Altered calcium handling in right ventricular heart failure induced by pulmonary hypertension

David Benoist*, Zhaokang Yang, Derek Steele and Ed White

Institute of Membrane and Systems Biology and Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, United-Kingdom.

* bsdb@leeds.ac.uk

The altered contractility that occurs in heart failure (HF) is often attributed to changes in Ca²⁺ handling properties (Hasenfuss et Pieske, 2002). Such changes have been less extensively studied in the right ventricle (RV), compared to the left ventricle (LV). The aim of this study was to investigate alterations in Ca²⁺ handling in RV HF in pulmonary hypertensive rats.

Male Wistar rats (200 g) were injected with monocrotaline to induced HF (identified by clinical symptoms) or with an equivalent volume of saline (CON). 3-4 weeks after injection RV cardiac myocytes were isolated. Cell shortening and Ca²⁺ transients were recorded in fura-4 AM loaded myocytes at 20-24°C. Caffeine (20 mM) was used to assess the sarcoplasmic reticulum (SR) calcium load. Ca²⁺ sparks were measured by confocal microscopy using fluo-4 AM.

Compared to CON hearts; there was a statistically significant increase in the ratio of RV to LV weight by 78% in HF heart (P < 0.05, n = 5-6 hearts in each group). Cell shortening was significantly decreased by 29% but Ca²⁺ transient amplitude significantly increased by 56% in HF myocytes, (P < 0.05 n = 17-20 myocytes in each group). SR load was also increased in HF by 61% myocytes (P < 0.05, n = 19-23 myocytes in each group). Consistent with an increase in SR load, the frequency, duration and width of Ca²⁺ sparks was significantly increased in HF but spark amplitude progressively reduced (P< 0.05, n= 24-32 myocytes in each group).

The increased SR load may explain the observed increase in Ca²⁺ transient amplitude and the increased number of Ca²⁺ sparks. However, these changes cannot be directly responsible for the reduced cell shortening, this is probably related to de-sensitization of the myofilaments to Ca²⁺ (Lamberts et al., 2007).

Hasenfuss G et Pieske B. J. Mol. Cell. Cardiol. 34: 951-969, 2002.

Lamberts RR et al. J. Physiol. 582: 695-709, 2007.