Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans.

AIM: The present study aims to explore the relationship between inflammatory cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers of fat distribution and endothelial function in healthy people across a wide range of body fatness. METHODS: Seventy-three healthy people (44 women; age range: 24-64 years) with body mass index (BMI) range of 18.6-73.1 kg/m2 were recruited. All participants underwent assessment of conduit artery endothelial-dependent vasodilatation by using flow-mediated vasodilatation (FMD) of the brachial artery and endothelial-independent vasodilatation to sublingual GTN. They had blood taken for measurement of plasma markers of glucose homeostasis (fasting insulin and glucose), systemic inflammation (interleukin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha receptor 2 (TNF-alpha R2)) and lipids (low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides). Morphometric assessment (waist circumference, BMI and waist-to-hip ratio (WHR)) and systolic and diastolic arterial pressure were also measured. RESULTS: Markers of total body fat/fat distribution (waist circumference, BMI and WHR), inflammation (IL-6, CRP and TNF-alpha R2), metabolism (fasting insulin, HDL, LDL and triglycerides) and BP (systolic and diastolic) correlated with FMD. Among these measurements, WHR was the only independent predictor of FMD (r2 = 0.30; p = 0.0001). CONCLUSIONS: WHR is an important marker of endothelial dysfunction in healthy people across a wide range of body fatness.

Pathophysiological implications of insulin resistance on vascular endothelial function.

BACKGROUND: Insulin resistance is a key component of the insulin resistance syndrome and is a crucially important metabolic abnormality in Type 2 diabetes. Insulin-resistant individuals are at significantly increased risk of cardiovascular disease, although the underlying mechanisms remain incompletely understood. The endothelium is thought to play a critical role in maintaining vascular homeostasis, a process dependent on the balance between the production of nitric oxide, superoxide and other vasoactive substances. Endothelial dysfunction has been demonstrated in insulin-resistant states in animals and humans and may represent an important early event in the development of atherosclerosis. Insulin resistance may be linked to endothelial dysfunction by a number of mechanisms, including disturbances of subcellular signalling pathways common to both insulin action and nitric oxide production. Other potential unifying links include the roles of oxidant stress, endothelin, the renin angiotensin system and the secretion of hormones and cytokines by adipose tissue. Lifestyle measures and drug therapies which improve insulin sensitivity and ameliorate endothelial dysfunction may be important in delaying the progression to overt cardiovascular disease in at risk individuals. METHODS: We conducted a literature search using Medline, restricted to articles published in the English language between 1966 and the present, and reviewed bibliographies of relevant articles. An initial search strategy employing combinations of the MeSH terms: insulin resistance; endothelium, vascular; insulin; nitric oxide or hyperinsulinaemia produced over 300 references. Focused searches using keywords relevant to the molecular aspects of endothelial function and insulin signalling, and lifestyle or pharmacological interventions relevant to insulin resistance or endothelial function, produced over 300 further references. Abstracts of all references were screened before selecting those relevant to this review.

Coronary artery perforation during percutaneous intervention: incidence and outcome.

OBJECTIVE: To examine the clinical outcome of percutaneous coronary intervention where the procedure was complicated by vessel perforation. SETTING: Tertiary referral centre. METHODS: The procedural records of 6245 patients undergoing coronary intervention were reviewed. In 52 patients (0.8%) the procedure was complicated by vessel perforation, ranging from wire exit to free flow of contrast into the pericardial space. The majority of lesions treated were complex (37% type B, 59% type C) and 9 of 52 (17%) were chronic occlusions. Ten patients (19%) received abciximab. Four underwent rotational atherectomy (8%). RESULTS: In 28 of 52 patients (54%) the perforation was benign and managed conservatively without the development of haemodynamically significant sequelae. In 24 of 52 (46%) a significant pericardial effusion ensued requiring drainage. Of these 24 procedures 6 had involved the treatment of a chronic occlusion (25%). Eight of the 24 patients were referred for emergency bypass surgery (33%), 3 of whom died. Of the remaining 16 not referred for surgery, 3 died. Of the 10 procedures complicated by vessel perforation where abciximab had been administered, 9 (90%) led to pericardial tamponade. Latterly 2 vessel perforations were successfully treated by the deployment of a covered stent. CONCLUSIONS: Coronary artery perforation with sequelae during intervention is rare--26 of 6245 (0.4%). This complication was seen in the treatment of chronic occlusions, which are therefore not risk-free procedures. The development of pericardial tamponade carries a high mortality. While prompt surgical intervention may be life saving, expertise in the use of covered stents may provide a valuable rescue option for this serious complication. Caution should be exercised where coronary perforation occurs and abciximab has been used.

Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans.

It is now well established that obesity is an independent risk factor for the development of coronary artery atherosclerosis. The maintenance of vascular homeostasis is critically dependent on the continued integrity of vascular endothelial cell function. A key early event in the development of atherosclerosis is thought to be endothelial cell dysfunction. A primary feature of endothelial cell dysfunction is the reduced bioavailability of the signalling molecule nitric oxide (NO), which has important anti atherogenic properties. Recent studies have produced persuasive evidence showing the presence of endothelial dysfunction in obese humans NO bioavailability is dependent on the balance between its production by a family of enzymes, the nitric oxide synthases, and its reaction with reactive oxygen species. The endothelial isoform (eNOS) is responsible for a significant amount of the NO produced in the vascular wall. NO production can be modulated in both physiological and pathophysiological settings, by regulation of the activity of eNOS at a transcriptional and post-transcriptional level, by substrate and co-factor provision and through calcium dependent and independent signalling pathways. The present review discusses general mechanisms of reduced NO bioavailability including factors determining production of both NO and reactive oxygen species. We then focus on the potential factors responsible for endothelial dysfunction in obesity and possible therapeutic interventions targetted at these abnormalities.

A randomised trial of endoluminal reconstruction comparing the NIR stent and the Wallstent in angioplasty of long segment coronary disease: results of the RENEWAL Study.

BACKGROUND: The role of coronary stents in reducing the incidence of acute complications and late restenosis after angioplasty has been established in randomized studies focusing on simple, short coronary lesions. The development of long coronary stents has provided a safe and predictable means of treating long coronary lesions, but this carries with it a higher risk of restenosis. By comparing the outcome of treating long lesions with two different stent types, we aimed to assess the influence of stent design rather than the nature of long lesions per se on the relatively high restenosis rates in this subgroup. METHODS: This study was designed to assess procedural complications and 6-month restenosis rates in a randomized trial comparing a slotted tube stent with a self-expanding stent for the treatment of long coronary lesions. Randomization of vessels to either stent occurred after successful balloon angioplasty. Intravascular ultrasound (IVUS) was used to assess and optimize stent deployment. The patients were restudied angiographically and by IVUS at 6 months. RESULTS: A total of 82 patients (85 vessels) were recruited (slotted tube stent, n = 44 vessels; self-expanding stent, n = 41 vessels). Successful deployment occurred in 41 (100%) of 41 of the self-expanding stent group and 41 (93%) of 44 of the slotted tube stent group. There was no difference in lesion length between the two groups (slotted tube stent, 26.6 +/- 6.9 [SD] mm; self-expanding stent, 28.7 +/- 9.8 [SD] mm; P = .2), but the mean length of the self-expanding stent was greater than that of the slotted tube stent (41.6 +/- 18.8 [SD] mm vs 35.4 +/- 16.2 [SD] mm, respectively; P < .05). There was no significant difference in the rate of major events between the two groups at 6-month follow-up. The angiographic restenosis rate at follow-up was less in the slotted tube stent group, but this did not reach statistical significance (26% vs 46%, respectively; P = .1) and the target lesion revascularization rate was similar for both groups (7.9% vs 7.7%, respectively; P = .8). IVUS assessment of plaque/stent ratios suggested a greater plaque burden in the self-expanding stent compared with the slotted tube stent at follow-up (0.42 +/- 1.2 [SD] vs 0.3 +/- 0.08 [SD]), but this was not statistically significant (P = .1). CONCLUSIONS: Long stents can be safely and successfully deployed in long segment coronary disease, with an acceptable 6-month target lesion revascularization rate. Our results showed a trend toward lower angiographic restenosis and a lesser in-stent plaque burden at follow-up in the slotted tube stent compared with the self-expanding stent. This suggests that stent design may influence the restenotic process in long coronary lesions.

Angiographic and clinical restenosis following the use of long coronary Wallstents.

This study assessed clinical and angiographic restenosis following the deployment of the long coronary Wallstent. Between May 1995 and June 1997, 182 Wallstents were deployed in 162 vessels in this unit. Forty-eight percent had an unstable coronary syndrome and 94% had AHA grade B or C lesions. The mean lesion length was 37 +/- 20 mm and the mean stent length was 48 +/- 20 mm. The procedural success rate was 99% and the primary success rate was 93%. Six in-patients suffered subacute stent thrombosis, the majority being in the era of anticoagulation rather than antiplatelet regimes. Seventy-three percent remained free of major adverse clinical events in the follow-up period, but 41% had angiographic restenosis. The Wallstent can be deployed in complex lesions with a high primary success rate and an acceptably low restenosis rate. The optimal management of in-stent restenosis remains to be defined.

Adverse effect of dietary vanadium, contributed by dicalcium phosphate, on albumen quality.

Two experiments were conducted to determine the effects of dietary vanadium (V) on egg albumen quality. In Experiment 1, White Leghorn hens fed 9.9 ppm V supplied from a commercial dicalcium phosphate (Dical B at 1.5% of the diet) or a diet containing 29.9 ppm V (28.5 ppm from ammonium vanadate and 1.4 ppm from Dical A) produced eggs with significantly poorer albumen quality (61.7 and 61.6 Haugh units, respectively) than those of hens fed 1.4 ppm V from Dical A (76.9 Haugh units). The decline in albumen quality occurred within 1 week of treatment and persisted through 4 weeks of V feeding. Inclusion of 28.5 ppm V as ammonium vanadate also reduced egg production and feed consumption but had no significant effect on egg weight or change in body weight during the 4-week test period. At the end of 4 weeks, all hens were fed the 1.4-ppm V diet. Improvement in albumen quality was observed within 1 week, and after 4 weeks of the recovery period, no significant differences among treatment groups were observed. Part 1 of Experiment 2 showed that albumen quality was significantly reduced by 6.0 and 7.9 ppm V, supplied from Dical B, but 2.0 or 4.0 ppm V did not significantly change albumen quality during a 4-week trial. In Part 2 of Experiment 2, the inclusion of 9.9 ppm V from Dical B again significantly reduced albumen quality within 1 week. The magnitudes of adverse effects of 6.0, 7.9, and 9.9 ppm V on albumen quality plateaued approximately 4 weeks after treatment began and remained relatively constant through 6 weeks of feeding 9.9 ppm V and through 10 weeks of feeding 6.0 or 7.9 ppm V. The results demonstrate that certain commercial dicalcium phosphates may contribute excessive V to the diet of hens, and, when present at levels of 6.0 ppm or more, V will adversely affect albumen quality.