Colin Deane

Nitric Oxide Synthase Inhibition in Humans Reduces Cerebral Blood Flow but Not the Hyperemic Response to Hypercapnia

BACKGROUND AND PURPOSE Animal studies suggest that nitric oxide (NO) is important in basal cerebral blood flow (CBF) regulation and that it may mediate the vasodilatory response to carbon dioxide. We investigated its role in the human circulation using the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). METHODS L-NMMA was administered as an intravenous bolus at three doses (1, 3, and 10 mg/kg). CBF was assessed by color velocity ultrasonic imaging of internal and common carotid artery volume flow (ICA flow and CCA flow) and transcranial Doppler ultrasound measurement of middle cerebral artery flow velocity (MCAv). The pressor effect of L-NMMA was controlled for by comparison with noradrenaline titrated to effect an equivalent blood pressure elevation. RESULTS L-NMMA produced a dose-dependent reduction in basal mean+/-SD CCA flow from 415.2+/-51.9 to 294+/-56.2 mL/min (at 10 mg/kg) and ICA flow from 268.8+/-59.4 to 226.2+/-72.6 mL/min (P<.005 and P<.05, respectively, comparing areas under the dose-response curve). This was reversed by L-arginine. Mean+/-SD systemic blood pressure rose from 85.2+/-6.4 to 100.8+/-9.6 mm Hg (P<.01). There was no significant reduction in MCAv. There was no significant change in the CBF response to either 6% or 8% carbon dioxide after L-NMMA. Noradrenaline produced a lesser fall in basal CCA flow (12.0%) but had a similar effect on the hypercapnic response. CONCLUSIONS Basal NO release is important in controlling human CBF, but intravenously administered L-NMMA does not inhibit the hypercapnic hyperemic response in humans. The discrepancy between CBF and MCAv after L-NMMA administration is consistent with MCA vasoconstriction. Neuronal NO synthase inhibition may be protective in stroke. However, our results suggest that nonselective NO synthase inhibitors such as L-NMMA should be used with caution because they reduce CBF.

Transplant renal artery stenosis in 77 patients--does it have an immunological cause?

Transplant renal artery stenosis (TRAS) is a common complication after transplantation and is an important cause of graft dysfunction. Damage from graft rejection, trauma, and atherosclerosis have been implicated as possible causes. We reviewed all 917 patients transplanted in our unit since 1978 to study the prevalence, clinical features, and possible causes of TRAS. Seventy-seven patients with TRAS were identified. The detected incidence was 2.4% before the introduction of color doppler ultrasonography (CDU) and rose to 12.4% after CDU was introduced in 1985, giving an overall incidence of 8.4% during a mean follow-up period of 6.9 years. The TRAS group was compared with a control group of 77 transplanted patients matched for age, year of transplant, sex, and number of previous grafts. Mean ages for the study and control groups were 43.6 +/- 15 and 44.8 +/- 13.7 yr. A total of 25% of cases of TRAS were diagnosed within the first 8 wk of transplantation and in 60% within the first 30 wk (median = 23 wk). All patients were treated with angioplasty, 28 patients had recurrence of TRAS requiring multiple angioplasties (maximum 5) and 1 went on to have surgery. Angioplasty resulted in a significant fall in plasma creatinine. Patient and graft survival were significantly worse in the TRAS group: 69% vs. 83% (P < 0.05) and 56% vs. 74% (P < 0.05) (TRAS vs. Control), respectively. There was a significantly higher incidence of rejection, especially cellular rejection in the TRAS group, 0.67 vs. 0.35 episodes per patient (P < 0.01) (TRAS vs. Control). Recurrence but not occurrence of TRAS was associated with the use of cyclosporine.

Colour velocity flow measurement: In vitro validation and application to human carotid arteries

Ultrasound measurement of volume blood flow is potentially useful for many clinical situations, yet practical implementation and use are restricted by the many instrumentation and blood flow limitations that can arise. Colour velocity imaging offers a number of theoretical advantages over methods based on duplex imaging. We evaluated a colour velocity flow measurement system (CVI-Q, Philips) both in a flow phantom and in vivo in the extracranial carotid arteries of normal volunteers. Over a range of constant (50-1200 ml/min) and pulsatile (92-366 ml/min) flows and using both steered and unsteered beams with beam angles of 30 degrees and 40 degrees, errors usually within 5% were obtained for constant flow and within 10% for pulsatile flow. However, with a beam angle of 70 degrees, higher errors of 20% were obtained for pulsatile flow. The reproducibility of flow measurements made using both anterior and posterior-lateral scanning approaches was determined in the common (CCA), internal (ICA) and external carotid (ECA) arteries of 18 volunteers. A greater reproducibility was found using the posterior-lateral approach (CCA 6.27%; ICA 9.8%), and mean (SD) flow values were 376 ml/min in the CCA and 255 ml/min in the ICA. The ratio of (ICA + ECA)/CCA flow calculated for each subject individually was mean (SD) 0.95 (0.11). Insonation from an anterior approach resulted in lower reproducibility and lower flow values. In conclusion, colour flow velocity imaging allows repeatable reproducible measurements of CCA and ICA flow, but results are optimal if a posterior-lateral scanning approach is used.

Glucose 6 phosphate dehydrogenase deficiency is not associated with cerebrovascular disease in children with sickle cell anemia

To the editor: Cerebrovascular disease is an important complication in children with sickle cell anemia (SCA).[1][1] Hemolysis is increasingly implicated in the pathogenesis.[2][2],[3][3] Recently, Bernaudin et al found that glucose 6 phosphate dehydrogenase (G6PD) deficiency was associated with

Extracranial internal carotid arterial disease in children with sickle cell anemia

Background Sickle cell anemia is one of the commonest causes of stroke in children. It is usually, but not always, associated with intracranial vasculopathy. We have assessed the value of ultrasound screening for extracranial internal carotid artery disease. Design and Methods Using Doppler ultrasound scanning, we assessed peak systolic blood velocity, tortuosity and stenosis in the extracranial internal carotid arteries of 236 children with sickle cell anemia. Seventeen of the children had previously had a stroke. All measurements were performed as part of routine clinical care. Results The median extracranial internal carotid artery velocity was 148cm/s (5th centile 84, 95th centile 236). Higher velocities were significantly correlated with younger age, higher white blood cell counts and higher rates of hemolysis. Fourteen (5.9%) had tortuous extracranial internal carotid arteries and 13 (5.4%) had stenosis or occlusion. None of the children with tortuous vessels but 8 of those with stenosis had previously had a stroke; the presence of stenosis was strongly associated with overt clinical stroke (OR 35.9, 95% C.I. 9.77–132, P<0.001). In 6 children, extracranial stenosis was part of extensive intracranial vasculopathy, but in 2 there was no evidence of intracranial disease. Stenosis seemed to be more common in older children. Conclusions Extracranial internal carotid artery stenosis is strongly associated with stroke in children with sickle cell anemia, and may explain some cases of stroke without overt intracranial vasculopathy. Doppler ultrasound scanning of extracranial internal carotid arteries is non-invasive and fairly quick to perform and may identify children at increased risk of stroke who would otherwise be missed. The value of extracranial internal carotid artery scanning should be studied prospectively.

A Simple Index Using Age, Hemoglobin, and Aspartate Transaminase Predicts Increased Intracerebral Blood Velocity as Measured by Transcranial Doppler Scanning in Children With Sickle Cell Anemia

OBJECTIVE. Increased intracerebral blood velocity measured by transcranial Doppler scanning identifies children with sickle cell anemia who are at increased risk of stroke. We have tried to develop an index based on routine clinical measurements that also predicts increased intracerebral blood flow. METHOD. Routinely collected clinical and laboratory data were correlated with transcranial Doppler measurements on children with sickle cell anemia seen in a single institution in 2006. The index produced was validated on a second independent data set from children with sickle cell anemia. RESULTS. The time-averaged mean of the maximum velocity in centimeters per second in the middle cerebral artery circulation correlated significantly with age, hemoglobin, lactate dehydrogenase, and aspartate transaminase levels, white blood cell count, and creatinine level. On multiple regression, hemoglobin and aspartate transaminase levels maintained their significance, whereas age had borderline significance, and an index was developed linked to a time-averaged mean of the maximum velocity of 220 − (8 × hemoglobin) − (1.4 × age) + (0.4 × aspartate transaminase). This detected a time-averaged mean of the maximum velocity of >170 cm/second with 100% sensitivity and 58% specificity. The index was validated on the second data set and again showed 100% sensitivity with 73% specificity. CONCLUSION. This simple index has the potential to identify children who are at higher risk of cerebrovascular disease to allow them to be prioritized for transcranial Doppler scanning and other intracerebral imaging.

Transcranial Doppler scanning and the assessment of stroke risk in children with haemoglobin sickle cell disease

Objective : To assess the role of transcranial Doppler (TCD) scanning in assessing the risk of stroke in children with haemoglobin SC (HbSC) disease. TCD scanning has an established role in primary stroke prevention in sickle cell anaemia but its value in HbSC is unknown. Design : A retrospective audit of routinely performed TCD scans and routinely collected clinical data. Setting : A paediatric sickle cell clinic in a teaching hospital in south London, UK. Patients : 46 children with HbSC disease who have undergone routinely performed TCD scans and steady-state blood tests. Main outcome measures: The time-averaged mean of the maximum velocity (TAMMV) in the middle cerebral artery circulation correlated with clinical and laboratory data. Results: The mean TAMMV was 94 cm/s, with a 98th centile of 128 cm/s. This is significantly less than the published ranges for HbSS, with a mean reading of 129 cm/s. One child had a stroke at the age of 5 years, when her TAMMV was measured at 146 cm/s. Conclusions: Further studies are needed to assess stroke risk in HbSC disease, but we suggest that TCD measurements are potentially useful in this condition, and that readings greater than 128 cm/s are abnormally high and warrant further investigation.

Transformation of the Multidisciplinary Diabetic Foot Clinic Into a Multidisciplinary Diabetic Foot Day Unit Results From a Service Evaluation

The natural history of the diabetic foot is aggressive and complex. To counteract this, we describe the transformation of a Multidisciplinary Diabetic Foot Clinic into a Multidisciplinary Diabetic Foot Day Unit, which delivers an emergency open access system for patients, with a “one-stop,” same day service in which investigations are performed, results reviewed and treatment implemented. It also provides joint clinics with vascular, orthopaedic, and plastic surgeons and specialized clinics for casting of complex neuropathic feet and for the administration of intravenous or intramuscular antibiotics on the same day. The aim was to document these increasingly wide-ranging facilities by undertaking a retrospective evaluation over a 6-week period, with analysis of notes, investigations, and an anonymous patient satisfaction survey. The clinic was visited by 597 patients who attended in 1076 appointments, of which 112 (10.4%) were emergency visits; these patients attended the clinic without a booked appointment but via an open access policy, 93 of whom were known to the clinic, but 19 were new self-referred patients to the service. Furthermore, 197 (18%) were seen in a Joint Vascular Diabetic Foot Clinic and 98 (9%) were seen in a Joint Orthopaedic Plastic Diabetic Foot Clinic, 570 (53%) were seen in an Active Ulcer Clinic and 97 (9%) in a Total Contact Casting Clinic. Forty-five percent of patients were prescribed antibiotics, including 188 (76%) as oral and 45(18%) as intravenous antibiotics and 15(6%) as intramuscular injections. Of the 1076 appointments, 150 (14%) patients were in the foot clinic for more than 4 hours. Sixty (10%) patients were reviewed 4 or more times over the 6-week period. Only 22 (2%) were admitted to hospital. Of the 125 survey responders, 98% were satisfied with this service, which has evolved from a Diabetic Foot Clinic into a Multidisciplinary Diabetic Foot Day Unit.

Arteriovenous access ischemic steal (AVAIS) in haemodialysis: a consensus from the Charing Cross Vascular Access Masterclass 2016

Arteriovenous access ischaemic steal (AVAIS) is a serious and not infrequent complication of vascular access. Pathophysiology is key to diagnosis, investigation and management. Ischaemia distal to an AV access is due to multiple factors. Clinical steal is not simply blood diversion but pressure changes within the adapted vasculature with distal hypoperfusion and resultant poor perfusion pressures in the distal extremity. Reversal of flow within the artery distal to the AV access may be seen but this is not associated with ischaemia in most cases. Terminology is varied and it is suggested that arteriovenous access ischemic steal (AVAIS) is the preferred term. In all cases AVAIS should be carefully classified on clinical symptoms as these determine management options and allow standardisation for studies. Diabetes and peripheral arterial occlusive disease are risk factors but a ‘high risk patient’ profile is not clear and definitive vascular access should not be automatically avoided in these patient groups. Multiple treatment modalities have been described and their use should be directed by appropriate assessment, investigation and treatment of the underlying pathophysiology. Comparison of treatment options is difficult as published studies are heavily biased. Whilst no single technique is suitable for all cases of AVAIS there are some that suit particular scenarios and mild AVAIS may benefit from observation whilst more severe steal mandates surgical intervention.

Occult carotid artery disease in patients who have undergone coronary angioplasty.

OBJECTIVES The aim was to evaluate the prevalence of asymptomatic mild (30-49%), moderate (50-69%) and severe (70-99%) ICA stenosis in patients who underwent previous coronary angioplasty (PTA). METHODS After obtaining ethics committee approval, 144 consecutive patients aged between 65 and 75 years were invited for carotid Duplex evaluation with a linear 6 MHz array transducer by trained vascular sonographers within a single unit. A peak systolic velocity >230 cm/s in the ICA was considered as significant (>70% stenosis). RESULTS Of the 144 patients approached, 117 (81%) attended (male:female ratio 3.2:1, age range 65-75 years, median age 71 years). Duplex ultrasound revealed one occlusion, 70% or more ICA stenosis in three patients (2.6%), 50-69% stenosis in 12 patients (10.3%) and 30-49% stenosis in 29 patients (24.8%). CONCLUSIONS Carotid artery disease with a luminal stenosis of 30% or more is common in patients who underwent previous PTA. The yield of significant ICA stenosis (70% or more), which would benefit from carotid endarterectomy according to the Asymptomatic Carotid Surgery Trial is low. Recommendation for initial screening and subsequent follow-up Duplex examination for evaluation of disease progression of such cohorts remains debatable.