Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy.
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.
Versluis
J Pieter
JP
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Univ. Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Heslinga
Johannes W
JW
Sipkema
Pieter
P
Westerhof
Nico
N
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
D001639:Bicarbonates; D002021:Buffers; D016686:Monocrotaline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006531:HEPES