Thromboxane inhibition improves renal perfusion and excretory function in severe congestive heart failure.
OBJECTIVE
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 A(2) (TxA(2)) is increased during cardiac failure.


METHODS
By oral administration of picotamide (a renal TxA(2) synthase and TxA(2)/prostaglandin H(2) receptor inhibitor), we blocked renal TxA(2). 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 B(2) (TxB(2)), the stable metabolite of TxA(2), 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 TxA(2) improves renal hemodynamics and kidney function and favorably affects indexes of cardiac performance.
Castellani
Sergio
S
Sezione Clinica Medica Generale e Cardiologia, Universita degli Studi di Firenze, Viale Morgagni 85, 50134 Florence, Italy. sergio.castellani@unifi.it
Paniccia
Rita
R
Di Serio
Claudia
C
La Cava
Giuseppe
G
Poggesi
Loredana
L
Fumagalli
Stefano
S
Gensini
Gian Franco
GF
Neri Serneri
Gian Gastone
GG
D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D008297:Male; D010795:Phthalic Acids / Q000494:pharmacology; D012039:Regional Blood Flow; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D013929:Thromboxane B2 / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D010795:Phthalic Acids; D013929:Thromboxane B2; D013928:Thromboxane A2; C011581:picotamide