Biomedical subjects

R K Winn

Publications and source records attributed to R K Winn.

59 records · Page 4Linked to original sources

PubMed1988

A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits.

Leukocytes have been shown to play an important role in the development of isolated organ injury after experimental ischemia and reperfusion. To examine the role of leukocytes in generalized ischemia-reperfusion injury we used the MAb 60.3 (directed to the human leukocyte adherence glycoprotein, CD18) to block leukocyte adherence functions in a rabbit model of hemorrhagic shock and resuscitation. In control animals subjected to 1 h of shock (mean blood pressure 45 torr and mean cardiac output 30% of baseline) followed by resuscitation, only 29% survived 5 d. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 100% of the MAb 60.3-treated animals survived 5 d (P less than 0.01) and organ injury was absent or markedly attenuated. The control animals also had a persistent acidosis, lost more weight, and had evidence of continued gastrointestinal bleeding in contrast to MAb 60.3-treated animals. We conclude that increased leukocyte adhesiveness plays an important role in the development of multiple organ injury and death after generalized ischemia-reperfusion and that this injury may be significantly reduced by blocking leukocyte adherence functions with the MAb 60.3.

Animals↗

PubMed1979

Cardiorespiratory responses to sudden release of circulatory occlusion during exercise.

Cardiovascular and respiratory parameters were measured during and after release of pressure in thigh cuffs which occluded circulation to the legs of four human subjects exercising on a bicycle ergometer. The subjects exercised at 200 kg/min while thigh cuffs were inflated for 4 min and then released. Responses from 6 to 8 identical experiments were ensemble averaged so the precise timing of delays could be obtained. Five to ten seconds following cuff release, end-tidal CO2 increased, marking arrival of the trapped blood at the lungs. Ten to eighteen seconds after this increase in end-tidal CO2, ventilation, respiratory rate and tidal volume increased. This delay in ventilation must have resulted in an increase in arterial PCO2 and suggests that arterial chemoreceptors mediated the responses, and that no venous chemoreceptors or CO2-flux or disequilibrium receptors in the lung need be postulated.

Adult↗

PubMedDate not supplied

Effects of body surface thermal injury on apparent renal and cutaneous blood flow in goats.

The etiology of postburn circulatory impairment ("burn shock") is multifactorial and incompletely understood. However, systemic vasoconstriction is a consistent observation during this period and occurs in spite of aggressive fluid resuscitation therapy. We studied the degree and time course of systemic vasoconstriction in goats for 24 hours following burns of two sizes (20% and 35% TBSA), in which fluid resuscitation was performed according to a common clinical crystalloid regimen. Cardiac index and urine output (reflecting renal perfusion) fell dramatically at two hours after burn, but returned slowly to preburn levels by 24 hours. The degree of fall and rate of recovery were dependent on burn size. Dermal perfusion was assessed by laser Doppler flowmetry in both burned and unburned skin. Dermal perfusion was negligible in burned skin. Unburned skin blood flow fell with increasing burn size, progressively recovered to preburn levels after the small burn, but at 24 hours remained significantly depressed after the larger burn. The stimulus for this persistent skin vasoconstriction is unclear.

Animals↗

PubMedDate not supplied

Antibiotic therapy determines subcutaneous Escherichia coli abscess formation after CD18 inhibition in rabbits.

Monoclonal antibodies (MAbs) that interrupt polymorphonuclear neutrophil (PMN)-endothelial cell adhesion can ameliorate PMN-mediated injury, including burn-induced inflammatory injury, but can also impair PMN-mediated defense against bacterial infection. We report the effects of combined anti-adhesion and antibiotic therapy on local infectious sequelae after subcutaneous Escherichia coli inoculation in rabbits treated with anti-CD18 (60.3) or anti-P-selectin (PB1.3) MAb. Ampicillin or ceftriaxone were administered for 72 hours. PMN emigration was assessed at 24 hours and local infectious sequelae at 7 days. In ampicillin/60.3-treated rabbits, E. coli inoculation resulted in impaired PMN emigration and increased infectious complications, with abscesses forming at a 10,000-fold lower inoculation concentration compared with other MAb-antibiotic treatment groups. We conclude that (1) CD18, but not P-selectin blockade interferes with PMN emigration and host defense to subcutaneous E. coli, and (2) appropriate antibiotic therapy can prevent the local infectious events caused by CD18 inhibition.

Abscess↗

PubMedDate not supplied

Role of protein synthesis and CD11/CD18 adhesion complex in neutrophil emigration into the lung.

The mechanism of neutrophil (PMN) emigration into the lung may be stimulus-dependent. This study examined PMN emigration in the lung induced by intratracheal instillation of lipopolysaccharide (LPS), Streptococcus pneumoniae (S. pneu) organisms, supernatant from S. pneu incubated with alveolar macrophages (AM phi), Escherichia coli (E. coli) organisms, or phorbol myristate acetate (PMA). Rabbits were pretreated with either the CD18 monoclonal antibody (MAb) 60.3, the protein synthesis inhibitor cycloheximide (Cx), or, in one case, both. Animals were then given one of the above stimuli to elicit PMN emigration. Four hours after the stimulus was instilled, animals were killed and total and differential cell counts were performed on bronchoalveolar lavage (BAL) fluid. PMN emigration in response to PMA was virtually abolished by MAb 60.3, but was not significantly inhibited by Cx. Emigration induced by LPS was inhibited by 80% by either MAb 60.3 or Cx, and greater than 94% when MAb 60.3 and Cx were given simultaneously. Emigration in response to E. coli organisms was 80% inhibited by MAb 60.3. Emigration induced by S. pneu was approximately 50% inhibited by MAb 60.3, but was greater than 90% blocked by Cx. The MAb 60.3 had approximately the same effect on PMN emigration toward the supernatant from co-incubation of AM phi with S. pneu as it did toward live S. pneu. It is concluded that the mechanism of PMN emigration into the lung is stimulus-dependent. The CD18-dependent mechanism is responsible for the majority of the emigration in response to PMA, E. coli LPS, and E. coli organisms. S. pneu and supernatant from S. pneu + AM phi produce a CD18-independent pathway. These data suggest the requirement for de novo protein synthesis for PMN emigration in response to LPS and S. pneu, but not for PMA-induced emigration.

Animals↗