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

Both the isolated perfused rabbit heart and kidney are capable of synthesizing prostaglandin (PG) I(2). The evidence that supports this finding includes: (a) radiochemical identification of the stable end-product of PGI(2), 6-keto-PGF(1alpha), in the venous effluent after arachidonic acid administration; (b) biological identification of the labile product in the venous effluents which causes relaxation of the bovine coronary artery assay tissue and inhibition of platelet aggregation; and (c) confirmation that arachidonic acid and its endoperoxide PGH(2), but not dihomo-gamma-linolenic acid and its endoperoxide PGH(1), serve as the precursor for the coronary vasodilator and the inhibitor of platelet aggregation. The rabbit heart and kidney are both capable of converting exogenous arachidonate into PGI(2) but the normal perfused rabbit kidney apparently primarily converts endogenous arachidonate (e.g., generated by stimulation with bradykinin, angiotensin, ATP, or ischemia) into PGE(2); while the heart converts endogenous arachidonate primarily into PGI(2). Indomethacin inhibition of the cyclo-oxygenase unmasks the continuous basal synthesis of PGI(2) by the heart, and of PGE(2) by the kidney. Cardiac PGI(2) administration causes a sharp transient reduction in coronary perfusion pressure, whereas the intracardiac injection of the PGH(2) causes an increase in coronary resistance without apparent cardiac conversion to PGI(2). The perfused heart rapidly degrades most of the exogenous endoperoxide probably into PGE(2), while exogenous PGI(2) traverses the heart without being metabolized. The coronary vasoconstriction produced by PGH(2) in the normal perfused rabbit heart suggests that the endoperoxide did not reach the PGI(2) synthetase, whereas the more lipid soluble precursor arachidonic acid (exogenous or endogenous) penetrated to the cyclooxygenase, which apparently is tightly coupled to the PGI(2) synthetase.
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PMID:Cardiac and renal prostaglandin I2. Biosynthesis and biological effects in isolated perfused rabbit tissues. 34 5

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.
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PMID:Comparative hemodynamic effects of coronary vasodilators and contrast material on the normal and ischemic canine myocardium: determination of the optimal agent for clinical augmentation of coronary blood flow. 40 73

Mitochondria isolated from rat kidney subject to in vitro ischemia at various time intervals demonstrated a continuous decline of the ability to accumulate calcium following a high initial stable phase of accumulation of calcium which is dependent both on ATP and respiration. This decline occurs during the reversible phase of cell injury and appears to be a sensitive indicator of membrane changes in a binding and/or transport protein or of other membrane permeability characteristics. The morphology of mitochondrial densities related to calcium accumulation in mitochondria varied. Any form of calcium accumulation, resulted in marked swelling of mitochondria. Control renal mitochondria in sucrose were highly condensed. Partially inhibited calcium accumulation in the presence of phosphate was also associated with numerous small spheric or punctate deposits in close relationship to the inner membrane. Uninhibited calcium accumulation resulted in the formation of needle-like structures radiating from such inner membrane associated sites.
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PMID:Studies on the pathogenesis of ischemic cell injury. VI. Accumulation of calcium by isolated mitochondria of ischemic rat kidney cortex. 41 33

The tissue H2O of rabbit heart and rat liver was partially exchanged in situ with D2O. In rat liver, the loss of ATP, resulting from normothermic ischemia, was decreased after perfusion with D2O. The maximal protective effect was found when the proportion of D2O in the water of the liver tissue was 0.20. In both organs the protective effect of D2O could be correlated with a marked decrease in severe ischemic damage of cellular organelles, in particular mitochondria. D2O also increased the protective action of Mg-ions in the heart.
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PMID:[Organ preservation by heavy water (D2O). Morphological and biochemical studies on heart and liver (author's transl)]. 43 27

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.
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PMID:Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart. 44 6

The effect of preliminary administration of alpha-tocopherol acetate (1 mg/kg) and sodium selenite (1 mg/kg) on RNA synthesis rate and changes in the macroergic content in ischemic myocardium was studied. It was shown to be conducive to ATP level maintenance after 30- and 60-minute heart ischemia. A statistically significant accumulation of RNA by the myocardium following I-hour ischemia as well as this polynucleotide synthesis activation were recorded. Preservation of the energetic resources by the cell along with RNA metabolism returning to normal contributes to inhibiting the emergence of irreversible cell damage and increases regenerative potentialities of the myocardium.
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PMID:[Effect of alpha-tocopherol acetate and sodium selenite on the change in ATP content and the RNA synthesis rate in the ischemic myocardium]. 44 4

In order to investigate possible differences in the reaction to hypoxic conditions between "red" and "white" skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6-P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP + CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP + CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that "red" muscles are more susceptible to metabolic derangement than "white" muscles during total ischemia, whereas during hypovolemia "red" muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.
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PMID:Metabolic responses in feline "red" and "white" skeletal muscle to shock and ischemia. 46 77

The isolated perfused rat heart was utilized to determine the maximum rate of adenosine incorporation into adenine nucleotides and the effect of ischemia on this rate. In aerobic hearts, the rates of [8-14C]adenosine incorporation into nucleotides in nanomoles/minute per gram dry tissue were ATP 34 +/- 2, ADP 6 +/- 0.4, AMP 3 +/- 0.3, and IMP, 1 +/- 0.2. Following ischemia these values were not significantly different except for the rate of incorporation into IMP, which doubled. The extent of adenosine deamination with one pass through the coronary vasculature was the same in aerobic and postischemic hearts: 2% and 7% of the perfusate adenosine was converted to hypoxanthine and inosine, respectively. These percentages were similar at 50, 100, and 200 micron adenosine. Perfusion of aerobic hearts for 5 h with adenosine did not change ATP concentrations. Therefore, [8-14C]adenosine incorporation into ATP in these hearts appeared to represent ATP turnover. In contrast, 5 h perfusion of postischemic hearts with adenosine restored ATP concentrations to control values. The synthesis rate calculated from the increase in ATP concentration was comparable to the synthesis rate calculated from [8-14C]adenosine incorporation. Thus, incorporation of [8-14C]adenosine into ATP in postischemic hearts represented net ATP synthesis.
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PMID:Myocardial adenosine salvage rates and restoration of ATP content following ischemia. 46 18

In rats, cerebral perfusion pressure were altered abruptly by aortic transection to determine the production by ischemic brain of adenosine and its metabolites, inosine and hypoxanthine. Brain samples were obtained after 0, 5, 10, 15, 30, and 60 seconds of ischemia. Also measured were ATP, ADP, AMP, phosphocreatine (PCr), lactate, and pyruvate. Blood pressure was monitored continuously, and arterial PO2, PCO2, and pH were measured just prior to induction of ischemia. Adenosine was elevated t 2.30 +/- 0.31 (SE) nmol/g at 5 seconds from a control value of 0.96 +/- 0.07. A significant elevation of adenosine continued to 60 seconds (5.50 +/- 1.24). Furthermore, inosine showed a progressive upward trend during the entire 60 seconds of ischemia, whereas no change in hypoxanthine occurred between the moment of transection (31.81 +/- 2.01 nmol/g) and 60 seconds of ischemia (34.72 +/- 2.93). PCr decreased by 1.24 mumol/g within the first 5 seconds. After the onset of hypotension, significant changes did not occur in AMP and ADP until 30 seconds, and in ATP and pyruvate until 60 seconds after aortic transection; lactate was elevated by 10 seconds. The rapid rise of cerebral adenosine within 5 seconds after the onset of ischemia supports a role for adenosine in the regulation of cerebral blood flow.
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PMID:Brain adenosine production in the rat during 60 seconds of ischemia. 47 71

The levels of the adenine nucleotides ATP, ADP, and AMP in the stria vascularis were measured under normal conditions, and following various durations of ischemia. The concentrations of these compounds were used for the calculation of the adenylate energy charge, the energy status and the phosphorylation state of the stria. Following 10 min of ischemia the adenylate energy charge had decreased three fold, the energy status seven fold and the phosphorylation state 14 fold. To study the potential for recovery of strial function following various brief and prolonged ischemic intervals, a method for the perfusion of the ear via the anterior inferior cerebellar artery was developed. For various reasons it was found advantageous to use "artifical blood" as perfusate, relying upon fluorocarbons as oxygen carriers. The endolymphatic potential was used as electrical indicator of strial function. Recovery of the endolymphatic potential following brief periods of ischemia was paralleled by a corresponding increase of the ATP levels and a drastic decrease of the AMP levels of the stria vascularis. Preliminary results on the effects of substrate-free perfusion are presented.
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PMID:Adenine nucleotides of the stria vascularis. 48 54


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