Combined Intravenous Sildenafil and l-Arginine Administration in a Porcine Animal Model: Hemodynamic Safety Profile and Effects on Coronary Blood Flow

Figures

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  Fig. 1. Flow chart of l-arginine, sildenafil, and mannitol infusion and blood sample collection during the experiment. l-Arginine hydrochloride was injected every 5 min for five times followed by a 2-h elimination period. Blood samples were taken at baseline (0 min) and then at 5-min intervals after each bolus (at 5, 10, 15, 20 and 25 min) as well as 35 min after the last bolus. Sildenafil was then administered intravenously for 1 min and equilibrated for 15 min. After this 15-min equilibration, l-arginine hydrochloride was again injected every 5 min for five times followed by a 2-h elimination period. Blood samples were taken as described when l-arginine was administered alone. Finally, a bolus of mannitol (12.5 g in 50 mL) was administered after 5 min of baseline data collection to assess the degree of CO changes in respect to osmolality. A blood sample was taken prior to and 5 min after the administration of mannitol. Please refer to Sect. 2 for detailed information about doses for each drug

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  Fig. 2. Mean concentration response curves of hemodynamic safety and effects after l-arginine vs l-arginine plus sildenafil infusions. The mean hemodynamic safety and effects of l-arginine alone (solid lines) and with sildenafil (dashed lines) are compared. a Cardiac output (CO). b Left anterior descending (LAD) flow. c Mean arterial pressure (MAP). d Central venous pressure (CVP). e Heart rate (HR). f Coronary vascular resistance (CVR). g Systemic vascular resistance (SVR). Data are expressed as sample mean ± standard error (SE). *Indicates a significant difference of at least p < 0.05 compared with baseline levels based on the linear mixed models of repeated measures

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  Fig. 3. Hemodynamic safety and effects of sildenafil over time (15 min). The mean trajectory of hemodynamic safety and effects of sildenafil over 15 min was shown. a Cardiac output (CO). b Left anterior descending (LAD) flow. c Mean arterial pressure (MAP). d Central venous pressure (CVP). e Heart rate (HR). f Coronary vascular resistance (CVR). g Systemic vascular resistance (SVR). Data are expressed as sample mean ± standard error (SE). *Indicates a significant difference of at least p < 0.05 compared with the baseline levels based on the linear mixed models of repeated measures