Protective effect of 2-chloroadenosine on lung ischemia reperfusion injury.
Reperfusion following ischemia yields an inflammatory response characterized by polymorphonuclear leukocyte (PMN) influx, inflammatory mediator release, microvascular permeability alteration, and protein-enriched fluid transudation. Evidence has accumulated suggesting that low-dose adenosine may "down-regulate" the PMN response. This study evaluated the effects of an adenosine analogue, 2-chloroadenosine (2CA), on ischemia-reperfusion (IR) injury in rabbit lungs. In these experiments the left pulmonary hilum was skeletonized, obliterating the bronchial circulation, and the left pulmonary artery and vein were occluded for 1 min for the sham ischemia (SI-V) group or for 1 hr for the ischemia (I-V) and 2CA-treated (I-A) groups. The left lung was inflated with nitrogen during the ischemic period. Saline (SI-V and I-V groups) or 2CA (I-A group) infusions were begun prior to and during the reperfusion period. After 4 hr of reperfusion and restored ventilation, selective left lung physiologic measurements and bronchoalveolar lavage (BAL) were performed. Groups (N = 8/group) were compared using analysis of variance. The I-A group demonstrated a significantly lower mean pulmonary artery pressure and higher cardiac output than the I-V group. Pulmonary vascular resistance was significantly elevated in group I-V compared to group I-A. A significantly greater alveolar WBC influx and protein transudation (BAL/plasma albumin) occurred in the ischemic group compared to the 2CA-treated animals and sham controls. Decreased PaO2 and increased venous admixture were noted in the ischemic group, but did not reach significance when compared to the 2CA group.(ABSTRACT TRUNCATED AT 250 WORDS)
Marts
B C
BC
Department of Surgery, St. Louis University Medical School, Missouri 63110.
Baudendistel
L J
LJ
Naunheim
K S
KS
Dahms
T E
TE
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D006439:Hemodynamics / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
D015762:2-Chloroadenosine; D000241:Adenosine