Background: Adenosine A2a receptor stimulation can increase coronary perfusion and also reduce leukocyte-mediated inflammatory responses in some conditions. Hextend is a novel colloid solution that may have antioxidant properties. All these actions might be beneficial after severe chest trauma, but have never been investigated. To fill these gaps, this study evaluated the therapeutic potential of a novel adenosine A2a agonist during fluid resuscitation from severe chest trauma with either standard-of-care crystalloid or Hextend.
Methods: Anesthetized, ventilated swine received unilateral, blunt trauma to the right chest via captive bolt gun, followed by a 10- to 12-mL/kg arterial hemorrhage. After 25 minutes of shock, ATL-146e was started (10 ng/kg/min intravenously for 180 minutes). After an additional 5 minutes, the minimum amount of either colloid (Hextend, 5% hetastarch in lactate-buffered, balanced electrolyte solution) or crystalloid (lactated Ringer's [LR] solution) was administered to maintain mean arterial pressure > 70 mm Hg and heart rate < 100 beats/min and to correct lactate for 180 minutes postinjury. Cardiopulmonary function was monitored and serial bronchoalveolar lavage samples were analyzed for protein, leukocyte infiltration, and expression of cyclooxygenase (COX)-1 and COX-2 isozymes as markers of the inflammatory cascade.
Results: Fluid requirements were reduced by half with Hextend compared with LR (p < 0.05). ATL-146e in either Hextend or LR transiently increased cardiac output, cardiac contractility, and systemic oxygen delivery (all p < 0.05). Pao(2)/Fio(2) ratio was 50 to 100 higher and bronchoalveolar lavage leukocytes were reduced by half with Hextend versus LR (both p < 0.05), but there was no added effect of ATL-146e. COX-1 expression was induced in macrophages (Mphis), whereas COX-2 was induced in neutrophils. Neither Hextend nor ATL-146e reduced COX expression.
Conclusion: Hextend reduced the volume for initial resuscitation, which may offer logistical advantages in prehospital field conditions or whenever there is limited medical resources or prolonged transport times; ATL-146e improved early cardiac performance without causing hypotension or bradycardia; when administered 25 to 30 minutes after injury, neither Hextend nor ATL-146e altered inflammatory changes in pulmonary Mphis or infiltrating PMNs; and further studies are needed to determine whether these short-term benefits correlate with long-term outcome.