Preharvest nitroprusside flush improves posttransplantation lung function.
BACKGROUND
Morbidity as a result of early allograft dysfunction remains a significant problem in clinical lung transplantation. We previously demonstrated that nitroprusside (NP), a potent nitric oxide donor, administered before storage and again during reperfusion, reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage effects, reperfusion effects, or both.


METHODS
Fifteen dogs underwent left lung allotransplant. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (FIO2 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase (MPO) activity and wet to dry weight (W/D) ratio were assessed. Animals were divided into three groups for timing of NP administration. Group I (n = 5) animals received no NP. In group II (n = 5), donor lungs received NP (10 mg/L) in the flush solution only. In group III (n = 5), recipient animals received NP (0.2 mg/kg) just before reperfusion, as well as a continuous infusion (0.1 mg/kg/hr) during the assessment period.


RESULTS
Significant improvement in gas exchange was apparent in groups II and III compared with group I, but there was no significant difference between groups II and III. After 6-hour reperfusion, mean PaO2 values were 85.46 +/- 13.32 mm Hg in group I, 298.74 +/- 61.25 mm Hg in group II (p < 0.05), and 311.12 +/- 43.39 mm Hg in group III (p < 0.05). Systemic vascular resistance was significantly lower in group III than in group I (p < 0.05). MPO activities decreased in groups II (p < 0.05) and III (p < 0.05), indicating reduced neutrophil sequestration. W/D ratio was significantly lower in groups II and III.


CONCLUSIONS
Both methods of NP administration are effective, but NP administration in the recipient is accompanied by a decrease in systemic vascular resistance. From a clinical point of view, NP administration in the flush solution is a sufficiently effective and practical method to reduce lung allograft reperfusion injury.
Fujino
S
S
Department of Surgery, Washington University School of Medicine, Barnes Hospital, St. Louis, Mo., USA.
Nagahiro
I
I
Yamashita
M
M
Yano
M
M
Schmid
R A
RA
Cooper
J D
JD
Patterson
G A
GA
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004285:Dogs; D006982:Hypertonic Solutions / Q000627:therapeutic use; D016040:Lung Transplantation / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000819:agonists; D009599:Nitroprusside / Q000008:administration & dosage / Q000627:therapeutic use*; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000008:administration & dosage / Q000627:therapeutic use*; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control; D013997:Time Factors; D014184:Transplantation, Homologous; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D019188:Organ Preservation Solutions; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D009195:Peroxidase; D010100:Oxygen