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

The protective effect of cardioplegia upon neonatal myocardium during ischemia has not been clearly established. This study evaluated the effects of cardioplegia on left ventricular function in isolated working neonatal rabbit hearts (aged 1 week) subjected to 120 minutes of global ischemia at 28 degrees C. Four groups were studied: Group 1, hypothermia alone; Group 2, intermittent washout with an oxygenated noncardioplegic solution; Group 3, multidose cardioplegia; Group 4, single-dose cardioplegia. After ischemia, cardiac output was reduced to 72% +/- 5% (mean +/- standard error of the mean) of control (p less than 0.02) in Group 1 and to 56% +/- 4% in Group 2 (p less than 0.001). In contrast, there was no significant reduction from baseline cardiac output in those animals receiving cardioplegic solution (Group 3, 93% +/- 6%, and Group 4, 97% +/- 4%). Group 2 hearts demonstrated significantly worse recovery of cardiac output and stroke volume than all other groups. After ischemia, the first derivative of left ventricular pressure fell to 73% +/- 13% of control in Group 1 (p less than 0.1) and to 89% +/- 5% in Group 2 (p less than 0.05). However, the first derivative of left ventricular pressure was restored to control values in Group 3 (118% +/- 11%) and Group 4 (114% +/- 9%). When compared to baseline, creatine kinase was higher 30 minutes after reperfusion in Group 1 (40 +/- 8 versus 143 +/- 32 IU/L/gm, p less than 0.05) and in Group 2 (39 +/- 7 versus 163 +/- 33 IU/L/gm, p less than 0.05). Creatine kinase remained unchanged from baseline in Groups 3 and 4. This study demonstrates excellent preservation of left ventricular function in the neonatal rabbit heart protected with cardioplegic solution. In contrast, neither hypothermia alone nor intermittent washout with an oxygenated noncardioplegic solution was effective in preventing myocardial dysfunction. As in adults, the administration of cardioplegic solution preserves ventricular function during ischemia in neonatal hearts.
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PMID:Protection of the neonatal myocardium during hypothermic ischemia. Effect of cardioplegia on left ventricular function in the rabbit. 359 97

Rat kidneys were made ischemic for 5 to 120 seconds. Segments of individual nephrons were dissected from freeze dried sections and analyzed for ATP, phosphocreatine, glycogen, glucose, glucose-6-phosphate, lactate and creatine kinase. ATP fell most rapidly in proximal convoluted and straight tubules (PCT, PST) and distal convoluted tubules (DCT), and most slowly in glomerulus and papilla. Phosphocreatine levels ranged fivefold and was highest in DCT, where it approached that of brain. Creatine kinase ranged 100-fold with lowest level in PCT, where the ischemic fall in phosphocreatine was so slow as to suggest a function other than that of an energy reserve. Glycogen varied tenfold from modest levels in distal segments to very low levels in PST, and was not used rapidly in any segment. Glucose consumption and lactate production were most rapid in distal portions. High-energy phosphate consumption for the first 7.5 seconds of ischemia, calculated from these data, indicates roughly-equal energy metabolism in proximal and distal segments, with lower levels in papilla, and especially in glomerulus. The absolute values suggest that the in vivo metabolic rate of the nephron continued almost unabated for 5 or 10 seconds of ischemia.
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PMID:Change in energy reserves in different segments of the nephron during brief ischemia. 361 2

The effects of the calcium antagonist, diltiazem, on myocardial injury during ischemia and reperfusion were studied both in vitro, in the isolated rat heart, and in vivo, in a closed-chest pig model. In the isolated rat heart, administration of diltiazem before or at the onset of ischemia resulted in a dose-dependent reduction of the incidence and duration of ventricular fibrillation. This reduction was associated with a dose-dependent reduction in overflow of ATP catabolites (adenosine, inosine, hypoxanthine and xanthine). Both changes were significant at concentrations of 3 X 10(-7) M diltiazem and higher. When 3 X 10(-7) M diltiazem was administered upon reperfusion no effect on the incidence of ventricular fibrillation and on ischemia induced total purine overflow was observed. However, the duration of ventricular fibrillation and purine overflow at 5 min after reperfusion were significantly reduced. In the pig experiments all untreated animals (n = 8) showed accelerated idioventricular rhythm (AIVR) upon reperfusion which lasted for 22 +/- 5 min after which sinus rhythm returned. Only two out of five treated animals (450 micrograms/kg/2 h) had an AIVR. Upon reperfusion both groups showed a substantial rise in noradrenaline concentration in the coronary sinus blood, but after 5 min this was significantly less in the treated group. Creatine kinase-kinetics were not altered by diltiazem, but the maximum creatine kinase level was significantly reduced. Within 4 days after the acute experiment 50% of the untreated animals died suddenly, whereas no sudden deaths occurred in the diltiazem group (P less than 0.05). Seven days after the acute experiment, sustained ventricular tachycardia could be induced with programmed electrical stimulation in three out of four surviving untreated pigs. In none of the diltiazem treated pigs was ventricular tachycardia inducible. The results of this study show that the calcium antagonist diltiazem can beneficially influence the events during ischemia and during reperfusion, both in vitro and in vivo; this benefit is associated with a reduction of ATP catabolism, creatine kinase release and noradrenaline overflow. Furthermore, diltiazem reduces electrical instability in the chronic phase of myocardial infarction.
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PMID:Effects of diltiazem on reperfusion-induced arrhythmias in vitro and in vivo. 382 Mar 17

The potential for enhancing myocardial protection by adding high-energy phosphates to cardioplegic solutions was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate (CP) was evaluated as an additive to the St. Thomas' Hospital cardioplegic solution. Dose-response studies (CP 0 to 50 mmol/L) revealed 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 40 minute period of normothermic (37 degrees C) ischemic arrest from 21.2% +/- 5.4% and 32.8% +/- 4.6% in the CP-free control group to 82.5% +/- 3.7% and 82.6% +/- 4.2% (p less than 0.001), respectively. Creatine kinase (CK) leakage was reduced by 68.7% (p less than 0.001) in the CP group. With hypothermic (20 degrees C) ischemia (240 minutes) and multidose (every 30 minutes) cardioplegia, recoveries of aortic flow and cardiac output were improved from 33.1% +/- 8.4% and 42.2% +/- 7.7% in the CP-free control group to 77.9% +/- 4.2% and 79.6% +/- 4.3% (p less than 0.001), respectively, in the drug group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias, significantly decreasing the time between cross-clamp removal and return of regular rhythm and also completely obviating the need for electrical defibrillation. 51Chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), an extracellular space marker, was used to study the disappearance of CP from the cardioplegic solution during its stasis in the heart. Upon reperfusion, two thirds of the infused dose appeared unchanged in the coronary effluent; the remainder was either degraded or accumulated by the myocardium. Despite its alleged inability to enter the myocardial cell, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas' Hospital cardioplegic solution. Although the mechanism of action remains to be elucidated, it may involve binding or uptake of the drug.
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PMID:Creatine phosphate: an additive myocardial protective and antiarrhythmic agent in cardioplegia. 669 10

We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary No. 2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into the great cardiac vein, which peaked immediately after reperfusion, reflecting CK washout. Thus, brief periods of ischemia, which when single do not cause necrosis, have a cumulative effect and may cause myocardial necrosis. This mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes. Since many dogs of this study did not have any myocardial necrosis, the findings also suggest that intermittent reperfusion has a beneficial effect and may prevent necrosis, even when total occlusion time exceeds 200 minutes.
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PMID:Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis. 713 94

Platelets have been shown to protect isolated perfused rat hearts from injury and dysfunction after ischemia and reperfusion. We examined the role of platelet-derived adenosine in the cardioprotective effects of platelets against reperfusion injury. Isolated perfused rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. The buffer-perfused hearts developed dysfunction, as indicated by 40 +/- 4% decrease in force of cardiac contraction (FCC) and 24 +/- 3% increase in coronary perfusion pressure (CPP). Creatine kinase (CK) was released in coronary effluent during reperfusion, indicating myocardial injury. At the end of reperfusion, myocardial CK content and superoxide dismutase (SOD) activity were lower than in sham ischemia-reperfused hearts. Perfusion of hearts with washed platelets resulted in protection against myocardial dysfunction and injury after ischemia and reperfusion, indicated by preservation of FCC (-2 +/- 5%) and CPP (-3 +/- 2%) (both p < 0.01 vs. buffer-perfused hearts). Myocardial CK and SOD activity were also preserved, and release of CK in the coronary effluent was minimal (all p < 0.05 vs. buffer-perfused hearts). The cardioprotective effects of platelets were attenuated by preincubation of platelets with adenosine deaminase. Perfusion with adenosine or the adenosine2 receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2- methylphenyl)-ethyl]adenosine (DPMA) also protected heart from myocardial dysfunction and injury after ischemia and reperfusion. Both adenosine and DPMA had salutary effects on indexes of cardiac injury. Platelet-derived adenosine contributes at least in part to the cardioprotective effects of platelets against ischemia and reperfusion in isolated rat heart.
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PMID:Platelet-derived adenosine contributes to the cardioprotective effects of platelets against ischemia-reperfusion injury in isolated rat heart. 753 56

The mechanism of cocaine-induced rhabdomyolysis and/or muscle damage has not been elucidated. To determine if cocaine has a direct effect on muscle, isolated soleus and EDL muscles were incubated in the presence of 1 mM and 0.2 mM cocaine using a pulse and continuous exposure protocol. The release of creatine kinase from the isolated EDL muscle was statistically significant only when muscles were exposed to 1 mM cocaine for a period of 30 minutes. These findings suggest that cocaine-induced creatine kinase release could be mediated by a direct action on the fibers. It is also possible, however, that cocaine-induced muscle damage and creatine kinase release may be mediated via an indirect effect. It is possible that cocaine's vasoconstrictor effects could lead to muscle damage via an ischemia-reperfusion injury leading to free radical formation and lipid peroxidation. This study, therefore, also investigated the possibility that cocaine-induced cytosolic enzyme release may be mediated via the formation of free radicals leading to lipid peroxidation. To test this hypothesis, muscle total glutathione levels, a free radical scavenger, and muscle thiobarbituric acid reactive substances (TBARS), a measurement of lipid peroxidation, were examined following an acute IV cocaine dose in mice. Sedentary BalbC mice were injected with cocaine (40 mg/kg) or normal saline via the tail vein. Creatine kinase levels in serum and total glutathione and TBARS in liver and muscle were determined at 4, 8, and 24 hrs. Serum creatine kinase levels were significantly elevated 5-fold, while TBARS were elevated 100% in the gastrocnemius muscle of cocaine-treated animals at 4 hrs compared to normal saline controls. However, serum creatine kinase levels, total glutathione and TBARS in the gastrocnemius muscle were not statistically different at 8 or 12 hrs; or in the liver and anterior tibialis muscle at 4, 8, or 24 hrs. The present findings suggests that lipid peroxidation may be occurring in skeletal muscle after a single IV cocaine dose in mice.
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PMID:Effects of cocaine on leakage of creatine kinase from skeletal muscle: in vitro and in vivo studies in mice. 756 4

It has been reported that CoQ10, ubiquionone, may have a protective effect on the mitochondrial injury induced by myocardial ischemia and reperfusion during open heart surgery. The purpose of this study was to investigate whether CoQ10 may enhance myocardial protection when given before ischemia, during ischemia or during reperfusion in the isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. In the first series of studies, this was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10. Hearts were then subjected to 39 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). The percent recovery of aortic flow (%AF) was 50.5 +/- 3.3% in the CoQ10 free controls versus 55.9 +/- 4.4, 62.1 +/- 3.1*% (*p < 0.05) in the 29, 44 and 58 mumol/L CoQ10 groups, respectively. Creatine kinase (CK) leakage during Langendorff reperfusion had a tendency to decrease in the 58 mumol/L group. In the second series of studies, 3 min of cardioplegia without CoQ10 and 38 min of ischemia (37 degrees C) were followed by a 15 min Langendorff reperfusion with 0 or 58 mumol/L of CoQ10 and 20 min working reperfusion. %AF was 53.2 +/- 2.7 and 39.2 +/- 7.1% in the 0 and 58 mumol/L CoQ10 groups, respectively. CK leakage had a tendency to increase in the 58 mumol/L group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of CoQ10 on myocardial ischemia/reperfusion injury in the isolated rat heart]. 760 95

One or more brief periods of ischemia, termed preconditioning, dramatically limits infarct size and reduces intracellular acidosis during subsequent ischemia, potentially via enhanced sarcolemmal proton efflux mechanisms. To test the hypothesis that preconditioning increases the functional activity of sodium-dependent proton efflux pathways, isolated rat hearts were subjected to 30 min of global ischemia with or without preconditioning. Intracellular sodium (Nai) was assessed using 23Na magnetic resonance spectroscopy, and the activity of the Na-H exchanger and Na-K-2Cl cotransporter was measured by transiently exposing the hearts to an acid load (NH4Cl washout). Creatine kinase release was reduced by greater than 60% in the preconditioned hearts (P < 0.05) and was associated with improved functional recovery on reperfusion. Preconditioning increased Nai by 6.24 +/- 2.04 U, resulting in a significantly higher level of Nai before ischemia than in the control hearts. Nai increased significantly at the onset of ischemia (8.48 +/- 1.21 vs. 2.57 +/- 0.81 U, preconditioned vs. control hearts; P < 0.01). Preconditioning did not reduce Nai accumulation during ischemia, but the decline in Nai during the first 5 min of reperfusion was significantly greater in the preconditioned than in the control hearts (13.48 +/- 1.73 vs. 2.54 +/- 0.41 U; P < 0.001). Exposure of preconditioned hearts to ethylisopropylamiloride or bumetanide in the last reperfusion period limited in the increase in Nai during ischemia and reduced the beneficial effects of preconditioning. After the NH4Cl prepulse, preconditioned hearts acidified significantly more than control hearts and had significantly more rapid recovery of pH (preconditioned, delta pH = 0.35 +/- 0.04 U over 5 min; control, delta pH = 0.15 +/- 0.02 U over 5 min). This rapid pH recovery was not affected by inhibition of the Na-K-2Cl cotransporter but was abolished by inhibition of the Na-H exchanger. These results demonstrate that preconditioning alters the kinetics of Nai accumulation during global ischemia as well as proton transport after NH4Cl washout. These observations are consistent with stimulation of the Na-K-2Cl cotransporter and Na-H exchanger by preconditioning.
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PMID:Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts. 765 18

Heat shock treatment induces expression of several heat shock proteins and subsequent post-ischemic myocardial protection. Correlations exist between the degree of stress used to induce the heat shock proteins, the amount of the inducible heat shock protein 70 (HSP70) and the level of myocardial protection. The inducible HSP70 has also been shown to be protective in transfected myogenic cells. Here we examined the role of human inducible HSP70 in transgenic mouse hearts. Overexpression of the human HSP70 does not appear to affect normal protein synthesis or the stress response in transgenic mice compared with nontransgenic mice. After 30 min of ischemia, upon reperfusion, transgenic hearts versus nontransgenic hearts showed significantly improved recovery of contractile force (0.35 +/- 0.08 versus 0.16 +/- 0.05 g, respectively, P < 0.05), rate of contraction, and rate of relaxation. Creatine kinase, an indicator of cellular injury, was released at a high level (67.7 +/- 23.0 U/ml) upon reperfusion from nontransgenic hearts, but not transgenic hearts (1.6 +/- 0.8 U/ml). We conclude that high level constitutive expression of the human inducible HSP70 plays a direct role in the protection of the myocardium from ischemia and reperfusion injury.
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PMID:Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. 770 92


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