Non-steady-state calcium handling in failing hearts from the spontaneously hypertensive rat

It is generally agreed that changes in Ca²⁺ cycling are often associated with heart failure, yet the impact of these changes on a beat-to-beat basis remains unclear. Measurements of isometric force and [Ca²⁺]_i were made at 37°C in left ventricular trabeculae from failing spontaneously hypertensive rat (SHR) hearts, and their normotensive Wistar–Kyoto (WKY) controls. At 1 Hz, peak stress was reduced in SHR (14.5?±?2.4 mN mm^?2 versus 22.5?±?6.7 mN mm^?2 for WKY), although the Ca²⁺ transients were bigger (peak [Ca²⁺]_i 0.60?±?0.08 μM versus 0.38?±?0.03 μM for WKY) with a slower decay of fluorescence (time constant 0.105?±?0.005 s versus 0.093?±?0.002 s for WKY). To probe dynamic Ca²⁺ cycling, two experimental protocols were used to potentiate force: (1) an interval of 30 s rest, and (2) a 30-s train of paired-pulses, and the recirculation fraction (RF) calculated for recovery to steady-state. No difference was found between rat strains for RF calculated from either peak force or Ca²⁺, although the RF was dependent on potentiation protocol. Since SR uptake is slower in SHR, the lack of change in RF must be due to a parallel decrease in trans-sarcolemmal Ca²⁺ extrusion. This view was supported by a slower decay of caffeine-induced Ca²⁺ transients in SHR trabeculae. Confocal analysis of LV free wall showed t-tubules were distorted in SHR myocytes, with reduced intensity of NCX and SERCA2a labelling in comparison to WKY.