Contraction kinetics of isolated human myometrium during menstrual cycle and pregnancy

Objective: To investigate the interaction between actin and myosin in the m yometrium by studying the contraction kinetics of isolated samples of human myometrium. Design: Experimental and observational cross-sectional study. Setting: Eppendorf University Hospital, Hamburg. Samples: Myometrium samples were taken from women in the follicular phase ( n = 6) or luteal phase (n = 6) of the menstrual cycle and during pregnancy at term (n = 25). Methods: The frequency, extent and rate of force development nt were determ ined in spontaneously active myometrial preparations. From a resting force of 2 mN, sustained tonic contractions were induced by K+-depolarisation (12 4 mM), or by protein kinase C activation (19.9 mu M indolactam). The steady force was reversibly interrupted by rapid length changes (100 Hz sinus vib rations lasting 1 s, 5% of muscle length). Extent (steady plateau), as well as rate of force increase after cessation of vibrations, were derived from bi-exponential functions fitted to the time course of force recovery. Results: Frequency of spontaneous contractions was higher in the follicular phase [mean (SD) 18.3 contractions/hour (1.0)] than in the luteal phase [1 3.4 contractions/hour (8.1)] or in pregnancy at term [8.8 contractions/hour (7.6)]. During indolactam treatment, steady force in pregnancy at term was significantly increased [8.8 mN (4.0)], compared with the follicular phase [3.7 mN (0.9)]. Force recovery was distinctly slower in pregnancy at term during indolactam treatment [time constant 99.2 s (57.9); P < 0.005] than d uring K+-depolarisation [time constant 29.1 s (5.9)], whereas in the follic ular phase the rate of force recovery was faster with indolactam [16.8 s (7 .1)] than with K+ depolarisation [24.4 s (5.9); P < 0.005]. Conclusions: The responses of human myometrium to contraction stimuli diffe r according to the reproductive state. Membrane depolarisation causes simil ar responses in all myometrial strips. In contrast, near term stimulation o f protein kinase C generates a large tonic force and slow contraction kinet ics, whereas early in the menstrual cycle contraction kinetics are fast.