Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.
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PMID:Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia. 371 20

The present study compared the effects of ATP-MgCl2 or ATP-Na2 administration on renal function and cellular metabolism following renal ischemia in rabbits. Following 100 min of ischemia, the blood flow to the kidney was allowed to reestablish itself, and the rabbits received either saline, ATP-MgCl2 (17.5 mumole/kg each), or ATP-Na2 (17.5 mumole/kg) intravenously. ATP-MgCl2 administration following ischemia significantly accelerated the recovery of renal function. However, administration of ATP-Na2 failed to show any beneficial effect on the recovery process. The changes in renal cellular ketone body ratio (acetoacetate/beta-hydroxybutyrate), energy charge, and pyruvate/lactate indicated that ATP-MgCl2, but not ATP-Na2, reversed ischemically induced impairment in renal cellular metabolism. Reduction in the renal blood flow caused by ischemia was also improved with ATP-MgCl2 treatment. These results indicate that ATP should be given in the form of ATP-MgCl2 for it to be effective following renal ischemia. The results also suggest that the salutary effect of ATP-MgCl2 following renal ischemia could occur through the improvement of cellular metabolism and concomitant improvement in tissue blood flow.
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PMID:Effects of ATP-MgCl2 and ATP-Na2 administration on renal function and cellular metabolism following renal ischemia. 383 26

We used high-resolution phosphate 31(31P)--nuclear magnetic resonance spectroscopy to study the effects of ischemia and reperfusion on intracellular adenosine triphosphate (ATP) and pH changes in isolated perfused rat kidneys. With renal ischemia, ATP levels fell rapidly and the inorganic phosphate (Pi) peak shifted, indicating acidosis. On reperfusion after 45 minutes of warm ischemia, there was a 56% rise in tissue ATP levels within ten minutes that then slowly declined; by 75 minutes the levels were only 33% of normal. Perfusate flow decreased from 21.2 +/- 0.9 mL/min (mean +/- SE) to 16.5 +/- 1.1 mL/min and the Pi peak did not shift during reperfusion. When 0.3mM ATP complexed to magnesium chloride (ATP-MgCl2) was added to the perfusate after ischemia, renal ATP levels increased to 69% of normal within ten minutes of reperfusion and by 75 minutes they were normal. Perfusate flow was also normal during reperfusion. The Pi peak shifted back to the normal frequency, indicating correction of the intracellular acidosis. Thus, intracellular acidosis, ATP depletion, and decreased flow during reperfusion injury were rapidly reversed and sustained by the postischemic administration of ATP-MgCl2.
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PMID:Adenosine triphosphate--magnesium chloride ameliorates reperfusion injury following ischemia as determined by phosphorus nuclear magnetic resonance. 387 13

Hepatic ischemia followed by reflow results in a myriad of metabolic and circulatory derangements that may eventually result in liver failure and death. In the present experiments we have used the technique of intravital fluorescence microscopy with fluoroscein isothiocyanate conjugated to bovine serum albumin as the intravascular fluorochrome to study the effects of ischemia and reperfusion on the hepatic microcirculation in vivo. Total hepatic ischemia was produced for 90 min to the left and median lobes of pentobarbital-anesthetized rats. After ischemia, reflow was allowed for 2 h. Three groups were studied: sham-ischemia controls and rats treated with either 1 ml saline or 12.5 mumol ATP-MgCl2 in 1-ml volume at the beginning of reflow. Although control rats exhibited stable microcirculation throughout the experiment, in saline-treated rats the number of perfused centrilobular areas and perfused sinusoids per unit area on the surface of the liver was decreased to approximately 50 and 40% of sham-ischemia controls, respectively. However, in rats treated with ATP-MgCl2 the density of perfused centrilobular areas and perfused sinusoids was 86 and 80% of sham-ischemia controls, respectively. From these results we conclude that intravital fluorescence microscopy is a potentially valuable method for the study of the hepatic microcirculation in vivo. Moreover, the results with ATP-MgCl2 treatment indicate that its effect on the microcirculation is a major factor in its beneficial effects on hepatic function after ischemia and reflow.
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PMID:Hepatic microcirculatory failure after ischemia and reperfusion: improvement with ATP-MgCl2 treatment. 392 42

Various metabolic, cellular, and subcellular alterations in cell function and morphology occur during shock or low-flow conditions. In attempting to find treatment programs that would be beneficial following shock, various substrates have been used. Infusion of hypertonic glucose during shock has been shown to improve survival; however, it is unlikely that the effect of glucose is by provision of energy until the circulation is restored. Infusion of glucose--insulin--potassium during shock has also been reported to be beneficial in certain clinical situations. Controversies exist concerning the efficacy of infusions of cyclic AMP, nicotinamide, and Krebs cycle intermediates during shock. Pretreatment of kidneys with inosine or raising glycogen stores of the myocardium have been shown to have protective effects of kidneys and myocardium during ischemia and these procedures may be suitable for organ preservation. Pretreatment with allopurinol has been shown to be beneficial in shock; however, it is unlikely that allopurinol by itself if given following shock would have any salutary effects. Treatment with ATP-MgCl2 has been shown to be beneficial following hemorrhagic shock, sepsis, endotoxin shock, burns, postischemic hepatic failure, and postischemic renal failure. Thus, provision of energy directly in the form of ATP during adverse circulatory conditions appears to be the most advantageous and direct method for the treatment of shock.
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PMID:The use of substrates and energy in the treatment of shock. 627 59

Following detailed investigation and definition of some of the critical factors relating to the composition and use of cardioplegic protective solutions, we have formulated the St. Thomas' Hospital cardioplegic solution number 2. This cardioplegic solution (NaCl 110.0 mM, NaHCO3 10.0 mM, KCl 16.0 mM, MgCl2 16.0 mM, CaCl2 1.2 mM, pH 7.8) is designed for routine clinical use combining optimal protection with simplicity of formulation and administration/infusion. In order to characterize the efficacy of this modified solution, experiments have been carried out in two species: the isolated rat heart and the in-situ dog heart. In parallel protocols, hearts were subjected to ischemic arrest of up to 4 hours. Multidose (every 40 minutes) cardioplegic infusion of the St. Thomas' solution combined with topical hypothermia extended the tolerable period of ischemia from less than 30 minutes to about 120 minutes in the rat and from less than 60 minutes to more than 180 minutes in the dog. These conclusions were based on the measurement of functional indices together with biochemical, cellular chemical and ultrastructural assessments. The studies confirmed the additive protective properties of hypothermia and chemical cardioplegia and the utility of the rat heart model in the assessment of protective interventions.
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PMID:The St. Thomas' hospital cardioplegic solution: a characterization in two species. 627 81

A singular scheme of progressive alterations in cell function with hemorrhagic shock and ischemia has been presented. Alterations in mitochondrial function during shock and ischemia with different substrates have been described in detail. These consist of decreases in the capability of mitochondria, alterations in mitochondrial cation contents, increased mitochondrial FFAs and Ca2+ levels, and decreased adenine nucleotide translocase activity. The potential mechanisms responsible for altered mitochondrial functions during shock and the potential consequences of such alterations have been discussed. In addition, the beneficial effects of ATP-MgCl2 on mitochondrial function following shock and ischemia have been described. The experimental evidence available indicates that infused ATP-MgCl2 improves cellular and mitochondrial functions directly and by way of long-term improvement in microcirculation but not through vasodilatation. Our results with ATP-MgCl2 therefore provide for the possibility of supporting cellular and mitochondrial functions during shock or low flow conditions.
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PMID:Alterations in electron transport and cellular metabolism with shock and trauma. 630 82

Various metabolic, cellular, and subcellular alterations in cell function and morphology occur during shock or low flow conditions. Alterations in mitochondrial function during low flow conditions consist of decreases in the metabolic capability of mitochondria, alterations in mitochondrial cation contents, increased mitochondrial free fatty acids and Ca2+, and decreased adenine nucleotide translocase activity. The cell membrane transport of Na+ and K+, transmembrane potential, cellular ATP and cyclic nucleotide levels, and other phenomena are also significantly altered. The potential mechanisms responsible for altered mitochondrial and cellular functions during shock and the consequences of such alterations are discussed. Based on the cellular alterations that occur during shock, attempts have been made to support cell function during such conditions. These (along with volume replacement) include substrates, membrane-stabilizing solutions, and energy compounds. Although provision of substrates may improve cellular energy levels, they may not necessarily improve microcirculation. The use of ATP-MgCl2 as an adjunct in the treatment of shock and ischemia has been described, and potential mechanisms of the beneficial effects of this compound are discussed.
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PMID:Cellular mechanisms in shock and ischemia and their correction. 630 22

To study the effects of ATP-MgCl2 on impaired protein synthesis and hepatic cell membrane potential (HCMP) in the postischemic liver, ATP-MgCl2 (50 or 150 mumole/kg) or saline was administered intravenously following 90 min of liver ischemia in rats. Protein synthesis was measured by determining rate of leucine incorporation into proteins in incubated liver slices. HCMP was registered in vivo with glass microelectrodes. No effects of the two doses of ATP-MgCl2 on protein synthesis or HCMP in the postischemic liver were found. The results indicate that beneficial effects of ATP-MgCl2 previously reported following liver ischemia are not primarily caused by direct energy provision to hepatocytes.
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PMID:Failure of an increased dose of ATP-MgCl2 to improve protein synthesis and transmembrane potential in the postischemic liver. 633 52

Isolated rat kidneys were subjected to 45, 60, and 90 min of normothermic ischemia. Kidneys reperfused with a saline solution after ischemia had very low initial whole kidney inulin clearances (Cin), urine flow rates (V), renal perfusate flow rates (RPF), and fractional absorption of sodium values that remained depressed throughout the 110 min of reperfusion. Kidneys subjected to 45 min of warm ischemia and reperfused with a solution containing 0.3 mM ATP-MgCl2 had higher initial Cin and attained complete recovery of Cin by 75 min of perfusion. Fractional absorption of sodium and water were also improved, and RPF, V, and tissue ATP levels returned to control values after 110 min of perfusion. Kidneys subjected to 60 min of ischemia and reperfused with a solution containing 0.3 mM ATP-MgCl2 also had higher initial Cin values and attained 50% recovery of Cin after 110 min of perfusion. RPF also improved, and V reached control levels. Kidneys subjected to 90 min ischemia showed no improvement in renal function even with 2 mM ATP-MgCl2. Because, even in isolated kidneys, administration of ATP-MgCl2 after 45 and 60 min of ischemia results in an early recovery of renal function, the beneficial effects of ATP-MgCl2 are exerted directly on the kidney and are not mediated via systemic effects.
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PMID:Accelerated functional recovery of isolated rat kidney with ATP-MgCl2 after warm ischemia. 633 46


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