Role of Endogenous Histamine in Altered Lung Mechanics in Rabbits

Abstract

Background: Unlike the effects of exogenous histamine, those of endogenous histamine on the lung mechanics have not yet been characterized. The site of endogenous histamine liberation by mivacurium was determined, as were the effects of this histamine on the airway and parenchymal mechanics in control rabbits (group C) and rabbits pretreated with H1 and H2 receptor blockers (group AH). The effectiveness of the receptor blockade was ensured by challenges with exogenous histamine.Methods: Pulmonary input impedance at low frequencies (ZL) was measured in anesthetized mechanically ventilated openchest rabbits under control conditions and every minute after administration of an intravenous bolus of mivacurium (2 mg/kg) and exogenous histamine (10 g/kg). Histamine levels were determined in serum samples taken from the carotid artery and jugular vein before and 1, 3, and 6 min after mivacurium injection. Parameters of airway resistance (Raw) and inertance and parenchymal damping (G) and elastance (H) were extracted from ZL spectra.Results: Mivacurium induced significant increases in plasma histamine levels, with the venous concentrations being significantly higher than those in the artery. The mivacurium-induced increase in Raw (28.7 ؎ 2.3%; mean ؎ SD) in group C was significantly higher than that in group AH (6.6 ؎ 3.4%), whereas the responses in G were not inhibited significantly (23.9 ؎ 6.9% vs. 15.5 ؎ 3.0%). The significant increases in Raw (70.6 ؎ 12.6%) and G (21.0 ؎ 4.9%) after exogenous histamine administration were virtually completely abolished by antihistamine pretreatment (3.6 ؎ 3.7% and 0.3 ؎ 2.6%).Conclusions: After mivacurium administration, endogenous histamine is liberated at least partly in the systemic circulation, and it induces primarily a heterogeneous airway constriction with minor changes in the parenchymal properties. This response was considerably reduced but not abolished by antihistamine pretreatment, a circumstance suggesting that mivacurium may liberate other constrictor mediators that might also contribute to the airway and parenchymal constriction.

Anaphylactic bronchospasm during general anesthesia is not related to asthma

“…One explanation for the association observed in this study would be that some NMBD injection leads to mast cell degranulation and release of bronchoconstricting mediators such as histamine and leukotrienes . Indeed, injection of antihistamines can abolish some of the bronchoconstrictor effects of NMBD in rabbits . Secondly, NMBD‐induced bronchospasm may be related to blockade of M2 muscarinic receptors on prejunctional parasympathetic nerves, leading to vagus nerve‐induced bronchospasm (via increased release of acetylcholine, activation of M3 muscarinic receptors and airway smooth muscle constriction) .…”

Mechanical Properties of the Lung

“…These parameters do, however, exhibit strong inverse dependencies on the size of the animal. Figure 8 shows the values of R N , Iaw, G, and H versus BW from published reports on mice (Bozanich et al, 2005;Hantos et al, 2008;Johnston et al, 1812e1819;Petak et al, 2001;Shalaby, Gold, Schuessler, Martin, Robichaud, 2010), rats (Hirai et al, 1999;Habre et al, 2001;Petak et al, 1998Petak et al, , 1997Sakai et al, 2001), guinea pigs (Adamicza et al, 1999(Adamicza et al, , 2001, rabbits (Habre et al, 2002Hantos et al, 1994), cats (Hantos et al, 1992b), minipigs , dogs Lutchen et al, 1994;Suki et al, 1997aSuki et al, , 1997b, adult humans (Kaczka et al, 1997;Babik et al, 2003;Hantos et al, 1986;Bachofen, 1968), and children (von Ungern-Sternberg et al, 2009). The results in mice were actually derived from Zrs, but this can be equated to Z L in this species because of the negligible contribution made by the chest wall .…”