Mechanism of the Negative Force-Frequency Relationship in Physiologically Intact Rat Ventricular Myocardium : Studies by Intracellular Ca^<2+> Monitor With Indo-1 and by ^<31>P-Nuclear Magnetic Resonance Spectroscopy

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We studied the subcellular mechanisms of the negative force-frequency relationship in rat myocardium by measuring 1) intracellular Ca^<2+> transients by indo-1 fluorometry and 2) intracellular pH (pH_i) and phosphate compounds with ^<31>P-nuclear magnetic resonance (NMR). The data were compared with those from guinea pig hearts, which show a positive force-frequency relationship. By increasing the pacing rate from 3 Hz to 5 Hz, the peak positive first derivative of left ventricular pressure (LVdP/dt) in rat heart decreased by 10±1% (n=6). In contrast to this negative inotropic response, simultaneously measured peak Ca^<2+> transients increased by 6±1%. Guinea pig heart (n=6) showed an increase in peak positive LVdP/dt (33±1%) which was associated with an increase in peak Ca^<2+> transients (8±1%). Under equivalent experimental conditions in an NMR spectrometer, this increase in the pacing rate did not affect intracellular levels of phosphate compounds in either rat (n=6) or guinea pig heart (n=6). In contrast, pH_i showed a decrease of 0.031±0.006 pH units in rat heart, while no changes were observed in guinea pig heart. These results suggest that in physiological rat myocardium, pH_i is susceptible to changes in the stimulus frequency and may affect the Ca^<2+>-responsiveness of contractile proteins, which results in the negative force-frequency relationship.
社団法人日本循環器学会の論文
1996-07-20