The role of neural and vasoactive mediators in the regulation of the pulmonary circulation during cardiopulmonary preservation.
The autoperfused working heart-lung preparation has been used for extended cardiopulmonary preservation for transplantation. However, acute lung injury and failure of the preparation can result from pulmonary hypertension, which previous investigators have linked to denervation. We studied the neural and vasoactive mediators of pulmonary vasoconstriction during normothermic autoperfusion of the heart and lungs from 13 calves. Pulmonary vascular resistance was quantitated by multipoint pulmonary artery pressure/flow plots generated by incremental reduction in venous return at three times: A, after sternotomy but before autoperfusion (control); B, during in situ autoperfusion (innervated heart-lung preparation); and C, after explanation (denervated heart-lung preparation). During hemodynamic measurements, left atrial blood samples were obtained for measurement of thromboxane B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Results show that pulmonary hypertension in the autoperfused working heart-lung preparation begins during autoperfusion before denervation and may be related to complement activation and to increased levels of circulating thromboxane B2 and 6-keto-prostaglandin F1 alpha (both the absolute levels and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha). After denervation, both prostaglandin intermediates were markedly increased, but their ratio was not significantly affected. These data suggest that there is an initial stage of pulmonary vasoconstriction at the onset of autoperfusion that is accompanied by increased circulating levels of vasoactive mediators and that denervation further contributes to this response.
Mashburn
J P
JP
Mayo Clinic, Rochester, MN 55905.
Kontos
G J
GJ
Hashimoto
K
K
Wilson
D M
DM
Schaff
H V
HV
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D001794:Blood Pressure; D002417:Cattle; D003167:Complement Activation; D003714:Denervation / Q000009:adverse effects; D006321:Heart; D006439:Hemodynamics; D007958:Leukocyte Count; D008168:Lung; D009926:Organ Preservation / Q000379:methods*; D010976:Platelet Count; D011652:Pulmonary Circulation; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood*
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha