title: Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy.
abstract: The objective of this study was to evaluate the role of right ventricular hypertrophy on developed tension (F(dev)) and contractile reserve of rat papillary muscle by using a model of monocrotaline (Mct)-induced pulmonary hypertension. Calcium handling and the influence of bicarbonate (HCO(3)(-)) were also addressed with the use of two different buffers (HCO(3)(-) 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 - F(dev)/F(max)) was calculated from F(dev) and maximal tension (F(max)). Calcium recirculation was determined with postextrasystolic potentiation. Both groups of muscles were superfused with either HCO(3)(-) (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 F(dev) was not changed. However, F(max) was decreased (P < 0.05). With HCO(3)(-), F(max) 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 HCO(3)(-), 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 HCO(3)(-) superfusion.
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Univ. Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: J Pieter
authors.initials: JP
authors.lastname: Versluis
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Heslinga
authors.forename: Pieter
authors.initials: P
authors.lastname: Sipkema
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002021:Buffers; D003326:Coronary Circulation / Q000502:physiology; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D009200:Myocardial Contraction / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001639:Bicarbonates; D002021:Buffers; D016686:Monocrotaline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006531:HEPES