D. Tighe

A NARROW RANGE, MEDIUM MOLECULAR-WEIGHT PENTASTARCH REDUCES STRUCTURAL ORGAN DAMAGE IN A HYPERDYNAMIC PORCINE MODEL OF SEPSIS

Objective: to compare diafiltered 6% pentastarch (Pentafraction-PDP, MWn 120000 and MWw 280000) and native pentastarch (Pentaspan-PSP, MWn 63000 and MWw 264000 dalton) in a porcine model of faecal peritonitis.Design: Randomised prospective study in 12 adolescent pigs.Interventions: Prior to infection the study solution was infused to increase Qt by 25%. Thereafter adjustments in infusion rate were made (up to 1 l/h) in an attempt to maintain Qt at 25% above baseline values.Measurements and results: Animals were sacrificed at 8h. Tissue was excised from the right lobe of liver and from the right lung and fixed for later electron microscopy and digital morphometric analysis. Patent sinusoidal lumen was significantly greater in group PDP compared to PSP (11.3%±2.3% of liver tissue versus 4.8%±1.1%,p<0.05) and this was accounted for by a significantly lower proportion of sinusoidal lumen occluded with white cells (2.1%±0.6% versus 6.6%±1.9%,p<0.05). Similarly, patent capillary represented a significantly higher proportion of lung tissue for group PDP versus PSP (26.2%±1.9% versus 18.5%±2.7%,p<0.05). The arithmetic mean alveolar capillary barrier thickness was significantly greater in group PSP than in group PDP (4.3±03 μm versus 2.5±03 μm,p<0.01).Conclusions: The molecular weight profile of Pentafraction was associated with less structural organ damage including less tissue oedema and less white cell occlusion.

The effects of dobutamine, dopexamine and fluid on hepatic histological responses to porcine faecal peritonitis

We studied the effects of two catecholamines with differing receptor profiles on hepatic blood flow and hepatic structure in a porcine model of faecal peritonitis. We treated animals with dopexamine (group Dp) or dobutamine (group Db) and fluid, or fluid alone as a control, to achieve a 2.5% increase in Qt from baseline values. After the induction of faecal peritonitis the increased Qt was maintained throughout the 8 h study period by adjustment of the fluid infusion rate. The dose of catecholamines remained constant. Hepatic blood flow was correspondingly maintained at above baseline values throughout the study. Post-mortem liver biopsy specimens were analysed from experimental animals and t sham animals who had not been instrumented or infected. In experimental animals there was a reduction in sinusoidal patency between sham and group Dp (76% of total sinusoid vs 51%,p<0.05) and group Dp and control (51% vs 33%,p<0.05) or groups Dp and Db (51% vs 34%,p<0,05) animals. This was accounted for by an increase in sinusoidal leukocytes and endothelial swelling. In addition to the changes noted above there was marked hepatocellular destruction in group Db. We conclude that maintenance of organ blood flow does not guarantee structural integrity in the sepsis syndrome and hepatocellular damage was greater in group Db than group Dp or control.

A phospholipase inhibitor modifies the pulmonary damage associated with peritonitis in rabbits

Peritonitis has been produced in rabbits by the spreading of 5 ml of caecal contents throughout the peritoneal cavity. After sacrifice at 5 h, electron microscopy revealed a increase of 600% in PMN and 1200% in lymphocytes in the pulmonary capillaries of the test animals when compared to the sham operated group. The pulmonary capillaries in the test group showed a 27% reduction in their luminal area, which was associated with a 73% reduction in their patency due to occlusion by WBC and cell debris. In addition there was endothelial and epithelial disruption with basement membrane exposure. The PMN were degranulated and adherent to the pulmonary endothelium. Pretreatment with the phospholipase inhibitor, mepacrine, significantly attenuated these responses, so that there was only an increase of 200% in PMN and 450% in lymphocytes in the lungs with no evidence of degranulation or adhesion to the pulmonary endothelium. Furthermore there was no change in capillary luminal area when compared to the sham operated group. In addition there was only slight damage to the endothelium and epithelium with no exposure of the basement membrane. Peripheral WBC in both the test and mepacrine groups showed a similar 62% and 75% reduction after 5 h when compared to baseline values. The sham group did not show this change. These results suggest that phospholipase inhibition plays an important role in attenuating the pulmonary response to faecal peritonitis and may be of potential benefit in treating clinical septicaemia.