title: Pharmacologically induced heart failure for the evaluation of circulatory assistance.
abstract: For the evaluation of the hemodynamic interaction between the natural heart and an assist device, a reversible pharmacological model based on the channel blocker Verapamil under hyperkalemia, was developed for deterioration of left ventricular function. Four calves weighing 70-90 kg underwent standard implantation for left atrioaortal assist (BioMedicus, BP-80), pump anesthesia (oxygen/isoflurane [1%]; 8 mg/kg of BW/h ketamine), and of ventricular demand pacing at 120 bpm. Left atrial pressure (LAP), ventricular pressure (LVP), aortic pressure (AoP), pulmonary arterial (Qpulm) pressures, and graft flow (Qgraft) were monitored. The hemodynamic effects of anesthetic overdose (2% Isoflurane) were compared with those of Verapamil (Isoptin: 0.2 mg/kg BW/h 5 mmol/kg of BW/h of KCl) medication. Both regimens caused a decreased in AoP to < or = 50%. For Isoflurane, a slight reduction in cardiac output (CO) of 10% at a nearly constant LAP and a strong decrease of the peripheral resistance (Rperi) of 35% could be seen where Isoptin caused a significant reduction in CO of 40% at an increased LAP (+25%) and changes in Rperi of < 10%. Because the vascular tonus remains nearly constant, the hemodynamic effects are controllable and reversible (antagonized with calcium chloride); thus we conclude that Verapamil administration under hyperkalemia conditions is a proper model for mimicking congestive heart failure with low systemic side effects.
authors.affiliation: Department of Cardio-Thoracic Surgery, Ludwig Boltzmann Institute for Cardiosurgical Research, University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.forename: I
authors.initials: I
authors.lastname: Schwendenwein
authors.forename: G
authors.initials: G
authors.lastname: Wieselthaler
authors.forename: K
authors.initials: K
authors.lastname: Roschal
authors.forename: H
authors.initials: H
authors.lastname: Schima
authors.forename: U
authors.initials: U
authors.lastname: Losert
authors.forename: E
authors.initials: E
authors.lastname: Wolner
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000633:toxicity; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D062787:Drug Overdose; D006333:Heart Failure / Q000097:blood* / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006353:Heart-Assist Devices / Q000592:standards*; D006947:Hyperkalemia / Q000139:chemically induced; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity; D016277:Ventricular Function, Left / Q000187:drug effects; D014700:Verapamil / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D014700:Verapamil; D007530:Isoflurane