Key result
Isoproterenol treatment combined with pacing induced synergistic phosphorylation of PLB and cTnI, promoting a higher degree of relaxation compared to pacing alone in isolated working hearts.
Synergistic phosphorylation of phospholamban and cardiac troponin I by isoproterenol induces a higher degree of relaxation, facilitating sufficient diastolic filling at higher heart rates compared to pacing alone.
Cautions against clinical extrapolation from isolated hearts; leaves open whether synergistic lusitropy translates to human tachycardia or HF.
We hypothesized that the extent of frequency-dependent acceleration of relaxation (FDAR) would be less than that of isoproterenol-(ISO-)dependent acceleration of relaxation (IDAR) at the same increment of heart rates, and ISO may improve FDAR. Cardiac function and phosphorylation of PLB and cTnI were compared in pacing, ISO treatment, and combined pacing and ISO treatment in isolated working heart. The increase in cardiac output and the degree of relaxation was less in pacing than in ISO treatment at the same increment of heart rates. The increasing stimulation frequency induced more significant relaxant effect in ISO perfusion than that in physiological salt perfusion. The pacing only phosphorylated PLB at Thr17, but ISO induced phosphorylation of cTnI and PLB at Ser16 and Thr17. Those results suggest that the synergistic effects of PLB and cTnI induce higher degree of relaxation which makes a sufficient diastolic filling of the ventricle at higher heart rate.
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Zhang et al. (2011) studied this question. Isoproterenol (ISO) treatment and pacing vs. Pacing alone was evaluated on Cardiac output, degree of relaxation, and phosphorylation of PLB and cTnI. Isoproterenol treatment combined with pacing induced synergistic phosphorylation of PLB and cTnI, promoting a higher degree of relaxation compared to pacing alone in isolated working hearts.
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