Arterial distensibility as a possible compensatory mechanism in chronic aortic regurgitation

OBJECTIVE: To evaluate elastic properties of conduit arteries in asymptomatic patients who have severe chronic aortic regurgitation. METHODS: Twelve healthy volunteers aged 30±1 years (control group) and 14 asymptomatic patients with severe aortic regurgitation aged 29±2 years and left ventricular ejection fraction of 0.61±0.02 (radioisotope ventriculography) were studied. High-resolution ultrasonography was performed to measure the systolic and diastolic diameters of the common carotid artery. Simultaneous measurement of blood pressure enabled the calculation of arterial compliance and distensibility. RESULTS: No differences were observed between patients with aortic regurgitation and the control group concerning age, sex, body surface, and mean blood pressure. Pulse pressure was significantly higher in the aortic regurgitation group compared with that in the control group (78±3 versus 48±1mmHg, P<0.01). Arterial compliance and distensibility were significantly greater in the aortic regurgitation group compared with that in the control group (11.0±0.8 versus 8.1±0.7 10-10 N-1 m4, P=0.01 e and 39.3±2.6 versus 31.1±2.0 10-6 N-1 m², P=0.02, respectively). CONCLUSION: Patients with chronic aortic regurgitation have increased arterial distensibility. Greater vascular compliance, to lessen the impact of systolic volume ejected into conduit arteries, represents a compensatory mechanism in left ventricular and arterial system coupling.

Corrected transposition of the great arteries with several associated anomalies in a 68-year-old patient

Few patients with corrected transposition of the great arteries survive past 50 years of age because of the association with congenital defects, development of total atrioventricular block, and right ventricular dysfunction. We report the case of a male patient with dextrocardia in situs solitus and corrected transposition of the great arteries associated with a wide atrial septal defect and severe pulmonary valvar and subvalvar stenoses. The patient also developed a large aneurysm on the pulmonary artery, total atrioventricular block diagnosed 8 years earlier, symptoms of dysfunction of the systemic ventricle in the previous 2 years, insufficiency of the left atrioventricular valve, and aortic regurgitation. Despite all these associated anomalies, the patient developed class III cardiac decompensation only at the age of 68 years, which makes this case a rarity. The patient was clinically treated, and was discharged from the hospital in good condition.

Comparison between Adventitial and Intimal Inflammation of Ruptured and Nonruptured Atherosclerotic Plaques in Human Coronary Arteries

OBJECTIVE: To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS: We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS: In the adventitia, the numbers of lymphocytes and microvessels/mm² were 69.5±88.3 and 60.9± 32.1 in culprit lesions and 16.4 ± 21.1 and 44.3±16.1 in stable lesions (p<0.05); within the plaques, the mean number of lymphocytes was 24±40.8 in culprit lesions and 10.9±13.2 in stable ones (p=0.17). The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001). The confocal images showed holes in the external elastic membrane. CONCLUSION: Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability.

Endothelium-dependent relaxation in response to poly-L-arginine in canine coronary arteries: implications about hyperpolarization as a mechanism of vasodilatation

OBJECTIVE: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation. METHODS: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37ºC and bubbled with 95% O2 / 5% CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2á and potassium chloride were used to contract the vascular rings. RESULTS: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin. CONCLUSION: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide.

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

Background:Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL).Objective:To investigate the relationships between p.Q192R SNP ofPON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317).Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques.Conclusion:In low-risk individuals, the presence of the p.192Q variant ofPON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Protective Effect of Aortic Stenosis on the Coronary Arteries. Hypothetic Considerations to an Old Enigma

Abstract A literature overview of angiographic studies has shown that the prevalence of significant coronary disease in patients with aortic stenosis (AS) varies from 20 to 60%. Early necropsy studies suggested that patients with AS had a lower than expected incidence of coronary artery disease (CAD), originating the concept of a protective effect of AS on the coronary arteries. The myth of AS protection against CAD would be better explained as endothelium-myocardial interaction (crosstalk) protection triggered by left ventricular overload. Therefore, the cGMP/NO pathway induced by the AS overload pressure would explain the low incidence of CAD, which is compatible with the amazing natural long-term evolution of this cardiac valve disease.

The carotid circulation in the domestic cat; by D. Dwight Davis and H. Elizabeth Story.

v.28:no.1(1943)

Extracorporeal membrane oxygenation support after heart explantation: a proposal on how to deal with hyperacute rejection of heart transplant

Purpose: In extreme situations, such as hyperacute rejection of heart transplant or major bleeding per-operating complications, an urgent heart explantation might be the only means of survival. The aim of this experimental study was to improve the surgical technique and the hemodynamics of an Extracorporeal Membrane Oxygenation (ECMO) support through a peripheral vascular access in an acardia model. Methods: An ECMO support was established in 7 bovine experiments (59±6.1 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with return through a carotid artery. After baseline measurements of pump flow and arterial and central venous pressure, ventricular fibrillation was induced (B), the great arteries were clamped, the heart was excised and right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect (ASD) over the cannula in the caval axis. Measurements were taken with the pulmonary artery (PA) clamped (C) and anastomosed with the caval axis (D). Regular arterial and central venous blood gases tests were performed. The ANOVA test for repeated measures was used to test the null hypothesis and a Bonferroni t method for assessing the significance in the between groups pairwise comparison of mean pump flow. Results: Initial pump flow (A) was 4.3±0.6 L/min dropping to 2.8±0.7 L/min (P B-A= 0.003) 10 minutes after induction of ventricular fibrillation (B). After cardiectomy, with the pulmonary artery clamped (C) it augmented not significantly to 3.5±0.8 L/min (P C-B= 0.33, P C-A= 0.029). Finally, PA anastomosis to the caval axis was followed by an almost to baseline pump flow augmentation (4.1±0.7 L/min, P D-B= 0.009, P D-C= 0.006, P D-A= 0.597), permitting a full ECMO support in acardia by a peripheral vascular access. Conclusions: ECMO support in acardia is feasible, providing new opportunities in situations where heart must urgently be explanted, as in hyperacute rejection of heart transplant. Adequate drainage of pulmonary circulation is pivotal in order to avoid pulmonary congestion and loss of volume from the normal right to left shunt of bronchial vessels. Furthermore, the PA anastomosis to the caval axis not only improves pump flow but it also permits an ECMO support by a peripheral vascular access and the closure of the chest.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials 2008 Issue 4, MEDLINE (1966 to January 2009), and EMBASE (1980 to January 2009). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate a pooled effect was estimated using a Mantel-Haenszel fixed effect method. MAIN RESULTS: We included eleven trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that CO measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other seven trials. One trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12; 95% CI 1.24 to 3.62). One trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77; 95% CI 1.04 to 7.41) but enrolled a population of light smokers. Five trials failed to detect evidence of a significant effect. One of these tested CO feedback alone and CO + genetic susceptibility as two different intervention; none of the three possible comparisons detected significant effects. Three others used a combination of CO and spirometry feedback in different settings, and one tested for a genetic marker. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. Only two pairs of studies were similar enough in term of recruitment, setting, and intervention to allow meta-analysis.

Epidemiology and prevention of cardiovascular disease in the Seychelles Islands (Indian Ocean)

This article presents selected findings and lessons from a cardiovascular research and prevention program initiated in 1989 in the Republic of Seychelles, a country in demographic and epidemiological transition. Rapid and sustained aging of the population (e.g., two-fold increase of people aged 30-39 from 1979 to 1995) implies, over the next few decades, further dramatic increase of the burden of chronic diseases, particularly cardiovascular disease (CVD). Epidemiological surveillance shows high age-specific rates of CVD (particularly stroke), high prevalence of peripheral atherosclerosis (plaques in carotid and femoral arteries), high prevalence of classical modifiable risk factors in the adult population (particularly hypertension), and substantial proportions of children with overweight. Stagnant life expectancy in men and an increase in women have been observed over the last two decades; this occurred despite largely improved health services and reduced infant mortality rates, and may reflect the large CVD burden found in middle-aged men (less so in middle-aged women). A national program of prevention of CVD has been initiated since 1991, which includes a mix of interventions to reduce risk factors in the general population and in high-risk individuals. Substantial research to back the prevention program indeed shows, at the moment, epidemiological patterns in Seychelles similar to those observed in Western countries (e.g., an association between peripheral atherosclerosis [as a proxy of CVD] and low density lipoprotein-cholesterol, smoking, diabetes, and [inversely] walking). This clearly supports the view that promotion of healthy lifestyles and control of conventional risk factors should be the main targets for CVD prevention and control.

Heterogeneity of atherosclerotic plaque phenotypes and composition in four different arterial beds: an intravascular ultrasound virtual histology study

Purpose: The purpose of this study was to compare the plaque morphology between coronary and peripheral arteries using intravascular ultrasound (IVUS). Methods: IVUS was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Results: Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P=NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P=0.02) was observed in all arteries. Compared to coronary arteries, VH-FA was less frequently observed in renal (P<0.001) and iliac arteries (P<0.006), while VH-PIT and VH-FC were prevalent in both of these peripheral arteries. Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary, carotid, and renal arteries compared to those with intermediate/negative remodeling (all P<0.01). There was positive relationship between RI and percent necrotic core area in all four arteries. Conclusions: Atherosclerotic plaque phenotypes were heterogeneous among four different arteries. In contrast, the associations of remodeling mode with plaque phenotype and composition were similar among the various arterial beds.

Impact of carotid plaque screening on smoking cessation and other cardiovascular risk factors: a randomized controlled trial.

BACKGROUND: Screening of peripheral atherosclerosis is increasingly used, but few trials have examined its clinical impact. We aimed to assess whether carotid plaque screening helps smokers to improve their health behaviors and cardiovascular risk factors. METHODS: We randomly assigned 536 smokers aged 40 to 70 years to carotid plaque ultrasonographic screening (US group) vs no screening (control group) in addition to individual counseling and nicotine replacement therapy for all participants. Smokers with at least 1 plaque received pictures of their plaques with a 7-minute structured explanation. The outcomes included biochemically validated smoking cessation at 12 months (primary outcome) and changes in cardiovascular risk factor levels and Framingham risk score. RESULTS: At baseline, participants (mean age, 51.1 years; 45.0% women) smoked an average of 20 cigarettes per day with a median duration of 32 years. The US group had a high prevalence of carotid plaques (57.9%). At 12 months, smoking cessation rates were high, but did not differ between the US and control groups (24.9% vs 22.1%; P = .45). In the US group, cessation rates did not differ according to the presence or absence of plaques. Control of cardiovascular risk factors (ie, blood pressure and low-density lipoprotein cholesterol and hemoglobin A(1c) levels in diabetic patients) and mean absolute risk change in Framingham risk score did not differ between the groups. The mean absolute risk change in Framingham risk score was +0.6 in the US group vs +0.3 in the control group (P = .56). CONCLUSION: In smokers, carotid plaque screening performed in addition to thorough smoking cessation counseling is not associated with increased rates of smoking cessation or control of cardiovascular risk factors. Trial Registration  clinicaltrials.gov Identifier: NCT00548665.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.

Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications.

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality. Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age. Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.