Base-line and postthermal injury plasma histamine in rats

Although plasma histamine concentration has been reported to increase after thermal injury in the rat to as much as 100-fold over normal human plasma levels, the pathophysiological significance and relevance to human disease is questionable. Lack of confidence in the rat as a model of histamine-mediated disease is based on reports that normal rat base-line plasma histamine concentration exceeds that of human plasma by 20- to 70-fold. The present study confirms that high concentrations of histamine (20-68.9 ng/ml) are found in rat plasma obtained in an uncontrolled manner; but concentrations are lower (1.17 +/- 0.49 ng/ml) or undetectable in a sensitive radioenzymatic assay when sampling technique and plasma isolation are controlled. The primary cause for falsely elevated values for plasma histamine concentration appeared to be due to manipulation of the rat. Plasma histamine concentration increased within 1 min after thermal injury and the increase was proportional to extent of surface area injured. In contrast to the finding of a single time-related peak of plasma histamine concentration after partial-thickness burn, a biphasic elevation was found after full-thickness injury. Thus the data indicate that normal rat plasma histamine concentration is similar to that of the human and below the reported threshold for modulation of a variety of immune responses. Furthermore, the data support a role for histamine and other mast-cell mediators in the local and systemic responses to injury.