Combined Intravenous Sildenafil and L-Arginine Administration in a Porcine Animal Model: Hemodynamic Safety Profile and Effects on Coronary Blood Flow
| Autor: | Kelsey Alloo, Ali Salahieh, Gabriela R. Dincheva, Celeste Wong, Chun-Miao Feng, Marek Brzezinski, Wynnis L. Tom, Arthur W. Wallace |
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| Rok vydání: | 2020 |
| Předmět: |
Swine
Vasodilator Agents Hemodynamics Vasodilation Cardiovascular 030226 pharmacology & pharmacy chemistry.chemical_compound 0302 clinical medicine Models Heart Rate Original Research Article Pharmacology & Pharmacy Central venous pressure Pharmacology and Pharmaceutical Sciences Heart Disease medicine.anatomical_structure Models Animal Combination Administration cardiovascular system Cardiology Administration Intravenous Drug Therapy Combination Female Intravenous Artery medicine.medical_specialty Mean arterial pressure Sildenafil RM1-950 Arginine Sildenafil Citrate 03 medical and health sciences Medicinal and Biomolecular Chemistry Drug Therapy Internal medicine Coronary Circulation medicine Animals Cyclic guanosine monophosphate Heart Disease - Coronary Heart Disease 030203 arthritis & rheumatology Pharmacology business.industry Animal Atherosclerosis chemistry Vascular resistance Vascular Resistance Therapeutics. Pharmacology business |
| Zdroj: | Drugs in R&D, vol 20, iss 3 Drugs in R&D Drugs in R&D, Vol 20, Iss 3, Pp 279-290 (2020) |
| Popis: | Background Endothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, l-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage. Objective This study examined the hemodynamic safety and effect profiles of the combined administration of l-arginine and sildenafil using an in-vivo pig model. Methods Hemodynamic safety including mean arterial pressure, central venous pressure, heart rate, coronary vascular resistance, and systemic vascular resistance, as well as effect profiles including cardiac output and left anterior descending blood flow were measured in ten female swine after administrations of l-arginine, sildenafil, as well as combined l-arginine and sildenafil. Measurements were compared using repeated-measures analysis of variance and linear mixed models. Results The combination of l-arginine and sildenafil produced a significant dose-dependent increase in left anterior descending flow and cardiac output. In contrast, mean arterial pressure, heart rate, central venous pressure, coronary vascular resistance, and systemic vascular resistance did not show any significant changes. No significant change in serum osmolality was observed after administrations of l-arginine. Conclusions The combined intravenous administration of sildenafil and l-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil and l-arginine plasma concentrations. Hyperosmolality was only a minor factor in l-arginine hemodynamic effects. |
| Databáze: | OpenAIRE |
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