The effects of fructose-1,6-diphosphate on the isolated rabbit heart

The effects of 0.1-100 mgm of fructose-1,6-diphosphate (FDP) were observed on the inotropic and chronotropic activity of the isolated, perfused rabbit heart, using a modified Langendorff technique. The preparations were treated with bolus injections of 0.1-100 mgm of FDP in gradually increasing concentrations following their recovery from previous injections. FDP produced a biphasic inotropic response with an initial decrease in contractility followed by an increase. The largest increases in contractility were observed at concentrations below 25 mgm while the greatest decreases occurred at the higher doses. The average maximal increase in contractility was 136.5 +/- 24% at an average dose of 1.53 +/- 0.6 mgm FDP. The average maximal decrease in the inotropic activity was 69 +/- 3% which was observed at an average dose of 92 +/- 8 mgm FDP. Recovery of the contractile activity following the observed effects of FDP was greater than or equal to pretreatment levels at all concentrations except 0.5 and 100 mgm FDP. The basal tone or tension of some hearts, especially after high doses of FDP, increased with some of these preparations contracting into a hard, putty-colored knot. FDP was also observed to exert an anti-arrhythmic effect on arrhythmic hearts. A negative chronotropic response was noted at all concentrations of FDP while a positive chronotropic response was observed only at the 0.1 mgm dose of FDP. The average increases and decreases in heart rate were 65 +/- 18 and 37 +/- 7%, respectively, at average respective doses of 9 +/- 6 and 40 +/- 15 mgm FDP. These data indicate that FDP exerts biphasic inotropic and chronotropic effects as well as an anti-arrhythmic effect on the isolated myocardium. They also indicate that FDP is toxic at higher cumulative doses.