Reduced contraction strength with increased intracellular [Ca 2+ ] in left ventricular trabeculae from failing rat hearts

Intracellular calcium ([Ca 2+ ] i ) and isometric force were measured in left ventricular (LV) trabeculae from spontaneously hypertensive rats (SHR) with failing hearts and normotensive Wistar‐Kyoto (WKY) controls. At a physiological stimulation frequency (5 Hz), and at 37 °C, the peak stress of SHR trabeculae was significantly ( P ≤; 0.05) reduced compared to WKY (8 ± 1 mN mm −2 ( n = 8) vs. 21 ± 5 mN mm −2 ( n = 8) , respectively). No differences between strains in either the time‐to‐peak stress, or the time from peak to 50 % relaxation were detected. Measurements using fura‐2 showed that in the SHR both the peak of the Ca 2+ transient and the resting [Ca 2+ ] i were increased compared to WKY (peak: 0.69 ± 0.08 vs. 0.51 ± 0.08 μ m ( P ≤ 0.1) and resting: 0.19 ± 0.02 vs. 0.09 ± 0.02 μ m ( P ≤ 0.05), SHR vs. WKY, respectively). The decay of the Ca 2+ transient was prolonged in SHR, with time constants of: 0.063 ± 0.002 vs. 0.052 ± 0.003 s (SHR vs. WKY, respectively). Similar results were obtained at 1 Hz stimulation, and for [Ca 2+ ] o between 0.5 and 5 m m . The decay of the caffeine‐evoked Ca 2+ transient was slower in SHR (9.8 ± 0.7 s ( n = 8) vs. 7.7 ± 0.2 s ( n = 8) in WKY), but this difference was removed by use of the SL Ca 2+ ‐ATPase inhibitor carboxyeosin. Histological examination of transverse sections showed that the fractional content of perimysial collagen was increased in SHR compared to WKY (18.0 ± 4.6 % ( n = 10) vs. 2.9 ± 0.9 % ( n = 11) SHR vs. WKY, respectively). Our results show that differences in the amplitude and the time course of the Ca 2+ transient between SHR and WKY do not explain the reduced contractile performance of SHR myocardium per se . Rather, we suggest that, in this animal model of heart failure, contractile function is compromised by increased collagen, and its three‐dimensional organisation, and not by reduced availability of intracellular Ca 2+ .