Biomedical subjects
Publications and source records attributed to Sarah A Hope.
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Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.
During mammalian follicle development, a fluid-filled antrum develops in the avascular centre of the follicle. We investigated the hypothesis that follicular fluid contains osmotically-active molecules, sufficiently large so as to not freely escape the follicular fluid. Such molecules could generate an osmotic differential and thus recruit fluid from the surrounding vascularised stroma into the antrum. Follicular fluid was collected from bovine follicles classified histologically as healthy (n = 4 pools) or atretic (n = 4 pools). Dialysis of the follicular fluid at 300 kDa or 500 kDa resulted in a reduction in colloid osmotic pressure of 35% and 60%, respectively, in fluid from healthy follicles and 29% and 80% from atretic follicles. Digestion of follicular fluid with Streptomyces hyaluronidase, chondroitinase ABC or DNase 1 followed by dialysis resulted in reductions in osmotic pressure of 43%, 53% and 43% respectively for fluids from healthy follicles and 34%, 20% and 31% for atretic follicles. Digestion with collagenase I, proteinase K, heparanase 1 or keratanase had no significant effect on the osmotic pressure of follicular fluid of healthy follicles. Ion exchange and size exclusion, Western blotting and ELISA identified the proteoglycans versican and inter-alpha trypsin inhibitor and the glycosaminoglycan hyaluronan in follicular fluid. We conclude that these molecules or aggregates of them are of sufficient size to contribute to the osmotic potential of follicular fluid and thus recruit fluid into the follicular antrum. DNA may also contribute but it is probably not a component that is regulated for this role.
The objective of this study was to investigate the determinants of aortic pressure waveform morphology in the thoracoabdominal aorta with specific reference to features of potential prognostic value for cardiovascular disease. In particular, we aimed to determine the location of major pressure wave reflection sites within the aorta. Aortic pressure waveforms were acquired with 2-Fr Millar Mikro-tip catheter transducers in 40 subjects (26 men, 14 women), and repeated in 10 subjects, at five predetermined points within the aorta: aortic root, transverse arch, and at the levels of the diaphragm, renal arteries, and aortic bifurcation. Waveforms were analyzed for augmentation index (AI), time to inflection point (Ti), and pressure parameters. AI decreased progressively between the aortic root and bifurcation (P < 0.001), and Ti increased (P < 0.01). There was the expected progressive peripheral amplification of systolic and pulse pressures and fall in time to peak pressure (all P < 0.001). There was no difference on repeat pullback or between sexes. These data are at variance with the concept that central AI results solely from pressure wave reflection, when Ti would be expected to decrease and AI increase with distal progression. Pressure wave propagation phenomena may contribute, and the potential role of frequency dispersion merits investigation.
BACKGROUND: Evidence for statin therapy in prevention of coronary artery disease is overwhelming. In spite of theoretical benefits, any additional advantage of its early introduction in the management of acute coronary syndrome is, however, uncertain. We therefore investigated differences between plasma levels of the systemic inflammatory markers intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, C-reactive protein and interleukin-6 in patients presenting with unstable angina or acute myocardial infarction, and assessed whether the 30-day levels of these markers are influenced by early instigation of the HMG-CoA reductase inhibitor pravastatin. MATERIALS AND METHODS: 170 (134 male) patients presenting with acute coronary syndrome, but without previous statin therapy, participated. Blood was taken within 24 h of onset of ischaemic pain and again at 30 days. In all, 87 (71 male) participants were treated with pravastatin (20-40 mg daily) and 83 (63 male) with a matched placebo. RESULTS: At presentation, interleukin-6 was higher in males than in females (P=0.008) and lower in those with a pre-existing history of myocardial infarction (P=0.038). C-reactive protein and interleukin-6 were greater in myocardial infarction, but this difference was lost at 30 days. Thirty-day changes in all parameters were inversely related to level at presentation but not to treatment with pravastatin. Hypertension (P=0.011) and smoking (P=0.042) were associated with elevation of C-reactive protein with no difference between unstable angina or acute myocardial infarction. The effect of these individual factors was cumulative. CONCLUSIONS: Interleukin-6 was greater in acute myocardial infarction than in unstable angina; E-selectin was positively associated with a previous myocardial infarction and inversely related to age. We found no effect of early introduction of pravastatin on systemic inflammatory markers 30 days after acute coronary syndrome.
We describe a young adult with an underlying diagnosis of pulmonary atresia with intact ventricular septum and Fontan physiology who presented with extreme dyspnoea on exertion. Coronary artery to right ventricular fistulae and reversible myocardial ischaemia secondary to a right ventricular steal phenomenon were present. The right coronary artery to right ventricular fistula was completely occluded with coils, by a transcoronary approach, with amelioration of symptoms. However, one coil embolised and lodged uneventfully in the left atrium during the procedure. This case demonstrates that a transcatheter approach may be successfully employed not only in patients with isolated coronary artery fistulae, but also in patients with coexistent complex congenital heart disease.
Transfer function techniques are increasingly used for non-invasive estimation of central aortic waveform characteristics. Non-invasive radial waveforms must be calibrated for this purpose. Most validation studies have used invasive pressures for calibration, with little data on the impact of non-invasive calibration on transfer-function-derived aortic waveform characteristics. In the present study, simultaneous invasive central aortic (Millar Mikro-tip catheter transducer) and non-invasive radial (Millar Mikro-tip tonometer) pressure waveforms and non-invasive brachial pressures (Dinamap) were measured in 42 subjects. In this cohort, radial waveforms were calibrated to both invasive and non-invasive mean and diastolic pressures. From each of these, central waveforms were reconstructed using a generalized transfer function obtained by us from a previous cohort [Hope, Tay, Meredith and Cameron (2002) Am. J. Physiol. Heart Circ. Physiol. 283, H1150-H1156]. Waveforms were analysed for parameters of potential clinical interest. For calibrated radial and reconstructed central waveforms, different methods of calibration were associated with differences in pressure (P<0.001), but not time parameters or augmentation index. Whereas invasive calibration resulted in little error in transfer function estimation of central systolic pressure (difference -1+/-8 mmHg; P=not significant), non-invasive calibration resulted in significant underestimation (7+/-12 mmHg; P<0.001). Errors in estimated aortic parameters differed with non-invasively calibrated untransformed radial and transfer-function-derived aortic waveforms (all P<0.01), with smaller absolute errors with untransformed radial waveforms for most pressure parameters [systolic pressure, 5+/-16 and 7+/-12 mmHg; pulse pressure, 0+/-16 and 4+/-12 mmHg (radial and derived aortic respectively)]. When only non-invasive pressures are accessible, analysis of untransformed radial waveforms apparently produces smaller errors in the estimation of central aortic systolic pressure, and other waveform parameters, than using a generalized transfer function.
OBJECTIVE: Optimal blood pressure control in subjects with diabetes reduces cardiovascular complications. There is theoretical benefit in the assessment of central aortic waveforms including the augmentation index, which is taken as a putative index of stiffness. Transfer functions may be used to reconstruct aortic from radial pressure waveforms; however, a single generalized transfer function may not be appropriate for all patients. We aimed to evaluate the technique in subjects with diabetes. RESEARCH DESIGN AND METHODS: Simultaneous invasive central aortic and noninvasive radial waveforms were acquired in 19 subjects with type 2 diabetes, and a diabetes-specific transfer function was derived. Similar data were acquired from 38 age- and sex-matched subjects without diabetes. Central waveforms were reconstructed using a generalized transfer function in all patients and the diabetes-specific transfer function in individuals with diabetes. RESULTS: There was no difference between groups in measured central pressures. The error in generalized transfer function-derived systolic pressure was greater in individuals with diabetes (6 +/- 7 mmHg) (mean +/- SD) than without diabetes (2 +/- 8 mmHg) (P<0.05). Errors in other parameters were no different. The diabetes-specific transfer function reduced the error in derived systolic pressure to 0 +/- 7 mmHg in individuals with diabetes--no different than that with the generalized transfer function in individuals without diabetes. The central augmentation index reconstructed by either transfer function was unrelated to that directly measured. CONCLUSIONS: A generalized transfer function is inappropriate for the derivation of central waveforms in subjects with type 2 diabetes. Errors in subjects with diabetes might be reduced with a diabetes-specific transfer function.
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OBJECTIVE: To investigate the utility and accuracy of radial-aortic arterial transfer functions for the derivation of central blood pressure waveforms. DESIGN Prospective measurement of central and peripheral waveforms in patients undergoing coronary angiography or percutaneous coronary intervention. METHODS: Simultaneous invasive central aortic and non-invasive radial pressure waveforms were recorded in 78 subjects (61 male : 17 female). Data were applied to a single-input/single-output model for the calculation of a transfer function (TF). Individual TFs were derived by two methods and ensemble averaged TFs obtained for the group. Reverse transformation was performed using each averaged TF applied to the radial data of each subject. RESULTS: There was close linear correlation between measured aortic parameters and both radial and TF-derived aortic systolic and diastolic pressures (P < 0.001) and most other waveform parameters. However, despite small mean differences between measured and most TF-derived aortic parameters (systolic pressure 0.8-2.9 mmHg, augmentation index 4.3-5.6%), individual scatter was marked, with 95% limits of agreement of +/- 14.6 mmHg (systolic pressure) and +/- 24.4% [augmentation index (AI)]. Indeed, scatter for AI was so marked that measured and derived values were not statistically significantly correlated. CONCLUSIONS: Transfer functions may be valid for the derivation of some central aortic waveform characteristics. However, in providing neither improved reproducibility nor data on parameters not obtainable from the radial waveform, transfer function techniques may offer no additional clinical benefit. The absence of correlation between measured and TF-derived aortic AI and wide limits of agreement of other parameters should be considered if this technique is utilized in clinical practice.
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BACKGROUND: Atherosclerosis is an inflammatory process in which adhesion molecules play an intimate role in both the initiation and progression of lesions. It is postulated that they also play a role in the presentation of acute coronary syndromes and that plasma levels thereafter may be of potential prognostic significance. The stability of sample levels under different laboratory conditions is unknown. METHODS: Stability of plasma levels was assessed in six healthy subjects under four different laboratory conditions. The time course of levels was studied in 57 patients with acute chest pain, 21 of non-cardiac aetiology, 23 unstable angina and 13 acute myocardial infarction, at mean times of 2.3, 8.2 and 17.3 h after the onset of pain. Samples were assayed for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, E-selectin and C-reactive protein (CRP). RESULTS: ICAM-1, VCAM-1, P-selectin and E-selectin levels did not differ under different laboratory conditions. Levels were similar at presentation in patients with acute chest pain of non-cardiac aetiology, unstable angina or acute myocardial infarction (median levels ICAM-1 269 microg/l, VCAM-1 379 microg/l, P-selectin 167 microg/l and E-selectin 53 microg/l). Levels did not change in the 24 h following the onset of pain. CRP levels did not differ at presentation between groups (median level 2.1 mg/l), but rose more than 12 h after the onset of pain in the group with acute myocardial infarction (P < 0.05). CONCLUSION: Adhesion molecule levels are stable under normal laboratory sample handling conditions. Levels do not change in the 24 h following the onset of chest pain of non-cardiac or acute ischaemic aetiology.
Arterial transfer functions have been promoted for the derivation of central aortic waveform characteristics not usually accessible noninvasively, but possibly of prognostic significance. The utility of generalized rather than gender-specific transfer functions has not been assessed. Invasive central aortic and noninvasive radial (Millar Mikro-tip tonometer) blood pressure waveforms were recorded simultaneously in 78 subjects (61 male and 17 female). Average transfer functions were obtained for the whole group and for each gender by two methods. Reverse transformation was performed with the use of each transfer function. Measured aortic waveform parameters were compared with those derived using average, gender-appropriate, and gender-inappropriate transfer functions. Differences in central waveform characteristics were demonstrated between men and women. Derived waveform parameters were significantly different from measured values [e.g., subendocardial viability index and augmentation index (P < 0.001)]. A gender-appropriate transfer function significantly improved the derivation of some parameters, including systolic pressure and systolic and diastolic pressure time integrals (P < 0.05). Generalized arterial transfer functions may not be universally applicable across all waveform parameters of potential interest, and gender-specific transfer functions may be more appropriate.