sodium-bicarbonate and Reperfusion-Injury

Hepatic injury induced by ischemia and reperfusion (HIRI) is a major clinical problem after liver resection or transplantation. The polarization of macrophages plays an important role in regulating the severity of hepatic ischemia/reperfusion injury. Recent evidence had indicated that the ischemia induces an acidic microenvironment by causing increased anaerobic glycolysis and accumulation of lactic acid. We hypothesize that the acidic microenvironment might cause the imbalance of intrahepatic immunity which aggravated HIRI. The hepatic ischemia/reperfusion injury model was established to investigate the effect of the acidic microenvironment to liver injury. Liposomes were used to deplete macrophages

Topics: Animals; Benzophenones; Cells, Cultured; Cellular Microenvironment; Disease Models, Animal; Hydrogen-Ion Concentration; Immunity, Innate; Kupffer Cells; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Reperfusion Injury; Severity of Illness Index; Signal Transduction; Sodium Bicarbonate; Tyrosine

Acidosis is one of the key components in cerebral ischemic postconditioning that has emerged recently as an endogenous strategy for neuroprotection. We set out to test whether acidosis treatment at reperfusion can protect against cerebral ischemia/reperfusion injury. Adult male C57BL/6 J mice were subjected to 60-minute middle cerebral arterial occlusion followed by 24-hour reperfusion. Acidosis treatment by inhaling 10%, 20%, or 30% CO2 for 5 or 10 minutes at 5, 50, or 100 minutes after reperfusion was applied. Our results showed that inhaling 20% CO2 for 5 minutes at 5 minutes after reperfusion-induced optimal neuroprotection, as revealed by reduced infarct volume. Attenuating brain acidosis with NaHCO3 significantly compromised the acidosis or ischemic postconditioning-induced neuroprotection. Consistently, both acidosis-treated primary cultured cortical neurons and acute corticostriatal slices were more resistant to oxygen-glucose deprivation/reperfusion insult. In addition, acidosis inhibited ischemia/reperfusion-induced apoptosis, caspase-3 expression, cytochrome c release to cytoplasm, and mitochondrial permeability transition pore (mPTP) opening. The neuroprotection of acidosis was inhibited by the mPTP opener atractyloside both in vivo and in vitro. Taken together, these findings indicate that transient mild acidosis treatment at reperfusion protects against cerebral ischemia/reperfusion injury. This neuroprotection is likely achieved, at least partly, by inhibiting mPTP opening and mitochondria-dependent apoptosis.

Topics: Acidosis; Animals; Brain Ischemia; Carbon Dioxide; Male; Mice; Neuroprotective Agents; Reperfusion Injury; Sodium Bicarbonate; Stroke

Buffers added to myocardial preservation solutions are considered to be critical for resisting myocardium pH changes from the accumulation of protons (H+). Our hypothesis is that mathematical modeling of three clinically used buffers will define their individual buffering capacities under simulated clinical conditions.. The buffers, tromethamine (THAM), sodium bicarbonate (HCO3-), and L-histidine, were compared in terms of their buffering capacity (beta) under specific temperatures and concentrations, using a mathematical model.. At 37 degrees C, the maximal beta (betamax) occurred at pH 7.75 for THAM, pH 6.10 for HCO3-, and pH 5.89 for L-histidine at equimolar concentrations. A decrease in temperature moved betamax to a higher pH value for each buffer. At clinical concentrations, L-histidine provided the greatest buffering capacity followed by HCO3- and THAM, respectively.. This model permitted comparison of the above buffers under simulated clinical conditions. The assumption was that the magnitude of betamax at a given temperature determines which buffer(s) could be most effective for myocardial preservation. Also, the assumption was taken that these buffers are used in a closed system--where there is no continuous blood flow--and that the buffering ability of THAM and L-histidine were not influenced by the accumulation of CO2 as is HCO3-. THAM and L-histidine were more effective at hypothermic temperatures compared with HCO3-; however, HCO3- provided buffering at normothermic temperatures. Through the theoretical considerations of this study, we propose that combining HCO3- with THAM or L-histidine could be most efficacious for myocardial preservation during open heart surgery or organ transplantation.

Topics: Acids; Buffers; Cardiopulmonary Bypass; Heart Transplantation; Histidine; Humans; Hydrogen-Ion Concentration; Models, Theoretical; Myocardium; Organ Preservation Solutions; Reperfusion Injury; Sodium Bicarbonate; Tromethamine

We report two drowning victims with hypothermic circulatory arrest who were resuscitated with the use of extracorporeal circulation (ECC). The first patient developed severe post-bypass pulmonary oedema and inspired us to use a leucocyte-depletion filter in the second patient to attenuate leucocyte-mediated pulmonary reperfusion injury.. In the first patient, a standard extracorporeal circuit was used. In the second patient, systemic leucocyte depletion was applied using leucocyte-depletion filters (Pall RS 1, Pall, Portsmouth, UK), in the venous side of the extracorporeal circuit. Circulating leucocyte counts were measured and arterial blood gas analysis and chest X-rays were performed.. Both patients showed a decrease of the circulating leucocyte counts during rewarming and had nearly similar leucocyte counts on arrival at the intensive care unit (ICU). The first patient developed severe pulmonary oedema, with poor arterial blood gases, whereas the second patient, who had leucocyte-depletion by filtration, did not develop severe pulmonary oedema, and had good arterial blood gases.. Profound leucocyte-depletion by means of filtration may have contributed to limit leucocyte-mediated pulmonary reperfusion injury.

Topics: Accidents, Traffic; Acidosis; Adult; Cardiotonic Agents; Child, Preschool; Dopamine; Extracorporeal Circulation; Fatal Outcome; Heart Arrest; Humans; Hypothermia; Leukocyte Reduction Procedures; Male; Multiple Organ Failure; Near Drowning; Polymerase Chain Reaction; Pulmonary Edema; Reperfusion Injury; Rewarming; Sodium Bicarbonate

Controversy surrounds the use of buffers during cardiac arrest to correct acidosis. The objective of this study was to determine whether attenuation or neutralization of cerebral acidosis by Carbicarb alters hippocampal glutamate levels, neuronal cell death, and neurologic deficits after reperfusion from asphyxial cardiac arrest in rats.. Rats were prospectively randomized to either a control (n=45), low-dose Carbicarb (LDC; 3 mL/kg, n=45), or high-dose Carbicarb (HDC; 6 mL/kg, n=45) group in a blinded fashion during resuscitation after 8 minutes of asphyxial cardiac arrest. Microdialysis was used to assess brain pH and glutamate. A neurologic deficit score and neuronal cell death in the hippocampus were determined at day 7.. Resuscitation was greatest in LDC rats (42/45) and least in HDC rats (28/45) versus that in control rats (34/45). Brain pH was higher in the LDC and HDC rats 10 minutes after resuscitation and remained higher than that of control rats for 120 minutes after resuscitation. Glutamate levels at 10 to 120 minutes after reperfusion were lowest in the LDC rats. LDC rats had the lowest neurologic deficit score (1+/-2) versus that of control rats (13+/-8) and HDC rats (19+/-6). Hippocampal neuronal cell death was lowest in LDC rats (30+/-20) versus that in control rats (86+/-47) and HDC rats (233+/-85).. LDC administered during resuscitation from asphyxial cardiac arrest attenuated acidosis, improved resuscitation, and reduced neurologic deficits and the number of dead hippocampal neurons. Neutralization of cerebral acidosis with HDC increased the number of dead hippocampal neurons and neurologic deficits after resuscitation from cardiac arrest in rats.

Topics: Acidosis; Animals; Asphyxia; Brain; Brain Ischemia; Carbonates; Cell Death; Disease Models, Animal; Drug Combinations; Glutamic Acid; Heart Arrest; Hippocampus; Neurons; Rats; Recovery of Function; Reperfusion Injury; Sodium Bicarbonate; Treatment Outcome

Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO, an oxidant-generating enzyme), released from reperfusing liver and intestines, mediating a significant component of this injury. Since pentastarch administration decreases intestinal reperfusion injury, we determined whether resuscitation with PentaLyte (a pentastarch-containing solution) would decrease hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung injury after aortic occlusion- reperfusion. Aortic occlusion was established in rabbits for 40 min, and was followed by 3 h of reperfusion, during which either PentaLyte or lactated Ringer's solution-based resuscitation was administered. Sham-operated animals served as controls. Hepatoenteric reperfusion injury, as manifested by release of the enzyme aspartate aminotransferase and decreased gastric intramucosal pH, was significantly (p < 0.0167) attenuated by PentaLyte administration after aortic occlusion-reperfusion, as compared with its occurrence in animals given lactated Ringer's solution. The release of XO after aortic occlusion-reperfusion was 4-fold smaller after PentaLyte administration than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte administration following aortic occlusion-reperfusion than after administration of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary injury is significantly decreased by concomitant PentaLyte-mediated reduction of hepatoenteric reperfusion injury and XO release.

Topics: Animals; Aorta, Thoracic; Aspartate Aminotransferases; Blood Proteins; Bronchoalveolar Lavage Fluid; Constriction; Electrolytes; Gastric Mucosa; Glucose; Hydrogen-Ion Concentration; Hydroxyethyl Starch Derivatives; Infusions, Intravenous; Intestines; Isotonic Solutions; L-Lactate Dehydrogenase; Liver; Male; Phenylephrine; Plasma Substitutes; Rabbits; Reperfusion Injury; Respiratory Distress Syndrome; Resuscitation; Ringer's Lactate; Sodium Bicarbonate; Xanthine Oxidase

To determine if gastric intramucosal pH is affected by hepatoneteric ischemia-reperfusion. We additionally proposed to determine if changes in gastric mucosal hydrogen ion concentration are associated with liver and lung injury following hepatoenteric ischemia-reperfusion. Finally, we hypothesized that gastric intramucosal pH is influenced by xanthine oxidase, an oxidant-generating enzyme released after hepatoenteric ischemia-reperfusion.. Randomized, controlled, animal study.. University-based animal research facility.. Thirty-six New Zealand white male rabbits (2 to 3 kg).. Anesthetized rabbits were randomly assigned to one of four groups (n = 9 per group): a) sham-operated group; b) sham-operated group pretreated with sodium tungstate (xanthine oxidase inactivator); c) aorta occlusion group; and d) aorta occlusion group pretreated with sodium tungstate. Descending thoracic aorta occlusion was maintained for 40 mins with a 4-Fr Fogarty embolectomy catheter, followed by 2 hrs of reperfusion.. Gastric tonometry was performed after completion of the surgical preparation (30-min equilibration) and at 30, 60, 90, and 120 mins of reperfusion. Plasma alanine aminotransferase activity was determined at 120 mins of reperfusion to assess hepatic injury. Bronchoalveolar lavage of the right lung was performed after 120 mins of reperfusion, and the protein content was determined as a measure of pulmonary alveolar-capillary membrane compromise. Descending thoracic aorta occlusion resulted in a significant decrease in gastric intramucosal pH as compared with sham-operated rabbits (p < .001). The change in gastric mucosal hydrogen ion concentration was significantly associated with plasma alanine aminotransferase activity (r2 = .48, p < .01) and bronchoalveolar protein content (r2 = .51, p < .01). Xanthine oxidase inactivation significantly improved gastric intramucosal pH after aortic occlusion and reperfusion (p < .001), with a concomitant attenuation of the release of plasma alanine aminotransferase (p < .05) and accumulation of bronchoalveolar protein (p < .05) during reperfusion.. Gastric intramucosal pH was significantly decreased after hepatoenteric ischemia-reperfusion. Furthermore, an increase in gastric intramucosal hydrogen ion concentration was associated with a concomitant increase in tissue injury, a presumed harbinger of multiple organ failure. Gastric intramucosal pH values improved during reperfusion after xanthine oxidase inactivation, concomitant with attenuation of hepatic and pulmonary injury. Gastric tonometry is an important clinical tool that can provide critical insight into the pathogenesis of multiple organ injury after hepatoenteric ischemia-reperfusion. Gastric tonometry may aid in the rapid assessment of pharmacologic interventions designed to attenuate multiple organ injury in similar clinical settings (e.g., trauma, shock, major vascular surgery).

Topics: Animals; Gastric Mucosa; Hydrogen-Ion Concentration; Ischemia; Liver; Lung; Male; Manometry; Phenylephrine; Rabbits; Random Allocation; Reperfusion Injury; Sodium Bicarbonate; Xanthine Oxidase

Post-reperfusion syndrome is the most common hemodynamic pattern in liver transplantation, manifesting mainly through decreased heart rate, mean arterial pressure and systemic vascular resistances. Five factors have been implicated in its genesis: the heart, the circulatory system, the metabolism, reflexes and surgery. Ventricular function, both right and left, has been shown to be normal during reperfusion, in which case the visceral and, especially, liver dilation that occurs would be the main cause of arterial hypotension. Patients in poor physical condition before the transplant are more likely to suffer the syndrome. Surgical technique (standard, venovenous shunt or preservation of the inferior vena cava), on the other hand, does not seem to play a major role. Prophylaxis with atropine prevents bradycardia but not hypotension. Administration of calcium chloride and sodium bicarbonate together with hyperventilation, mitigates symptoms. Finally, treatment with phenylephrine is rapidly effective.

Topics: Body Temperature; Calcium Chloride; Disease Susceptibility; Hemodynamics; Humans; Liver Transplantation; Models, Biological; Phenylephrine; Prognosis; Reflex; Reperfusion Injury; Sodium Bicarbonate; Splanchnic Circulation; Syndrome; Vasodilation

The ischemia-reperfusion syndrome, first described by Haimovici in 1960, is a severe complication following surgery for acute ischemia. We evaluated the incidence of this complication in 264 patients operated on between 1972 and 1981 (1st group) and compared it with another of 392 patients operated on between 1982 and 1991 (2nd group), our aim being to assess the effects of pharmacological prophyiaxis based on preoperative overhydration followed by an intra-arterial bolus of 250 ml 14/1000 HCO3-, containing 1 g dexamethasone and 2500 I.U. sodium heparin, injected into the femoral artery before suturing the arteriotomy. This regimen was based on the measurement of myoglobin and glutathione levels respectively carried out in two subgroups of 25 patients. The results of experimental ischemia-reperfusion syndromes induced in animal using radical scavengers and membrane-protective compounds were also taken into consideration. Following experimental research on sheep, 5 patients in the second group with very severe ischemia due to aortic occlusion received local dialysis in the extracorporeal circulation using hemodialysis or hemofiltration techniques. Mortality was 6.3% in the first group and 5.4% in the second, while the amputation rate was 3% and 1.8% respectively. The overall incidence of the reperfusion syndrome was 3% in the 1st period and 1.8% in the second. Our findings confirm the protective effect of hyper-hydration, radical scavengers and dexamethasone in the ischemia reperfusion syndrome, and indicate that local hemodialysis is a useful adjunct in very severe ischemia.

Topics: Aged; Animals; Case-Control Studies; Dexamethasone; Extracorporeal Circulation; Free Radical Scavengers; Glutathione; Heparin; Hindlimb; Humans; Incidence; Infusions, Intravenous; Leg; Middle Aged; Myoglobin; Peripheral Vascular Diseases; Reperfusion Injury; Sheep; Sodium Bicarbonate; Treatment Outcome

"Declamping shock" is observed after aortic crossclamping, with hypovolemia, hypotension, and metabolic acidemia invariably present. We hypothesized that oxidants derived from xanthine oxidase influence the resuscitative interventions required to maintain baseline hemodynamic and acid-base status after aortic occlusion and reperfusion in rabbits. We also hypothesized that inactivation of xanthine oxidase with sodium tungstate could reduce systemic injury as assessed by the release of lactate dehydrogenase and alkaline phosphatase. To test these hypotheses, we established aortic occlusion in rabbits (n = 10, standard diet; n = 8, tungstate diet) for 40 minutes by inflation of a 4F Fogarty catheter in the descending thoracic aorta followed by 2 hours of reperfusion. Sham-operated rabbits (n = 10, standard diet; n = 9, tungstate diet) served as controls. Tungstate-pretreated rabbits required significantly less Ringer's solution (28%), phenylephrine (68%), and sodium bicarbonate (30%) during reperfusion (p < 0.005). Lactate dehydrogenase and alkaline phosphatase release during reperfusion was significantly attenuated by tungstate pretreatment (p < 0.05). Tungstate pretreatment resulted in plasma xanthine oxidase activities significantly lower than those in the sham group administered a standard diet (p = 0.007). Resuscitation requirements and systemic injury were reduced by inactivation of xanthine oxidase in a rabbit model that simulates the situation of human thoracic aorta operations.

Topics: Acid-Base Equilibrium; Alkaline Phosphatase; Analysis of Variance; Animals; Aorta, Thoracic; Constriction; Enzyme Activation; Hemodynamics; Isotonic Solutions; L-Lactate Dehydrogenase; Male; Phenylephrine; Rabbits; Reperfusion Injury; Resuscitation; Ringer's Solution; Shock, Surgical; Sodium Bicarbonate; Tungsten Compounds; Xanthine Oxidase

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetates; Animals; Aorta; Cardioplegic Solutions; Disease Models, Animal; Drug Evaluation, Preclinical; Gluconates; HEPES; Hypothermia, Induced; Magnesium Chloride; Male; Paraplegia; Postoperative Complications; Potassium Chloride; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Reproducibility of Results; Sodium Acetate; Sodium Bicarbonate; Sodium Chloride; Spinal Cord; Time Factors

The protective effect of intravenous 8.4 per cent sodium bicarbonate on renal function after ischaemia was evaluated in rats subjected to 45 or 90 min warm unilateral renal ischaemia. Two groups of control animals received normal or 3 per cent saline. All solutions were given by bolus injection 3 h before ischaemia. Renal function was significantly protected in animals receiving bicarbonate. Vascular congestion of the inner stripe of the renal medulla was prevented. The survival rate in the group undergoing 90-min ischaemia was 70 per cent for animals receiving bicarbonate and nil in those given saline. Preoperative alkalinization confers significant functional and morphological protection in the ischaemic kidney.

Topics: Animals; Bicarbonates; Hydrogen-Ion Concentration; Injections, Intravenous; Ischemia; Kidney; Kidney Diseases; Rats; Rats, Wistar; Reperfusion Injury; Sodium; Sodium Bicarbonate