Combined therapy of pentastarch, dexamethasone, and dibutyryl-cAMP or beta 2-agonist attenuates ischaemia/reperfusion injury of rat lung.
We hypothesised that combined therapy with macromolecules that seal endothelial damage [pentastarch (Penta)], an anti-inflammatory agent [dexamethasone (Dex)], and an agent that reabsorbs alveolar fluid [beta(2)-agonist or dibutyryl-cAMP (Bt(2)-cAMP)] would have additive ameliorating effects on ischaemia/reperfusion (I/R) injury of the lung. We perfused one of the following solutions into isolated rat lungs in a closed circulating system, either prior to I/R injury (groups 1-5) or following 60 min of ischaemia (groups 6-10): (1) 0.9% normal saline (NS), (2) Penta, (3) Penta+Dex, (4) Penta+Bt(2)-cAMP, (5) Penta+beta(2)-agonist inhalation, (6) Penta+Dex, (7) Penta+Bt(2)-cAMP, (8) Penta+beta(2)-agonist inhalation, (9) Penta+Dex+Bt(2)-cAMP, or (10) Penta+Dex+beta(2)-agonist inhalation. Haemodynamics, lung weight gain (LWG), capillary filtration coefficient (K(fc)), cytokine mRNA levels, and lung pathology were assessed. Results showed that Dex, Bt(2)-cAMP, or beta(2)-agonist as an additive to Penta decreased K(fc) and LWG below values seen with Penta alone. Furthermore, LWG and K(fc) values in groups with three protective agents were lower than those in groups with two protective agents. Significantly lower levels of TNF-alpha and IL-1 mRNAs were observed in groups treated with Dex. Histopathological studies showed decreased injury profiles for all combined therapy groups. We conclude that the addition of Dex, Bt(2)-cAMP, or beta(2)-adrenergic agonist to Penta solution promoted attenuation of I/R injury. Furthermore, combination therapy with three protective agents (Penta+Dex+beta(2)-adrenergic agonist) caused the greatest attenuation of I/R.
Lu
Hsiu-Ling
HL
Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan.
Chiang
Chi-Huei
CH
D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003994:Bucladesine / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006895:Hydroxyethyl Starch Derivatives / Q000031:analogs & derivatives / Q000627:therapeutic use; D055370:Lung Injury / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010952:Plasma Substitutes / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014655:Vascular Resistance / Q000187:drug effects
D058672:Adrenergic beta-2 Receptor Antagonists; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D003994:Bucladesine; D003907:Dexamethasone