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Biomedical subjects

Christopher S Hayward

Publications and source records attributed to Christopher S Hayward.

8 recordsLinked to original sources

Comparison of flow characteristics and vascular reactivity of radial artery and long saphenous vein grafts [NCT00139399].

BACKGROUND: The morphological and functional differences between arteries and veins may have implications on coronary artery bypass graft (CABG) survival. Although subjective differences have been observed between radial artery (RA) and long saphenous venous (LSV) grafts, these have not been quantified. This study assessed and compared the flow characteristics and in-vivo graft flow responses of RA and LSV aorto-coronary grafts. METHODS: Angiograms from 52 males taken 3.7 +/- 1.0 months after CABG surgery were analyzed using adjusted Thrombolysis in Myocardial Infarction (TIMI) frame count. Graft and target coronary artery dimensions were measured using quantitative coronary angiography. Estimated TIMI velocity (V(E)) and volume flow (F(E)) were then calculated. A further 7 patients underwent in-vivo graft flow responses assessments to adenosine, acetylcholine and isosorbide dinitrate (ISDN) using intravascular Doppler. RESULTS: The V(E) for RA grafts was significantly greater than LSV grafts (P = 0.002), however there was no difference in volume F(E) (P = 0.20). RA grafts showed positive endothelium-dependent and -independent vasodilatation, and LSV grafts showed no statistically significant response to adenosine and acetylcholine. There was no difference in flow velocity or volume responses. Seven RA grafts (11%) had compromised patency (4 (6%) > or = 50% stenosis in the proximal/distal anastomoses, and 3 (5%) diffuse narrowing). Thirty-seven (95%) LSV grafts achieved perfect patency and 2 (5%) were occluded. CONCLUSION: The flow characteristics and flow responses of the RA graft suggest that it is a more physiological conduit than the LSV graft. The clinical relevance of the balance between imperfect patency versus the more physiological vascular function in the RA graft may be revealed by the 5-year angiographic follow-up of this trial.

Acetylcholine↗

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital cardiac disease.

AIMS: Bosentan is efficacious in idiopathic pulmonary arterial hypertension, and the variants associated with connective tissue disease, but not currently approved for treatment of pulmonary arterial hypertension due to Eisenmenger's syndrome. We sought to evaluate its effect in adults with Eisenmenger's syndrome. METHODS: We administered bosentan on the basis of compassionate use in 23 patients with Eisenmenger's syndrome, aged 37 plus or minus 14 years. Of the patients, 17 had never received specific treatment for pulmonary arterial hypertension, five were transitioned from treprostinil, and one from beraprost to bosentan. We measured functional class, saturation of oxygen, haemoglobin levels and six-minute walk distance at baseline, one, six months and at most recent follow-up. RESULTS: Baseline functional class was IV in three, III in fifteen, and II in five patients. At follow-up, with a mean of 15 plus or minus 10 months, 13 of the 23 patients (57%) had improved by at least one functional class, from a median baseline of III to II (p equal to 0.016), mean saturation of oxygen at rest had increased from 81% to 84% (p equal to 0.001), and levels of haemoglobin had decreased from 178 plus or minus 26 grams per litre to 167 plus or minus 19 grams per litre (p equal to 0.001). Overall, the six-minute walk distance did not change from baseline of 335 metres. The distance walked by those not previously receiving specific therapy, however, improved from 318 plus or minus 129 to 345 plus or minus 123 metres (p equal to 0.03). CONCLUSION: Treatment of adults with Eisenmenger's syndrome using bosentan significantly improved functional class, saturation of oxygen at rest, and decreased levels of haemoglobin. Treatment with bosentan was associated with improvement in six-minute walk distance in those not previously receiving specific therapy. In patients already in receipt of specific therapy, transition to bosentan resulted in no clinical deterioration.

Adult↗

Physical activity reduces genetic susceptibility to increased central systolic pressure augmentation: a study of female twins.

OBJECTIVES: We sought to examine associations between the augmentation index (AI) and metabolic, adiposity, and lifestyle factors, independent of genetic influences, and to determine whether gene-environment interactions modulate these relationships. BACKGROUND: Reported associations between AI, an index of systemic arterial stiffness, and metabolic, adiposity, and lifestyle factors remain contradictory. The modulating effect of genetic risk is unknown. METHODS: We studied 684 female twins (age 18 to 71 years); AI was derived from the pressure waveform measured at the radial artery by applanation tonometry. Percentage of total body fat (TBF) and percentage of central abdominal fat (CAF) were assessed by dual-energy X-ray absorptiometry. RESULTS: In univariate analysis, age-adjusted AI was significantly associated with fasting triglyceride levels (r = 0.1, P = 0.03), apolipoprotein-B/A1 (r = 0.1, P = 0.04), percentage of TBF (r = 0.11, P = 0.006), and percentage of CAF (r = 0.11, P = 0.004). In co-twin case-control (monozygotic twin) analysis, a 3.1% absolute within-pair difference in percentage of CAF accounted for a 6% within-pair difference in AI, independent of genetic effects. Smokers and subjects with alcohol intakes >15 U/week had higher AI than nonsmokers (p = 0.01) and nondrinkers (p = 0.02), respectively. Forty percent of the variance in AI was explained by age, central mean arterial pressure, heart rate, height, percentage of CAF, and smoking. In gene-environment interaction analysis, subjects at high genetic risk of increased AI participating in regular leisure-time physical activity had AI values similar to low genetic risk subjects. CONCLUSIONS: Central abdominal adiposity is a significant determinant of AI in female twins, independent of hemodynamic, lifestyle, and, importantly, genetic effects. Smoking is associated with increased AI, even after controlling for abdominal obesity and other AI determinants. Physical activity reduces genetic predisposition to increased AI.

Adolescent↗

Effects of radial artery harvesting on forearm function and blood flow.

BACKGROUND: There is little information on the effects of radial artery harvesting on postoperative forearm function and blood flow. We evaluated the early changes in forearm neural sensation, circumference, grip power, cyclical exercise fatigue, and blood flow after radial artery harvesting for coronary artery bypass graft (CABG) surgery. METHODS: Twenty-three patients with negative Allen's test of the nondominant forearm were recruited preoperatively and underwent assessment of bilateral forearm function (soft touch and pin-prick neural sensation, circumference, handgrip power, cyclical exercise fatigue) and blood flow measurements (forearm plethysmography). All vasoactive drugs were stopped 24 hours before assessments. Identical follow-up assessments were conducted (mean +/- SEM) 3.4 +/- 0.4 months postoperatively. RESULTS: At the time of postoperative assessment all harvested forearm wounds were healed. There was no reduction of postoperative soft touch sensation but in 3 patients objective pinprick sensation was reduced in the distribution of the lateral antebrachial cutaneous nerve of the harvested forearms. Postoperative forearm circumference (p < 0.05) and grip power (p < 0.05) were significantly reduced in both forearms, however cyclical exercise fatigue was improved in both forearms. Preoperative and postoperative forearm blood flow at rest and in exercise-induced ischemic reperfusion were not significantly different in both forearms. CONCLUSIONS: In patients with a negative Allen's test, harvesting of the radial artery does not adversely affect subsequent forearm function or blood flow to a clinically significant degree.

Coronary Artery Bypass↗

Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women. METHODS AND RESULTS: Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (>1 year use; mean age 29+/-4 years) and in 10 controls (mean age 30+/-4 years, P=0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (n=12) in DMPA users and during menstruation and midcycle (n=9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively P<0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, P<0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, P=0.23). Estradiol levels were significantly correlated to FMD (r=0.43, P<0.01). CONCLUSIONS: Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.

Adult↗

Assessment of endothelial function using peripheral waveform analysis: a clinical application.

OBJECTIVES: The study was done to determine whether radial artery applanation tonometry can be used as a noninvasive method of assessing global endothelial function. BACKGROUND; It is known that beta(2)-receptor stimulation results in endothelial release of nitric oxide. Furthermore, for over a century glyceryl trinitrate (GTN) has been known to markedly affect the arterial pressure waveform, even in the absence of significant blood pressure (BP) changes. Therefore, it was hypothesized that the change in the peripheral pressure waveform, as measured using tonometry and quantified using the augmentation index (AIx) and in response to Salbutamol (Salb), would allow assessment of global endothelial function. METHODS: The study contained three parts. In the first study, Salb (400 microg) was administered to 11 healthy subjects via inhalation after either intravenous N-omega-nitro-monomethyl-L-arginine (L-NMMA) (3 mg/kg over 5 min) or control solution (normal saline) in the supine, rested, fasted condition. The BP, heart rate and waveform responses were recorded each 5 min following Salb for 20 min. Next, GTN was given and responses recorded 5 min later. In the second study, both the reproducibility of Salb and the GTN responses were assessed in 9 subjects studied twice on separate days. In the third study, the Salb and GTN responses of 12 subjects with angiographic coronary artery disease (CAD) were compared with 10 age-matched control subjects with no atherosclerotic risk factors. RESULTS: After control infusion, AIx decreased following Salb, from 50.8 +/- 4.3% to 44.8 +/- 4.2%, a change of -11.8 +/- 3.7%, p < 0.01. After L-NMMA, AIx did not significantly change following Salb (54.2 +/- 5.1% vs. 52.9 +/- 5.3%, -2.0 +/- 3.1%). The GTN-induced decreases in AIx were similar after either infusion (35.1 +/- 3.3% vs. 36.5 +/- 3.3%). Reproducibility of Salb-induced changes in AIx between studies performed on separate days was good (r = 0.80, p < 0.01). Salb-induced changes in AIx in CAD patients were significantly less compared to control subjects (-2.4 +/- 1.9% vs. -13.2 +/- 2.4%, respectively, p < 0.002). The GTN-induced changes were not significantly different (-27.6 +/- 4.2 vs. -38.9 +/- 4.4%, p = 0.07). CONCLUSIONS: The peripheral arterial pressure waveform is sensitive to beta(2)-stimulation. Changes are related to nitric oxide release, are reproducible and can distinguish between clinical subject groups. Arterial waveform changes following Salb may thus provide a noninvasive method of measuring "global" arterial endothelial function.

Adrenergic beta-Agonists↗

A comparison of brachial artery reactivity measured by external and intravascular ultrasound.

External ultrasound (US), EXUS, is widely used to measure brachial artery (BA) diameter changes in the assessment of vascular function; however, it has not been compared with other imaging modalities. We simultaneously measured BA diameter responses to hyperaemic flow and nitrate using EXUS and intravascular ultrasound (US), IVUS, in 10 patients. Mean diameters measured across all time periods correlated closely (r = 0.67, p < 0.001). Percent diameter change to hyperaemia and nitrate also correlated well (r = 0.67, p < 0.01). IVUS cross-sectional area (CSA) was significantly different from that calculated from EXUS using pir(2) (23.95 +/- 4.89 vs. 20.35 +/- 4.51 mm(2), respectively, p < 0.001). Orthogonal diameters measured by IVUS were significantly different (5.45 +/- 0.85 vs. 5.17 +/- 0.79 mm, respectively, p < 0.005). In conclusion, EXUS and IVUS BA diameter measurements correlated well; however, discrepancies in absolute measurements were revealed. The cross-section of the BA is oval; therefore, deriving CSA by pir(2) is inaccurate.

Adult↗