2,3-Butanedione Monoxime Suppresses Primarily Total Calcium Handling in Canine Heart

Abstract

Whether 2,3-butanedione monoxime (BDM, ≤5 mmol/l) suppresses primarily crossbridge cycling or total Ca²⁺ handling in the blood-perfused whole heart remains controversial. Although BDM seems to suppress primarily total Ca²⁺ handling in canine hearts, more evidence is lacking. We therefore analyzed the cardiac mechanoenergetics, namely, E_max (contractility), PVA (total mechanical energy), and O₂ consumption of canine BDM-treated hearts by our recently developed integrative method to assess myocardial total Ca²⁺ handling. This method additionally required the internal Ca²⁺ recirculation fraction. We obtained this from the beat constant of the exponential decay component of the postextrasystolic potentiation. Our analysis indicated significant decreases in both internal Ca²⁺ recirculation fraction and total Ca²⁺ handling in the BDM-treated heart, but virtually no change in the reactivity of E_max to total Ca²⁺ handling. This result corroborates the view that BDM suppresses primarily total Ca²⁺ handling rather than crossbridge cycling in the canine blood-perfused heart.