Biomedical subjects

Alfred Königsrainer

Publications and source records attributed to Alfred Königsrainer.

24 records · Page 2Linked to original sources

PubMed2003

Evidence for genetic heterogeneity in lymphedema-cholestasis syndrome.

Lymphedema-cholestasis syndrome (LCS, Aagenaes syndrome) is the only known form of hereditary lymphedema associated with cholestasis. A locus, LCS1, has recently been mapped to chromosome 15q in a Norwegian kindred. In a consanguine Serbian Romani family with a neonate who had a combination of lymphedema and cholestasis with features atypical for Norwegian LCS, haplotype and linkage analysis of markers spanning the LCS1 region argue that a second LCS locus may exist. The infant may represent an instance of a previously undescribed lymphedema-cholestasis syndrome.

Cholestasis↗

PubMed2003

Vasopressin, but not fluid resuscitation, enhances survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.

BACKGROUND: The authors compared the effects of vasopressin fluid resuscitation on survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. METHODS: A midline laparotomy was performed on 23 domestic pigs, followed by an incision, and subsequent finger fraction across the right medial liver lobe. During hemorrhagic shock, animals were randomly assigned to receive either 0.4 U/kg vasopressin (n = 9), or fluid resuscitation (n = 7), or saline placebo (n = 7), respectively. A continuous infusion of 0.08 U x kg(-1) x min(-1) vasopressin in the vasopressin group, or normal saline was subsequently administered in the fluid resuscitation and saline placebo group, respectively. After 30 min of experimental therapy, bleeding was controlled by surgical intervention, and blood transfusion and rapid fluid infusion were subsequently performed. RESULTS: Maximum mean arterial blood pressure during experimental therapy in the vasopressin-treated animals was significantly higher than in the fluid resuscitation and saline placebo groups (mean +/- SD, 72 +/- 26 vs 38 +/- 16 vs 11 +/- 7 mmHg, respectively; P< 0.05). Subsequently, mean arterial blood pressure remained at approximately 40 mmHg in all vasopressin-treated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (approximately 15 mmHg) within approximately 20 min of experimental therapy initiation. Total blood loss was significantly higher in the fluid resuscitation pigs compared with vasopressin or saline placebo after 10 min of experimental therapy (65 +/- 6 vs 42 +/- 4 vs 43 +/- 6 ml/kg, respectively; P< 0.05). Seven of seven fluid resuscitation, and seven of seven saline placebo pigs died within approximately 20 min of experimental therapy, while 8 of 9 vasopressin animals survived more than 7 days (P < 0.05). CONCLUSIONS: Vasopressin, but not fluid resuscitation or saline placebo, ensured survival with full recovery in this liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.

Animals↗

PubMed2003

Arginine vasopressin, but not epinephrine, improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs.

OBJECTIVE: Epinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DESIGN: Prospective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SETTING: University hospital laboratory. SUBJECTS: A total of 21 pigs weighing 32 +/- 3 kg. INTERVENTIONS: The anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean +/- sem loss of 40% +/- 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units.kg-1.min-1, n = 7), or epinephrine (45 microg/kg and 5 microg.kg(-1).min(-1), n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem arterial blood pressure at 2.5 and 10 mins was significantly (p <.001) higher after vasopressin vs. epinephrine vs. saline placebo (82 +/- 14 vs. 23 +/- 4 vs. 11 +/- 3 mm Hg, and 42 +/- 4 vs. 10 +/- 5 vs. 6 +/- 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p <.01) higher when compared with epinephrine or saline placebo (9 +/- 5 vs. 121 +/- 3 vs. 54 +/- 22 mL/min and 150 +/- 20 vs. 31 +/- 17 vs. 0 +/- 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo-treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p <.01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. CONCLUSIONS: Vasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.

Animals↗

PubMed2002

Evaluation of mitochondrial respiratory function in small biopsies of liver.

Mitochondrial respiratory function was studied in permeabilized pig liver biopsies. The cell membrane was permeabilized mechanically in tissue samples of 2-7 mg, for application of a standardized substrate/inhibitor titration protocol in high-resolution respirometry. Specific respirometric tests demonstrated complete plasma membrane permeabilization and accessibility of substrates to intact mitochondria. High respiratory adenylate control ratios and cytochrome c conservation in the tissue preparation were comparable or even better than in isolated mitochondria. Citrate synthase and cytochrome c oxidase activities remained at 85% of controls after up to 98 h storage of liver tissue at 0 degrees C in histidine-tryptophan-ketoglutarate solution. Multiple mitochondrial defects, however, were indicated after 48 h cold storage by the decline in respiratory capacity, which was lowered to a larger extent with complex I substrates compared to respiration with substrates for complex II or IV, measured in the absence of cytochrome c. After prolonged ischemia, the adenylate control ratio was significantly reduced, and cytochrome c depletion was detected by the stimulatory effect of cytochrome c. High-resolution respirometry allows the assessment of mitochondrial function in a few milligrams of permeabilized liver tissue, without isolation of mitochondria. This provides a basis for the analysis of mitochondrial function in human liver biopsies.

Animals↗

PubMed2002

Duodenal histology for monitoring treatment of acute rejection in pancreaticoduodenal allografts in rats.

BACKGROUND: Although the value of duodenal histology as a means to diagnose acute rejection in pancreaticoduodenal allografts has been validated, it is not known how the duodenum responds to antirejection treatment in comparison with the pancreas. METHODS: Diabetic Lewis rats received a pancreaticoduodenal allograft. Cyclosporine was given for 5 days and then discontinued for 2 days (group 1), for 4 days (group 2), for 6 days (group 3), for 8 days (group 4), for 9 days (group 5), and for 10 days (group 6). Two animals of each group were killed for histology at the end of immunosuppressive-free intervals. In the remaining rats, rejection was treated with methylprednisolone on 3 consecutive days. Duodenal histology was compared with pancreatic morphology before and after treatment of rejection. RESULTS: Duodenal histology had a positive and negative predictive value of 100% for detection of acute rejection in the pancreatic portion of the graft. After antirejection treatment, duodenal morphology was however less accurate (positive predictive value, 96%; negative predictive value, 67%). The Spearman correlation coefficient (p) of duodenal and pancreatic rejection grades was higher before antirejection treatment (p=1.0) than thereafter (p=0.724). Considering interstitial and vascular changes separately, vascular rejection correlated to a higher extent than interstitial rejection between the two portions of the graft (p=0.725 vs. p=0.677). CONCLUSIONS: Duodenal histology accurately predicts the initial diagnosis of rejection of the pancreas. However, after treatment of acute rejection, duodenal morphology is more likely to recover from rejection than the pancreas. Awareness of this phenomenon might be important for the interpretation of duodenal follow-up biopsies.

Animals↗

PubMedDate not supplied

Lactate stimulates endothelial cell migration.

The significance of the high lactate levels that characterize healing wounds is not fully understood. Lactate has been shown to enhance collagen synthesis by fibroblasts and vascular endothelial growth factor (VEGF) production by macrophages and endothelial cells. VEGF has been shown to induce endothelial cell migration. However, it has not been shown whether accumulated lactate correlates with the biological activity of VEGF. Therefore, we investigated the effect of lactate on migration of endothelial cells. Human umbilical vein endothelial cells and human microvascular endothelial cells were cultured to subconfluent monolayers in standard six-well tissue culture plates. Following a 24-hour serum starvation, cells were treated with the indicated concentrations of l-lactate. Cell migration was assessed using a modified Boyden chamber. VEGF protein in the cell culture supernatant was measured by enzyme-linked immunoassay. Lactate-enhanced VEGF protein synthesis in a time- and dose-dependent manner. Lactate added into the bottom well did not stimulate cellular migration from the upper well. However, lactate when added together with endothelial cells to the bottom well of the Boyden chamber increased cellular migration in a dose-dependent manner. This effect was blocked by anti-VEGF and by cycloheximide. Lactate enhances VEGF production in endothelial cells, although lactate, itself, is not a chemoattractant. We conclude that the lactate-mediated increase in cellular migration is regulated by VEGF.

Cell Movement↗