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

Myocardial ATP, ADP, and AMP were measured from cardiac biopsy in 11 dogs after intracoronary injection of 6 mL of sodium-meglumine diatrizoate (SMD), iohexol (IOH), or 0.9% sodium chloride (NaCl), and in three of the dogs at baseline before any injection. The ATP at baseline and after SMD, IOH, and 0.9% NaCl were 5.39 +/- 0.41, 3.72 +/- 0.70, 5.52 +/- 0.82, and 5.44 +/- 1.40 mumol/g wet weight, respectively. There were significant differences between SMD and IOH (P less than .02), and between SMD and 0.9% NaCl (P less than .05). The energy charge of SMD was 0.82 +/- 0.08, which differed from 0.89 +/- 0.02 for NaCl or 0.9 +/- 0.05 for baseline (P less than .05), but not from 0.85 +/- 0.04 for IOH. In conclusion, diatrizoate caused significant depletions in ATP stores in comparison with iohexol, but there was no significant difference with respect to energy charge. Nonionic contrast media would be preferable for coronary arteriography in patients whose high-energy stores might be depleted from severe ischemia.
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PMID:Effects of intracoronary administration of contrast media on myocardial high-energy phosphate. A comparison of sodium meglumine diatrizoate and iohexol. 173 78

To evaluate the effects of pulsatile reperfusion (PR) on the postischemic myocardial phosphometabolites, 17 sheep were put on cardiopulmonary bypass (CPB) and randomly divided into a pulsatile group (P group) and nonpulsatile group (NP group). The heart was arrested by global ischemia for 45 minutes, then defibrillated and reperfused for 2 hours while the circulation was supported by CPB. Myocardial needle biopsies were obtained, and ATP, ADP, and AMP were measured with high performance liquid chromatography. There were no significant differences between the two groups in myocardial ADP and AMP. However, after 120 minutes of reperfusion, the myocardial ATP was restored in the P group, but continued to decrease further in the NP group. Experimental results imply that PR might reduce reperfusion injury and promote recovery of the ischemic myocardium.
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PMID:Effect of pulsatile reperfusion on myocardial high energy phosphates following global ischemia. 175 Dec 46

Excitatory amino acids (EAAs) have been implicated to play a part in the development of hypoxic-ischemic brain injury in the neonate. The aim of the present study was to follow changes of intra- and extracellular (microdialysis) amino acids in the cerebral cortex in a model where cortical hypoxic-ischemic damage is produced consistently. Hypoxic-ischemia (unilateral ligation of the carotid artery + 2 h of exposure to 7.8% oxygen) caused a depletion of tissue ATP, phosphocreatine and glucose with a concomittant accumulation of AMP and lactic acid in cortical tissue. These changes were accompanied by a decrease of tissue aspartate and glutamine whereas the contents of gamma-aminobutyric acid (GABA), phenylalanine, leucine, isoleucine, valine and alanine increased. In the extracellular fluid GABA, glutamate, aspartate, taurine, glycine and alanine all increased multi-fold during hypoxic-ischemia. Aspartate and glutamate returned to near initial levels 2 h after the end of the insult, whereas the elevation of glycine persisted during recovery. In conclusion, the high extracellular levels of EAAs and glycine may exert injurious effects during and after hypoxic-ischemia.
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PMID:Intra- and extracellular changes of amino acids in the cerebral cortex of the neonatal rat during hypoxic-ischemia. 178 36

Cultured chick heart muscle cells degrade ATP during metabolic inhibition via ADP to AMP. Whether AMP is primarily deaminated to IMP or dephosphorylated to adenosine depends on the 'metabolic block' (glycolysis vs. oxidative phosphorylation). Inhibition of glycolysis (deoxyglucose) results in an inosine/adenosine ratio greater than 1 in the supernatant, whereas the nucleoside ratio is less than or equal to 1 during inhibition of oxidative phosphorylation (hypoxia, rotenone). EHNA, a blocker of adenosine deaminase, has little effect on inosine release during metabolic inhibition, consistent with the reported low activity of adenosine deaminase in cardiac muscle cells. The amount of adenosine and inosine released can be largely attenuated by two nucleoside carrier inhibitors, nitrobenzyl-thioinosine and dipyridamole, which suggests that nucleosides are produced intracellularly and subsequently released. These results indicate that the amount of inosine or adenosine released from the cardiomyocyte during impaired energy metabolism (e.g. ischemia) can be controlled by the metabolic state of the cell.
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PMID:Adenine nucleotide degradation in cultured chick heart muscle cells. 179 25

We tested the hypothesis that loss of mitochondrial adenine nucleotides during myocardial ischemia is induced by the accumulation of inorganic phosphate (Pi) and a decrease in cytosolic ATP. In the isolated perfused rat heart, loss of mitochondrial adenine nucleotides (ATP + ADP + AMP) was preceded by the rise in tissue Pi and the loss of tissue ATP. After 30 min ischemia, the average rate of loss of mitochondrial adenine nucleotides was c. 1.5% of the initial pool/min. In isolated heart mitochondria, there are two pathways for adenine nucleotide release: a 'fast', phosphate-dependent pathway, which is inhibited by atractyloside; and a 'slow', phosphate-independent pathway, which is insensitive to atractyloside. Decreasing the pH from 7.4 to 6.5 significantly decreased the rate of release by the phosphate-dependent pathway (but not the phosphate-independent pathway). Analysis of release rates indicated that HPO4-2 is responsible for the phosphate-induced release; Vmax = 53.8% of the pool/per minute, Km = 7.5 mM. In vitro, extramitochondrial ATP inhibited adenine nucleotide release in the presence of Pi such that the rate of release was inversely proportional to the extramitochondrial [ATP]; extrapolation to zero ATP indicated a release rate of 2 to 3% of the pool/per minute, which is approximately equal to the rate of the 'slow' phosphate-independent pathway. Moreover, increasing the Pi concentration did not increase the rate of adenine nucleotide release in the presence of extramitochondrial ATP. Accumulation of mitochondrial adenine nucleotides was observed when the mitochondria were incubated in the presence of 4 mM or greater ATP. The results suggest that the rise in intracellular Pi during myocardial ischemia does not induce the loss of adenine nucleotides from the mitochondrial compartment, but rather that degradation of cytosolic ATP results in a slowing of ATP influx such that the rate of efflux (phosphate-independent) exceeds the rate of influx.
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PMID:Mechanism of loss of adenine nucleotides from mitochondria during myocardial ischemia. 181 Oct 58

Hepatic failure often occurs following transplantation. This is primarily due to cold ischemia during preservation, warm ischemia during implantation, and finally reperfusion damage after transplantation and reflow. The possibility that this ischemia and reperfusion-induced damage can be reduced by preischemic application of a xanthine derivative (pentoxiphylline) was examined using 31P NMR spectroscopy and electron microscopy (EM) studies of bioenergetic and ultrastructural changes in oxygenated erythrocyte-perfused rat livers. EM illustrated that the hepatocytes and the mitochondria appeared to be relatively unaffected by cold preservation of the liver, whereas the endothelial cells lining the sinusoids became disrupted. After reperfusion, NMR spectroscopy showed a partial recovery of ATP levels, and EM indicated progressive mitochondrial injury. This progressive injury to the liver was probably due to endothelial cell damage which resulted in microcirculatory malfunction and free radical formation during reperfusion. Pentoxiphylline pretreated livers showed better preservation of the cell morphology and exhibited better ATP recovery than untreated livers. Pentoxiphylline is known to prevent the loss of precursors of ATP resynthesis by inhibiting AMP dephosphorylation during ischemia and improves the microcirculation via vasodilatory properties following ischemia. Thus, it is concluded that pentoxiphylline may ameliorate ischemia-induced cell damage during transplantation.
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PMID:Effect of pentoxiphylline on the recovery of the preserved rat liver: 31P NMR and ultrastructural studies. 181 7

Replantation of major extremities after long periods of ischemia can lead to viable replants in many cases, but functional restoration is often poor owing to fibrosis of the muscle. In this study, maximum hypothermic time in tissue transfers containing skeletal muscle using hindlimbs of Lewis rats preserved in 4 degrees C Euro-Collins solution was investigated. After preserving midthigh amputated legs in this solution for 6, 9, and 12 hours, the legs were transplanted to other inbred rats using microsurgical technique, and 1 week later, gastrocnemii were obtained to analyze ATP, ADP, and AMP using high-performance liquid chromatography. The values were compared with those for healthy legs, nonischemic operated control legs, and legs preserved in the same manner for 6, 9, and 12 hours. Histologic and serologic examinations were conducted. ATP values of the 9-hour preservation group resumed those of the nonischemic operated control group, with the values of the 12-hour preservation group remaining at 61 percent. Histologically, focal necrosis, hyaline degeneration, and regeneration processes were the most characteristic manifestations in the muscles transplanted after cold ischemia of 12 hours. It was concluded that skeletal muscle could be preserved for 9 hours in 4 degrees C Euro-Collins solution.
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PMID:Preservation of skeletal muscle in tissue transfers using rat hindlimbs. 144 16

Effects of pretreatment with L-propionylcarnitine (50 mg/kg, n = 9) or saline (n = 10) were studied in open-chest anesthetized pigs, in which ischemia was induced by decreasing left anterior descending coronary artery blood flow to 20% of baseline. After 60 min of ischemia, myocardium was reperfused for 2 h. In both groups, flow reduction abolished contractile function of the affected myocardium and caused similar decreases in ATP (by 55%) and energy charge [(ATP + 0.5ADP)/(ATP + ADP + AMP); decrease from 0.91 to 0.60], mean arterial blood pressure (by 10-24%), the maximum rate of rise in left ventricular pressure (by 26-32%), and cardiac output (by 20-30%). During reperfusion, "no-reflow" was attenuated by L-propionylcarnitine, because myocardial blood flow returned to 61 and 82% of baseline in the saline- and L-propionylcarnitine-treated animals, respectively. Cardiac output of the saline-treated animals further decreased (to 52% of baseline), and systemic vascular resistance increased from 46 +/- 3 to 61 +/- 9 mmHg.min.l-1, thereby maintaining arterial blood pressure. In L-propionylcarnitine-treated pigs, cardiac output remained at 75% of baseline, and systemic vascular resistance decreased from 42 +/- 3 to 38 +/- 4 mmHg.min.l-1. In both groups, energy charge but not the ATP level of the ischemic-reperfused myocardium tended to recover, whereas the creatine phosphate level showed significantly more recovery in saline-treated animals. We conclude that L-propionylcarnitine partially preserved vascular patency in ischemic-reperfused porcine myocardium but had no immediate effect on "myocardial stunning." Potential markers for long-term recovery were not affected by L-propionylcarnitine.
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PMID:L-propionylcarnitine increases postischemic blood flow but does not affect recovery of energy charge. 185 18

The effect of dipyridamole (DYP) on postischemic myocardial function and metabolism was studied using the isolated rabbit heart model. Twenty-one isolated rabbit heart preparations were divided into two groups: KH (control N = 10) were reperfused after 24 min normothermic hyperkalemic arrest with modified Krebs-Henseleit buffer (KH) while DYP (N = 11) were reperfused with KH and 5 X 10(-6) M DYP. Hearts were analyzed for myocardial function (DP, developed pressure, +dp/dt, -dp/dt) and metabolic function (ATP, CrP, ADP, AMP, purines, and lactate levels). Data analysis revealed significant reperfusion depression in DYP myocardial function compared with KH (P less than 0.05): DP (42 +/- 6 vs 89 +/- 7 mm Hg), +dp/dt (390 +/- 21.6 vs 1227 +/- 48.4), and -dp/dt (280 +/- 20.1 vs 677 +/- 19.8). Comparison of DYP to KH metabolic parameters was also significantly different (P less than 0.05): ATP (5.8 +/- 0.7 vs 9.5 +/- 1.4), ADP (2.1 +/- 0.2 vs 3.2 +/- 0.6), CrP (9.6 +/- 0.3 vs 17.2 +/- 1.3). Tissue purines (adenosine and inosine) were significantly elevated (P less than 0.01) in the DYP group, while coronary sinus purines and lactate loss were similar. Thus, the data suggest that DYP, present during postischemic reperfusion, depresses myocardial function by inhibiting adenosine phosphorylation, thereby decreasing the generation of high-energy phosphates without increased substrate loss or ischemia.
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PMID:Metabolic and functional cardiac impairment after reperfusion with persantine. 186 75

We studied the efficacy of defibrotide, a prostacyclin-stimulating agent, in preventing ischemia reperfusion injury in Wistar rat heart by using three experimental models: (1) hearts from donors were perfused with the drug (32 mg/kg/hr) during 15, 30, 45, and 60 min of cold ischemia following 5, 10, and 15 min of warm ischemia; (2) hearts from donors treated with the drug were cold-stored for 12 or 24 hr; and (3) procured hearts perfused with the drug were isografted, after 30 or 60 min of warm ischemia, in recipient rats treated daily with defibrotide. Hearts perfused with saline and/or vehicle of the drug were used as controls. At the end of established ischemia times, and after 30 min, and 2, 4, 7 and 14 days from transplantation, hearts were rapidly cooled in liquid nitrogen. ATP, ADP, AMP, cAMP contents, and NAD+/NADH ratios were evaluated in prepared tissue extracts. Cardiac ATP and ADP levels and NAD+/NADH ratios were significantly higher in defibrotide-treated organs than in controls. Isografted defibrotide-treated hearts were also significantly preserved, with respect to controls, from the loss of ATP levels until rejection occurred. Our results demonstrate the protective activity of the drug against the myocardial metabolic damage due to ischemia-reperfusion.
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PMID:Protection of rat heart from damage due to ischemia-reperfusion during procurement and grafting by defibrotide. 192 39


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