raffinose and Hemorrhage

This study investigated the role of a novel nutrient-rich preservation solution in alleviating intestinal ischemia-reperfusion (IR) injury in a large animal model.. Porcine intestines were treated in vivo with the following intraluminal flush solutions: group 1, none; group 2, University of Wisconsin solution; group 3, an amino acid-based solution, previously shown to be effective in reducing IR injury in rodent models. Intestinal ischemia was induced in vivo for 60 min, followed by 180 min reperfusion. Key metabolic aspects were assessed in relation to two fundamental kinase mechanisms that govern cell fate, AMP kinase, and Jun kinase.. After 180 min reperfusion, groups 1 and 2 exhibited clefting, denudation, and mucosal hemorrhage, whereas injury was markedly reduced in group 3 (median grades 4.5 and 5 vs. 0; P<0.05). In contrast to groups 1 and 2, group 3 tissues exhibited a full recovery of adenylates (ATP, total adenylates) and an effective control of oxidative stress throughout reperfusion. Neutrophil-mediated inflammation was abrogated in group 3. An up-regulation of two key enzymes (glutaminase and alanine aminotransferase) provided a mechanism for the superior recovery of energetics and the preservation of mucosal integrity in group 3. A strong activation of AMP-activated protein kinase resulting in the up-regulation of a primary proapoptotic kinase mechanism, Jun kinase, was evident in groups 1 and 2.. A strategy of intraluminal administration of a nutrient-rich solution represents a potential therapy for alleviating intestinal IR injury; these findings suggest a more effective method for the ischemic storage of intestine.

Topics: Adenosine; Adenylate Kinase; Alanine Transaminase; Allopurinol; Animals; Glutaminase; Glutathione; Hemorrhage; Insulin; Intestinal Mucosa; Intestine, Small; Organ Preservation; Organ Preservation Solutions; Raffinose; Reperfusion Injury; Swine

This study assessed the effect of oxygen affinity and molecular weight (MW) of o-raffinose cross-linked hemoglobin based oxygen carriers (HBOCs) on cerebral oxygen delivery and mean arterial blood pressure (MAP) following hemorrhage and resuscitation in rats.. Isoflurane anesthetized rats (n = 6-7 per group) underwent 30% hemorrhage and resuscitation with an equivalent volume of one of three different HBOCs: 1) High P50 Poly o-raffinose hemoglobin (Poly OR-Hb, P50 = 70 mmHg); 2) High P50 > 128 Poly OR-Hb (MW > 128 kDa, P50 = 70 mmHg) and 3) Low P50 > 128 Poly OR-Hb (MW >128 kDa, P50 = 11 mmHg). Hippocampal cerebral tissue oxygen tension, regional cerebral blood flow (rCBF), MAP, total hemoglobin concentration and arterial blood gases were measured. Data analysis by two-way ANOVA and post hoc Tukey tests determined significance (P < 0.05, mean +/- SD).. Hippocampal tissue oxygen tension increased in all HBOC groups following resuscitation. The rCBF remained unchanged after HBOC resuscitation in all groups. Following resuscitation, the peak MAP was higher in the High P50 Poly OR-Hb group (152 +/- 13 mmHg) when compared to either the Low or High P50 large MW, (> 128 kDa) HBOC group (119 +/- 15 mmHg or 127 +/- 18 respectively, P < 0.05 for both).. O-raffinose polymerized HBOC, with or without lower MW components, maintained cerebral tissue oxygen delivery following hemorrhage and resuscitation in rats. The higher MW HBOCs showed a decrease in peak MAP, which did not alter oxygen delivery. No significant effect of oxygen affinity on cerebral tissue oxygen tension or blood flow was observed.

Topics: Animals; Blood Pressure; Cerebrovascular Circulation; Hemodilution; Hemoglobins; Hemorrhage; Hippocampus; Male; Models, Animal; Molecular Weight; Raffinose; Rats; Rats, Sprague-Dawley; Resuscitation

Several different preparations of cross-linked hemoglobin (CLHb) are being evaluated for their efficacy and safety as red cell substitutes in a variety of preclinical and clinical settings. Because CLHb is known to sequester nitric oxide (NO) and inhibit NO-mediated processes, we hypothesized that CLHb would have a hemostatic effect by enhancing platelet reactivity, inducing vasoconstriction, or both. Infusion of o-raffinose CLHb shortened the prolonged microvascular bleeding time and decreased blood loss from ear incisions in rabbits rendered anemic and thrombocytopenic. Moreover, this hemostatic effect persisted for at least 24 hours after infusion. Phenylephrine induced a degree of vasoconstriction similar to that induced by CLHb but did not shorten the bleeding time or decrease blood loss, suggesting that vasoconstriction alone cannot account for the hemostatic effect of CLHb. There was no evidence of CLHb-induced activation of coagulation in vivo, since infusion of CLHb did not increase circulating levels of thrombin-antithrombin complex. In vitro, CLHb abolished the inhibitory effect of the NO donor 3-morpholinosydnonimine on platelet aggregation and enhanced the aggregation of stimulated but not resting platelets. This potentiating effect was not attenuated by the addition of superoxide dismutase or catalase. To evaluate the potential arterial thrombogenicity of CLHb, a model of carotid artery thrombosis was developed in rabbits without thrombocytopenia or anemia. Compared with albumin infusion, CLHb infusion shortened the time to complete carotid occlusion. These data suggest that CLHb may shift the thromboregulatory balance toward clot formation, resulting in decreased bleeding in anemic and thrombocytopenic rabbits and possibly increasing arterial thrombogenicity in normal rabbits.

Topics: Adrenergic alpha-Agonists; Anemia; Animals; Antithrombin III; Bleeding Time; Carotid Artery Thrombosis; Cross-Linking Reagents; Disease Models, Animal; Dose-Response Relationship, Drug; Hemoglobins; Hemorrhage; Hemostasis; Kinetics; Male; Microcirculation; Peptide Hydrolases; Phenylephrine; Platelet Aggregation; Rabbits; Raffinose; Rats; Rats, Sprague-Dawley; Serum Albumin; Thrombocytopenia; Vasoconstriction

Topics: Adenosine; Allopurinol; Animals; Dogs; Fetal Tissue Transplantation; Glutathione; Hemorrhage; Hypertonic Solutions; Insulin; Kidney Transplantation; Liver Transplantation; Organ Preservation Solutions; Perfusion; Raffinose; Swine; Swine, Miniature; Transplantation, Heterologous