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The endovascular treatment of carotid atherosclerosis with carotid artery stenting (CAS) remains controversial. Carotid endarterectomy remains the benchmark in terms of procedural mortality and morbidity. At present, there are no consensus Australasian guidelines for the safe performance of CAS.We applied a modified Delphi consensus method of iterative consultation between the College representatives on the Carotid Stenting Guidelines Committee (CSGC).Selection of patients suitable for CAS needs careful consideration of clinical and patho-anatomical criteria and cannot be directly extrapolated from clinical indicators for carotid endarterectomy (CEA). Randomized controlled trials (including pooled analyses of results) comparing CAS with CEA for treatment of symptomatic stenosis have demonstrated that CAS is more hazardous than CEA. On current evidence, the CGSC therefore recommends that CAS should not be performed in the majority of patients requiring carotid revascularisation. The evidence for CAS in patients with symptomatic severe carotid stenosis who are considered medically high risk is weak, and there is currently no evidence to support CAS as a treatment for asymptomatic carotid stenosis. The use of distal protection devices during CAS remains controversial with increased risk of clinically silent stroke. The knowledge requirements for the safe performance of CAS include an understanding of the evidence base from randomized controlled trials, carotid and aortic arch anatomy and pathology, clinical stroke syndromes, the differing treatment options for stroke and carotid atherosclerosis, and recognition and management of periprocedural complications. It is critical that all patients being considered for a carotid intervention have adequate pre-procedural neuro-imaging and an independent, standardized neurological assessment before and after the procedure. Maintenance of proficiency in CAS requires active involvement in surgical/endovascular audit and continuing medical education programs. These standards should apply in the public and private health care settings.These guidelines represent the consensus of an inter-collegiate committee in order to direct appropriate patient selection and the range of cognitive and technical requirements to perform CAS. Advances in endovascular technologies and the results of randomized controlled trials will guide future revisions of these guidelines.

Risk stratification is often used to determine the need and priority for coronary angiography. We investigated the contemporary value of Framingham and SCORE risk models, individual risk factors, B-type natriuretic peptide and high-sensitivity C-reactive protein (hs-CRP) in the current era of intensive risk management.Coronary artery disease (CAD) was obstructive (or=50% stenosis) in 328 of 539 patients referred for elective diagnostic coronary angiography (61%). Lower rates of smoking, more exercise and lower cholesterol were noted in those with angiographic CAD, compatible with risk factor modification in these patients. Framingham and SCORE were associated with CAD both in patients with and without prior cardiovascular disease (CVD). In multivariate analysis only age, male sex, diabetes, chest pain and prior CVD were independent predictors of CAD; odds ratio 1.74 per 10 years (95% confidence interval: 1.34-2.27), 5.48 (3.36-8.92), 2.57 (1.44-4.60), 1.69 (1.02-2.81) and 2.61 (1.65-4.12), respectively. Classification of disease was not improved by B-type natriuretic peptide or hs-CRP when added to conventional risk factors, although the latter seems to have value in patients without earlier CVD and low-density lipoprotein-cholesterol of less than 3.4 mmol/l; the adjusted odds ratio for hs-CRPor=2 mg/l in this sub-group was 2.49 (1.12-5.51, P=0.024).Framingham and SCORE risk models can be used in clinical practice to predict angiographic coronary disease although risk factor modification limits the predictive value of smoking, blood pressure, lipid profiles and cardiac biomarkers.

Tako-tsubo cardiomyopathy is an increasingly recognised phenomenon characterised by chest pain, ECG abnormalities, cardiac biomarker elevation and transient left ventricular dysfunction without significant coronary artery obstruction.To report the clinical and echocardiographic characteristics from a large single-centre Australian series of patients with Tako-tsubo syndrome.We prospectively collected data on 23 consecutive patients presenting between November 2005 and November 2007. Baseline demographics, ECG, echocardiography and coronary angiography were performed on nearly all patients.All patients presented with chest pain; 87% were female. Various stressors were noted and cardiac Troponin-T was elevated in 91% of patients. All patients had non-obstructive coronary disease at angiography. 19/23 patients had initial and subsequent echocardiography. Mean ejection fraction was 50% at baseline and 64% at follow-up (p0.0001). Right ventricular dysfunction was present in eight, dynamic left ventricular outflow tract obstruction in two, diastolic dysfunction in seven and two patients had the mid-cavity variant.This large prospective single-centre Australian series of Tako-tsubo syndrome is in concert with previous published series. Complete recovery of left ventricular function on echocardiographic follow-up was typical. Although its pathogenesis remains unclear, early distinction from acute coronary syndromes is important and the prognosis is reassuringly good.

Although post-mortem studies would suggest that cardiac metastases occur frequently, many of these metastases remain clinically silent. However, symptomatic lesions may also remain unrecognized due to overshadowing by other symptoms of the primary malignancy. Patients undergoing treatment for cancer are not routinely screened using echocardiography, unless their chemotherapeutic regimen includes cardiotoxic agents. The current era of research and development of targeted biological agents (such as trastuzumab and epidermal growth factor receptor inhibitors) for cancer may lead to prolonged survival of oncology patients. In future, metastases that were once rare may become increasingly recognized as these new treatments augment the natural history of the disease. There have been several case reports of small, asymptomatic left ventricular metastases, but clinically significant ventricular metastases are very rare. There are no reports in the current literature of a symptomatic ventricular metastasis, occurring in the absence of other metastatic disease. We report an unusual case of a large solitary ventricular metastasis, leading to left ventricular outflow tract obstruction and haemodynamic compromise. Echocardiographic imaging led to the diagnosis of a recurrence of soft-tissue fibrosarcoma 9 years after original resection.

Purpose: To report a case of carotid artery stenting for asymptomatic carotid restenosis performed in an outpatient setting. Methods and Results: A 68-year-old man with right carotid restenosis after repeat carotid endarterectomy underwent carotid angioplasty and stenting on an ambulatory basis. The procedure to implant a Smart stent required 45 minutes; the femoral access site was closed with a puncture closure device. The patient experienced no sequelae to this procedure and is well 6 months after treatment. Conclusions: Outpatient delivery of percutaneous carotid stenting may be feasible in appropriately selected patients.

Renal impairment (RI) is known to be an independent risk factor for the progression of cardiovascular disease. Its impact, however, on the outcomes in patients undergoing percutaneous coronary intervention (PCI) especially in the era of drug-eluting stents (DES) is not well known. We analysed data from patients undergoing PCI from April 1, 2004, to September 30, 2006, who were part of the Melbourne Interventional Group registry. RI was defined as an estimated glomerular filtration rate (eGFR), calculated using Cockcroft-Gault formula, of

a Department of Cardiology, Eastern Health, 8 Arnold Street, Box Hill, Victoria 3128, Australia b Monash University, Eastern Health Clinical School, 5 Arnold Street, Box Hill, Victoria 3128, Australia c Department of Obstetrics and Gynaecology, Eastern Health, 8 Arnold Street, Box Hill, Victoria 3128, Australia d Department of Cardiology, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia

J. Yeoh1,∗, N. Andrianopoulos 2, V. Chand2, B. Yan2,3, D. Clark4, S. Duffy 5, A. Brennan2, G. New6, D. Eccleston1, M. Sebastian7, C. Reid2, M. Yudi 4, W. Wilson1, A. Ajani 1 1 Royal Melbourne Hospital, Melbourne, VIC, Australia 2 Monash University CCRET Centre of Cardiovascular Research & Education in Therapeutics, Melbourne, VIC, Australia 3 Chinese University of Hong Kong, Department of Medicine & Therapeutics, Hong Kong 4 Austin and Repatriation Medical Centre, Melbourne, VIC, Australia 5 Alfred Hospital, Melbourne, VIC, Australia 6 Box Hill Hospital, Box Hill, VIC, Australia 7 University Hospital, Geelong, VIC, Australia

The purpose of the study was to examine the safety and efficacy of 17-beta-estradiol-eluting stent implantation on coronary de novo lesions.Recent animal data indicate that local delivery of 17-beta-estradiol promotes re-endothelialization, inhibits cell migration and proliferation, and prevents restenosis.A total of 30 consecutive patients underwent 17-beta-estradiol-eluting BiodVysio (Biocompatibles Ltd., London, United Kingdom) stent implantation for the treatment of coronary de novo lesions. Clinical, angiographic, and intravascular ultrasound (IVUS) analysis was performed at six-month follow-up.All stents were successfully deployed and patients were discharged home without clinical events. A total of two patients exceeded 50% intra-stent narrowing by angiography, whereas no patients experienced edge restenosis. One patient had focal intra-stent restenosis (60% diameter stenosis) with no symptoms and negative stress test, whereas the other patient had diffuse restenosis, requiring target vessel revascularization. No other patient experienced any major adverse cardiac event. Follow-up IVUS revealed a neointimal hyperplasia volume of 32.3 +/- 16.4 mm(3), whereas the stent volume was 143.7 +/- 43.7 mm(3), resulting in a neointimal volume obstruction of 23.5 +/- 12.5%. None of the patients hador =50% volume obstruction by IVUS.Implantation of 17-beta-estradiol-eluted BiodVysio stents appears feasible and safe, showing low rates of binary restenosis and revascularization. These results warrant further confirmation with a large, randomized multicenter trial.

Previous studies investigating the effect of gender on outcomes after percutaneous coronary intervention (PCI) have reported that women have higher in-hospital adverse event rates and a higher mortality rate than men. 1,2 This has been attributed to both the smaller size of women 3,4 and to the older age of women at the time of PCI. Older populations who undergo PCI are associated with increased rates of comorbid disease and an increased cardiac risk factor profi le. 5 Because women tend to have smaller coronary arteries than men, we hypothesized that the adverse outcomes may be partly due to the smaller coronary artery diameters. To test this hypothesis we compared men and women with small coronary arteries to evaluate whether gender remained a determinant

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in-stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17β-estradiol–eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low-dose, or high-dose 17β-estradiol–eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high-dose stents compared with control stents (2.54 ± 1.0 vs. 4.13 ± 1.1 mm2, for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17β-estradiol–eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in-stent restenosis. Estrogen-coated stents may have a potential benefit in the prevention and treatment of in-stent restenosis. Cathet Cardiovasc Intervent 2002;57:266–271. © 2002 Wiley-Liss, Inc.

Object. Carotid artery (CA) angioplasty with stent placement has been proposed as an alternative technique for revascularization in cases of CA stenosis. In this report the authors review the results of a multicenter Phase I study in which they evaluated the safety and feasibility of using a new self-expanding nitinol stent, the Bard Memotherm, to treat CA stenosis. Methods. Enrollment was limited to patients in whom there was either 50% or greater symptomatic or 70% or greater asymptomatic stenosis of the internal CA. The primary endpoint was a technically successful implantation procedure (delivery of the stent to the target site and retrieval of the delivery device), resulting in less than 30% residual stenosis demonstrated on immediate postprocedure (control) angiograms, and no incidence of mortality, ipsilateral stroke, Q-wave myocardial infarction, or other major cardiovascular events immediately after or within 30 days following the procedure. Stent placement was attempted for 73 lesions in 71 patients (mean age 71.3 ± 8.5 years), 43 (61%) of whom were men. The mean degree of stenosis was 82.6 ± 9%. The stenosis was symptomatic in 27 (37%) and asymptomatic in 46 (63%) of 73 lesions. In four procedures the stent could not be delivered or released. The mean residual stenosis observed on angiograms was 3.8 ± 6.9% in the 69 lesions treated with the Bard Memotherm stent; residual stenosis was greater than 30% in one of the 69 procedures. The primary endpoint was achieved in 65 (89%) of the 73 procedures. One patient experienced a major ischemic stroke and another patient died of intracerebral hemorrhage. The overall 1-month stroke rate was 2.7% for 73 attempted procedures. One patient died of pneumonia and acute respiratory distress syndrome, which occurred 3 weeks after the stent procedure and was unrelated to the procedure. Conclusions. The Memotherm stent can be used to treat patients with CA stenosis and is associated with a low periprocedure complication rate. Long-term follow-up studies are underway to determine the impact of stent placement on the risk of ipsilateral ischemic events.

Purpose: To document the feasibility of brachial artery access for carotid stenting with distal-balloon protection of the internal carotid artery (ICA). Technique: Via percutaneous access to the brachial artery, a large double-curve catheter is advanced into the aortic arch over a hydrophilic guidewire to cannulate the left common carotid artery. Following sheath exchange, a GuardWire distal-protection balloon is positioned within the left ICA distal to the stenosis. The lesion is dilated, followed by deployment and dilation of a self-expanding stent. Transcranial Doppler monitoring shows only scarce microembolic signals during the procedure. Conclusions: Carotid stenting with distal balloon protection via the brachial artery appears feasible as an alternative to standard femoral access.

O ST E R A B ST R A C T S Basal characteristics, group A and B, respectively n (%): age 61,6 11,2 vs 59 14,5; masculine sex 28(85) vs 18(86); diabetes 9(27) vs 7(33); prior infarct 7(21) vs 5(24); prior revascularization 5(15) vs 3(14); LVEF 39,6 16 vs 46,5 21; anterior infarct 10(30) vs 9(43); anterior descending artery affected 18(54) vs 19(90); presence of collateral circulation 10(30) vs 3(14); use of IABP 11(33) vs 3(14); use of GP IIbIIIa 10(30) vs 2(9); use of tromboaspiration 3(9) vs 2(9); millimeters of stent implanted 46 32 vs 71,5 32; implant of drug eluting stents 5(15) vs 8(38); dye material 263,1 121 vs 305,2 93 ml; time of fluoroscopy 25,3 21,5 vs 23,7 16,4 minutes. Results: Group A and B n (%), respectively: mortality intrahospitalary 7(21) vs 2(9); reinfarct 0 vs 2 (9); early occlusion coronary 1(3) vs 2(9); renal insufficiency pos PCI 0 vs 1(5). In the average follow-up to 20 months of the 96% population there demonstrated, group A and B n (%), respectively: total mortality to 6 months 10(30) vs 4(19); cardiac mortality to 6 months 10(30) vs 2(9) p1⁄40,05; reinfarct 1(4) vs 0; need of coronary revascularization 7(27) vs 1(5) and events combined of cardiac death, reinfarct and new revascularization 18(54) vs 5(21) p1⁄40,02. Conclusion: The complete coronary revascularization in the same session in STEMI and cardiac failure and MVD, demonstrated to be more favorable in terms of total mortality and adverse major combined events that the PCI only of the culprit vessel. Disclosure of Interest: None Declared

R A L A B ST R who discontinued on the day of surgery. Fifty-one percent of current smokers resumed smoking in the year after surgery, with 80% of these resuming within 2 weeks. Conclusion: The timing of smoking cessation prior to surgery does not impact on cardiovascular, major medical outcomes or death in the perioperative period. Therefore, physicians seeing a patient even within 8 weeks of surgery should have no reservations about encouraging abstinence. Resumption of smoking after surgery is common and indicates that there are opportunities to encourage more sustained abstinence. Disclosure of Interest: None Declared A C T S O063

O ST E R A B ST R A C T S care in the delivery of medical interventions. Cardiovascular interventions including Percutaneous Coronary Intervention (PCI) are high cost activities that have become widely adopted across the region. Registries in individual institutions and countries are valuable, however, the establishment of a collaboration across the Asia Pacific Region to inform on variations in patient and procedural characteristics and associated clinical outcomes would enable regional benchmarking of quality performance. Objectives: An inaugural Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Collaboration meeting was held in Singapore in July 2012 with 27 hospital representatives attending. The proposed aims of the collaboration included a) to identify the characteristics of patients undergoing PCI across the Asia Pacific region, b) to report on outcomes of patients undergoing PCI across the Asia Pacific Region, c) to develop an appropriate ethnic specific risk adjustment model for patients undergoing PCI across the Asia Pacific Region and d) to establish a registry framework for research, education and training in the area of cardiovascular interventions across the Asia Pacific Region. Methods: Following agreement, common fields were identified from data sets of existing local registries and an initial report on patient characteristics across the region was proposed. Descriptive characteristics of patients undergoing PCI over a 12 month period were collated and reported. Results: In every country, males predominated PCI activity. Subjects were older and had higher rates of family history of cardiovascular disease in Australia, while Asian subjects had higher rates of diabetes, dyslipidaemia and renal failure. STEMI presentation was higher in Australia than in Asia and Drug eluting stent use was higher in Asia. Procedural success rates were similar across the region (>95%). Conclusion: Resolution of cross border individual patient data transfer and collation of pooled data in a central registry is ongoing. Patient characteristics differ across countries in Asia in terms of pre-procedural risk factors and clinical presentation, however procedural success was similar. Impact on patient outcomes at 30 days and longer term outcomes are being assessed. Disclosure of Interest: None Declared

Background The distal-balloon protection system is being evaluated for its efficacy in preventing embolic neurological events during carotid stenting (CAS). We sought to determine the effect of this system on the frequency of Doppler-detected microembolic signals (MES) during CAS. Methods and Results Using transcranial Doppler, we compared the frequency of MES during CAS in 2 groups: 39 patients without distal protection and 37 who used the distal-balloon protection system (GuardWire). There were no significant differences in the clinical or angiographic characteristics between the 2 groups. Three phases with increased MES counts were identified during unprotected CAS; these were stent deployment, predilation, and postdilation (75±57, 32±36, and 27±25 METS, respectively). The distal-balloon protection significantly reduced the frequency of MES during CAS (MES counts: 164±108 in the control versus 68±83 in the protection group; P =0.002), particularly during these 3 phases. MES in the protection group were detected predominantly during sheath placement, guidewire manipulation, and distal-balloon deflation. Conclusion Three phases with increased MES counts were identified during unprotected CAS (eg, stent deployment, predilation, and postdilation). The distal-balloon protection system significantly reduced the frequency of MES during CAS, particularly during these 3 phases.

Purpose: To describe a potential route for embolization to the middle cerebral artery (MCA) during carotid stenting with the distal balloon protection system. Case Report: An 82-year-old man with symptomatic severe carotid artery stenosis underwent elective carotid stenting with distal-balloon protection. Despite complete occlusion of the distal internal carotid artery, frequent emboli were detected in the ipsilateral MCA by transcranial Doppler (TCD) during the procedure. Intracranial angiography, performed during the distal-balloon protection, revealed filling of the MCA through collaterals from the ipsilateral external carotid artery. The procedure was successfully completed without complications. The patient remains asymptomatic at 6 months. Conclusions: During carotid stenting with distal-balloon protection, asymptomatic embolization into the ipsilateral MCA may occur through collateral circulation. The clinical significance of these emboli is uncertain.

1. The aim of the present study was to determine whether anti-oxidant therapy with vitamin E and/or cholesterol-lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia. 2. Endothelium-dependent and -independent, nitric oxide (NO)-mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti-oxidant or cholesterol- lowering therapy, although these treatments may be synergistic. 3. We compared FBF at rest, in response to isotonic exercise, the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in 26 young, otherwise healthy volunteers (mean (+/-SD) age 29+/-7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double-blinded in a 2 x 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography. 4. Vitamin E therapy increased plasma alpha-tocopherol from 39.5+/-9.6 to 75.7+/-33.8 micromol/L (P < 0.001). Simvastatin reduced total cholesterol from 6.9+/-1.7 to 4.9+/-0.8 mmol/L and low- density lipoprotein (LDL) from 4.8+/-1.7 to 3.0+/-0.7 mmol/L (both P < 0.001), although total and LDL-cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1+/-0.3 to 2.4+/-0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1+/-4.2 to 36.1+/-3.4 units (P = 0.01), but the reduction in resting FBF with L-NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E-simvastatin groups. NG-Monomethyl-L-arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment. 5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO-dependent pathways. Metabolic vasodilation and responses to the NO-mediated vasodilators ACh and SNP were not favourably affected by anti-oxidant or cholesterol-lowering therapy, either alone or in combination.

Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia.We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-L-arginine (L-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n = 20) and control (n = 20) subjects were age- and gender-matched.Total cholesterol (6.9 +/- 0.3 vs. 4.6 +/- 0.1 mmol/l, P0.0001), low density lipoprotein (4.9 +/- 0.4 vs. 2.7 +/- 0.1 mmol/l, P0.001) and triglyceride (1.3 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P = 0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1 +/- 1.9 vs. 17.6 +/- 2.2 ml/100 ml/min, P = 0.03), and reduced the peak response to sodium nitroprusside (6.0 +/- 0.4 vs. 8.1 +/- 0.6 ml/100 ml/min, P0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1 +/- 1.0 vs. 13.2 +/- 1.0 ml/100 ml/min, P = 1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by L-NMMA to a similar degree (by 33% vs. 40%, P = 0.17) in both groups. Although L-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P = 0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups.Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation.

We have previously shown that chronic estrogen therapy improves endothelium-dependent vasodilation in the resistance vessels of biological males. Whether this is nitric oxide (NO) mediated and whether estrogen improves metabolic vasodilation is unknown. Resting forearm blood flow (FBF), ACh-induced vasodilation, and functional hyperemic blood flow (exercise) were assessed before and after the inhibition of NO with N G-monomethyl-l-arginine (l-NMMA) in 15 male-to-female transsexuals prescribed estrogen and in 14 age-matched males. Resting FBF was similar in the two groups and was similarly ( P = 0.44) but significantly reduced by 48% after infusion ofl-NMMA ( P < 0.0001). The ACh dose-response relationship was shifted upward and to the left in the transsexual compared with the male group ( P < 0.01). After the inhibition of NO, however, the difference in the ACh dose-response curve between the two groups was abolished ( P= 0.15). Peak functional hyperemic blood flow was similar for the two groups ( P = 0.94).l-NMMA produced a significant ( P < 0.01) but similar ( P = 0.64) reduction in peak hyperemia in the two groups. The volume of blood repaid to the forearm 1 and 5 min after exercise was also reduced by l-NMMA ( P < 0.0001); however, there were no differences between the two groups. This suggests that ACh-mediated NO-dependent vasodilation may be more sensitive to the effects of chronic estrogen than exercise-induced vasodilation. Long-term estrogen does not appear to improve exercise-induced metabolic vasodilation in biological males, despite the fact that NO contributes to this process.

Although many factors are thought to contribute to the regulation of metabolic vasodilation in skeletal muscle vasculature, recent interest has focused on the role of the endothelium. We examined the relative roles of nitric oxide (NO) and of vasodilator prostanoids in the control of metabolically induced functional hyperemia in the forearm of humans. In 43 healthy volunteers [24 ± 5 (SD) yr] we assessed resting and functional hyperemic blood flow (FHBF) in response to 2 min of isotonic forearm exercise before and after inhibition of NO and/or vasodilator prostanoid production with intra-arterial N G-monomethyl-l-arginine (l-NMMA, 2 mg/min) and aspirin (ASA, 3 mg/min), respectively. Blood flow was measured using venous occlusion plethysmography.l-NMMA and ASA decreased resting forearm blood flow by 42% ( P < 0.0001) and 23% ( P < 0.0001), respectively, whereas infusion of ASA followed byl-NMMA reduced flow by a further 24% ( P < 0.05).l-NMMA reduced peak FHBF by 18% [from 13.9 ± 1.0 to 11.4 ± 1.1 (SE) ml ⋅ 100 ml forearm−1 ⋅ min−1, P = 0.003] and the volume “repaid” after 1 and 5 min by 25% (8.9 ± 0.7 vs. 6.7 ± 0.7 ml/100 ml, P < 0.0001) and 37% (26.6 ± 1.8 vs. 16.8 ± 1.6 ml/100 ml, P < 0.0001). ASA similarly reduced peak FHBF by 19% (from 14.5 ± 1.1 to 11.8 ± 0.9 ⋅ 100 ml forearm−1 ⋅ min−1, P < 0.001) and the volume repaid after 1 and 5 min by 14% (7.5 ± 0.6 vs. 6.4 ± 0.6 ml/100 ml, P = 0.0001) and 20% (21.2 ± 1.5 vs. 16.9 ± 1.5 ml/100 ml, P < 0.0001), respectively. The coinfusion of ASA andl-NMMA did not decrease FHBF to a greater extent than either agent alone. These data suggest that endothelium-derived NO and vasodilator prostanoids contribute to resting blood flow and metabolic vasodilation in skeletal muscle vasculature in healthy humans. Although these vasodilator mechanisms operate in parallel in exercise-induced hyperemia, they appear not to be additive. Other mechanisms must also be operative in metabolic vasodilation.