Cardiovascular effects of the soluble guanylyl cyclase activator BAY 58-2667 in anesthetized dogs

Materials and methods Nine female and male Beagle dogs (age 1.5–3 years, body weight 10 – 15 kg) were anesthetized (neuroleptic anesthesia with droperidol/fentanyl) and artificially ventilated (N2O/O2) [2]. Hemodynamic parameters systolic and diastolic arterial blood pressure (BPS, BPD), left ventricular systolic and end diastolic pressure (LVP, LVEDP), left ventricular dP/dt (LVdP/dt), cardiac output (CO), central venous pressure (CVP), and heart rate (HR) were measured continuously. Total peripheral resistance (TPR) was calculated as mean arterial pressure (BPM) divided by cardiac output. ECG was recorded with standard lead II and RR, PQ, QRS, and QT interval were evaluated. QT was corrected for heart rate by Fridericia's formula (QTcF). Groups of n = 3 dogs received 3 cumulative infusion steps of placebo (1 mM Tris buffer at pH 8.6–8.8 in saline, 0.44–0.67–3.33 ml/kg/h) or BAY 58–2667 at low (1–5– 25 μg/kg/h) or at high (5–15–45 μg/kg/h) infusion rates. Infusion rates were consecutively increased every hour followed by a 2 hour washout period after stop of the final infusion step.