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

To evaluate the effects of adenosine 5-triphosphate-magnesium chloride (ATP-MgCl2) on myocardial function following ischemia, mongrel dogs were placed on cardiopulmonary bypass with separate coronary perfusion pressures at 80 mm Hg. An intraventricular balloon was used to assess cardiac function as the area under the pressure-volume curve (PV), compliance (C), and cardiac contractility (dP/dT). Control measurements were made of coronary flow (Q), myocardial oxygen consumption and PV, C, and dP/dT. Myocardial ischemia was then induced for 45 minutes, followed by reperfusion (R). In group 1 (n = 5), no ATP-MgCl2 was infused into the coronary perfusion line. In group 2 (n = 5), low-dose ATP-MgCl2 (0.13 mg/min/kg) was infused during the first 30 minutes of reperfusion (R0 to R30), and in group 3 (n = 5), high-dose ATP-MgCl2 (3.2 mg/min/kg) was infused from R0 to R30. Use of ATP-MgCl2 therapy produced marked coronary vasodilation. After 20 minutes of reperfusion (R20), coronary resistance was 81% +/- 12%, 55% +/- 15%, and 31% +/- 3% of control in groups 1, 2, and 3, respectively. The high-dose ATP-MgCl2 (group 3) caused a marked systemic hypotension, but the low-dose ATP-MgCl2 (group 2) did not. After 75 minutes of reperfusion (R75), compliance was decreased in all groups. In groups 1 and 3, both function (PV) and dP/dT were significantly decreased. However, for group 2 (low-dose ATP-MgCl2), function (PV), and dP/dT were not different from the control group, indicating an excellent recovery. Thus, at low doses, ATP-MgCl2 appears to be a promising adjunct to the treatment of the ischemic myocardium.
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PMID:Improved myocardial recovery from ischemia. Treatment with low-dose adenosine triphosphate-magnesium chloride. 633 7

The effects of ATP-MgCl2 and dipyridamole were evaluated in a canine model. Twenty-five adult mongrel dogs were divided into five equal groups. All dogs underwent left nephrectomy and 30 min of warm ischemia followed by Collins' C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy were then performed. Group A served as controls; Group B was pretreated with intravenous ATP-MgCl2 (2.5 mM); Group C with intravenous dipyridamole (10 mg), and Group D with both ATP-MgCl2 (2.5 mM) and dipyridamole (10 mg). Group E was treated with ATP-MgCl2 (2.5 mM) at the time of transplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In Groups A and E there were no survivors, whereas Groups B, C, and D had 40, 60, and 40% graft survival. In Groups B and D, ATP and energy charge (EC) were greater than that of controls after 24 hr of preservation, with Group D values being significantly greater (P less than 0.01). AMP and ADP levels were significantly greater (P less than 0.02) in Group C when compared to Group A. One hour posttransplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals, but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with ATP-MgCl2 or dipyridamole maintains intracellular nucleotide levels and has a beneficial effect on graft survival in ischemically injured kidneys undergoing cold-storage preservation.
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PMID:The effects of ATP-MgCl2 and dipyridamole in cold-storage preservation. 634 14

Spinal cord ischemia was produced in rabbits by temporary occlusion of the abdominal aorta just distal to the renal arteries; and recovery, or failure to recover, was assessed by examining the rabbits for permanent loss of sensory and motor function in the hind limbs. A temperature reduction of 3 degrees C during the period of circulatory impairment caused a doubling of the duration of ischemia that could be reversibly sustained. Intravenous administration of 5 mmoles/kg of MgCl2 before the ischemia (a dose sufficient to produce neuromuscular blockade) caused a 50% increase in the tolerable duration. The combination of the 3 degrees C reduction in temperature and the elevated Mg++ increased by about 3 fold the duration of ischemia that could be sustained before irreversible damage occurred. These results may have implications for the care of patients subjected to marginal degrees of CNS ischemia.
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PMID:Mild hypothermia and Mg++ protect against irreversible damage during CNS ischemia. 646 63

Infusion of ATP-MgCl2 following hepatic ischemia significantly improves the survival of animals. To determine the subcellular effects of infused ATP-MgCl2 and whether such effects are mediated through vasodilatation, global hepatic ischemia in rats was produced for 90 min followed by reperfusion. The rats then received iv 0.5 ml of saline, dopamine, papaverine, or ATP-MgCl2. At various intervals following reflow, hepatic mitochondria were isolated. ADP-to-O ratio and respiratory control ratio (RCR) were significantly lower 1 h following reflow, and there was a further decrease in these parameters 3 h after reflow in mitochondria from saline-treated rats. Dopamine and papaverine treatment did not improve RCR, however, ATP-MgCl2 treatment resulted in a progressive and significantly higher ADP/O and RCR following reflow. Hepatic ATP levels in saline, dopamine, and papaverine-treated rats were found to be 50% lower 3 h following reflow, however, treatment with ATP-MgCl2 resulted in significantly higher ATP levels and energy charge. Hepatic blood flow was markedly depressed 1 h following reflow in the saline-treated rats but was significantly higher in the ATP-MgCl2 group. Three hours following reflow, hepatic blood flow decreased further in the saline-treated rats, whereas in the ATP-MgCl2-treated rats there was a progressive increase in flow. Dopamine treatment resulted in an initial restoration in flow, however, this effect was not sustained. Hepatic ultrastructure deteriorated progressively following reflow in the saline-treated rats, however, it was normal in the ATP-MgCl2-treated rats 1 h as well as 20 h following reflow. These results lead us to conclude that infused ATP-MgCl2 improves mitochondrial and cellular functions either directly or by way of long-term improvement in microcirculation but not through vasodilatation.
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PMID:Studies on the mechanism of beneficial effects of ATP-MgCl2 following hepatic ischemia. 660 16

Rat kidneys were flushed in situ with selected preservation solutions prior to clamping the renal vessels for 1 hour. Collins and Euro-Collins flushing solutions did not appear to protect the physiologic or morphologic status of rat kidneys when examined 2 days after the ischemic insult. These experimental groups exhibited serum creatinine levels similar to those seen in ischemic controls, correspondingly low urine creatinine levels, anuria, and significant deterioration of the uriniferous tubules as revealed by light and electron microscopy. In situ flushing with hypertonic Sacks or isotonic phosphate-buffered sucrose solutions, however, resulted in significant improvements in serum and urine creatinine levels, prevented anuria, and dramatically improved the morphologic integrity of the uriniferous tubules. Flushing with a phosphate-buffered sucrose solution that contained ATP-MgCl2 further improved the physiologic and morphologic status of ischemic kidneys to the point that they were indistinguishable from the nonischemic controls. The degree of protection obtained by flushing kidneys with the isotonic phosphate-buffered sucrose solution plus ATP-MgCl2 is greater than that provided by any other single pretreatment or posttreatment for ischemia that is currently available. We, therefore, believe that the use of this procedure can provide a valuable approach to surgical situations in which postischemic acute renal failure is a potential problem.
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PMID:Protection of kidneys from acute renal failure resulting from normothermic ischemia. 660 9

The present study was undertaken to investigate the effect of ATP-MgCl2 on the recovery of renal function following renal ischemia. Bilateral renal ischemia was produced for 90 minutes in dogs. Immediately after the release of ischemia, ATP-MgCl2 (50 mumoles/kg) was given intravenously. Serum creatinine and FeNa were measured following the release of ischemia. Renal cellular energy charge, glomerular endothelial thickness and per cent circularity of interstitial cells were measured. Creatinine and FeNa were significantly lower in ATP-MgCl2 treated dogs compared to those in saline treated controls. Changes in energy charge, glomerular endothelial thickness and per cent circularity indicated ischemically induced renal cellular edema was reversed with ATP-MgCl2 through the improvement of energy metabolism. Taking those experimental data into consideration, ATP-MgCl2 was given to 16 acute renal failure patients and 13 patients survived. ATP-MgCl2 administration is effective for the treatment of acute renal failure.
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PMID:Experimental and clinical study on ATP-MgCl2 administration for postischemic acute renal failure. 660 31

The postischemic infusion of ATP-MgCl2 will enhance the recovery of both glomerular and tubular function. To assess the effect of ATP-MgCl2 on tissue nucleotides, 31P nuclear magnetic resonance (31P-NMR) spectra were obtained continuously in vivo from the left kidney of rats that had been subjected to 45 min of renal ischemia and then infused with either normal saline or ATP-MgCl2. 31P-NMR spectra with distinct peaks for alpha-, beta-, and gamma-phosphate of ATP, sugar phosphate, and inorganic phosphate were collected every 7 min before, during, and after renal artery occlusion. During ischemia, the ATP beta-peak (the only peak unique to ATP) fell rapidly to 10% of control values in both groups of animals. By 120 min after the ischemic insult, the animals treated with ATP-MgCl2 had recovery of renal ATP to 89 +/- 2.6%, which is significantly greater (P less than 0.001) than 65.2 +/- 1.8% found in rats given normal saline. These data indicate that 1) 31P-NMR can be used to assess renal ATP levels continuously in vivo; 2) during renal ischemia ATP levels fall quickly to less than 10% of control values; 3) tissue ATP returns relatively slowly to control values in rats given normal saline, whereas postischemic treatment with ATP-MgCl2 results in an accelerated recovery of tissue ATP levels. These findings provide a biochemical correlate to the improvement in renal function previously described.
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PMID:Enhanced recovery of renal ATP with postischemic infusion of ATP-MgCl2 determined by 31P-NMR. 660 93

Models of post-ischemic acute renal failure were prepared in rats. The effects of adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration following renal ischemia on possible changes in renal function and renal cellular metabolism following ischemia were studied using the model. The results obtained revealed the following: 1) Over 40 minute-renal ischemia led to significant lowerings of renal cellular ATP level and energy charge (EC) by as much as 45 to 57% and 4.1 to 7.4% of the control, respectively, at 90 min following re-establishment of renal blood flow. Significant increases in Na+ in renal tissues were observed, but no changes in K+. Further, lactate level in renal tissues tended to increase with prolonged ischemic time by as much as 27 to 31% of the control, with a renal cellular anaerobic metabolism observed. On the other hand, at 24 hr following recirculation of the kidney, plasma creatinine (P-Cr), blood urea nitrogen (BUN) and fraction excretion of sodium (FENa) increased significantly, and creatinine clearance (C-Cr) and urine osmotic pressure decreased significantly, as compared with the control, indicating ischemic acute renal failure. 2) Intravenous injection of ATP-MgCl2 at a dose of 25 mumole/kg and a rate of 1.0 mumol/min after 40 min of renal ischemia led to significant lowerings of P-Cr, BUN and FENa to 36, 35 and 35% of the control (injected with physiological saline solution), respectively, and to significant elevation of C-Cr and urine osmotic pressure by as much as 41 to 31% of the control respectively, at 24 hr after reperfusion. The above results suggested that the ischemic acute renal failure was caused by the decreases in renal cellular ATP and EC with ischemia, resulting in renal cellular metabolic disturbances. It was further suggested that ATP-MgCl2 administered for such a pathological condition could make significant improvements in renal function.
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PMID:[Effect of adenosine triphosphate-magnesium chloride administration for post-ischemic acute renal failure (I)]. 660 69

To determine whether infused ATP-MgCl2 affects mitochondrial adenine nucleotide translocase (ANT) activity, free fatty acids (FFAs), and Ca2+ levels, total hepatic ischemia in rats was produced for 90 min after which blood flow was allowed to return to the liver. Immediately on reflow, the animals received intravenously 0.5 ml of either saline, ATP-MgCl2 (12.5 mumol), or dopamine (6 mg/kg). Three hours after ischemia and reflow, hepatic mitochondrial FFAs and Ca2+ levels increased; however, ATP-MgCl2 infusion significantly lowered FFAs and restored Ca2+ levels. The depressed mitochondrial ANT activity was somewhat improved but not restored by circulatory support with dopamine; however, ATP-MgCl2 infusion following ischemia restored that activity. Thus the present results suggest that the improved organ function that occurs with ATP-MgCl2 infusion following ischemia may be mediated through an improvement in ischemia-induced mitochondrial function.
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PMID:Improved mitochondrial function following ischemia and reflow by ATP-MgCl2. 660 48

Recent studies have shown that infusion of ATP-MgCl2 following hepatic ischemia significantly improved mitochondrial function and hepatic blood flow 1 hr after treatment. To determine if the improvement in the above parameters by ATP-MgCl2 is short-lived or whether it persists for prolonged periods of time after treatment, hepatic ischemia in rats was produced for 90 min followed by reperfusion. The rats then received iv 0.5 ml of saline or ATP-MgCl2 (12.5 mumole each). Twenty-four hours after reflow, hepatic blood flow was measured by H2 polarography following which the animals were sacrificed and hepatic mitochondria isolated. The results indicated that 24 hr after reflow, mitochondrial state 3 respiration, respiratory control ratio, adenine nucleotide translocase activity, ATP synthetic activity, and hepatic blood flow were depressed by approximately 50% in animals which were treated with saline after hepatic ischemia. In addition, there was a fourfold increase in mitochondrial free fatty acid levels of such animals. Animals which were treated with ATP-MgCl2 following hepatic ischemia showed significantly improved mitochondrial function (used as an index of cellular recovery) and hepatic blood flow. These results in conjunction with previous results suggest that infused ATP-MgCl2 improves mitochondrial function and blood flow and that these effects persist even 24 hr after administration of ATP-MgCl2. Thus, infusion of ATP-MgCl2 following severe ischemia produces sustained improvement in cellular function.
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PMID:ATP-MgCl2 produces sustained improvement in hepatic mitochondrial function and blood flow after hepatic ischemia. 661 53


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