title: Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure.
abstract: Pharmacological support with inotropes and vasodilators to control decompensated hemodynamics requires strict monitoring of patient condition and frequent adjustments of drug infusion rates, which is difficult and time-consuming, especially in hemodynamically unstable patients. To overcome this difficulty, we have developed a novel automated drug delivery system for simultaneous control of systemic arterial pressure (AP), cardiac output (CO), and left atrial pressure (Pla). Previous systems attempted to directly control AP and CO by estimating their responses to drug infusions. This approach is inapplicable because of the difficulties to estimate simultaneous AP, CO, and Pla responses to the infusion of multiple drugs. The circulatory equilibrium framework developed previously (Uemura K, Sugimachi M, Kawada T, Kamiya A, Jin Y, Kashihara K, and Sunagawa K. Am J Physiol Heart Circ Physiol 286: H2376-H2385, 2004) indicates that AP, CO, and Pla are determined by an equilibrium of the pumping ability of the left heart (SL), stressed blood volume (V), and systemic arterial resistance (R). Our system directly controls SL with dobutamine, V with dextran/furosemide, and R with nitroprusside, thereby controlling the three variables. We evaluated the efficacy of our system in 12 anesthetized dogs with acute decompensated heart failure. Once activated, the system restored SL, V, and R within 30 min, resulting in the restoration of normal AP, CO, and Pla. Steady-state deviations from target values were small for AP [4.4 mmHg (SD 2.6)], CO [5.4 ml x min(-1) x kg(-1) (SD 2.4)] and Pla [0.8 mmHg (SD 0.6)]. In conclusion, by directly controlling the mechanical determinants of circulation, our system has enabled simultaneous control of AP, CO, and Pla with good accuracy and stability.
authors.affiliation: Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita 565-8565, Japan. kuemura@ri.ncvc.go.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uemura
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hidaka
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.forename: Shuji
authors.initials: S
authors.lastname: Shimizu
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shishido
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshizawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016279:Atrial Function, Left / Q000187:drug effects*; D001331:Automation; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004280:Dobutamine / Q000008:administration & dosage / Q000627:therapeutic use; D004285:Dogs; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D007262:Infusions, Intravenous; D008955:Models, Cardiovascular; D009599:Nitroprusside / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D009599:Nitroprusside; D004280:Dobutamine; D005665:Furosemide