Increase In Red Cell Flux Research Articles

The Upper Limit of Cerebral Blood Flow Autoregulation Is Decreased with Elevations in Intracranial Pressure.

The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized. We sought to delineate the ULA in a neonatal swine model. Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF; n = 10), controlled cortical impact (CCI; n = 10), or impact + infusion (CCI + INF; n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flux recordings during arterial hypertension until lethality. An increase in red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression and static rates of autoregulation (SRoRs) were determined above and below this inflection. When identified, the ULA (median [interquartile range]) was as follows: sham group: 102 mmHg (97-109), INF group: 75 mmHg (52-84), CCI group: 81 mmHg (69-101), and CCI + INF group: 61 mmHg (52-57; p = 0.01). Both groups with interventricular infusion had significantly lower ULA compared with the sham group. Neonatal piglets without intracranial pathological conditions tolerated acute hypertension, with minimal perturbation of cerebral blood flow. Piglets with acutely elevated intracranial pressure, with or without trauma, demonstrated loss of autoregulation when subjected to arterial hypertension.

Endothelium-dependent and endothelium-independent vasodilatation of the cutaneous circulation in sickle cell disease

Whilst there is evidence of endothelial dysfunction in sickle cell disease (SCD), whether this affects regulation in the microcirculation is not known. We studied 19 patients with SCD, eight with sickle cell-haemoglobin C (HbSC), 11 with homozygous sickle cell (HbSS) disease and 11 matched control subjects with normal haemoglobin genotype (HbAA). Vasodilator responses were evoked by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) in finger and forearm, cutaneous red cell flux (RCF) being measured by laser Doppler fluximetry. Increases in RCF evoked in the finger by ACh were not different between SCD and HbAA subjects (P = 0·789), but were smaller in patients with HbSS than HbSC (P < 0·05). By contrast, increases in RCF evoked in forearm by ACh were greater in SCD than HbAA subjects (P < 0·05) and similar in patients with HbSC and HbSS. Increases in RCF evoked by SNP did not differ between patients with SCD and HbAA subjects in finger or forearm. Our results indicate that endothelium-dependent cutaneous vasodilatation is augmented in forearm of patients with SCD relative to HbAA subjects, but impaired in the finger of SCD patients with the more severe HbSS genotype. Thus, endothelial dysfunction associated with SCD is not accompanied by generalised impairment in endothelium-dependent dilatation, but with more localised impairment that includes the fingers of patients with HbSS.

Contribution of prostanoids to endothelium-dependent vasodilatation in the digital circulation of women with primary Raynaud's disease

In 15 women with PR (primary Raynaud's) disease and in 15 matched control women, ACh (acetylcholine) was delivered by iontophoresis to the dorsum of the finger (seven 20 s pulses of 0.1 mA, followed by one 20 s pulse of 0.2 mA, applied at 60 s intervals). Cutaneous RCF (red cell flux) was recorded from the same site by the laser Doppler technique. ACh evoked progressive increases in RCF that were comparable in pre- and post-menopausal women with PR [maxima of 294+/-113 and 259+/-59 pu (perfusion units) respectively, n = 7 and 8 respectively], and in pre-menopausal controls (225+/-92 pu, n = 7), but smaller in post-menopausal controls (140+/-63 pu, n = 8; P < 0.05). Aspirin (600 mg, orally), a COX (cyclo-oxygenase) inhibitor, potentiated the ACh-evoked dilator responses in pre- and post-menopausal women with PR (343+/-129 and 311+/-48 pu respectively) and post-menopausal controls (277+/-124 pu; P < 0.05), but had no effect in pre-menopausal controls (225+/-92 pu). These results suggest that vasoconstrictor COX products limit ACh-evoked endothelium-dependent cutaneous dilatation in the digits in pre- and post-menopausal women with PR and in post-menopausal, but not pre-menopausal, control women. We propose that PR disease is associated with abnormality in the ability of oestrogen to modulate the synthesis of endothelium-dependent vasodilator and/or vasoconstrictor COX products.

The modification of human tumour blood flow using pentoxifylline, nicotinamide and carbogen

Aim: To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux.Methods and materials: Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40mgkg−1 and pentoxifylline 1200mg 2h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30min, recording pre-, during and post-carbogen breathing for 10min each.Results: Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (±0.09, 95% confidence interval (CI)) was observed after 6min of carbogen breathing, 2h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (±0.39, 95%CI) after nicotinamide with carbogen and 1.15 (±0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing.Conclusions: A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing.

Analysis of the responses evoked in the cutaneous circulation of one hand by heating the contralateral hand

In 9 healthy human subjects, cutaneous red cell flux in the thenor eminence of the left hand was measured by a Laser Doppler meter, while the right hand was transferred sequentially from water at 33°C, to water at 42°C for 5 min, to water at 33°C (first experimental run) and then to water at 42°C for 2 min (second experimental run). Red cell flux increased significantly by the end of the 2nd min of heating and had increased further by the end of the 5th min. Mean arterial pressure, measured by sphygmomanometry from the left arm, had not changed at either times indicating that the changes in red cell flux reflected progressive cutaneous vasodilatation. Meanwhile heart rate was significantly increased by the 5th min. By contrast, when these experiments were carried out on 8 subjects with a cuff on the right arm inflated to approximately 60 mm Hg to impede venous outflow from the heated limb, red cell flux in the contralateral hand showed a significant increase by the 5th min of heating, but this was accompanied by a fall in arterial pressure and no change in heart rate. By the 5th min after release of the occlusion and while the right arm was still in warm water, there was a further increase in red cell flux in the contralateral hand, but arterial pressure was not significantly different from the original control level and heart rate was significantly increased. Occlusion per se had no effect on red cell flux. Thus, we propose that heating one hand evokes reflex cutaneous vasodilatation in the contralateral hand which is partly mediated by peripheral thermoreceptors in the warm hand and partly by core thermoreceptors that are affected by blood temperature. We suggest that this cutaneous vasodilatation is part of a widespread peripheral vasodilatation which tends to reduce arterial pressure if not counteracted by an increase in cardiac output. We suggest that an increase in heart rate contributes to the latter and that this is initiated predominantly by core thermoreceptors.