Left ventricular hypertrophy (LVH) is accompanied by a rise of [Na⁺]_i, the mechanism of which is unclear (Gray et al. 2001). A primary increase of [Ca²⁺]_i would, via Na⁺-Ca²⁺ exchange, lead to an increase of [Na⁺]_i. The possibility that in LVH the ability of the myocyte to regulate sarcoplasmic Ca²⁺ as a result of reduced sarcoplasmic reticulum (SR) function was investigated.

LVH was induced by placing a plastic clip (2 mm diameter) around the ascending aorta under anaesthesia (0.22 ml kg^-1 sodium pentobarbitone, followed by 49 %-49 %-2 %, N₂O-O₂-halothane mixture inhalation). Sham-operated and unoperated animals served as controls. After 40-100 days the heart was removed from humanely killed animals and the heart-to body weight ratio (HBR) recorded; myocytes were isolated as described previously (Hall & Fry, 1992). Intracellular [Ca²⁺] was measured using epifluorescence microscopy using fura-2 AM (5 mM, 30 min incubation). Myocytes were superfused with HCO₃^–/CO₂-buffered Tyrode solution at 37°C. To estimate the SR Ca²⁺ content, the rise of [Ca²⁺]_i when released by 10 mM caffeine was recorded. Ca²⁺ efflux rate was estimated from the time constant (t₁) of decay of the caffeine response (Varro et al. 1993). Results are expressed as means ± S.D. and statistical significance assessed using Student’s t test.

Caffeine (10 mM) generated a Ca²⁺ transient in all cells (n = 74) from control hearts and in 40 of 46 cells from AC hearts. The magnitude of the transient was on average 55 % in the AC group compared with control (P < 0.01). t₁ was slower in myocytes from AC hearts (15.0 ± 5.5, n = 40, vs. 9.7 ± 3.9 s, n = 46, P < 0.001) and correlated with HBR (r = 0.57, P < 0.01). A transient undershoot of [Ca²⁺]_i was observed in a number of myocytes on removal of caffeine and the time constant of this was prolonged in myocytes from AC hearts (71.2 ± 33.9, n = 24 vs. 51.8 ± 16.3 s, n = 16, P < 0.05) and also correlated with HBR (r = 0.73, P < 0.01). Reduction of extracellular [Na] from 147 to 29 mM increased [Ca²⁺]_i by a similar magnitude in myocytes from AC and control hearts (604 ± 716, n = 39 vs. 540 ± 591 nM, n = 64, P > 0.05). t₁ in myocytes from control and AC hearts were prolonged compared with those in 147 mM Na⁺ Tyrode (10.0 ± 3.9 vs. 17.3 ± 10.3 s, n = 27, P < 0.001 for control and 15.1 ± 5.7 vs. 19.4 ± 9.6 s, n = 17, P < 0.05 for aortic constricted group, paired t tests).

These findings suggest that SR Ca²⁺ regulation is impaired in this model of LVH and that Na⁺-Ca²⁺ exchange activity is also modulated.

We thank the British Heart Foundation for financial assistance.

All procedures accord with current UK legislation.