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Protective effect of 2-chloroadenosine on lung ischemia reperfusion injury
B C Marts1, L J Baudendistel, K S Naunheim
1Department of Surgery, St. Louis University Medical School, Missouri 63110.
Abstract:
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)
Insights
Low-dose 2-chloroadenosine (2CA) mitigates lung injury from ischemia-reperfusion (IR). This adenosine analogue reduced inflammatory cell influx and fluid leakage, protecting lung function after IR.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Cardiovascular Physiology
Background:
- Ischemia-reperfusion (IR) injury triggers lung inflammation, involving polymorphonuclear leukocyte (PMN) influx and increased vascular permeability.
- Adenosine, particularly at low doses, shows potential in down-regulating inflammatory responses.
- 2-chloroadenosine (2CA), an adenosine analogue, was investigated for its protective effects against lung IR injury.
Purpose of the Study:
- To evaluate the efficacy of 2-chloroadenosine (2CA) in mitigating ischemia-reperfusion (IR) injury in a rabbit lung model.
- To assess the impact of 2CA on inflammatory cell infiltration and microvascular permeability during lung reperfusion.
Main Methods:
- A rabbit model was used with left pulmonary artery and vein occlusion for 1 hour to induce ischemia.
- 2-chloroadenosine (2CA) or saline was administered prior to and during reperfusion.
- Physiologic measurements and bronchoalveolar lavage (BAL) were performed after 4 hours of reperfusion.
Main Results:
- The 2CA-treated group exhibited significantly lower mean pulmonary artery pressure and higher cardiac output compared to the untreated ischemic group.
- Pulmonary vascular resistance was significantly elevated in the ischemic group versus the 2CA group.
- Alveolar white blood cell influx and protein transudation were significantly reduced in the 2CA-treated animals compared to ischemic controls.
Conclusions:
- 2-chloroadenosine (2CA) effectively attenuates lung injury caused by ischemia-reperfusion.
- 2CA demonstrates protective effects by reducing inflammatory cell infiltration and protein leakage into the lung interstitium.
- Adenosine analogues represent a promising therapeutic strategy for managing lung IR injury.