Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.
BACKGROUND
If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade.


METHODS
Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP.


RESULTS
Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade.


CONCLUSIONS
The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.
Takashima
Seiki
S
Department of Cancer and Thoracic Surgery, University of Okayama Graduate School of Medicine and Dentistry, Okayama, Japan.
Schlidt
Scott A
SA
Koukoulis
Giovanna
G
Sevala
Mayura
M
Egan
Thomas M
TM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply* / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014019:Tissue Donors
D000319:Adrenergic beta-Antagonists; D000242:Cyclic AMP; D007545:Isoproterenol