A Combined In Vivo and In Vitro Approach to the Study of Endotoxemia in Swine Importance of Neuropeptides and Implications for Human Adult Respiratory Distress Syndrome

The cardiopulmonary effects of endotoxin administration (1 microgram/kg) were evaluated in 8-10 week old SPF-derived Yorkshire pigs, both because endotoxemia is a common and important swine problem, and because the pig is a good model for human adult respiratory distress syndrome. Physiological changes included sustained increases in mean pulmonary artery pressure, pulmonary vascular resistance, pulmonary arterial wedge pressure, heart rate, hematocrit, and the arterial partial pressure of carbon dioxide. Transient increases were also observed in central venous pressure and airway pressure. Transient increases, followed by decreases, were observed in mean systemic arterial pressures and systemic vascular resistance. Decreases were seen in cardiac output, cardiac index, arterial partial pressure of oxygen and oxygen saturation. The number of circulating leukocytes, lymphocytes and segmented neutrophils decreased with endotoxin infusion. To investigate the role of airway smooth muscle, bronchial rings were isolated and exposed to contractile agents in tissue baths. A hyperresponsiveness of the third generation bronchi to substance P, carbachol, bradykinin and electric field stimulation was observed. However the increase in response to bradykinin and electric field stimulation were not statistically significant. Histopathology of the lungs demonstrated congestion, hemorrhage and neutrophilic infiltration.