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Thorac Cardiovasc Surg 2002; 50(1): 49-54
DOI: 10.1055/s-2002-20163
Original Thoracic
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Effects of Trifluoperazine on the Contraction Kinetics
of the Isolated Intact Tracheal and Pulmonary Artery Smooth Muscle

N.  Kayhan1 , T.  M.  Schmidt1 , A.  Bonz2 , K.  Sonnenberg1 , C.  F.  Vahl1 , S.  Hagl1
  • 1Department of Cardiac Surgery, University of Heidelberg, Germany
  • 2Department of Cardiology, University of Würzburg, Germany
Further Information

Publication History

May 17, 2001

Publication Date:
15 February 2002 (online)

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Abstract

Background: We studied the effect of the calmodulin antagonist trifluoperazine (TFP) on isolated intact rat tracheal and pulmonary artery smooth muscle contractile behaviour. Methods: Experimental series: 1) TFP-dose-response curves for TFP's effect on force generation were constructed using rat tracheal smooth muscles and rat pulmonary artery preparations (n = 8). A concentration of 1 µmol/l TFP was chosen for the subsequent experimental series. 2) Tracheas and pulmonary arteries (n = 14) were dissected in three segments. One of them was used immediately for experiments (“native”), the other two were treated for 12 h in 4 °C Tyrode solution without (“12 h cold storage”) or with 1 µmol/l TFP (“12 h cold storage + TFP”). These preparations contracted after supramaximal effective electrical field stimulation. The force-clamping technique was used to analyse kinetic and mechanical parameters of smooth-muscle contraction in both types of preparation (measurement conditions: resting tension 2 mN, 37 °C, modified Krebs-Henseleit solution). Results: 1) TFP decreased developed force dose-dependently in pulmonary artery and tracheal smooth muscle. 2) During sustained tonic activation, the contraction kinetics become slower both with and without TFP treatment (p < 0.0001). 3) TFP caused a dramatic retardation of the velocity of force generation in both types of preparation for any given time interval during the course of a tonic activation (p < 0.0005). 4) The dramatic effects of TFP on the contraction kinetics were not associated with effects on the extent of force generation. Conclusions: These results support the assumption that tracheal and pulmonary artery smooth muscle cross-bridge rates are controlled by a calcium-calmodulin-dependent myosin light chain kinase. This finding suggests the involvement of a calmodulin-independent regulator process responsible for the changes observed in the cross-bridge cycling rates during sustained tonic activation. A direct intervention on the contractile apparatus level is a measure for reduction of smooth-muscle tone without negative inotropic side effects.

Key words

Calmodulin - Contraction kinetics - Cross-bridge cycling - Rat smooth muscle - Trifluoperazine

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Dr. N. Kayhan

Labor Herzchirurgie

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone: + 49-6221-566246

Fax: + 49-6221-429987

Email: kayhan.nalan@web.de

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