy subjects (-25%), further decreased upon ischemia (-35%), dropped to their lowest values within the first 10 min of reperfusion (-46%), and did not recover their initial values within 30 min following reflow. Cardiac index measurements revealed a still depressed heart function 4 h postdeclamping and a more delayed tissue injury was evidenced by cardiac myosin and myoglobin release in plasma. DMSO/AFR levels at early reperfusion were slightly (+ 12%) higher in plasma obtained from coronary sinus samples than in plasma from peripheral blood, suggesting an extra ascorbate release from the injured heart tissue. The close analogy between these results and the reported measurements of other plasma markers of oxidative stress, including ascorbate, indicates that the present method could be of great value in clinical practice.
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PMID:Ascorbyl free radical: a noninvasive marker of oxidative stress in human open-heart surgery. 800 38

At the present time there is no final explanation for the etiology of Bell's palsy. The theory of pathophysiology involving a combined primary and/or secondary ischemia is now well-accepted. As such, it is supposed that there is a dysfunction of the blood vessels which supply the nerve. This is followed by a hyperpermeability and transudation which lead to edema of the nerve and compression of the blood supply. The vicious circle starts and the final result is facial paralysis. The blood supply of the facial nerve has been described previously in the literature, although there have been no experimental investigations on in vivo perfusion of the nerve. In the present study we evaluated the percentage of those vessels perfused among the total blood vessels found in facial nerves of Wistar rats. Animals were examined after i.v.-injections of Evans blue dye, with perfused vessels demonstrable under a fluorescence microscope. Forty-eight hours later, the same tissue section was stained by indirect immunofluorescence and the primary antibody used was directed against myosin of non-muscle sources. This antibody cross-reacted with myosin of vascular endothelial cells and thus allowed identification of any existing blood vessels. More than 90% of the immunostained vessels were labeled with the dye, showing that almost all vessels were perfused.
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PMID:[Blood supply to the facial nerve]. 802 Nov 58

Orotic acid accelerates compensatory myocardial hypertrophy after regional ischemia and improves left ventricular function acutely after global ischemia. In this study, the effect of orotic acid on left ventricular function was investigated 4 days after global ischemia (75 minutes, 21 degrees C) using heterotopically transplanted rabbit hearts (n = 18). Experimental animals received daily 100-mg/kg doses of intraperitoneally administered orotic acid, starting 1 day before transplantation, and showed a threefold increase in the serum level of orotic acid by 4 days. After 1 hour of reperfusion, the developed pressure was equally depressed in both the control and experimental groups; however, 4 days later, the developed pressure in control animals was decreased by 3 +/- 3 mm Hg (versus the developed pressure measured at 1 hour) while the developed pressure in experimental animals was significantly increased by 25 +/- 8 mm Hg. Heterotopically transplanted hearts manifested diminished systolic function (stemming from ischemia and unloading) as well as decreased expression of adult myosin. Because orotic acid has been observed to produce an increase in protein synthesis in other models, we investigated whether this improvement in systolic function resulted from an orotic acid-mediated augmentation (or preservation) or normal adult myosin expression. Both orotic acid-treated and untreated hearts manifested decreased expression of the beta-myosin heavy chain protein and steady-state messenger RNA levels. Because function improved with decreased beta-myosin heavy chain expression, an alternate mechanism underlying orotic acid-mediated improvement in function is implicated. Nevertheless, orotic acid may be a therapeutic agent facilitating long-term recovery from global ischemia.
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PMID:Orotic acid improves left ventricular recovery four days after heterotopic transplantation. 806 40

Ultrastructural findings in 350 endomyocardial biopsy specimens and 59 autopsy or explanted hearts from cardiac transplant recipients are reviewed. Myocyte degeneration can be readily distinguished from necrosis by the technique described. Vascular changes of endothelial activation, endothelial cell damage, and basement membrane reduplication can be readily identified. In addition, the myofilament composition of ischemic hearts in patients with allograft coronary artery disease is distinctive: There is a disproportionate loss of actin over myosin, giving a coarse appearance to the myofilaments. These changes are useful in further defining the morphologic features associated with rejection and ischemia in cardiac transplant recipients.
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PMID:Ultrastructural findings in cardiac transplant recipients. 779 52

Serum levels of cardiac myosin light chain 1 after heart transplantation were studied in 24 infants and children who underwent heart transplantation between June 1990 and April 1991. The ages of the patients ranged from 4 days to 6 years 7 months (mean, 9.9 months), and their body weights ranged from 2.2 to 20 kg (mean, 5.6 kg). The ages of the donors ranged from 2 days to 8 years, 7 months (mean, 26.6 months), and their body weights ranged from 2.5 to 26 kg (mean, 11.4 kg). The donor heart ischemic time ranged from 90 minutes to 482 minutes (mean, 279 minutes). Peak myosin levels after heart transplantation showed significant correlation with the duration of graft ischemia (p < 0.01) and with diastolic cardiac function in the first posttransplant week (p < 0.05). Peak myosin levels did not correlate with systolic cardiac function, age of the donor, or age of the recipient. Myosin levels of the 15 patients with graft ischemic times exceeding 4 hours averaged 6.30 +/- 3.50 ng/ml. These levels were significantly higher than those of patients with graft ischemia lasting less than 4 hours (2.60 +/- 1.20 ng/ml; p < 0.01). Both of the values are higher than previously reported values of normal controls but lower than previously reported values of patients with myocardial infarction. Preservation techniques used for this series of transplant operations provided good clinical protection of the donor heart for up to 8 hours, although release of the cardiac myosin light chain fragment correlated with duration of graft ischemia. Cardiac myosin levels appeared to be a good indicator of heart graft damage during ischemic preservation. It remains to be determined at what level of myosin release (and, hence, at what duration of graft ischemia) irreversible myocardial damage, which might result in permanent functional compromise, occurs.
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PMID:Myosin light chain efflux after heart transplantation in infants and children and its correlation with ischemic preservation time. 836 Nov 87

Effects of reduction of blood pressure and regression of left ventricular hypertrophy following hydralazine and captopril therapy on ischemic cardiac function and myocardial metabolism were studied in spontaneously hypertensive rats (SHR). Hydralazine (1.5 or 3 mg/kg/day) and captopril (50 or 100 mg/kg/day) were administered to SHR from 19 to 26 weeks of age. Both hydralazine and captopril significantly decreased arterial blood pressure in SHR, but only captopril significantly reduced left ventricular weight. The percentage of V3 myosin isozyme significantly decreased in captopril-treated SHR compared to hydralazine-treated SHR. At the end of long-term treatment, hearts were removed and perfused for 15 min by the working heart technique, and then global ischemia was induced for 30 min. The ischemic heart was reperfused for 30 min. In hydralazine-treated SHR and captopril-treated SHR, the pressure-rate product and extent of recovery of the coronary flow during reperfusion following 30 min of ischemia were higher than those in control SHR, but this difference was significant only in captopril-treated SHR. Hydralazine and captopril treatment improved the restoration of the levels of ATP, creatine phosphate, total adenine nucleotide and energy charge potential in SHR after reperfusion following 30 min of ischemia, but only captopril had a significant effect. In conclusion, regression of left ventricular hypertrophy is more important than lowering of blood pressure in order to improve the ischemic myocardial damage.
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PMID:Effect of regression of cardiac hypertrophy on ischemic myocardial damage in spontaneously hypertensive rats. 845 May 99

Programmed cell death in the myocardium has been linked to ischemia reperfusion injury as well as to excessive mechanical forces associated with increases in ventricular loading. Moreover, hypoxia activates the suicide program of cardiac myocytes in vitro. Because the supplied portion of the ventricular wall is ischemic and subjected to high levels of systolic and diastolic stresses (acutely after coronary artery occlusion), apoptosis and necrosis may contribute independently to myocyte cell death after infarction. Therefore, myocardial infarction was produced in rats, and, after the determination of ventricular hemodynamics, the contribution of apoptotic and/or necrotic myocyte cell death to infarct size was measured quantitatively from 20 minutes to 7 days after coronary artery occlusion. Programmed cell death was assessed by the terminal deoxynucleotidyl transferase assay and by the electrophoretic detection of DNA laddering. Myocyte necrosis was evaluated by myosin monoclonal Ab labeling. Moreover, the expression of Bcl-2, Bax, and Fas proteins in myocytes was examined by immunocytochemistry. Myocyte cell death by apoptosis and necrosis comprised nearly 3 million myocytes at 2 hours. Apoptotic cell death involved 2.8 million cells and necrotic cell death only 90,000 myocytes. Apoptosis continued to represent the major independent form of myocyte cell death, affecting 6.6 million myocytes at 4.5 hours. Myocyte necrosis peaked at 1 day, including 1.1 million myocytes. DNA electrophoretic analysis confirmed these observations by showing nucleosomal ladders at 2-3 hours, 4.5 hours, 1 day, and 2 days after coronary artery occlusion. Myocytes showing both DNA strand breaks and myosin labeling were a prominent aspect of myocardial damage only after 6 hours. Finally, the expression of Bcl-2 and Fas in myocytes increased 18-fold and 131-fold, respectively. In conclusion, programmed myocyte cell death is the major form of myocardial damage produced by occlusion of a major epicardial coronary artery, whereas necrotic myocyte cell death follows apoptosis and contributes to the progressive loss of cells with time after infarction. The enhanced expression of Fas may be implicated in the activation of apoptosis in spite of the increase in Bcl-2, which tends to preserve cell survival.
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PMID:Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. 856 1


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