AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 286: H979-H984, 2004. First published October 2, 2003; doi:10.1152/ajpheart.00536.2002
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Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy

J. Pieter Versluis, Johannes W. Heslinga, Pieter Sipkema, and Nico Westerhof

Laboratory for Physiology, Institute for Cardiovascular Research, Vrije University Medical Center, 1081 BT Amsterdam, The Netherlands

Submitted 27 June 2002 ; accepted in final form 16 September 2003

The objective of this study was to evaluate the role of right ventricular hypertrophy on developed tension (Fdev) and contractile reserve of rat papillary muscle by using a model of monocrotaline (Mct)-induced pulmonary hypertension. Calcium handling and the influence of bicarbonate () were also addressed with the use of two different buffers ( and HEPES). Wistar rats were injected with either Mct (40 mg/kg sc) or vehicle control (Con). Isometrically contracting right ventricular papillary muscles were studied at 80% of the length of maximal developed force. Contractile reserve (1 – Fdev/Fmax) was calculated from Fdev and maximal tension (Fmax). Calcium recirculation was determined with postextrasystolic potentiation. Both groups of muscles were superfused with either (Con-B and Mct-B, both n = 6) or HEPES (Con-H and Mct-H, both n = 6) buffer. With hypertrophy, contractions were slower but Fdev was not changed. However, Fmax was decreased (P < 0.05). With , Fmax decreased from 23.8 ± 6.5 mN·mm–2 in Con-B, to 13.7 ± 3.3 mN·mm–2 in Mct-B. With HEPES, it decreased from 16.3 ± 3.5 mN·mm–2 (n = 6, Con-H) to 8.3 ± 1.6 mN·mm–2 (Mct-H). Contractile reserve during hypertrophy was therefore also decreased (P < 0.05). With , it decreased from 0.73 ± 0.03 (Con-B) to 0.55 ± 0.04 (Mct-B). With HEPES, it decreased (P < 0.001) from 0.64 ± 0.07 (Con-H) to 0.19 ± 0.06 (Mct-H). The recirculation fraction decreased (P < 0.05) from 0.59 ± 0.04 in Con-B to 0.44 ± 0.04 in Mct-B. We conclude that contractile reserve and recirculation fraction are impaired during hypertrophy, with a stronger effect under HEPES than superfusion.

calcium; intracellular ions; sarcoplasmic reticulum function; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid



Address for reprint requests and other correspondence: P. Sipkema, Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Univ. Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands (E-mail: p.sipkema{at}vumc.nl).







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