A study of perfused isolated dog saphenous vein

The venous valve agger and plasma noradrenaline-mediated venodilator feedback

“…Segments were perfused with a 341C oxygenated Tyrode solution, at constant flow, from a perfusion reservoir to which drugs were added. 21,22 When using the constant flow technique, a rising pressure in the perfusion circuit indicated the Segment was constricting and a falling pressure indicated it was dilating. Turbulence was induced in the perfusate of the Segment to increase reflux volume and amplify its feedback effect by a variety of means, used singly or in combination.…”

The balance between the pro-inflammatory effect of plasma noradrenaline and the anti-inflammatory effect of neuronal noradrenaline determines the peripheral effects of noradrenaline

“…Isolated CLSV segments were obtained from large dogs, preferably greyhounds, put down by electrocution [9]. Initially, only in vitro segments were employed but after 2-3 years in situ segments were far more commonly employed.…”

“…However, shortly after becoming aware of the bimodal responses I made a series of speculative 3ml injections of isoprenaline (ISO), a proven intraluminal dilator of the CLSV segment [9], into the distal end of a major tributary of the segment and found they caused dose related, localised constrictor effects [12]. The fact the responses were located 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 9 upstream from where the injected tributary emptied into the perfused segment (fig 1) and upstream also of a competent valve in the lumen of the segment, meant it was impossible for ISO to have constricted the segment by an intraluminal effect at the constricted site.…”

“…The first evidence I had that exogenous and overspill endogenous NA could cause dilator effects emerged during a routine pharmacological investigation of the responses of a perfused, doubly cannulated, in vitro preparation of segments of the CLSV to NA (Levophed) and electrical stimulation [8], [9]. Early in the course of the investigation an occasional segment displayed bimodal responses to stimulation [10] and that, in the context of the constant flow perfusion technique being employed, implied exogenous NA and overspill NA were causing dilator as well as constrictor effects.…”

Imbalances in the neurotrophic effects of noradrenaline, favouring the positive in the child and the negative in the mother, are the cause of preeclampsia

“…My interest in the effect of drugs stimulating tissues through their microcirculations resulted from an observation I made when investigating the responses of the CLSV segment to a range of drugs, including, in particular isoprenaline (ISO) and NA [17]. The former had been proven to dilate the segment, when constricted by intralumenal NA, by a b 1 agonist effect, when it acted intralumenally.…”