Thromboxane receptor blockade does not attenuate pulmonary pressor response in porcine single lung transplantation.
BACKGROUND
The ischemia-reperfusion lung injury is characterized by increased pulmonary vascular resistance, edema, and subsequent deterioration of oxygenation. Other models of acute lung injury suggest that thromboxane A2 may contribute to the pulmonary hypertension after transplantation.


METHODS
We studied the effects of the selective thromboxane A2 receptor antagonist SQ 30741 on pulmonary hemodynamics and gas exchange in porcine single lung transplantation using extracorporeal circulation (right heart bypass) with separate cannulations of the right and left pulmonary arteries. Pulmonary vascular resistance was measured at equal and constant flow to each lung. Flow distribution between the lungs was registered at equal pulmonary artery pressures. Twelve pigs (weight 17 to 23 kg) were studied. At the onset of reperfusion a bolus dose of the drug (5 mg/kg) was injected into both pulmonary arteries followed by an infusion (5 mg/kg/hr) for 1 hour (SQ group, n = 6). The control group (n = 6) received an equal amount of vehicle. The systemic and pulmonary hemodynamics and blood gas values were registered during 2 hours of reperfusion.


RESULTS
The pulmonary vascular resistance of the transplanted lung was significantly higher compared with the native lung (p < 0.001). Administration of SQ 30741 failed to ameliorate the pulmonary pressor response of the graft in comparison with the control group. No difference was found in the systemic arterial oxygen tension between the two groups.


CONCLUSIONS
Thromboxane does not seem to be among the principal mediators in the pulmonary hypertension after transplantation.
Kukkonen
S
S
Department of Anesthesiology, Helsinki University Central Hospital, Finland.
Heikkilä
L
L
Verkkala
K
K
Mattila
S
S
Toivonen
H
H
D000818:Animals; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D016040:Lung Transplantation / Q000009:adverse effects* / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000502:physiology* / Q000627:therapeutic use
D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2