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Biomedical subjects

A A D'Sa

Publications and source records attributed to A A D'Sa.

9 recordsLinked to original sources

Gut mucosal injury is attenuated by recombinant bactericidal/permeability-increasing protein in hind limb ischemia-reperfusion injury.

Lower limb ischemia-reperfusion injury (IRI) is associated with increased gut permeability to endotoxin, which not only directly damages enterocytes but also stimulates a systemic inflammatory response syndrome (SIRS), compounding gut injury. Recombinant bactericidal/permeability-increasing protein (rBPI21) is a novel anti-endotoxin therapy with proven benefit in sepsis. Its potential role in modulating remote gut injury in hind limb IRI was studied. Male Wistar rats were chosen for a prospective randomized control trial (n = 10 per group). The control group and two groups undergoing 3 hr bilateral hind limb ischemia with 2 hr reperfusion (I/R) were randomized to receive intravenously either control protein thaumatin at 2 mg/kg or rBPI21 at 2 mg/kg, respectively. Quantitative morphometric assessment of the small bowel was used as a measure of gut injury and, using an ex vivo everted gut sac model, translocation of 14C-labeled polyethylene glycol (PEG) was used as a measure of gut permeability. Our results indicate that hind limb IRI is associated with remote gut mucosal injury and increased permeability to macromolecules. rBPI21 anti-endotoxin therapy modulates remote gut injury associated with lower limb IRI in this model.

Animals↗

Reperfusion injury is greater with delayed restoration of venous outflow in concurrent arterial and venous limb injury.

BACKGROUND: Complex limb trauma often involves combined arterial and venous injury, and the resultant ischaemia-reperfusion injury (IRI) causes both local and remote organ injury. This study assessed the influence of the timing of restoration of venous drainage on IRI. METHODS: Male New Zealand white rabbits (n = 36) were randomized into six groups: sham operation (group 1) and unilateral hind limb arterial and venous occlusion for 1 h followed by no reflow for 2 h (group 2), arterial and venous reflow for 2 h (group 3), arterial reflow alone for 2 h (group 4), arterial reflow alone for 1 h followed by arterial and venous (delayed) reflow for a further 1 h (group 5), and pretreatment with an enteral combination antioxidant before occlusion of both artery and vein and delayed venous reflow (group 6). Plasma hydroperoxide (HPO) and glutathione peroxidase concentration, hind limb skeletal muscle and lung tissue wet : dry weight ratios and myeloperoxidase (MPO) concentration were measured. RESULTS: The plasma HPO level in the femoral vein effluent was significantly greater after delayed venous reflow (mean(s.e.m.) 2. 02(0.54) micromol/l) than in control animals (0.98(0.10) micromol/l) (P < 0.05). There was also a significantly greater tissue wet : dry weight ratio after delayed venous reflow than in controls, in skeletal muscle (mean(s.e.m.) 6.89(0.14) versus 5.34(0.54); P < 0. 05) and lung (9.20(1.14) versus 7.23(0.38); P < 0.05) tissue. Lung tissue MPO activity was significantly greater after delayed venous reflow compared with controls (3.20(0.28) versus 1.86(0.14) units/g; P < 0.005), and also in comparison to simultaneous arterial and venous reflow (2.40(0.24) units/g; P < 0.05). In the antioxidant pretreatment group there was no significant increase in plasma HPO concentration, tissue MPO level or tissue wet : dry weight ratio compared with the control group. CONCLUSION: In combined major arterial and venous injury of the limb, delayed restoration of venous drainage leads to significantly greater local skeletal muscle injury and remote neutrophil-mediated lung injury. These results support the clinical rationale for early restoration not only of arterial inflow but also venous drainage by means of intraluminal shunts.

Animals↗

Outflow resistance and early occlusion of infrainguinal bypass grafts.

Distal outflow vascular resistance (VR) has been measured intra-operatively during 67 infrainguinal bypass procedures to establish whether it might have a role as a predictive test for early graft thrombosis. The graft outflow was popliteal artery above the knee (48), popliteal artery distal to the knee (6) or a single calf vessel (13). VR was measured before anastomosis of the graft, calculated from the relationship between pressure and flow in the outflow artery during infusion of the patient's own blood at a constant rate. VR was measured before and after vasodilation with papaverine. Primary graft patency at 30 days was documented. In the 10 limbs in which graft thrombosis occurred, VR was 1167 +/- 367 mPRU, significantly higher than VR in 57 limbs with a patent graft, 850 +/- 310 mPRU (P = 0.02, Mann-Whitney U test). After papaverine, VR was 823 +/- 368 mPRU in the limbs with a thrombosed graft, significantly higher than that of limbs with a patent graft, 463 +/- 211 mPRU (P = 0.001). VR appeared to show most promise as a predictor of early thrombosis in the group of femoro-tibial and femoro-peroneal grafts. In this group, the value of 800 mPRU after papaverine was 92% efficient and was 80% sensitive, 100% specific and had a predictive value of 100% for early thrombosis. Distal outflow VR is an important factor in early graft thrombosis and might have a practical application as a predictor of early thrombosis of femoro-distal bypass grafts.

Aged↗

A decade of missile-induced vascular trauma.

During 10 years of serious strife the Royal Victoria Hospital, Belfast, has dealt with trauma inflicted by a wide variety of missiles. Injuries involving 316 vessels were sustained by 192 patients. A group of "knee-cappings' accounted for a large proportion of popliteal vessel injuries. A majority of patients also suffered damage to other regions of the body. Hypotension was a notable feature and several patients arrived in extremis, particularly those with injuries to a major vessel trunks and vital organs. The benefits of rapid evacuation in relation to ischaemia time are discussed. The operative management of a wide range of arterial and venous injuries is described. The use of simple and compound vein grafts allowed adequate excision of damaged vessels. The advantages of meticulous repair, timely fasciotomy, and early reintervention are reflected in the results, contributing to the small lower-lib amputation rate of 5.1%.

Abdomen↗

Prevention of secretagogue-induced ulcers in the rat.

An inhibitor of gastric secretion, Pfizer UK -9040, a derivative of the antihistamine triprolidine, was given orally 50 to 100 mg per kg 1 hr before and at various times during a 24-hr subcutanwous infusion of ulcerogenic secretagogues. The higher the dose and the more frequent the dosage, the lower was the incidence, severity, number, and perforations of duodenal ulcers. The mechanisms by which UK -9040 prevents these ulcers is probably inhibition of gastric secretion.

Animals↗