[Effects of PNU282987 on organ function and survival in dogs with lethal burn shock].

Abstract

Objective: To investigate the effects of PNU282987, a α7 nicotinic acetylcholine receptor agonist (α7nAChR), on organ function and survival rate in dogs with lethal burn shock.

Methods: Twelve adult male Beagle dogs were subjected to 50% total body surface area (TBSA) full-thickness flame injury, and then they were randomly divided into a burn group and a PNU282987 group (PNU group), each n=6. The dogs in PNU group received PNU282987 (0.38 mg/kg, venous pumping) and the dogs in burn group received equal amount of normal saline solution as the control group. The mean arterial pressure (MAP) and the plasma levels of tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), creatinine (Cr), blood urea nitrogen (BUN) were continuously determined before and 0.5, 2, 4, 8, 12, 24 hours after burn. All the above measurements were performed with animals in conscious and cooperative state. At the end of 24-hours-period experiment, the survival rate was recorded.

Results: The MAP significantly decreased after burn compared with the baseline data before-injury. The level of MAP in PNU group were significantly higher than those of the burn group from 4 hours after burn, and it returned to 83.6% of baseline level at 24 hours. In contrast, those in the burn group progressively decreased with time till death. The plasma levels of TNF-α in PNU group were significantly lower than those of burn group at each time points post injury. The ALT, Cr, BUN and CK-MB of the burn group increased persistently, while those of the PNU group increased at first and decreased subsequently except for ALT increased persistently, and they were all significantly lower than those of the burn group till to the time point of 12 hours (ALT:51.2±7.0 U/L vs. 104.8±7.4 U/L, Cr:42.7±5.4 μmol/L vs. 88.5±4.8 μmol/L, BUN:4.9±1.2 mmol/L vs. 14.7±1.4 mmol/L, CK-MB:564.0±39.1 U/L vs. 734.0±35.9 U/L, all P<0.05). At the end of 24-hours-period experiment, the survival rate of the PNU group was 50% (3/6) and significantly higher than that of the burn group 0(0/6).

Conclusions: The results indicated that PNU282987 decrease the levels of inflammatory cytokine, improve the organ functions and increase 24-hour survival rate in dogs with lethal burn injury. And PNU282987 may have potential clinical application.