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Laboratory of "Pathophysiologie cellulaire et moléculaire de linsuffisance cardiaque," Institut National de la Santé et de la Recherche Médicale (INSERM) U572 Centre Hospitalo-Universitaire (CHU) Lariboisière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris; Departments of Physiology and Internal Medicine, CHU Bicêtre, AP-HP, University Paris Sud; Department of Anesthesiology and Critical Care and Laboratory of Anesthesiology, Hôpital Pierre Bénite, CHU Lyon-Sud, Hospices Civils de Lyon, University Claude Bernard (EA 1896), Lyon; Laboratory of Anesthesiology, Departments of Anesthesiology and Critical Care, and of Emergency Medicine and Surgery, CHU Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie, Paris, France
Address correspondence and reprint requests to Catherine Coirault, MD, PhD, INSERM U572, Hôpital Lariboisière, 41 Bd de la Chapelle, 75475 Paris Cedex 10, France. Address e-mail to coirault{at}larib.inserm.fr.
Our aim was to determine how isoflurane modified crossbridge (CB) number and kinetics in airway smooth muscle (ASM) and to compare its effects in Fisher and Lewis rats, two strains with differences in airway responsiveness. The effects of isoflurane (2 MAC) on isotonic and isometric contractility in tracheal ASM strips were investigated after methacholine (106 M)-induced contraction. CB mechanics and kinetics were analyzed using the formalism of Huxleys equations adapted to ASM. After isoflurane, maximum velocity did not differ from baseline in Lewis rats, whereas it was significantly less than baseline in Fisher rats (
25%), the most reactive strain. Isoflurane totally reversed methacholine-induced increase in active CB number in Lewis rats (2.4 ± 0.5 versus 1.8 ± 0.4 109/mm2 after methacholine and isoflurane, respectively) whereas reversal was only partial in Fisher rats (2.7 ± 0.4 versus 2.1 ± 0.3 109/mm2 after methacholine and isoflurane, respectively). Isoflurane induced a 40% increase in attachment step duration in both strains and an almost twofold increase in the CB cycle duration compared with baseline in Lewis rats. The isoflurane-induced increase in detachment step duration was less in Lewis than in Fisher rats (P < 0.05). We concluded that isoflurane modulated CB number and CB cycling rates of isolated rat ASM differently depending on the level of airway responsiveness.
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