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)

Although ATP-MgCl2 produces a myriad of beneficial effects following organ ischemia and simple hemorrhagic shock in animal models which involved heparinization and/or blood resuscitation, it is not known whether ATP-MgCl2 has any salutary effect on the depressed active hepatocellular function (AHF) and hepatic microvascular blood flow (HMBF) in a nonheparinized model of trauma and severe hemorrhage in the absence of blood resuscitation. To determine this, rats underwent a midline laparotomy (i.e., trauma induced) and were 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). The animals were then resuscitated with four times the volume of shed blood with RL. ATP-MgCl2, 50 mumoles/kg body weight (BW) each or an equivalent volume of normal saline, was infused intravenously for 95 min during and following crystalloid resuscitation. At 1.5 and 4 hr after resuscitation, AHF (Vmax, maximal velocity of indocyanine green clearance; Km, efficiency of the active transport process) was determined without blood sampling by using an in vivo indocyanine green clearance technique. HMBF was measured with laser Doppler flowmetry. Results indicate that Vmax, Km, and HMBF decreased significantly at 1.5-4 hr after hemorrhage and resuscitation. ATP-MgCl2 infusion restored the depressed Vmax, Km, and HMBF and prevented the occurrence of hepatic edema. The restoration of AHF with ATP-MgCl2 treatment may be due to its direct salutary effect on the active indocyanine green transport process and/or due to improvement in hepatic microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ATP-MgCl2 restores the depressed hepatocellular function and hepatic blood flow following hemorrhage and resuscitation. 202 Jan 88

Subsarcolemmal and interfibrillar mitochondria were isolated from the hearts of the diving muskrat and non-diving guinea pig and direct and indirect measurements of calcium uptake were examined in vitro. The calcium-stimulated respiration rate and 45Ca uptake were measured and found to be greater in muskrat than in guinea pig mitochondria. Muskrat mitochondria were able to endure a greater external calcium concentration than guinea pig mitochondria before exhibiting indications of inner membrane damage. Calcium uptake by muskrat heart mitochondria was inhibited more by 1 mmoll-1 MgCl2 than was uptake by guinea pig mitochondria. No differences were detected between the interfibrillar and subsarcolemmal populations of mitochondria within species. An increased ability to sequester calcium by mitochondria without causing them damage may aid an animal during recovery from hypoxia, ischemia or acidosis.
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PMID:Calcium uptake by mitochondria isolated from muskrat and guinea pig hearts. 206 4

The ATP-sensitive potassium channel current (IK-ATP) was studied in excised inside-out patches from rat ventricular cells at 20-23 degrees C. The bath solution contained 140 mM KF, and the pipette solution contained 140 mM KCl and 1.2 mM MgCl2. ATP (0.5 mM) in the bath inhibited IK-ATP. In the absence of ATP, 10 microM quinidine decreased open probability 67 +/- 1% (n = 6) at -50 mV and 28 +/- 12% at -130 mV (n = 5) without affecting single channel conductance (48-52 pS). The block increased with 25 and 50 microM quinidine and could be reversed on washing quinidine for several minutes. Interburst (closed) intervals were increased by quinidine, whereas open and closed time distributions within bursts were not changed. We conclude that quinidine blocks IK-ATP in a "slow" and voltage-dependent manner in clinically relevant concentrations. Because of the postulated role for IK-ATP in cardiac ischemia, quinidine block of this channel may play a role in ischemic arrhythmias.
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PMID:Quinidine blocks adenosine 5'-triphosphate-sensitive potassium channels in heart. 224 Feb 58

The available information indicates that shock and ischemia are associated with such phenomena as diminished microcirculatory blood flow and diminished metabolic (including ATP levels) and cellular capabilities, and that these phenomena are associated with altered cellular functions. Infusion of ATP-MgCl2 as an adjunct following shock or ischemia significantly improves microcirculatory blood flow, tissue and mitochondrial magnesium levels, tissue ATP levels, cellular functions, and overall survival of animals. Administration of ATP or MgCl2 alone after such conditions was ineffective in improving cellular functions or the survival of animals. Thus, it could be concluded that ATP together with MgCl2 is required for an effective treatment. ATP-MgCl2 can be administered safely in normal volunteers as well as in patients following various adverse circulatory conditions. Administration of this agent in humans produces positive inotropic, negative chronotropic, and peripheral vasodilatory actions, which clearly suggests the potential use of this agent in patients with low-flow conditions or organ ischemia. Clinical trials of ATP-MgCl2 treatment in patients with various adverse circulatory conditions are underway at several institutions in this country as well as in Japan.
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PMID:Use of ATP following shock and ischemia. 229 15

The calcium antagonists protect the myocardium against the deleterious effects of ischemia and postischemic reperfusion provided that they are used prophylactically. This requires chronic therapy. Experiments were undertaken to establish whether chronic verapamil therapy alters the cardiac noradrenaline reserves or provokes a change in beta 1 adrenoceptor density. Sprague-Dawley (SD) rats were fed a diet containing placebo, or placebo plus dl verapamil (V) to provide plasma V levels of around 100 ng/ml. After 6 weeks of therapy the hearts were excised and assayed for noradrenaline (NA), adrenaline (A), and dopamine (DA) using high performance liquid chromatography. In addition, cardiac membranes were isolated in the presence of Tris, 10 mM MgCl2 and 9 microM phenylmethylsulfoxylfluoride and assayed for beta 1 adrenoceptor density (Bmax) and affinity (KD), using [3H]dihydroalprenolol as the ligand. Three days of therapy reduced left ventricular NA by 45%. Asymptote was reached within 11 days, when the NA content has decreased (p less than 0.001) to only 0.9 +/- 0.1 mu/g dry wt, mean +/- SEM, n = 6. The tissue level of DA was also reduced from 0.14 +/- 0.02 to 0.08 +/- 0.01 microgram/g dry weight (p less than 0.02). Further treatment for up to 6 weeks caused no further change in NA, A, or DA. Even after 6 weeks of therapy the density (35.5 +/- 1.9 before and 31.2 +/- 2.3 fmol/mg protein after therapy) and affinity (0.24 +/- 0.02 and 0.21 +/- 0.02 nM) of the beta 1 adrenoceptors were unchanged. These results show that although chronic verapamil therapy depletes the cardiac reserves of NA, beta-adrenoceptor density remains constant.
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PMID:Chronic calcium antagonist therapy: some unexpected results. 246 14

Both Mg2+ and Ca2+ have been implicated as having roles in the pathomechanisms of cerebral ischemia. To further study the effects of these ions on postischemic histologic outcome, fasted rats were given one of three intravenous infusions: 5.0 mmol/kg MgCl2, 5.0 mmol/kg MgCl2 + 0.035 units/kg regular insulin, or 1.0 mmol/kg CaCl2. This resulted in elevated plasma Mg2+ or Ca2+ concentrations in the corresponding groups. A fourth group received 0.9% NaCl (saline). Preinfusion plasma glucose concentration was similar for all groups and was unchanged after infusion in rats receiving either saline or MgCl2 + insulin. In contrast, postinfusion glucose concentration was increased in the MgCl2 group (p less than 0.001) and decreased in the CaCl2 group (p less than 0.001) relative to saline-treated rats. Following respective infusions, all rats underwent 10 minutes of reversible forebrain ischemia (bilateral carotid artery occlusion and systemic hypotension) followed by 7 days' recovery. Six of 12 CaCl2-treated rats died 2-3 days after ischemia; all other rats remained neurologically indistinguishable, without gross neurologic deficits. Histologic injury in the neocortex and caudate was moderate in all groups. In the hippocampus, MgCl2 + insulin resulted in 66 +/- 6% (mean +/- SD) dead CA1 pyramidal cells, which was similar to the amount in saline-treated rats (68 +/- 10%). Injury was increased in the MgCl2 group (79 +/- 4% dead cells), while in surviving CaCl2-treated rats, injury was decreased (54 +/- 13%). We conclude that the increased injury in MgCl2-treated rats and the decreased injury noted in surviving rats receiving CaCl2 are due to the plasma glucose concentrations present prior to ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of elevated plasma magnesium versus calcium on cerebral ischemic injury in rats. 264 53

The information available indicates that following hepatic ischemia and reflow, there is decreased tissue ATP levels, decreased tissue and mitochondrial magnesium levels, and decreased mitochondrial capability. Associated with these changes are altered cellular functions. Administration of ATP-MgCl2 following ischemia significantly improves total and microcirculatory blood flow, tissue and mitochondrial magnesium levels, tissue ATP stores, cellular functions, and the survival of animals. In contrast to ATP-MgCl2, administration of ATP or MgCl2 alone after ischemia was ineffective in improving cellular functions and tissue and mitochondrial magnesium levels. ATP-MgCl2 therefore appears to be a promising adjunct to the treatment of shock and ischemia.
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PMID:ATP-MgCl2 and liver blood flow following shock and ischemia. 265 90

The biochemical factors that mediate secondary or delayed damage to the central nervous system (CNS) remain speculative. We have recently demonstrated that brain injury in rats causes a rapid decline in brain intracellular free magnesium (Mg2+) and total magnesium concentrations that is significantly correlated with the severity of injury. In order to further investigate the relationship between Mg2+ and brain injury, we examined the effect of Mg2+ treatment on posttraumatic neurological outcome following fluid-percussion brain injury (2.0 atm) in rats. Since administration of ATP-MgCl2 has been shown to be beneficial in a variety of models of organ ischemia, we also examined the efficacy of ATP-MgCl2 or ATP alone in the treatment of experimental brain injury. Animals treated with low (12.5 mumol) or high (125 mumol) dose MgCl2 at 30 min postinjury showed a significant dose-dependent improvement in neurological function when compared to saline-treated controls. Treatment with ATP-MgCl2 (12.5 mumol) or ATP alone (12.5 mumol) caused no significant improvement in chronic neurological outcome. MgCl2-treated animals showed no change in postinjury mean arterial blood pressure (MAP), whereas animals treated with either ATP-MgCl2 or ATP alone showed a transient but significant fall in MAP (P less than 0.01) during the drug-infusion period. Our results suggest that postinjury treatment with MgCl2 is effective in limiting the extent of neurological dysfunction following experimental traumatic brain injury in the rat.
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PMID:Magnesium protects against neurological deficit after brain injury. 278 89

This last part of the oxygen story seems to stray from the line followed till now, and contradict itself, by electing ATP instead of oxygen as its protagonist. Yet, of course, this deviation is only apparent: in reality the hypoxanthine, which is at the basis of the production of superoxide, during the post-ischemic perfusion, is just a catabolic product of the intercellular reserves of ATP, pillaged by the ischemia itself. The attempts to resolve the ischemia and cellular anoxia through the supply, added to the volemic and respiratory reintegration, of performed packets of energy, such as ATP with MgCl2, FDP, etc., cannot be unimportant for traumatologist surgeon, accustomed to face the multiform physiopathologic facets of the shock. Although the flattering results tend to increase, some doubts remain about the effectiveness of such measures, especially ATP, and someone also suggests possible negative effects, partly framed in the well known and complex consequences of the "drug" on the cardiovascular dynamics, partly put forth by its not enough defined metabolic outline. Evidently, the way of the straight energetic supply, which, undoubtedly, represents the fulfillment of a "mirage" of release, at least partially, and in critical situations, from oxygen, although still long and burdened with problems, is also, decidedly, suggestive with promises. It seems surgeon, the true protagonist of such investigations, wants to seek a new dimension in them, being aware, and transplantations supplied an exemplary lesson in such sense, the biologic language is congenial to him, as it is high time.
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PMID:[The story of oxygen. (3)]. 299 96

The aim of this study was to determine whether ATP-MgCl2 or isoproterenol pretreatment would attenuate the increase in canine gracilis muscle vascular resistance and permeability associated with 4 h of occlusive ischemia followed by 1 h of reperfusion. To this end, the osmotic reflection coefficient for total plasma proteins (omega), isogravimetric capillary pressure (Pci), precapillary resistance (Ra), postcapillary resistance (Rv), and total vascular resistance (Rt) were determined for the following conditions: control, ischemia, and ischemia plus pretreatment with ATP-MgCl2 or isoproterenol. Reperfusion, after ischemia, significantly reduced omega from 0.94 +/- 0.02 to 0.64 +/- 0.02, whereas Pci was decreased by 50 +/- 4%, indicating a dramatic increase in vascular permeability. Ischemia-reperfusion was also associated with an increase in Rt of 230 +/- 22%. Similar results were obtained in muscles pretreated with isoproterenol. However, in muscles pretreated with ATP-MgCl2, omega averaged 0.98 +/- 0.09, Pci was reduced by only 15 +/- 8%, and Rt was increased by just 25 +/- 12%. The effect of ATP-MgCl2 on neutrophilic oxidative metabolism was evaluated by measuring superoxide production by activated neutrophils in the presence and absence of ATP-MgCl2. Superoxide production by activated neutrophils was significantly attenuated by ATP-MgCl2. The results of these studies indicate that pretreatment with ATP-MgCl2, but not isoproterenol, is remarkably effective in attenuating the increase in skeletal muscle vascular resistance and permeability induced by ischemia-reperfusion. The protective effect of ATP-MgCl2 may be related in part to its ability to inhibit neutrophilic superoxide production.
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PMID:Vascular injury in dogs during ischemia-reperfusion: improvement with ATP-MgCl2 pretreatment. 325 77


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