Postischemic Hyperemia Research Articles

Influence of rheological parameters on the velocity of erythrocytes passing nailfold capillaries in humans

One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role.

The Prevalence of Endothelial Dysfunction in Patients With and Without Coronary Artery Disease

Endothelial dysfunction (ED) is frequently present in patients presenting with acute or stable coronary artery disease (CAD), but it is also found in patients presenting with chest pain without angiographic coronary lesions. We hypothesized that even in patients without CAD, the presence of cardiovascular (CV) risk factors will correlate with the presence of ED. Our study included a total of 341 consecutive patients referred for coronary angiography. We used pulse wave analysis with a finger plethysmograph (peripheral arterial tonometry) to determine endothelial function. Hyperemia ratio was calculated as the ratio of the postischemic hyperemia response relative to baseline measurement. The hyperemia ratio was significantly higher in patients without CAD (2.02 ± 0.52) compared with patients with chronic CAD (1.81 ± 0.44, P = 0.001) or acute CAD (1.74 ± 0.49, P < 0.001). Prevalence of ED was 33%, 46%, and 58%, respectively. In multivariate analysis, the presence of CAD, diabetes, and cigarette smoking, and the total number of CV risk factors, were strong predictors of ED. In 67% of the patients without CAD but with ≥3 CV risk factors, ED was present. Prevalence of ED in patients with chest pain depends on the presence of CAD and CV risk factors. Patients without CAD but with ≥3 risk factors frequently presented with ED. Such patients may be at increased risk for future CV events and may profit from intensified therapy to control CV risk factors.

Vascular reactivity at rest and during exercise in middle-aged obese men: effects of short-term, low-intensity, exercise training

Although increased blood flow (BF) in exercising muscles is thought to be impaired in obese subjects and may contribute to physical inactivity, data are scarce in this regard and the involvement of endothelium dysfunction remains partly hypothetical. A total of 16 middle-aged obese men (body mass index, BMI ≥ 30 kg m(-2)) and 16 normal-weight men (BMI<25 kg m(-2)), matched for age, were recruited. We used ultrasonography to compare intima-media thickness (IMT) and distensibility of the carotid artery, flow-mediated dilation (FMD), nitrate-dependent dilation (NDD) and peak BF during post-ischemic hyperemia in the brachial artery (a conduit artery), and leg BF during knee-extensor exercise (indicative of resistance vessel function) in obese and in normal-weight men. In addition, 10 obese men participated in an 8 week individualized low-intensity training program. Compared with normal-weight men, obese men had higher carotid IMT (0.50 ± 0.01 vs 0.62 ± 0.04 mm, P < 0.05) but lower carotid distensibility (0.26 ± 0.03 vs 0.11 ± 0.03 mm Hg(-1) 10(-2), P < 0.05), FMD (5.7 ± 0.4 vs 3.3 ± 0.5%, P < 0.05) and peak BF during post-ischemic hyperemia (398 ± 52 vs 229 ± 24%, P < 0.05), despite similar maximal shear rate, without NDD differences. Lower limb BF (ml min(-1) 100 g(-1)) increased significantly from rest to maximal exercise in both groups with lower values in obese men (at peak power, 36.9 ± 1.6 vs 31.5+2.2 ml min(-1) 100 g(-1), P < 0.05). Exercise training normalized carotid distensibility (0.14 ± 0.04 before vs 0.23 ± 0.03 mm Hg(-1) 10(-2) after training, P = 0.09) and FMD (2.7 ± 0.4 before vs 4.8 ± 0.5% after training, P < 0.05), but did not improve brachial post-ischemic peak BF or exercising leg BF. In obese men, conduit and resistance vessel reactivity is depressed, but a short-term low-intensity exercise training improves distensibility and endothelium dependent vasodilation in the large conduit artery, but not post ischemic or exercise muscle BF.

Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients

This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n=15) or cyclosporin A (CsA, n=14) associated with mycophenolate mofetil (MMF) and steroids (6months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119±3 vs. CsA: 138±4mmHg, P<0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1±0.9 vs. CsA: 9.9±0.9%, P<0.05) without any difference for hyperaemia, endothelium-independent dilatation and GFR (SRL: 66.7±1.05 vs. CsA: 67.5±1.22ml/min). Our results demonstrate that a CNI-free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure.

Microvessel changes after post-ischemic benign and malignant hyperemia: experimental study in rats

BackgroundThe present investigation was designed to elucidate the use of dynamic contrast enhanced perfusion MR imaging (DCE pMRI) in characterizing hyperemia, including microvessel changes, and to examine whether DCE pMRI can predict benign or malignant hyperemia.MethodsSprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) by intraluminal suture placement. All rats were randomized to 4 groups: MCAO for 0.5 hours followed by saline treatment (10 ml/kg; group 1); MCAO for 3 hours followed by treatment with saline (group 2) or urokinase (25000 IU/kg; group 3); and MCAO for 6 hours followed by urokinase treatment (group 4). Relative cerebral blood volume (rCBV) and relative maximum slope of increase of the signal intensity time curve (rMSI) were quantitatively analyzed from MRI. Microvessel diameter and blood-brain barrier disruption obtained by laser scanning confocal microscopy (LSCM) as well as transmission electron microscopy (TEM) were obtained for correlative study.ResultsBenign hyperemia was noticed only in group 1; malignant hyperemia was seen in group 3. Although the rCBV of malignant hyperemia was slightly higher than in benign hyperemia (P > 0.05), the rMSI, on the other hand, was significantly lower (P < 0.05). Fluoro-isothiocyanate dextran (FITC-dextran) extravasations, marked glial end-foot process swelling, and significant vasodilatation were seen in malignant hyperemia, while no or mild leakage of FITC-dextran and slight glial end-foot process swelling occurred in benign hyperemia.ConclusionOur findings indicate that DCE pMRI can characterize post-ischemic hyperemia and correlates well with microvascular damage.

Early stage detection of conduit artery endothelial dysfunction in patients with type 1 diabetes

Flow-mediated dilatation evaluation using hand skin heating may possibly be more accurate than post-ischaemic hyperaemia to detect conduit artery endothelial dysfunction in type 1 diabetes. We measured in 24 type 1 diabetic patients (n=16 without microangiopathy) and 24 healthy matched subjects radial artery diameter (echotracking), blood flow and mean wall shear stress during heating and post-ischaemic hyperaemia. Compared with controls, flow-mediated dilatation was lower in diabetic patients during post-ischaemic hyperaemia and heating. However, in the subgroup of uncomplicated patients, a decreased flow-mediated dilatation was only apparent during heating (17.1+/-1.6% vs. 24.3+/-0.7%, p<0.05) but not during post-ischaemic hyperaemia (10.1+/-1.1% vs. 10.5+/-0.6%, NS). This was confirmed by the lower slope of the diameter-mean wall shear stress relationship in these patients in the absence of modification in endothelium-independent dilatation. We conclude that hand skin heating permits the early detection of conduit artery endothelial dysfunction in type 1 diabetic patients with normal response to post-ischaemic hyperaemia. This procedure could be useful to investigate the prognostic role of vascular dysfunction and the impact of vasculoprotective treatments in this patient population.

Early post-ischemic hyperemia on transcranial cerebral oxygen saturation monitoring in carotid endarterectomy is associated with severity of cerebral ischemic insult during carotid artery clamping

Background and objective: In animal models, the magnitude of early post-ischemic hyperemia tends to correlate with the duration and intensity of prior ischemic insult. The aim of this study was to determine whether early post-ischemic hyperemia in human brain during carotid endarterectomy (CEA) is associated with the severity of cerebral ischemic insult during clamping of the internal carotid artery (ICA).Methods: Transcranial cerebral oxygen saturation using near-infrared spectroscopy was monitored intraoperatively in 171 patients undergoing CEA for ipsilateral ICA stenosis (>70%) to assess the intensity of cerebral hemispheric ischemia during ICA clamping and the magnitude of early post-ischemic hyperemia after ICA declamping.Results: Early post-ischemic hyperemia peaked within 3 minutes after ICA declamping and resolved at 20 minutes after ICA declamping. A significant correlation was observed between the magnitude of early post-ischemic hyperemia and the intensity of cerebral ischemia (r=0.697; p<0.0001). Eight patients recovered from anesthesia with a new minor neurological deficit on the side contralateral to the CEA (4.7%). Analysis by receiver operating characteristics (ROC) curve was used to estimate the ability to discriminate between patients with and without post-operative development of new neurological deficits. Area under the ROC curve was significantly greater when analysing the magnitude of early post-ischemic hyperemia (1.00; 95% CI: 0.99–1.00) when compared with the intensity of cerebral ischemia (0.93; 95% CI: 0.89–0.98) (p<0.01).Conclusion: Early post-ischemic hyperemia in CEA is correlated with the severity of cerebral ischemic insult during clamping of the ICA.

Haptoglobin genotype and endothelial function in diabetes mellitus: a pilot study

Endothelial function (EnF) is impaired in patients with diabetes mellitus (DM) due in large part to an increase in oxidative stress. Haptoglobin (Hp) is a potent antioxidant protein which is encoded by two different alleles (1 and 2) with the Hp 1 protein being a superior antioxidant to the Hp 2 protein. We hypothesized that DM individuals with the Hp 2-2 genotype would have greater endothelial dysfunction as compared to DM individuals with the Hp 1-1 genotype. We studied EnF in 16 Hp 2-2, 14 Hp 1-1 DM individuals and 14 healthy subjects. DM patients' groups were matched in terms of age, cardiovascular risk factors and metabolic characteristics. EnF was assessed using post-ischemic reactive hyperemia and strain gauge plethysmography and expressed either as the maximal flow after the ischemic period or as the area under the flow-time curve (AUC). We showed that EnF indices, AUC and maximal flow, were also higher in the healthy and Hp 1-1 groups compared with Hp 2-2 genotype group (615 +/- 60 and 600 +/- 40 vs. 450 +/- 50 ml dl(-1), 29 +/- 2.6 and 25 +/- 3 vs. 14 +/- 1.8 ml min(-1) dl(-1), P < 0.003 and P < 0.05, for AUC and maximal flow, one-way ANOVA, respectively). We concluded that Hp 2-2 diabetic patients had a worse EnF than controls and Hp 1-1 diabetic subjects.

Commentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular function

VIEWPOINTCommentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular functionFaisel KhanFaisel KhanPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.90314.2008MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: It is accepted that a single test is unlikely to be able to provide a measure of vascular function that is truly representative of general arterial function and of the microcirculation. Holowatz and colleagues (4) in their Viewpoint article effectively highlight the ability to obtain a generalized measure of microvascular function by using the cutaneous circulation as a surrogate. An important point they discussed is that methodologies used to explore the cutaneous microcirculation evoke an integrated vascular response, which represents in vivo human integrative physiology that is not unique to the cutaneous microvascular bed. Thus, when used in the correct manner, and accounting for the possible endothelial, neural, and smooth muscle pathways involved (3), the skin circulation offers great potential as a valuable, easily accessible site for monitoring the development and progression of microvascular dysfunction (5), and for characterizing overall cardiovascular risk (6). Techniques such as flow-mediated dilatation of the brachial artery provide valuable information of the role of endothelial function in vascular disease (2). However, the methodology in obtaining such measurements with adequate sensitivity and accuracy requires technical expertise and is highly operator dependent, making its applicability challenging in a clinical setting. The strive to provide vascular testing as a realistic approach to improving cardiovascular risk assessment depends on the ability to make relatively simple, operator independent assessments of the vasculature. Methods for probing the skin microvasculature, such as those using laser-Doppler technology, offer such potential (1).REFERENCES1 Binggeli C, Spieker LE, Corti R, Sudano I, Stojanovic V, Hayoz D, Lüscher TF. Statins enhance postischemic hyperaemia in the skin circulation of hypercholesterolemic patients. A monitoring test of endothelial dysfunction for clinical practice? J Am Coll Cardiol 42: 71–77, 2003.Crossref | PubMed | ISI | Google Scholar2 Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel J. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. A Report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39: 257–265, 2002.Crossref | PubMed | ISI | Google Scholar3 Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR. Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 27: 503–508, 2006.Crossref | PubMed | ISI | Google Scholar4 Holowatz LA, Thompson-Torgerson CS, Kenney WL. The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol; doi:10.1152/japplphysiol.00858.2007.Link | ISI | Google Scholar5 Khan F, Elhadd TA, Greene SA, Belch JJF. Impaired skin microvascular function in children, adolescents, and young adults with type I diabetes. Diabetes Care 23: 215–220, 2000.Crossref | PubMed | ISI | Google Scholar6 Kruger A, Stewart J, Sahityani R, O'Riodan E, Thompson C, Adler S, Garrick R, Vallance P, Goligorsky MS. Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal failure patients: correlation with cardiovascular risk. Kidney Int 70: 157–164, 2006.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: F. Khan, Univ. Dundee, Dundee, UK (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 105Issue 1July 2008Pages 385-385 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.90314.2008PubMed18641227History Published online 1 July 2008 Published in print 1 July 2008 Metrics

Fixed Combination of Perindopril and Indapamide at Low Dose Improves Endothelial Function in Essential Hypertensive Patients After Acute Administration

Fixed combination of angiotensin-converting enzyme inhibitors (ACEIs) with thiazide-type diuretics at low dose has been used as first-line therapy for the treatment of essential hypertension but their effect on conduit artery endothelial dysfunction remains unknown. Thirteen hypertensive patients were assessed after acute administration of a placebo, fixed combination of perindopril-indapamide at low dose: D1 (2 mg/0.625 mg) and twice this dose: D2 (4 mg/1.25 mg), during a double-blind, randomized, crossover study, and were compared with 13 matched controls. Mean arterial pressure (MAP), radial artery diameter (echotracking) and flow (Doppler) were measured during flow-mediated dilatation (FMD) induced by post-ischemic hyperemia (PIH). PIH was characterized by peak flow and duration of hyperemia (t(1/2)). Endothelium-independent dilatation was assessed by trinitrine. In hypertensive patients compared with controls, basal radial artery diameter and flow, peak flow, and trinitrine responses were similar while MAP was increased (115 +/- 3 vs. 87 +/- 2 mm Hg), t(1/2) was decreased (11.1 +/- 1.9 vs. 17.2 +/- 2.2 s), and FMD was altered (radial diameter increase: 203 +/- 14 vs. 304 +/- 15 microm). Compared with placebo, only D2 decreased MAP (placebo: 115 +/- 3; D1: 112 +/- 4; D2: 103 +/- 4 mm Hg) and increased t(1/2) (placebo: 11.1 +/- 1.9; D1: 8.7 +/- 1.5; D2:13.0 +/- 1.9 s). Conversely, D1 and D2 increased FMD (placebo: 203 +/- 14; D1: 218 +/- 22; D2: 227 +/- 23 microm) with no change in basal diameter and flow, peak flow, and trinitrine responses. These results demonstrate that a fixed combination of ACEI/diuretic at low dose significantly improves radial artery FMD in hypertensive patients and suggest a direct effect on conduit artery endothelium that may contribute to vascular protection.

Impaired Hyperaemic and Rhythmic Vasomotor Response in Type 1 Diabetes Mellitus Patients: A Predictor of Early Peripheral Vascular Disease

The smooth muscle of distal vascular networks exhibits periodical contraction and relaxation known as rhythmical vasomotion. The nature of microvascular vasomotion has been shown to correlate with severity of peripheral vascular disease. We present basal and post-ischaemic hyperaemic laser doppler flowmetry vasomotion in control and type 1 adult diabetic patients. Prospective case control study. Laser Doppler flowmetry was used to measure vasomotion and hyperaemic responses in age and body mass index matched male subjects (25 type 1 Diabetes Mellitus and 13 controls), all with ankle/brachial pressure index (ABPI) >1.0 but <1.2. The frequency of resting vasomotion was raised in diabetics compared to controls 8 (5-9)min(-1) vs. 5 (4-6)min(-1) (median (range); p<0.0001). The post ischaemic hyperaemia response was significantly higher in the diabetic group compared to the controls 11 (7-12)min(-1) vs. 6 (5-7)min(-1) (median (range); p<0.05). Post ischaemic hyperaemic flux (expressed as percent increase from resting) was significantly lower in the diabetic group compared to controls (234+/-62 vs. 453+/-155%, p<0.01). The time to achieve peak post ischaemic response was also significantly increased in the diabetic group compared to control: 21.4+/-0.4 vs. 12.8+/-5.4sec (mean+/-SD, p<0.05). Vasomotion frequency and its change during hyperaemic insult is significantly different in Type 1 Diabetes Mellitus subjects compared to controls. The results are similar to patients with macrovascular atherosclerosis. Long term studies of these groups of patients will be required to determine the significance of these findings and whether these changes could be used as a non invasive screening test to predict peripheral early vascular disease in type 1 diabetic patients.

Effect of graded leg cycling on postischaemic forearm blood flow in healthy subjects

This study assessed in healthy subjects, the effect of leg cycling on the forearm vascular responses to ischaemia to confirm previous results showing that exercise-induced sympathetic activation during leg cycling reduced postischaemic forearm hyperaemia. Seven young healthy subjects performed two bouts of cycling exercises at 50% and 80% of their maximal aerobic capacity (Ex(50), Ex(80) respectively) during which forearm arterial blood flow was successively occluded for 40, 90 and 180 s. Control forearm blood flow (FBF) and postischaemic forearm blood flow (pi-FBF) measured at the release of arterial occlusions were assessed using plethysmography. Digital arterial pressure was continuously monitored allowing calculation of control and postischaemic forearm conductance (FC and pi-FC respectively). At rest, pi-FBF increased with the duration of ischaemia (5 +/- 1, 19 +/- 3, 29 +/- 3, 31 +/- 4 ml min(-1) 100 ml(-1) after 0, 40, 90 and 180 s of ischaemia respectively). During Ex(50), FBF and pi-FBF did not change significantly although pi-FC was significantly reduced (Deltapi-FC = -39%, -33%, -27% for 40, 90, 180 s of ischaemia respectively). During Ex(80), there was a further dramatic decrease in pi-FC (-53%, -66%, -62% from rest) and pi-FBF were largely blunted (13 +/- 4 versus 19 +/- 3, 14 +/- 4 versus 29 +/- 3, 17 +/- 5 versus 31 +/- 4 ml min(-1) 100 ml(-1)). These results demonstrated that forearm responses to ischaemia depended on leg activities. It was suggested that exercise-induced sympathetic activation may have interfered on local vasodilatation because of ischaemia.

Blunted post-ischemic increase of the endothelial skin blood flowmotion component as early sign of endothelial dysfunction in chronic kidney disease patients

With the aim to investigate microvascular endothelial function in chronic kidney disease (CKD) patients on conservative treatment, skin blood flowmotion (SBF) was explored by spectral Fourier analysis of skin forearm laser Doppler tracing, registered before and following forearm ischemia in 32 III to V stage CKD patients (23 males, mean age: 52 ± 12 years), without diabetes or cardiovascular disease, and in 32 age and sex matched healthy subjects. The power spectral density (PSD) of the 0.009–1.6 Hz total spectrum SBF, as well as of five sub-intervals, each of them related to endothelial (0.009–0.02 Hz), sympathetic (0.02-0.06 Hz), myogenic (0.06–0.2 Hz), respiratory (0.2–0.6 Hz) or cardiac (0.6–1.6 Hz) activity, was measured in PU 2/Hz (PU=perfusion unit; 1 PU = 10 mV). Under basal conditions CKD patients and controls did not differ in skin perfusion or in PSD of total spectrum SBF, as well as of each of the five subintervals considered. No substantial difference was also observed in skin post-ischemic hyperemia between patients and controls. A significant post-ischemic increase in the normalized value of endothelial sub-interval was observed in controls ( p<0.05, GLM ANOVA analysis of variance), but not in CKD patients. A lower per cent increase in absolute PSD value of endothelial sub-interval was also observed in CKD patients compared to controls (185 ± 98 % vs 279 ± 243 %, p<0.05). The post-ischemic per cent increase in absolute PSD of endothelial sub-interval was negatively related to the systolic blood pressure ( r = − 0.45, p<0.01), to the mean arterial blood pressure ( r = − 0.40, p<0.05) and to the PTH serum levels ( r = − 0.38, p<0.05) in CKD patients. The blunted post-ischemic increase of the endothelial SBF sub-interval can be considered an early sign of microvascular endothelial dysfunction in the CKD studied patients. Arterial hypertension seems to be the main factor related to this SBF abnormality, together with the hormonal CKD related abnormalities.

Cutaneous microcirculatory function predicts the responsiveness to tadalafil in patients with erectile dysfunction and coronary artery disease

Despite the proven clinical efficacy of phosphodiesterase inhibitors in the treatment of erectile dysfunction (ED), some patients do not respond to the medication. By means of nailfold capillary microscopy in patients with concomitant coronary artery disease (CAD) and ED, it was evaluated whether the extent of microvascular dysregulation predicts the responsiveness to tadalafil (TAD) in terms of erectile function. The ED of each patient was assessed by the International Index of Erectile Function (IIEF). Patients presenting both, documented CAD and ED, showed a significantly reduced capillary red blood cell velocity (v(RBC)) at rest and after 3 min of ischemia compared with age-matched controls. At 2 h after intake of 20 mg of TAD, a significant increase of v(RBC) at rest as well as during postischemic hyperemia was found. Patients who reported no improvement of their ED after the use of TAD demonstrated no changes in the duration of postischemic (DpH) hyperemia, or even a reduction of the DpH. The majority of the patients, who reported at least one successful sexual intercourse due to TAD, had a prolongation of DpH. We conclude that assessment of microvascular regulation by nailfold capillary microscopy can predict the probability of a treatment failure with phosphodiesterase inhibitors in patients with ED. Moreover, as endothelial dysfunction is the common underlying pathophysiological process of ED and cardiovascular diseases, the test may help to identify patients at risk for the development of atherosclerosis and following cardiovascular events.

Post-ischaemic peak flow and myogenic flowmotion component are independent variables for skin post-ischaemic reactive hyperaemia in healthy subjects

The aim of this study was to clarify whether the post-ischaemic amplification of skin blood flowmotion (SBF) influences the extent of skin post-ischaemic hyperaemia. Forearm skin perfusion was measured by means of laser Doppler flowmetry (LDF) and forearm SBF was examined using Fourier analysis of LDF signal, under basal conditions and following forearm ischaemia in 50 healthy subjects. Power spectral density (PSD) of SBF total spectrum (0.009 – 1.6 Hz), as well of the frequency intervals (FI) related to endothelial (0.009–0.02 Hz), sympathetic (0.02–0.06 Hz), myogenic (0.06–0.2 Hz), respiratory (0.2 – 0.6 Hz) and cardiac (0.6 – 1.6 Hz) activity was measured in PU 2 (LDF perfusion unit)/Hz. Multiple regression analysis evaluated whether post-ischaemic peak-flow, as an indicator of shear stress, or post-ischaemic SBF independently affected the post-peak-flow hyperaemia calculated as corrected area under the LDF curve (C-AUC). Following ischaemia, we observed a statically significant increase in skin perfusion (from basal of 11.7 ± 5.8 PU to peak flow of 62.3 ± 41.4 PU, p < 0.0000005) and in PSD of SBF total spectrum ( p < 0.01) as well of the different FI considered ( p < 0.005 for the endothelial and myogenic FI; p < 0.05 for the sympathetic, respiratory and cardiac FI) compared to baseline. Multiple regression analysis showed that peak flow and post-ischaemic SBF component of myogenic origin were significant independent variables for the C-AUC ( p = 0.0000001 and p = 0.009, respectively). These findings suggest that not only increased shear stress but also post-ischaemic amplification of myogenic SBF component independently contributes to the more prolonged phase of post-ischaemic skin re-perfusion in healthy subjects.

Detailed exploration of the endothelium: parameterization of flow-mediated dilation through principal component analysis

Endothelial dysfunction is associated with cardiovascular diseases and their risk factors (CVRF), and flow-mediated dilation (FMD) is increasingly used to explore it. In this test, artery diameter changes after post-ischaemic hyperaemia are classically quantified using maximum peak vasodilation (FMDc). To obtain more detailed descriptors of FMD we applied principal component analysis (PCA) to diameter–time curves (absolute), vasodilation–time curves (relative) and blood-velocity–time curves. Furthermore, combined PCA of vessel size and blood-velocity curves allowed exploring links between flow and dilation. Vessel diameter data for PCA (post-ischaemic: 140 s) were acquired from brachial ultrasound image sequences of 173 healthy male subjects using a computerized technique previously reported by our team based on image registration (Frangi et al 2003 IEEE Trans. Med. Imaging 22 1458). PCA provides a set of axes (called eigenmodes) that captures the underlying variation present in a database of waveforms so that the first few eigenmodes retain most of the variation. These eigenmodes can be used to synthesize each waveform analysed by means of only a few parameters, as well as potentially any signal of the same type derived from tests of new patients. The eigenmodes obtained seemed related to visual features of the waveform of the FMD process. Subsequently, we used eigenmodes to parameterize our data. Most of the main parameters (13 out of 15) correlated with FMDc. Furthermore, not all parameters correlated with the same CVRF tested, that is, serum lipids (i.e., high LDL-c associated with slow vessel return to a baseline, while low HDL-c associated with a lower vasodilation in response to similar velocity stimulus), thus suggesting that this parameterization allows a more detailed and factored description of the process than FMDc.

The ADP receptor P2Y1 mediates t-PA release in pigs during cardiac ischemia

The endothelial ADP receptor P2Y(1) is responsible for a large part of the reactive hyperemia following cardiac ischemia. Tissue plasminogen activator (t-PA) increases during reactive hyperemia. We postulated that the release of t-PA during reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor. t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus in a porcine model. The stable ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery through the tip of a coronary angioplasty balloon. In separate pigs the coronary artery was occluded with the balloon for 10 min. During the first and tenth minute of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion in 8 pigs, 10 pigs were used as controls. 2-MeSADP increased levels of t-PA in the coronary sinus, which could be significantly inhibited by co-infusion with MRS2179. During cardiac ischemia and reperfusion, t-PA increased significantly, an effect that could be significantly inhibited by MRS2179. Intra coronary administered MRS2179, a selective P2Y(1) receptor blocker, significantly reduces the increased levels of t-PA caused by both 2-MeSADP and cardiac ischemia in coronary arteries. Thus, ADP acting on the endothelial P2Y(1) receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP. Abbreviated Abstract We postulated that the release of t-PA during post ischemic reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor in a porcine model. The ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a the P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery. In separate pigs the coronary artery was occluded for ten min. During the first and tenth min of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion. t-PA was measured in peripheral arterial blood and also from the Coronary Sinus. We found that levels of t-PA in the blood from the coronary Sinus increased during infusion with 2-MeSADP as well as during ischemia and reperfusion. In pigs treated with MRS2179 levels of t-PA in the Coronary Sinus were significantly reduced during both coinfusion with 2-MeSADP and during ischemia/reperfusion. Thus, ADP acting on the endothelial P2Y(1) M receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP.

Water immersion in preeclampsia

Preeclampsia is associated with profound vasoconstriction in most organ systems and reduced plasma volume. Because water immersion produces a marked central redistribution of blood volume and suppresses the renin-angiotensin system response and sympathetic activity, we hypothesized that water immersion might be useful in the treatment of preeclampsia. The effects of thermoneutral water immersion for 3 hours on central and peripheral hemodynamics were evaluated in 7 preeclamptic patients, 7 normal pregnant control patients, and 7 nonpregnant women. Finger plethysmography was used to determine hemodynamic measurements (cardiac output and total peripheral resistance), and forearm blood flow was measured by strain gauge plethysmography. Postischemic hyperemia was used to determine endothelium-dependent vasodilation. Analysis was by analysis of variance for repeated measurements. During water immersion cardiac output increased while diastolic blood pressure and heart rate decreased, although systolic blood pressure remained unchanged in each group. Forearm blood flow increased significantly in the normal pregnant and preeclamptic subjects. Total peripheral resistance decreased in all groups, but values in preeclamptic patients remained above those of normotensive pregnant women. Water immersion had no effect on endothelium-dependent vasodilation in the preeclamptic group, and most hemodynamic changes that were observed reversed to baseline within 2 hours of completion of the procedure. Although water immersion results in hemodynamic alterations in a manner that is theoretically therapeutic for women with preeclampsia, the effect was limited and short-lived. In addition water immersion had no effect on endothelium-dependent vasodilation in women with preeclampsia. The therapeutic potential for water immersion in preeclampsia appears to be limited.

Flow-mediated vasodilatation of carotid and branchial arteries in healthy subjects and in lacunar stroke patients

The vasodilatory response of arteries can be measured by ultrasound, and it was previously shown that brachial artery (BA) vasodilatation can be tested by postischemic hyperemia. In the current study, the primary objective was to determine if hypercapnia can be used to assess common carotid artery (CCA) flow-mediated vasodilatation (FMVD) in healthy subjects. Secondary objectives were to investigate CCA-FMVD in lacunar patients and whether BA-FMVD parallels CCA-FMVD. We used ultrasound to measure flow-mediated and nitroglycerin (NTG)-mediated vasodilatation in the CCA and BA in 20 healthy subjects and in 17 lacunar patients. BA-FMVD was induced by a postischemic maneuver. For the CCA, FMVD was induced by hypercapnia from CO 2-enriched inhalation. BA and CCA vasodilatation were measured after sublingual NTG administration. BA dilated significantly in healthy (6.7%) and stroke subjects (4.2%) under postischemic conditions. The CCA dilated significantly after CO 2 inhalation (11.4% in healthy subjects and 4% in lacunar patients) and NTG administration (18% in healthy subjects and 10.6% in lacunar patients). Surprisingly, there was a strong negative correlation between CCA- and BA-FMVD in healthy subjects. CCA vasodilatation induced by CO 2 inhalation and NTG administration can be measured. The strong negative correlation between CCA- and BA-FMVD suggests that there could be different mechanisms of vasodilatation. (E-mail: philippa.lavallee@bch.aphp.fr)

Spectral analysis of laser Doppler skin blood flow oscillations in human essential arterial hypertension

The aim of this study was to investigate whether human essential arterial hypertension (EHT) is associated with modification of the skin blood flowmotion (SBF), which could be a sign of skin microcirculatory impairment. Forearm skin perfusion was measured by laser Doppler flowmetry (LDF) in conventional perfusion units (PU) before and after ischemia in 20 middle-age newly diagnosed EHT untreated patients, in 20 middle-age long standing EHT treated patients and in 30 age and sex matched healthy normotensive subjects (NS). Power spectral density (PSD) of SBF total spectrum (0.009–1.6 Hz), as well of five different frequency intervals (FI), each of them related to endothelial (0.009–0.02 Hz), sympathetic (0.02–0.06 Hz), myogenic (0.06–0.2 Hz), respiratory (0.2–0.6) or cardiac (0.6–1.6) activity, was also measured in PU 2/Hz before and after ishemia, using Fourier analysis of LDF signal. The three studied groups did not differ in basal and post-ischemic skin perfusion or in basal SBF parameters considered. However, while a significant post-ischemic increase in PSD of total spectrum SBF ( P < 0.001) and of its different FI, with the only exception of respiratory FI, was observed in NS, a significsnt post-ischemic increase in PSD was observed only for total spectrum ( P < 0.01) and for endothelial FI ( P < 0.001) in newly diagnosed EHT patients and only for myogenic FI ( P < 0.05) in long standing EHT patients. These findings suggest that the mechanisms which mediate the post-ischemic increment of SBF are perturbed earlier in human EHT than the mechanisms which mediate the skin post-ischemic hyperaemia. The same findings also suggest that the impairment of the endothelial mechanism involved in SBF control occurs by the time in the course of EHT.