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CLINICAL RESEARCH: HEART FAILURE/TRANSPLANTATION

Thromboxane inhibition improves renal perfusion and excretory function in severe congestive heart failure

Sergio Castellani, MD^*,*, Rita Paniccia, PhD^*, Claudia Di Serio, PhD, Giuseppe La Cava, MD, Loredana Poggesi, MD^*, Stefano Fumagalli, MD, Gian Franco Gensini, MD^* and Gian Gastone Neri Serneri, MD^*

^* Sezione Clinica Medica Generale e Cardiologia, Firenze, Italy
Sezione Gerontologia e Geriatria, Dipartimento di Area Critica Medico Chirurgica, Firenze, Italy
Sezione di Medicina Nucleare, Dipartimento di Fisiopatologia Clinica, Università degli Studi di Firenze and Azienda Ospedaliera Careggi, FirenzeItaly

Manuscript received July 25, 2002; revised manuscript received March 19, 2003, accepted March 27, 2003.

^* Reprint requests and correspondence: Prof. Sergio Castellani, Dipartimento di Area Critica Medico-Chirurgica, Sezione Clinica Medica Generale e Cardiologia, Viale Morgagni 85, 50134, Firenze, Italy.
sergio.castellani{at}unifi.it

OBJECTIVES: The aim of this study was to evaluate whether thromboxane inhibition can favorably affect renal perfusion and clinical conditions in patients affected by severe heart failure.

BACKGROUND: The renal formation of the vasoconstrictor thromboxane A₂ (TxA₂) is increased during cardiac failure.

METHODS: By oral administration of picotamide (a renal TxA₂ synthase and TxA₂/prostaglandin H₂ receptor inhibitor), we blocked renal TxA₂. Fourteen patients in New York Heart Association functional class IV were studied according to a randomized, double-blinded, cross-over design. Each of the two eight-day periods of testing was preceded by a three-day period during which certain vasoactive medications were stopped.

RESULTS: Daily 24-h total urinary thromboxane B₂ (TxB₂), the stable metabolite of TxA₂, dropped at the end of picotamide treatment (p < 0.01 vs. baseline). Compared with placebo, effective renal plasma flow and the glomerular filtration rate increased (p < 0.01 and p < 0.05, respectively), thus leading to a significant decrease in the filtration fraction (p < 0.01). Renal vascular resistance decreased consistently (p < 0.01). In all patients, picotamide treatment was associated with an increase in diuresis and natriuresis (p < 0.001 vs. baseline). Plasma creatinine decreased (p < 0.05 vs. baseline). Patients also showed improvement in several clinical parameters, including a significant decrease in both pulmonary and venous pressure (p < 0.01 vs. baseline).

CONCLUSIONS: These results indicate that renal thromboxane formation plays an important role in renal vascular resistance in patients with severe heart failure, such as those described in the present study. Inhibition of TxA₂ improves renal hemodynamics and kidney function and favorably affects indexes of cardiac performance.

Abbreviations and Acronyms   ACE   angiotensin-converting enzyme   CHF   congestive heart failure   ERPF   effective renal plasma flow   FF   filtration fraction   GFR   glomerular filtration rate   mPAP   mean pulmonary artery pressure   NYHA   New York Heart Association   PG   prostaglandin   RIA   radioimmunoassay   RVR   renal vascular resistance   TxA2   thromboxane A2   TxB2   thromboxane B2   UCr   urinary creatinine

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