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Biomedical subjects

R S Bonser

Publications and source records attributed to R S Bonser.

At least 37 records · Page 2Linked to original sources

Incremental shuttle walk test in the assessment of patients for heart transplantation.

OBJECTIVE: To compare the incremental shuttle walk test (ISWT) with treadmill exercise testing (TT) derived measurement of peak oxygen consumption (peak VO(2)) in patients undergoing assessment for cardiac transplantation. DESIGN: Prospective comparison. All investigations occurred during a single period of admission for transplant assessment. SETTING: Single UK cardiothoracic transplantation unit. PATIENTS: 25 patients recruited (21 men). Mean age was 53 years. INTERVENTIONS: Patients underwent two TT of peak VO(2) using the modified Naughton protocol and three (one practice) ISWT. Investigations were performed on consecutive days. MAIN OUTCOME MEASURES: Main outcome measures were repeatability of TT and ISWT assessments; relation between peak VO(2) and distance walked in the ISWT; and receiver operating characteristic (ROC) analysis to establish a distance walked in the ISWT that predicted which patients would have a peak VO(2) greater than 14 ml/min/kg. RESULTS: Both the ISWT and the TT were highly reproducible. Following the first practice walk, mean (SD) ISWT distances were 400.0 (146) m (ISWT2) and 401.3 (129) m (ISWT3), r = 0.90, p < 0.0001. Mean peak VO(2) by TT was 15.2 (4.4) ml/kg/min (TT1) and 15.0 (4.4) ml/kg/min (TT2), r = 0.83, p < 0.0001. The results revealed a strong correlation between distance covered in the ISWT and peak VO(2) obtained during TT (r = 0.73, p = 0.0001). ROC analysis showed that a distance walked of 450 m allowed the selection of patients with a peak VO(2) of over 14 ml/min/kg. CONCLUSIONS: This work confirms the utility of the ISWT in the assessment of exercise capacity in patients with severe heart failure undergoing assessment for cardiac transplantation. ISWT may provide a widely applicable surrogate measure for peak VO(2) estimation in this population. Shuttle distance walked may therefore allow the convenient, serial assessment of patients with heart failure before referral for transplantation.

Exercise Test↗

Retrograde perfusion and true reverse brain blood flow in humans.

OBJECTIVE: Reversal of brain blood flow is necessary for retrograde cerebral perfusion (RCP) to have any metabolic benefit, but RCP is commonly used with little clinical evidence of the true incidence of reverse brain blood flow and impact. S-100B is exclusive to the brain and spinal cord and released during hypothermic circulatory arrest (HCA). True reverse brain blood flow (tRBBF) during RCP may be determined by demonstrating an excess of S-100B in the effluent blood from the common carotid artery compared to blood entering the brain. METHODS: Simultaneous blood samples were drawn from the jugular bulb and left common carotid artery during RCP at 5 min intervals in ten patients undergoing aortic surgery, utilizing HCA and subjected to blood gas, glucose and S-100B quantification. RCP was instituted at maximum pressure of 25 mmHg. Trans-cranial Doppler (TCD) continuously monitored the middle cerebral artery velocity (MCAV). RESULTS: The mean HCA and RCP durations were 31 min (20-50 min). Reversal of MCAV was demonstrated in only 6/10 cases (mean, 6 cm/s). Veno-arterial (V-A) extraction of oxygen and glucose occurred in all cases (P<0.001), with the mean effluent pO(2) falling to 14 mmHg. V-A S-100 gradients greater than 5% were demonstrated in 8/10 cases and correlated with higher oxygen extraction (P<0.01). In patients with and without MCAV reversal, the S-100 gradients were 1. 7 and 0.3 micromol/l, respectively (P<0.01). CONCLUSIONS: tRBBF occurred in nearly all patients. MCAV reversal appears to be a specific but insensitive guide to reverse perfusion. The de-saturation of effluent blood is not a reliable guide to true brain perfusion, and despite RCP, the brain remains ischaemic.

Biomarkers↗

Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

Biopsy↗

Differential time scale of fluid and solute permeability following hypothermic lung preservation.

BACKGROUND: Assessment of the quality of lung graft preservation by simple functional measures in some laboratory models may fail to detect endothelial injury. The effects of hypothermic preservation in isolation were investigated by measuring the pulmonary capillary filtration coefficient (Kf) and the albumin surface area product (PS) at various cold ischemic intervals. METHODS: Rat lungs were flushed with University of Wisconsin solution at 4 degrees C. Following storage at 4 degrees C, lungs for Kf measurement were subjected to a change in pulmonary arterial pressure. Kf was calculated from the change in rate of weight gain as a function of hydrostatic stress. PS lungs were exposed to Tris buffered Ringer's solution containing 1125 albumin (20 microM) in an isogravimetric state. Following a vascular flush the lungs were homogenized and underwent scintillation counting. Using the Kedem-Katchalsky equation PS was calculated. RESULTS: The Kf for the control, 4-hour, and 7-hour groups were 0.778, 1.816, 4.853 g/ cm H2O/min/100 g wet lung tissue, respectively. There was a significant increase in Kf with each time increment (P,0.01). The Kf for the 24-hour group was 5.587 g/cm H2O/min/100 g wet lung tissue; not an additional significant increase. PS for the control and 4-hour groups (0.0115 and 0.0101 cm3/g wet lung tissue/minute, respectively) were not significantly different. After 7 hours there was a significant increase to 0.171 cm3/g wet lung tissue/min. PS could not be measured after 24 hours. CONCLUSIONS: Significant endothelial injury occurs after 4 hours of cold ischemic preservation. There is progressive injury with time. Increase in water permeability is not secondary to increase in albumin permeability.

Albumins↗

Reduction of endothelial injury after hypothermic lung preservation by initial leukocyte-depleted reperfusion.

OBJECTIVES: Leukocyte depletion has been shown to ameliorate the effects of reperfusion injury in many organ systems. The aim of this study was to investigate the effects of leukocyte depletion on functional and endothelial markers of pulmonary performance after cold ischemic injury. METHOD: Groups of 6 rat lungs were flushed with University of Wisconsin solution and then stored at 4 degrees C for 4 hours. They then underwent sanguine reperfusion for 30 minutes, during which time functional measures (gas exchange, pulmonary artery, and airway pressures) were made and after which the lungs underwent estimation of endothelial permeability by measurement of the capillary filtration coefficient (in grams per centimeter of water per minute per grams of wet lung tissue) by a gravimetric technique. Four groups were studied: group 1 underwent no reperfusion, group 2 underwent 30 minutes of reperfusion, group 3 underwent 30 minutes of leukocyte-deplete reperfusion with an in-line leukocyte filter (PALL), and group 4 underwent 10 minutes of leukocyte-depleting reperfusion followed by 20 minutes of normal reperfusion. RESULTS: The capillary filtration coefficient increased between group 1 and group 2 animals (1.05 +/- 0.32 to 3.07 +/- 0.47 [mean +/- SEM]; P <.01). Complete leukocyte depletion caused the greatest diminution in the capillary filtration coefficient (0.392 +/- 0.07, P <.001), but initial leukocyte depletion (group 4) also showed a significant diminution (0.74 +/- 0.3, P <.01). Complete or initial leukocyte depletion caused no significant change in functional measures of pulmonary performance. Complete leukocyte depletion produced less pulmonary leukostasis, as assessed by means of myeloperoxidase activity. CONCLUSION: Initial and continued leukocyte depletion are associated with amelioration of reperfusion-induced endothelial injury after cold ischemic injury.

Animals↗

Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake.

BACKGROUND: In patients with postischaemic left ventricular dysfunction, segments recovering function after revascularisation (hibernating myocardium) may not respond during dobutamine echocardiography, despite preserved [(18)F] 2-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography. OBJECTIVE: To investigate whether this lack of response might reflect the degree of ultrastructural change in hibernating myocardium. METHODS: Transmural biopsies were obtained from 22 dysfunctional segments in 22 patients during coronary artery bypass grafting and examined by light and electron microscopy. Wall motion scores and coronary vasodilator reserve were assessed before and after coronary artery bypass grafting (CABG). RESULTS: Mean (SD) wall motion score improved in all segments following CABG (from 2.24 (0.4) to 1.55 (0.4); p < 0.0001), confirming hibernating myocardium. In these segments myocardial blood flow (positron emission tomography with H(2)(15)O) before CABG was similar to that in normal volunteers (1.02 (0.24) v 1.02 (0.23) ml/min/g), while the coronary vasodilator reserve was blunted (1.26 (0.7) v 3.2 (1.6); p < 0.0001). Myocardial blood flow was unchanged after CABG, whereas coronary vasodilator reserve increased to 2.10 (0.90) (p < 0.0007). In hibernating myocardium myofibrillar loss, interstitial fibrosis, and glycogen-rich myocytes were more marked than in control donor hearts. On the basis of the response to dobutamine before CABG, two functional groups were identified: group A, segments with inotropic reserve (n = 15); group B, segments without inotropic reserve (n = 7). FDG uptake was similar in group A and group B (0.40 (0.1) v 0.44 (0.1) micromol/min/g). In group B there was more myofibrillar loss (26 (8)% v 11 (5)%; p = 0.0009) and glycogen-rich myocytes (28 (11)% v 17 (10)%; p = 0.02), whereas interstitial fibrosis, myocardial blood flow, and coronary vasodilator reserve were similar in the two groups. Myofibrillar loss was the only independent predictor of inotropic reserve (p = 0.01). CONCLUSIONS: Hibernating myocardium is characterised by a reduced coronary vasodilator reserve which improves on revascularisation and shows a spectrum of ultrastructural changes that influence the response to dobutamine, while FDG uptake is invariably preserved.

Adult↗

Coronary arteries from a single coronary ostium in the right coronary sinus: a previously unreported anatomy.

The coronary circulation originating from a single coronary ostium is rare. All possible anatomical variations were the basis of a recent classification. This case report describes a previously unreported IID(1) pattern, comprising a solitary coronary ostium in the right coronary sinus with an anatomical course of the right coronary artery. The left circumflex coronary artery arises from the proximal right coronary artery coursing behind the aorta to the left. The left anterior descending coronary artery arises from the proximal right coronary artery coursing to the left side anterior to the right ventricle.

Aortic Dissection↗

Clinical and patho-anatomical factors affecting expansion of thoracic aortic aneurysms.

OBJECTIVE: To examine the expansion of aneurysmal aortic segments (> or = 35 mm) and to assess the impact of clinical and patho-anatomical factors on aneurysm expansion. DESIGN: 87 consecutive patients (mean age 63.6 years, range 22-84 years) were studied using serial (six month intervals) computed tomographic or magnetic resonance imaging to monitor progression of thoracic aortic aneurysms. Aortic diameter was measured at seven predetermined segments and at the site of maximum aortic dilatation (MAX). RESULTS: 780 segment intervals were identified. The median overall aneurysm expansion rate was 1.43 mm/year. This increased exponentially with incremental aortic diameter (p < 0.01) and varied by anatomical segment (p < 0.05). The presence of intraluminal thrombus (p < 0.01) but not dissection or calcification was associated with accelerated growth. Univariate analysis identified thrombus (p < 0.001), previous stroke (p < 0.002), smoking (p < 0. 01), and peripheral vascular disease (p < 0.05) as factors associated with accelerated growth in MAX. Dissection, wall calcification, and history of hypertension did not affect expansion. beta Blocker treatment was not associated with protection. Multivariate analysis confirmed the positive effect of intraluminal thrombus and previous cerebral ischaemia, and the negative effect of previous aortic surgery on aneurysm growth. These findings translated into a mathematical equation describing exponential aneurysm expansion. CONCLUSIONS: Aneurysmal thoracic aortic segments expand exponentially according to their initial size and their anatomical position within the aorta. The presence of intraluminal thrombus, atherosclerosis, and smoking history is associated with accelerated growth and may identify a high risk patient group for close surveillance.

Adult↗

S-100beta release in hypothermic circulatory arrest and coronary artery surgery.

BACKGROUND: Aortic surgery utilizing profound hypothermic circulatory arrest (HCA) has a higher incidence of neurological injury than coronary artery bypass grafting (CABG). S-100beta is a potential marker of cerebral ischemic injury. The aim of this study is to assess its use in investigating cerebral injury during HCA. METHODS: We studied 40 patients (10 CABG, 30 HCA). The mean cardiopulmonary bypass (CPB) times were 72 and 158 minutes, respectively. Mean HCA duration was 27.6 min, with retrograde cerebral perfusion (RCP) used in 18 patients (mean 28.5 minutes, 95% CI 16-25). Perioperative venous blood samples were subjected to S100beta assay. RESULTS: S100beta levels with HCA (peak: 2.68 microg/L, 95% CI 1.99-3.38 microg/L; calculated area under the curve [AUC]: 1596 microg/L/min, 95% CI 825-2368 microg/L/min) were significantly higher (peak, p = 0.028 and AUC, p = 0.007) than with CABG (peak: 1.16 microg/L, 95% CI 0.25-2.1 microg/L and AUC: 53.4 microg/L/min 95% CI 3.0-103.8). Peak S100beta correlated with CPB time in CABG cases (r = 0.76, p < 0.05), and with both CPB and HCA time in HCA cases: without RCP (r = 0.46 and 0.21, respectively, p > 0.05) and with RCP (r = 0.88 and 0.33, respectively, p < 0.05). There was no significant difference in the S100beta levels between HCA groups with and without RCP, but HCA time was longer in the RCP group (p = 0.05). CONCLUSIONS: S100beta release correlates with duration of CPB and HCA. Elevated serum S100 indicates astrocyte death or activation, and suggests blood-brain barrier dysfunction. The continuing release of S100 after the end of operation suggests that HCA may be associated with greater injury than CABG. RCP did not influence S-100beta release in this study.

Aorta↗

Does retrograde cerebral perfusion affect risk factors for stroke and mortality after hypothermic circulatory arrest?

BACKGROUND: In aortic surgery requiring hypothermic circulatory arrest (HCA), retrospective studies identify age and duration of the arrest period as predictors of stroke and mortality. Retrograde cerebral perfusion (RCP) has been reported to reduce the risk of stroke when compared with historical controls. The aim of this study was to ascertain if RCP affected mortality, stroke, or the risk factors for these end points in a consecutive series of HCA patients. METHODS: We investigated the impact of RCP in 130 patients, mean age 62.7 years (range 20-84); 78 were men and 35% were emergencies. Overall mortality was 16.9% (elective 9.5%) and the incidence of stroke was 6.9%. Mean HCA time was 30.1 min (95% confidence interval [CI] 27.9-34). RCP was instituted in 96 cases for a mean of 24.4 min (95% CI 21.9-27.0). RESULTS: Perioperative univariate predictors of mortality were emergency status, acute rupture, long HCA and cardiopulmonary bypass duration, and postoperative complications. For stroke, age (p = 0.007), hypertension (p = 0.05), and long HCA duration (p = 0.01) were predictive. RCP did not decrease mortality (p = 0.18, OR 0.55) or incidence of stroke (p = 0.57, OR 1.26). Mortality after stroke was 44.4% (p = 0.04, OR 4.6). Multiple logistic regression showed severe aortic atherosclerosis and RCP duration (p = 0.038) as risk factors for mortality, and myocardial ischemic time (p = 0.012) and HCA duration (p = 0.05) as risk factors for stroke. HCA and RCP groups differed in HCA duration (HCA mean 25 min [10-80], RCP mean 32 min [10-69]; p < 0.019). CONCLUSIONS: Age and HCA duration remain risk factors for stroke and mortality despite RCP. However, HCA times were longer in the RCP patients, and the patients were not randomized. The role of RCP in cerebral protection requires further prospective randomized studies.

Adult↗

Prediction of thoracic aortic aneurysm expansion: validation of formulae describing growth.

BACKGROUND: The expansion rate of thoracic aortic aneurysms may be an important and clinically relevant index of the risk of rupture. The aims of this study were to assess the validity of three published exponential equations that predict expansion rate in a separate sample population, and to calculate an expansion rate formula for this cohort of patients. METHODS: We studied 88 consecutive patients undergoing serial computed tomographic or magnetic resonance imaging scanning to monitor thoracic aortic aneurysm progression. In interval scans of at least 6 months, we measured minimum coronal aortic diameter at seven set levels and maximal diameter, yielding 780 segment-intervals. RESULTS: The linear expansion rate (mean 2.6 mm/year) increased with incremental aortic diameter (aortic diameter < 40 mm: 2.0; 40-49 mm: 2.3; 50-59 mm: 3.6; > or = 60 mm: 5.6 mm/year; p < 0.01). Regression analysis showed close correlation between predicted and sample data, but there were significant differences between observed and expected measurements. The Yale formula underestimated growth by 0.8 mm, while Mt. Sinai and Osaka formulae overestimated actual change by 1.5 and 0.2 mm, respectively. The expansion rate derived from our population was: last diameter = initial diameter x e(0.00367 x time) (r = 0.617). CONCLUSIONS: Although formulae derived from one thoracic aortic aneurysm sample population may not extrapolate exactly to others, there is close concordance of results for patient populations in three different continents.

Aortic Aneurysm, Thoracic↗

Insulin resistance in patients with cardiac hypertrophy.

OBJECTIVE: Animal studies suggest that left ventricular hypertrophy might be associated with insulin resistance and alterations in glucose transporters. We have previously demonstrated myocardial insulin resistance in patients with post-ischemic heart failure. The aim was to investigate whether myocardial insulin resistance could be demonstrated in human cardiac hypertrophy in the absence of hypertension, diabetes and coronary artery disease. METHODS: Eleven normotensive nondiabetic patients with cardiac hypertrophy due to aortic stenosis and angiographically normal coronary arteries were compared to 11 normal volunteers. Myocardial glucose uptake (MGU) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose during fasting (low insulinemia) or during euglycemic-hyperinsulinemic clamp (physiologic hyperinsulinemia). Myocardial biopsies were obtained in order to investigate changes in insulin-independent (GLUT-1) and insulin-dependent (GLUT-4) glucose transporters. RESULTS: During fasting, plasma insulin (7 +/- 1 vs. 6 +/- 1 mU/l) and MGU (0.12 +/- 0.05 vs. 0.11 +/- 0.04 mumol/min/g) were comparable in patients and controls. By contrast, during clamp, MGU was markedly reduced in patients (0.48 +/- 0.02 vs. 0.70 +/- 0.03 mumol/min/g, p < 0.01) despite similar plasma insulin levels (95 +/- 6 vs. 79 +/- 6 mU/l). A decreased GLUT-4/GLUT-1 ratio was shown by Western blot analysis in patients. CONCLUSIONS: Insulin resistance seems to be a feature of the hypertrophied heart even in the absence of hypertension, coronary artery disease and diabetes and may be explained, at least in part, by abnormalities in glucose transporters.

Aortic Valve Stenosis↗

Replacement of the proximal aorta and aortic valve using a composite bileaflet prosthesis and gelatin-impregnated polyester graft (Carbo-Seal): early results in 143 patients.

OBJECTIVE: We report the combined early results from two centers in the United Kingdom using a composite conduit consisting of a bileaflet mechanical valve incorporated into a gelatin-impregnated, ultra-low porosity, woven polyester graft (Carbo-Seal; Sulzer Carbomedics, Inc, Austin, Tex). METHODS: Between August 1992 and March 1997, 143 patients underwent aortic root replacement with the Carbo-Seal composite prosthesis. The indication for surgery was acute type A dissection in 31 (22%), chronic type A dissection in 9 (6%), ascending aortic aneurysm without dissection in 100 (70%), and false aneurysm of the ascending aorta in 3 (2%). Twenty-seven patients (19%) had undergone previous sternotomy, and 40 (28%) were seen as emergencies. Concomitant procedures were performed in 38 (27%), including 18 aortic arch or hemiarch replacements. Total follow-up is 270 patient-years. Follow-up is 100% complete. RESULTS: The early (30-day) mortality was 7% (10 patients). Permanent neurologic events occurred in 2%. At a mean follow-up of 23 months, 94% of survivors were in New York Heart Association functional class I. Freedom from reoperation was 97.2% +/- 1.6% (1 standard error [1 SE]) at 12 months and 95.7% +/- 2.2% at 48 months. Including early mortality, survival was 90.1% +/- 2.6% at 12 months and 83.1% +/- 3. 5% at 48 months. CONCLUSIONS: Aortic root replacement with use of the Carbo-Seal prosthesis can be undertaken with a relatively low early mortality and morbidity. A low reoperation rate and high intermediate-term survival can be expected, but continued follow-up is needed to determine the long-term efficacy of this prosthesis.

Aged↗

Aortic regurgitation in rheumatoid arthritis necessitating aortic valve replacement.

Four cases of patients with aortic incompetence secondary to rheumatoid arthritis are presented. All survived aortic surgery (two having bioprosthetic aortic valve replacement and two a homograft aortic root replacement). A review of the pathophysiology and pathology of this rare cause of aortic regurgitation is presented. A rationale for the choice of aortic valve prosthesis is discussed.

Adult↗

Reproducibility of thoracic aortic diameter measurement using computed tomographic scans.

OBJECTIVES: Decisions to recommend elective surgical repair of thoracic aortic aneurysms (TAA) may be based on size or expansion rate, which are used as indices of the risk of rupture. Measurement error may thus affect clinical decision-making. In order to evaluate the reproducibility of aortic diameter measurements of TAA, we assessed departmental inter- and intra-observer variability of measurement of pre-selected computed tomographic scan images of aneurysmal segments of the thoracic aorta. METHODS: We compared measurements of minimum aortic diameter made by four observers in 50 pre-selected scans and at different times by two observers using a calliper method and a measurement tool within the scan. Differences in measured dimension were analysed using Wilcoxon's signed ranks test and the repeatability assessed using the method of Bland and Altman. RESULTS: There were no significant inter-observer differences among three observers but there were significant differences between another observer and two other observers (P < 0.05). No significant intra-observer differences existed. The best intra-observer repeatability was 2.25 while the worst inter-observer repeatability was 4.37. The mean and maximum difference in measurement were +/-0.88 mm and +/-8.0 mm, respectively. Variability of measurement increased with aortic diameter. CONCLUSIONS: Calliper measurement of TAA is an acceptable measurement method for surveillance of TAA but appears most accurate with a single observer. Increasing error is seen with increasing diameter which may compound error in estimation of expansion rate. Standardisation of technique is advisable for multiple observers and aortic units should adopt quality assurance protocols to minimise error.

Aortic Aneurysm, Thoracic↗

Myocardial revascularization for the treatment of post-ischemic heart failure.

Heart failure due to coronary artery disease is a major public health problem. Medical treatment ameliorates symptoms and prognosis, although mortality remains high. Heart failure occurs when a sizeable number of myocytes do not contract. This may be due to irreversible myocyte loss (infarct) and/or dysfunctional but viable myocytes (hibernating), which can resume function following coronary artery bypass surgery. The presence of hibernating myocardium can be predicted by noninvasive nuclear imaging using both single photon (SPECT) and positron emission tomography, and also by stress echocardiography. A number of uncontrolled studies have demonstrated a promising role for coronary artery bypass surgery in patients with heart failure in whom a substantial amount of hibernating myocardium is present. These findings, particularly the magnitude of the benefits reported, justify the need for a randomized trial in this patient population.

Angina, Unstable↗