Different effects of cagA+/vacA [s1a/m1] H-pylori on rat gastric mucosal microcirculation in vivo (vol 42, pg 74, 1998)

Background: We have previously demonstrated that pooled extracts of H. pylori from duodenal ulcer/gastritis patients induce platelet aggregation but not leukocyte activation within rat gastric mucosal microcirculation (GMMC) in vivo [Gut 97;41:748-52]. However, the more pathogenic strains may exert greater effects on the microcirculation. Aims: To determine the acute effects of two pure extracts of cagA(+)/vacA[s1a/m1] strains, from two patients, on rat GMMC in vivo. Specifically, macromolecular leakage of labelled albumin, platelet and leukocyte activation and vessel diameters were assessed. Methods: An incision made in the exteriorised stomach of anaesthetised rats (hypnorm:diazepam 1:1 ratio; 0.1mg/100g) allowed visualisation of the mucosal surface. 0.5mls of an aqueous extract from strain 60190 (n=12) or J104 (n=10) was administered topically. Acridine red (0.1ml/100g; i.a) was used to quantitate leukocyte and platelet activity. Fluoroscein-labelled albumin (0.2ml/100g; i.a) was used to quantitate macromolecular leakage (MML) and alterations in capillary and post-capillary venule (PCV) diameters. Observations were made every 15 mins for 2 hrs using fluorescent in vivo microscopy. Results: Strain 60190 induced significant sustained increases in MML, by 5 mins (41%; p<0.01). Less leakage was observed with J104 which was transient, reaching significance at 60 mins only (18%; p<0.05). 60190 induced rapid leukocyte adhesion within 5 mins (8.60 +/- 2.67; p<0.05) with significant rolling leukocytes at 45 mins (2.90 +/- 1.28; p<0.05;). J104 induced significant leukocyte adhesion after 45 mins (11.65 +/- 3.60; p<0.05;). Platelet emboli were only observed with 60190 treated animals at 60 mins (2.30 +/- 0.99; p<0.05). PCV vasoconstriction was observed only at 5 mins with 60190 (24.2 mu m +/- 1.62 mu m to 18.94 mu m +/- 1.81 mu m; p<0.05). Values represent mean above baseline +/- S.E.M. Conclusions: Extracts of H. pylori strains possessing both cagA and the vacA [s1a/m1] genotype are associated with marked disturbances within the GMMC. The data suggests that some cagA*/vacA[s1a/m1] strains are more toxic and/or other genes may be involved.