Excessive
inflammation and high vasopermeability can lead to blood volume loss and tissue
edema, which can affect the
resuscitation and prognosis for serious
burn patients. In this experiment, we investigated the effect of
PNU-282987, an α7
nicotine cholinergic receptor agonist on the hemodynamic parameters and survival rate by inhibiting vasopermeability and tissue
edema during the fluid
resuscitation for lethal
burn shock. Forty Beagle dogs with intubation of the carotid artery and jugular vein 24 hours before the injury were subjected to 50% TBSA full-thickness
burns, and were randomly divided into following four groups: no
resuscitation group (group NR), venous fluid
resuscitation group (group R),
PNU-282987 treatment group (group P), and fluid
resuscitation group plus
PNU-282987 group (group RP), with 10 dogs in each group. Hemodynamic variables and biochemical parameters were determined with animals in a conscious and cooperative state. The plasma volume and the vasopermeability were determined by
indocyanine green and
fluorescein isothiocyanate-dextran, respectively. The level of
tumor necrosis factor-α and interleukin-1β in plasma, and the water content of different organs were also determined. The mean arterial pressure, cardiac output, and plasma volume of all dogs decreased significantly, and the lung extravascular water index and pulmonary vascular permeability index increased remarkably after
burn. The hemodynamic parameters deteriorated continually in group N dogs, and then
anuria, hyperlactacidemia, and multiple organ dysfunctions developed. The mean arterial pressure and cardiac output of dogs in group R and group RP returned to preinjury levels at 48 hours postburn. The lung extravascular water index and pulmonary vascular permeability in group R were higher than those before preinjury. The dogs in group RP were found to have a significant increase in plasma volume and urine output, and a remarkable decrease in the levels of
tumor necrosis factor-α, interleukin-1α,
lactic acid, and organ functions compared with those of group R (P <.05). The survival rate of RP group (100%; 10/10) was significantly higher than that of group N (0; 0/10), group P (20%; 2/10), and group R (60%; 6/10).
PNU-282987 combined with intravenous fluid
resuscitation significantly improved hemodynamics and the survival rate in the early period after this lethal
burn shock. The mechanism may be attributable to the lowering of the level of proinflammatory mediators, amelioration of vasopermeability-induced visceral
edema, less of blood volume loss, and protection of vital organs through activation of cholinergic anti-inflammatory pathway.