MECHANISM OF THE NEGATIVE FORCE-FREQUENCY-RELATIONSHIP IN PHYSIOLOGICALLY INTACT RAT VENTRICULAR MYOCARDIUM - STUDIES BY INTRACELLULAR CA2-1 AND BY P-31-NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY( MONITOR WITH INDO)

We studied the subcellular mechanisms of the negative force-frequency relationship in rat myocardium by measuring 1) intracellular Ca2+ tran sients by indo-1 fluorometry and 2) intracellular pH (pH(i)) and phosp hate compounds with P-31-nuclear magnetic resonance (NMR). The data we re compared with those from guinea pig hearts, which show a positive f orce-frequency relationship. By increasing the pacing rate from 3 Hz t o 5 Hz, the peak positive first derivative of left ventricular pressur e (LVdP/dt) in rat heart decreased by 10+/-1% (n=6). In contrast to th is negative inotropic response, simultaneously measured peak Ca2+ tran sients increased by 6+/-1%. Guinea pig heart (n=6) showed an increase in peak positive LVdP/dt (33+/-1%) which was associated with an increa se in peak Ca2+ transients (8+/-1%). Under equivalent experimental con ditions in an NMR spectrometer, this increase in the pacing rate did n ot 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 i n guinea pig heart. These results suggest that in physiological rat my ocardium, pH(i) is susceptible to changes in the stimulus frequency an d may affect the Gaze-responsiveness of contractile proteins, which re sults in the negative force-frequency relationship.