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Ann Thorac Surg 2004;78:1433-1437
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Effects of a New Phosphodiesterase Enzyme Type V Inhibitor (UK 343-664) Versus Milrinone in a Porcine Model of Acute Pulmonary Hypertension

^a Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA
^b Division of Thoracic and Cardiovascular Surgery, University of Florida College of MedicineGainesville, Florida, USA
^c North Florida/South Georgia Veterans Health System, Malcolm B. Randall Veterans Affairs Medical Center, Gainesville, Florida, USA

Accepted for publication April 12, 2004.

^* Address correspondence to Dr Lobato, Department of Anesthesiology, University of Florida College of Medicine, Box 100254, Gainesville, FL 32610-0254, USA
elobato{at}anest.ufl.edu

BACKGROUND: Perioperative pulmonary hypertension remains a clinical challenge. The phosphodiesterase enzyme type III inhibitor milrinone produces pulmonary vasodilation but lacks selectivity. Sildenafil, a phosphodiesterase enzyme type V inhibitor, can also induce relaxation of the pulmonary vasculature; however, only the oral formulation is presently available. This study evaluated the effects of a new intravenous sildenafil analogue—UK 343-664—compared with milrinone during acute pulmonary hypertension in a porcine model of thromboxane-induced pulmonary hypertension.

METHODS: After acute pulmonary hypertension, 24 adult swine were randomized to 3 groups. Group 1 (n = 9) received an intravenous dose of 500 µg of UK 343-664, group 2 (n = 8) received milrinone 50 mg/kg, and group 3 (n = 7) received 10 mL of normal saline solution. All agents were administered for more than 5 minutes. Data were recorded continuously for 30 minutes.

RESULTS: Both milrinone and UK 343-664 partially reversed thromboxane-induced pulmonary hypertension, with a notable decrease in mean pulmonary artery pressure and pulmonary vascular resistance and a concomitant increase in cardiac output. In addition, milrinone improved right ventricular contractility but produced marked systemic vasodilatation. In contrast, the administration of UK 343-664 was associated with pulmonary vasodilatation, without appreciable changes in systemic arterial pressure or vascular resistance.

CONCLUSIONS: Milrinone and UK 343-664 were equally effective as pulmonary vasodilators; however, only UK 343-664 exhibited a high degree of pulmonary selectivity. Potential uses for this new phosphodiesterase enzyme type V inhibitor warrant further study.

This article has been cited by other articles:

				E. B. Lobato, T. Beaver, J. Muehlschlegel, D. S. Kirby, C. Klodell, and A. Sidi Treatment with phosphodiesterase inhibitors type III and V: milrinone and sildenafil is an effective combination during thromboxane-induced acute pulmonary hypertension Br. J. Anaesth., March 1, 2006; 96(3): 317 - 322. [Abstract] [Full Text] [PDF]