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.
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