Computationally managed bradycardia improved cardiac energetics while restoring normal hemodynamics in heart failure

In acute heart failure, systemic arterial pressure (AP), cardiac output (CO), and left atrial pressure (P (LA)) have to be controlled within acceptable ranges. Under this condition, cardiac energetic efficiency should also be improved. Theoretically, if heart rate (HR) is reduced while AP, CO, and P (LA) are maintained by preserving the functional slope of left ventricular (LV) Starling's curve (S (L)) with precisely increased LV end-systolic elastance (E (es)), it is possible to improve cardiac energetic efficiency and reduce LV oxygen consumption per minute (MVO (2)). We investigated whether this hemodynamics can be accomplished in acute heart failure using an automated hemodynamic regulator that we developed previously. In seven anesthetized dogs with acute heart failure (CO < 70 mL min(-1) kg(-1), P (LA) > 15 mmHg), the regulator simultaneously controlled S (L) with dobutamine, systemic vascular resistance with nitroprusside and stressed blood volume with dextran or furosemide, thereby controlling AP, CO, and P (LA). Normal hemodynamics were restored and maintained (CO; 88 +/- 3 mL min(-1) kg(-1), P (LA); 10.9 +/- 0.4 mmHg), even when zatebradine significantly reduced HR (-27 +/- 3%). Following HR reduction, E (es) increased (+34 +/- 14%), LV mechanical efficiency (stroke work/oxygen consumption) increased (+22 +/- 6%), and MVO (2) decreased (-17 +/- 4%) significantly. In conclusion, in a canine acute heart failure model, computationally managed bradycardia improved cardiac energetic efficiency while restoring normal hemodynamic conditions.