HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thomas M. Beaver Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bonnell, M. R. Articles by Lobato, E. B. Search for Related Content PubMed PubMed Citation Articles by Bonnell, M. R. Articles by Lobato, E. B. Related Collections Cardiac - pharmacology

Ann Thorac Surg 2004;77:238-242
© 2004 The Society of Thoracic Surgeons

---

Original article: cardiovascular

Effects of sildenafil analogue UK 343-664 on a porcine model of acute pulmonary hypertension

^a Department of Surgery, Gainesville, Florida, USA
^b Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, Florida, USA

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

Presented at the Forty-ninth Annual Meeting of the Southern Thoracic Surgical Association, Miami Beach, FL, Nov 7–9, 2002.

BACKGROUND: Sildenafil (Pfizer Pharmaceuticals, Sandwich, Kent, UK) has been associated with pulmonary vasorelaxation. A more potent Sildenafil analogue (UK 343-664 [Pfizer Pharmaceuticals]) has been developed, but its effects in vivo have not been studied. This study evaluated the effects of UK 343-664 (Pfizer) during acute pulmonary hypertension.

METHODS: Fourteen adult swine were anesthetized with 1 minimum alveolar concentration isoflurane and were mechanically ventilated with an FIO₂ of 50%. End tidal CO₂ was maintained between 32 and 36 mm Hg. Micromanometer tipped catheters were placed in the ascending aorta, pulmonary artery, and right ventricle. Pulmonary flow was measured with a perivascular probe using transit time ultrasound. Pulmonary hypertension was induced with a continuous infusion of the thromboxane analogue U46619. Animals were randomized into two groups. Group 1 (n = 9) received 500 µg of UK 343-664 (Pfizer) intravenously for more than 2 minutes. Group 2 (n = 5) served as the control group. Data were recorded continuously for 60 minutes. Statistical analyses were performed with the analysis of variance and t tests. A p less than 0.05 was considered significant.

RESULTS: Pulmonary hypertension was achieved in all animals. The administration of UK 343-664 (Pfizer) was associated with a significant decrease in pulmonary artery pressure (30.3%; p < 0.05) and pulmonary vascular resistance (42%; p < 0.05) with mild systemic vasodilatation. These effects were partially maintained at 30 minutes (a 17.3% and 39% decrease, respectively; p < 0.05).

CONCLUSIONS: The administration of UK 343-664 (Pfizer) was associated with predominant pulmonary vasodilatation without systemic hypotension. This may represent a significant advance in the treatment of acute pulmonary hypertension. Potential clinical implications for this new phosphodiesterase enzyme type V (PDEV) inhibitor merit further study.

This article has been cited by other articles:

				F Urdaneta, E. Lobato, T Beaver, J. Muehlschlegel, D. Kirby, C Klodell, and A Sidi Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog Perfusion, March 1, 2008; 23(2): 117 - 125. [Abstract] [PDF]

				S. A. Barman Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L472 - L479. [Abstract] [Full Text] [PDF]

				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]

				C. A. Dias-Junior, D. C. Souza-Costa, T. Zerbini, J. B. T. da Rocha, R. F. Gerlach, and J. E. Tanus-Santos The Effect of Sildenafil on Pulmonary Embolism-Induced Oxidative Stress and Pulmonary Hypertension Anesth. Analg., July 1, 2005; 101(1): 115 - 120. [Abstract] [Full Text] [PDF]

				A. L. Trachte, E. B. Lobato, F. Urdaneta, P. J. Hess, C. T. Klodell, T. D. Martin, E. D. Staples, and T. M. Beaver Oral Sildenafil Reduces Pulmonary Hypertension After Cardiac Surgery Ann. Thorac. Surg., January 1, 2005; 79(1): 194 - 197. [Abstract] [Full Text] [PDF]