Potential for pulmonary protection by nebulized milrinone during warm ischemia.
OBJECTIVE
A method to compensate for the donor shortage may be the utilization of donation after cardiac death. The control of lung injury against warm ischemia is crucial in manipulating donors after cardiac death. Nebulization is a simple and feasible drug delivery route after cardiac death. Herein we have examined the potential effect of nebulized milrinone, a phosphodiesterase III inhibitor, on pulmonary warm ischemia.


METHODS
Deeply anesthetized rats were euthanized by exsanguination. Lungs were exposed to warm ischemia with ventilation up to 2 hours. Milrinone was nebulized for 10 minutes at the beginning of warm ischemia (n = 5). In the control group (n = 5), normal saline was nebulized for the same time. At given intervals, the lungs were partially resected to measure adenine nucleotide and cyclic adenosine monophosphate levels.


RESULTS
In both groups, lung tissue cyclic adenosine monophosphate levels decreased significantly at 2 hours after warm ischemia; however, there was no significant difference between the groups. Lung tissue adenosine triphosphate levels significantly decreased at 2 hours after ischemia in the control group, while they did not drop up to 2 hours in the milrinone group. Further, lung tissue adenosine triphosphate levels at 2 hours after ischemia were higher in the milrinone group than the control group.


CONCLUSIONS
Our results confirmed that milrinone nebulization during warm ischemia maintained lung tissue adenosine triphosphate levels. Therefore, milrinone nebulization may have potential for lung protection against warm ischemia.
Chen
F
F
Department of Organ Preservation Technology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Zhang
J
J
Aoyama
A
A
Okamoto
T
T
Fujinaga
T
T
Bando
T
T
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D007511:Ischemia / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020105:Milrinone / Q000008:administration & dosage / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
D000227:Adenine Nucleotides; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D000242:Cyclic AMP; D020105:Milrinone