Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

Abstract

Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.

Analytical Representation of Four-dimensional Hemodynamics for Drug Therapy Simulation in Acute Heart Failure Treatment

“…Assuming x is measurable or possible to estimate, the patient's initial CV parameters x 0 are given. Next, let the input u be the drug infusion 5 which are key drugs used in treatment of AHF: Dobutamine (DOB) as a positive inotrope, Norepinephrine (NE) as a vasopressor, Sodium Nitroprusside (SNP) as a vasodilator, Dextran (DEX) as a fluid, and Furosemide (FRO) as a diuretic, respectively. Then, let y be the CV metrics y :=…”

“…To manage multiple hemodynamics, automated drug therapeutic systems that control up to three-dimensional hemodynamics were proposed via PID control [5]- [7]. To mathematically analyze hemodynamics, we proposed a drug infusion system with the analytical solutions of three-dimensional hemodynamics [8].…”