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

In an isolated rat liver perfusion system the effects of normothermal ischemia on hepatic functions were investigated. After 30 minutes of anoxy bile production and BSP elimination capacity of the liver are significantly reduced. The quantity of secreted "ascites" from the surface of the liver several times high after anoxic damage, while oxygen consumption, portal venous pressure and ammonia elimination do not differ significantly from the controls. Pretreatment with insulin plus glucose, isoproterenol, hypoxanthine, chlorpromazine and glucagon (5 micrograms/100 g i.v., or 0.2 mg/100 g s.c.) does not reduce noticeably the normothermal anoxic lesion of the liver Glucagon (50 micrograms/100 g i.v.), allopurinol, dibenzyline, ATP-MgCl2 and aspartic acid enhance significantly the ischemia-tolerance of liver in vitro.
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PMID:Ischemic damage of the liver. Part I: In vitro investigation of the prevention of the ischemic lesion of the liver. 49 24

A new model for the study of ischemic liver lesion on rats has been worked out. Pretreatment with allopurinol, dibenzyline, methylprednisolone, glucagon, ATP-MgCl2 and aspartic acid reduced the overall mortality of ischemic liver injury. Administered after the anoxic hepatic lesion only glucagon and aspartic acid had beneficial effect on the survival rate. Under the influence of 30 minutes of normothermal ischemia the DNA synthetizing ability of the liver decreased. Aspartic acid, glucagon and ATP-MgCl2 significantly enhanced the regeneration of the ischemically damaged liver. These procedures might be suitable for donor pretreatment in liver transplantation, as well as for the treatment of other pathological states, causing a normothermal ischemia of the liver.
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PMID:Ischemic damage of the liver. Part II: In vivo investigation of the prevention of the ischemic lesion of the liver. 49 25

Although adenosine triphosphate-magnesium chloride (ATP-MgCl2) has demonstrated cytoprotective effects in a variety of adverse pathophysiologic conditions, its ability to alter radiation injury is unknown. The purpose of this study, therefore, was to assess the effects of ATP-MgCl2 on colorectal radiation injury after preoperative pelvic radiotherapy. Mixed-breed pigs (n = 36) received 4250 cGy preoperative external-beam pelvic radiotherapy (350 cGy fractions three times per week for 4 weeks). During radiotherapy, animals were randomly assigned to one of three treatment groups: (1) intravenous infusions of normal saline during radiotherapy, (2) intravenous ATP-MgCl2 (30 mumol/kg) during radiotherapy, or (3) intravenous ATP-MgCl2 (60 mumol/kg) during each radiotherapy session. After completion of radiotherapy and a 4-week rest period, animals underwent colorectal resection by either the two-layer hand-sewn (n = 18) or stapled end-to-end anastomosis technique (n = 18). Laser Doppler velocimetric readings were obtained to assess mural colonic blood flow after completion of anastomosis. A second laparotomy on postoperative day 5 or 11 was done to examine the following anastomotic parameters: (1) repeat laser Doppler velocimetry, (2) gross inflammatory scoring, (3) bursting pressure, (4) preoperative barium enema to identify leak or stenosis, (5) analysis of anastomotic hydroxyproline content, and (6) incidence of cutaneous injury in the radiation portals. ATP-MgCl2 administered intravenously at 60 mumol/kg led to (1) diminished colorectal seromuscular ischemia evidenced by laser Doppler velocimetric readings, (2) decreased skin and subcutaneous tissue injury in the treatment portals, (3) significantly decreased perianastomotic inflammatory reaction, and (4) increased early hydroxyproline content. There was no significant difference in the incidence of leakage or stenosis between the study groups, nor was the anastomotic bursting strength significantly different between the treatment groups. Therefore the administration of ATP-MgCl2 (60 mumol/kg) appears to offer significant cytoprotection from preoperative pelvic radiation therapy.
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PMID:Adenosine triphosphate-magnesium chloride in radiation injury. 144 Feb 47

The effect of different processing factors on tissue valve calcification were studied in the subdermal rat model. Factors evaluated, were the influence of tissue ischaemia (4 degrees and 25 degrees C), different blocking reagents (KH2PO4, T6, MgCl2 and AlCl3), fixation pressures (0, 10 and 20 mmHg) and the pH (3.72 and 7.40) of the fixative. Tensile strength tests performed, showed that all blocking reagents tend to weaken valve tissue. Histologically calcification originated mainly in the spongiosa of the valve leaflets. Tissue ischaemia at 4 degrees C significantly (p less than 0.05) decreased the calcification potential of the valve tissue. Ischaemia at 25 degrees C significantly (p less than 0.05) increased this process. Blocking reagents KH2PO4, T6 and MgCl2 significantly (p less than 0.05) reduced calcification of valve tissue. AlCl3 pretreatment virtually prevented it to such an extend that the calcification process was down to 92% of the control group. Different fixation pressures had no influence on the calcification potential of the tissue. AlCl3 was dependent on a low pH (3.72) to act as a blocking reagent on tissue calcification. It is concluded that certain processing factors do influence the calcification potential of valve tissue. These factors should be considered when constructing bioprostheses with glutaraldehyde-treated porcine valves.
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PMID:Processing factors as determinants of tissue valve calcification. 153 9

ATP-MgCl2 has been found to be helpful in experimental animals after shock and ischemia with improvement in organ function and survival. The reasons for this pharmacologic action are unclear. To evaluate the clearance and circulation of ATP and its metabolites after intravenous injection, 20 rabbits received ATP-MgCl2 as a bolus injection or a continuous intravenous infusion. Arterial blood was withdrawn, and ATP and its metabolites were measured using a high-performance liquid chromatography (HPLC) technique with ultraviolet (UV) absorption. Forty seconds following a bolus injection, only 1% of the injected dose was present in arterial blood as ATP, and at 280 sec only inosine remained. With a 60 min continuous ATP-MgCl2 infusion, the inosine level peaked at 62.9% at 30 min and was 37.6% at 60 min, whereas ATP was 4.9% and AMP was 17.4% at 60 min. Thus a single dose of ATP-MgCl2 has a half-life of less than 40 sec as ATP. With a continuous infusion, although some ATP circulates, inosine and AMP are the major remaining nucleotides. Thus, the beneficial effects of ATP-MgCl2 may be through ATP itself with magnesium or with adenine nucleotide metabolites for recycling of the nucleotides, phosphorylation of cell membrane inositides, and/or its vasoactive effects.
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PMID:Clearance and maintenance of blood nucleotide levels with adenosine triphosphate-magnesium chloride injection. 155 Nov 86

Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 mumol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flow-metry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation.
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PMID:ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage. 160 Apr 70

A number of beneficial effects of ATP-MgCl2 administration have been demonstrated in preheparinized models of shock and ischemia. However, it is not known whether ATP-MgCl2 restores and maintains the depressed cardiac output in a nonheparinized model of trauma and severe hemorrhage in which resuscitation following shock was provided only with crystalloid. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL). Animals were then resuscitated with 4 times the volume of shed blood with RL (4 X RL) during and following which ATP-MgCl2 (50 mumol/kg body weight each or an equivalent volume of normal saline) was infused intravenously. Cardiac output was determined every 15-30 min for 4.5 hr, using an in vivo hemoreflectometer and indocyanine green dilution technique. Resuscitation with 4 X RL transiently restored but did not maintain cardiac output; however, ATP-MgCl2 treatment restored and maintained cardiac output at control values. ATP-MgCl2 infusion also significantly decreased total peripheral resistance and attenuated tissue water content. Thus, ATP-MgCl2 appears to be a promising adjunct to the treatment of trauma-hemorrhage even in the absence of blood resuscitation.
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PMID:ATP-MgCl2 restores the depressed cardiac output following trauma and severe hemorrhage even in the absence of blood resuscitation. 162 71

Using patch-clamp techniques, we examined the effects of pH on properties of ATP-regulated K+ channels in single myocytes isolated from cat left ventricles. ATP-K+ channels of inside-out patches were bilaterally exposed to 140 mM K+ solutions (22 degrees C). In the absence of ATP and Mg2+, the channels had a linear current-voltage relationship during hyperpolarizing pulses (20-100 mV negative to the reversal potential) at both intracellular pH (pHi) 7.4 and 6.5, but the slope conductance was 66 +/- 2 pS at pHi 7.4 and 46 +/- 2 pS at pHi 6.5. Lowering pHi from 7.4 to 6.5 increased the mean open time (from 15.9 +/- 4.6 to 35.9 +/- 7.9 ms, P less than 0.01) but decreased the open-state probability measured at 50 mV positive to the reversal potential (from 0.35 +/- 0.04 to 0.16 +/- 0.04, P less than 0.01). However, in the presence of both 0.2 mM ATP and 1 mM MgCl2, lowering pHi from 7.4 to 6.5 increased the mean open time (from 5.0 +/- 2.6 to 17.9 +/- 5.9 ms, P less than 0.01) and the open-state probability (from 0.025 +/- 0.010 to 0.098 +/- 0.024, P less than 0.01). These data indicate that increases in intracellular H+ concentration modulate cardiac ATP-K+ channel properties. Ischemia-associated decreases in pHi may enhance the opening of cardiac ATP-regulated K+ channels and resultant action potential shortening.
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PMID:Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes. 188 23

In order to elucidate the pattern of redistribution of cellular energy and the restoration of basic cellular metabolism following an ischemic renal insult, suspensions enriched in proximal tubule segments were studied after 45 min of bilateral artery occlusion and 15 min and 2 h of reflow from rats given either normal saline (control), ATP-MgCl2 (which enhances postischemic recovery of ATP), or alpha, beta-methyl adenosine diphosphate (AMPCP), which inhibits nucleotide degradation during ischemia. In non-ischemic control animals, approximately half of the energy is distributed to functional pump activity and half directed for non-transport purposes. When cellular ATP is reduced to 56% of control values, functional pump activity is significantly reduced to 61% of control, while energy delegated for non-transport purposes is decreased by a significantly smaller increment to only 78% of control at 15 min of reflow. In animals given ATP-MgCl2, the cellular and metabolic profile at 15 min of reflow was no different from ischemic control animals with cellular ATP levels similar at 58%. However, by 2 h, cellular ATP levels had increased significantly to 74%, and this was associated with a redistribution of cellular energy to functional pump activity (119% of control) with little change in non-transport function (76%). In animals treated with AMPCP, the cellular ATP levels were 74% of controls, similar to ATP-MgCl2-treated rats after 2 h of reflow. Despite the differences in reflow interval, the distribution of cellular energy was similar (functional pump activity 120% and non-transport activity 79%). By 2 h, cellular ATP was at 95% and both functional pump activity and non-transport activity were 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redistribution of cellular energy following renal ischemia. 191 Nov 45

Inductively coupled plasma emission spectrometry analysis was applied to determine ischemia-induced changes of Mg2+ and Ca2+ in vulnerable regions of rat brain. This method can provide an accurate quantification and lower detection limits, as compared to atomic absorption spectrophotometry or several other methods. In the hippocampus, Mg2+ content significantly increases 24 h following 20 min of ischemia, followed by a gradual decrease between 48 and 72 h. Ca2+ accumulation was found at 48 and 72 h. At the cell membrane, Mg2+ plays a role as an endogenous calcium channel blocker of both the receptor-operated and voltage-dependent gates and, in the mitochondria, Mg2+ inhibits Ca2+ uptake processes. We propose that the mobilization of Mg2+ after 24 h reperfusion may counteract the process of ischemia-induced neuronal damage and that decreases of Mg2+ may be correlated with the degree of brain injury. However, in the natural concentration of Mg2+, the counteraction may not be sufficient for a neuroprotective effect. Therefore, after 24 h reperfusion, an artificial enhancement of Mg2+ is necessary for neuroprotection. In order to test the above hypothesis, MgCl2, (50 mM) was administered directly to the CA1 sector of the rat hippocampus before and at various intervals following 20 min of ischemia. Pyramidal cells were evaluated seven days later and neuronal density was determined. Consistent with the hypothesis, a neuroprotective effect was observed, even when MgCl2 was administered 24 h, but not 48 h, after the ischemic episode.
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PMID:Mg2+ administered up to twenty-four hours following reperfusion prevents ischemic damage of the Ca1 neurons in the rat hippocampus. 194 89


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