Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy

Abstract

. Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy. Am J Physiol Heart Circ Physiol 286: H979-H984, 2004. First published October 2, 2003 10.1152/ajpheart.00536.2002The 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 Ϫ ) were also addressed with the use of two different buffers (HCO 3 Ϫ 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 Ϫ F dev/Fmax) was calculated from Fdev and maximal tension (Fmax). Calcium recirculation was determined with postextrasystolic potentiation. Both groups of muscles were superfused with either HCO 3 Ϫ (Con-B and Mct-B, both n ϭ 6) or HEPES (Con-H and Mct-H, both n ϭ 6) buffer. With hypertrophy, contractions were slower but F dev was not changed. However, Fmax was decreased (P Ͻ 0.05). With HCO 3 Ϫ , Fmax decreased from 23.8 Ϯ 6.5 mN⅐mm Ϫ2 in Con-B, to 13.7 Ϯ 3.3 mN⅐mm Ϫ2 in Mct-B. With HEPES, it decreased from 16.3 Ϯ 3.5 mN⅐mm Ϫ2 (n ϭ 6, Con-H) to 8.3 Ϯ 1.6 mN⅐mm Ϫ2 (Mct-H). Contractile reserve during hypertrophy was therefore also decreased (P Ͻ 0. We evaluated the role of hypertrophy on F dev , twitch characteristics, and F max and potentiation in the rat papillary muscle with the use of the Mct model of right ventricular hypertrophy. We also studied the effect of hypertrophy on calcium handling by calculating the fraction of calcium recirculating to the sarcoplasmic reticulum (SR). To study the possible role of pH regulation, we used both the HCO 3 Ϫ and HEPES buffer because it was shown that changing the buffer from HEPES to HCO 3 Ϫ affects cytosolic pH (pH i ) in cardiac muscle (7,21,23). We also mimicked the HEPES buffer by using the Cl Ϫ /HCO 3 Ϫ exchanger blocker 4,4Ј-diisothiocyanostilbene-2,2Ј-disulfonic acid (DIDS), preventing HCO 3 Ϫ from entering the cell, and thus establishing the importance of HCO 3 Ϫ ions. METHODSAnimals. All animals were treated in accordance with the "Guiding Principles in the Care and Use of Laboratory Animals," as approved by the Council of the American Physiological Society and under the regulations of the Institutional Animal Care and Use Committee.Male Wistar rats (Harlan; Zeist, The Netherlands), weighing 170-190 g, were injected subcutaneously with either a single dose (29) of Mct (40 mg/kg in saline) or vehicle (Con).Papillary muscle preparation. Three weeks after Mct injection, the hearts were rapidly removed under ether anesthesia and transferred to ice-cold Tyrode solution. The hearts were transferred to a Langendorff setup and a papillary muscle was dissected as described before (38). The muscle was placed in a muscle bath and suspended between a Perspex pla...

Effects of endogenous sulfur dioxide on monocrotaline-induced pulmonary hypertension in rats1

“…Also, GSH/GSSG, which is believed to be a major element in the detoxification of SO 2 [38] , and MDA, lipid peroxidation production, increased markedly in the lung tissues of the rats in the MCT group. These results are in accordance with those previously reported [31,32] . Interestingly, when the endogenous SO 2 was inhibited by HDX, the antioxidative enzyme (SOD and CAT) activities and GSH levels in the lung tissues decreased significantly compared with the MCT group, suggesting that endogenous SO 2 could increase the antioxidative ability in MCT-treated rats.…”

Gene Transfer of Extracellular Superoxide Dismutase Ameliorates Pulmonary Hypertension in Rats

“…First, we used a relatively low dose of MCT, in accordance with previous reports (39,40). The MCT dose selected might have resulted in the beneficial effects of EC-SOD transfer on PH.…”

Myocardial dysfunction and neurohumoral activation without remodeling in left ventricle of monocrotaline-induced pulmonary hypertensive rats

“…The FFR is an important intrinsic regulatory mechanism of cardiac contractility; normal myocardium increases developed force with higher frequencies of stimulation over the frequency range close to the physiological heart rate, showing normal contractile reserve, but failing or dysfunctional myocardium loses this reserve, and therefore FFRs are excellent indicators for evaluating the severity of cardiac contractile dysfunction and cardiac reserve capacity as well as for the evaluation of the effectiveness of therapeutic agents in congestive HF (5). The normal myocardium from sham rat LV muscle strips presented positive FFR as expected (5,16), whereas the muscle strips from the LV of MCT-treated rats showed overall negative FFR indicative of reduced contractile reserve (5), resembling the hypertrophied RVs of MCT-treated rats in earlier stages of PH (16,34).…”