Cerebral hemodynamic and metabolic changes in porcine endotoxemia

Abstract

Conclusion(s):Glipzide improved haemodynamics in ovine endotoxaemia and may represent a beneficial therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome (SIRS). Background and Goal of Study:We established a hemoperfused in vitro system for isolated organ perfusion giving access to investigations on intestinal function. Since coagulation is an important aspect in research on microcirculation and sepsis we investigated different heparinisation protocols, with respect to both functionality and sensitivity of the system's behaviour. Materials and Methods: Porcine jejunal segments (191 Ϯ 40 g), normotherm, hemoperfusion for 3h in an isolated perfusion circuit including an oxygenation unit; n ϭ 4-5 per group; anticoagulation with unfractionated heparin was performed in 2-3 steps: 1. animal, 2. blood reservoir, 3. with (w) or without (w/o) priming (P) of the perfusion circuit. Heparin doses in the blood reservoir were high (Hi) versus low (Lo); total heparin doses given in I.U.: group 1: 40.819 Ϯ 910 (HiHep w P), group 2: 15.750 Ϯ 500 (HiHep w/o P), group 3: 10.904 Ϯ 413 (LoHep w P), group 4: 6.375 Ϯ 679 (LoHep w P). Viability criteria were: oxygen consumption, vascular resistance (SVR), edema formation (i.e. organ weights before/after), thromboplastin time (TPZ), fibrinogen, ATIII, and platelets. Non parametric tests, median [inter-quartile range], p Ͻ 0.05. Results and Discussion: Groups 1 and 2 (HiHep w P and w/o P) showed massive bleeding (mucosa ϩ serosa and mucosa, respectively), whereas both LoHep groups did not show bleeding. Group 4 (LoHep w/o P) showed significantly higher SVR compared to group 3 (LoHep w P) (0.53 [0.35] vs. 0.17 [0.14] mmHg*min/ml*100 g). Significantly highest oxygen consumption was found in group 3 (143.7 [78.4] vs. 66.7 [39.7] mol/min*100 g). Group 4 was characterised by a tendency for activated TPZ-INR (1.1 [0.16]) and constant decrease in fibrinogen and ATIII-concentrations. Group 3, in contrast, showed stable values of the coagulation pattern. Platelets were stable in all groups. Group 3 (LoHep w P) provided stable perfusion conditions, and a still maintained functional capacity. Conclusion: This study shows that each heparinisation protocol is associated with a particular pattern of viability criteria in isolated perfused intestine. The latter should be taken into account for comparison of data obtained from different in vitro models and in vivo versus in vitro comparison. Background and Goal of Study: Immunological interventions in endotoxemia and sepsis have been tested in experimental [1] and clinical studies [2].Our group evaluated the effects of an IgM-enriched preparation in a model of gram negative bacteraemia. Materials and Methods: After institutional approval 10 New Zealand White rabbits (2-3 kg) were randomized to a treatment or control group. In the intervention group IgM-enriched solution (Pentaglobin ® : 2 ml/kg/h) was applied. In addition, LPS was infused in both groups at a rate of 40 g/kg/h. After intravenous ...