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SUMMARYThe underlying cause of heart failure should be established, where possible. In particular the failure to respond to diuretic and vasodilator therapy requires careful evaluation.

Inflammation of the blood vessel u a l l has been implicated i n the pathogenesis of diseases as apparently diverse as septic shock and unstable angina and acute myocardial infarction. Ue have developed a method that allows individual vessels to be exposed t o i n f l a m t o r y signals and r e a c t i v i t y t o be assessed i n these vessels i n their usual physiological environent. Nethods: b c s s w n t of vascular react i v i t v i n vive : Subjects l a y one hand placed on an angled s q p r t .The diameter of a single vein on the hand uas recorded by measuring the tinear displacement of a l i g h t ueight probe placed on the skin overlying the s m i t of the vein uhen the pressure i n a congesting cuff i s deflated from 40-OmnHg. D r g s uere infused continucurly t h r y h a 23SUG ne.edle placed 5-1Onm daunstream frm the t i p of the probe.lnstillstion of endotoxin I E T X l end cvt -: A lecgth of the vein wder study was isolated frm the c i r c u l a t i o n by means of tuo wedges placed 2-3cm apart M the skin overlying the vessel. ETX (100 E.U.) o r CTX (11-18 lng, TNFa lng, I L -6 1OOpg) was injected i n t o the isolated segment. One hour later the contents of the segment uere aspirated and the wedges r a v e d . Constrictor dose r m s e curves : A dose response curve t o noradrenaline CNAI was constructed before end f o r several hours a f t e r ETX or CTX. I n a separate s t W dose response curves t o NA uere constructed i n 2 veins on the same hand, only one of uhich received ETX or CTX. Cyclo-oxygenase inhibitors, n i t r i c oxide-synthase [NOS] irhibitors. and hydrocortisone were used t o explore the mechanisms of the effects seen. p i l a t o r dose r m s e cu rvei: I n a d i f f e r e n t series of studies dose response curves t o bradykinin [BKI (a stirmlator of n i t r i c oxide synthesis). arachidonic acid [MI (the precursor of prostanaid production) and GTN (a NO donor) uere constructed before and lh, 24h. 48h and 7 days after ETX or cytokine. m: Specimens of saphenous vein were preconstricted subnaximlly with phenylephrine. Endothelial i n t e g r i t y was determined by relaxation t o BK. I n endotheliun-intact s a p h e m vein. concentration response curves were constructed to BK and GTN before and l h a f t e r ETX. w: ETX caused a rightward s h i f t i n the dose response curve t o NA. The effect uas greatest a t l h ( m a x i m constriction pre-ETX: 8 7 d 4 past-endotoxin: 52*8%. n=4. ~0 . 0 5 ) and returned t o normal by 4h. l n s t i l l a i i o n of ETX d a i l y for 3'days'resulted i n the developnent of tolerance ( m a x i m constriction f a HA post-ETX: day 1-39*6%; day2-67iTX; day3-8 5 i R ) . Cyclo-oxygenase andlor NO synthase (NOS) i n h i b i t o r s d i d not a l t e r the response t o ETX i n these vessels whereas p r i o r adninistration of hydrocortisooe abolished the effects. E n also attenuated the dose-response curves to BK and AA but not GTN. This e f f e c t persisted for a t least 48h and had recovered by 7 days. I L -1 produced an attenuation i n the constrictor re...