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Biomedical subjects

J H Dark

Publications and source records attributed to J H Dark.

At least 19 recordsLinked to original sources
PubMed1996

Vasopressin release during orthostatic hypotension after cardiac transplantation.

At the time of cardiac transplantation all nerves from the donor ventricles are cut. These nerves may regrow, but there is no method of measuring any regrowth. Arginine vasopressin (AVP) release was studied during hypotension induced by head-up tilt and lower body negative pressure (LBNP) in transplant recipients and in normal controls. Subjects were tilted to 60 degrees for up to 60 min or until symptomatic. Lower body negative pressure (40 mmHg) was applied for 10 min after 30 min rest. Seven of 17 transplant recipients and 11 of 12 controls became symptomatic during tilt testing, and 9 of 12 controls and 9 of 17 transplant recipients became symptomatic after 10 min of LBNP. Symptoms during tilt did not predict symptoms during LBNP. Resting AVP levels were similar but osmolality was greater in transplant recipients. Resting haematocrit was reduced, and atrial natriuretic peptide increased in transplant recipients, suggesting increased plasma volume. In symptomatic subjects, changes in humoral concentrations were similar when compared between transplant recipients and normals, except that the rise in AVP at the time of symptoms was reduced in transplant recipients, with a comparable drop in blood pressure consistent with persistent cardiac afferent denervation in a subset of transplant recipients.

Adult↗
PubMed1996

Vascular complications of lung transplantation.

BACKGROUND: The data on vascular anastomotic complications after single-lung and bilateral lung transplantation are scant. METHODS: We reviewed the data on our patients having single and bilateral lung transplantation to examine our experience and management of vascular anastomotic complications. RESULTS: We retrospectively identified 5 of 109 consecutive patients undergoing lung transplantation who had postoperative pulmonary arterial or venous obstruction. There were 4 women and 1 man (age range, 32 to 53 years). Three patients had left single-lung transplantation, 1 patient had right single-lung transplantation, and 1 patient underwent bilateral sequential lung transplantation. Complications comprised two right-sided and two left-sided pulmonary artery stenoses and one combined left pulmonary arterial and venous obstruction. Isotope perfusion scanning was used in 3 patients and suggested a vascular stenosis in all of them. Pulmonary angiography was used in each as a confirmatory test and to demonstrate anatomic details. Transesophageal echocardiography was used in 1 patient and did not detect a right pulmonary artery stenosis. One patient underwent revision of a pulmonary artery stenosis with a period of warm ischemia and subsequent fatal lung injury. Two revisions were undertaken on cardiopulmonary bypass with a cold blood flush to the transplanted lung. One venous anastomotic angioplasty with stent insertion was performed. Two patients died before treatment. All 5 patients died between 5 and 630 days postoperatively. CONCLUSIONS: Vascular complications carry a high mortality. Reoperation, preferably using cardiopulmonary bypass and a cold blood flush technique to avoid further lung injury, is recommended. In high-risk patients, dilation or stent insertion can be considered.

Adult↗
PubMed1996

Pulmonary endothelial permeability changes after major lung resection.

BACKGROUND: Increased pulmonary endothelial permeability has been proposed as a cause of postpneumonectomy pulmonary edema. This study investigated changes in pulmonary endothelial permeability after major lung resection. METHODS: Lung scintigraphy was performed in 21 men (median age, 66 years; range, 34 to 73 years) after pneumonectomy (10 patients) or lobectomy (11 patients). Pulmonary endothelial permeability was measured by the net pulmonary accumulation of intravenous technetium-99m-labeled albumin, calculated as a ratio of lung:heart radioactivity counts. Pulmonary hemodynamics were monitored continuously by a pulmonary artery catheter, and serum levels of inflammatory cytokines were assayed. RESULTS: The lung:heart radioactivity ratio increased significantly in the initial 8 hours after pneumonectomy but not after lobectomy (p < 0.01). Mean pulmonary artery pressure and pulmonary vascular resistance both increased significantly during pneumonectomy (p < 0.05). The intraoperative increase in mean pulmonary artery pressure was inversely related to preoperative mean pulmonary artery pressure (r = -0.47; p = 0.02). The postoperative change in lung:heart radioactivity ratio to the perioperative increase in pulmonary vascular resistance (r = 0.54; p = 0.02) but not to the increase in mean pulmonary artery pressure (r = 0.14; p > 0.05). Serum interleukin-8 and neutrophil elastase levels were elevated in all patients preoperatively. The postoperative change in lung:heart radioactivity ratio was related to preoperative elastase levels (r = 0.61; p = 0.02). CONCLUSIONS: Pulmonary endothelial permeability appears to be increased after pneumonectomy. Preoperative neutrophil activation and the adaptation of the remaining pulmonary vasculature may be etiologic factors.

Adult↗
PubMed1996

Healing of the bronchus in pulmonary transplantation.

OBJECTIVE: To review the results of bronchial healing in a consecutive series of 100 isolated pulmonary transplants, performed at one centre between 1987 and 1994. METHODS: A retrospective review of 123 assessable bronchi (61 in single lung and 62 in bilateral lung) transplants was carried out. All anastomoses were assessed by bronchoscopy at 7-10 days, and follow up was from one to seven years. The effect on bronchial dehiscence or stenosis requiring endobronchial stent, of suture technique, pre and post operative steroid administration, bronchial wrap, donor ischaemic time and time to first rejection episode was assessed. RESULTS: Complications of airways healing occurred in four patients: stenosis in two and dehiscence in two (1.6% of bronchi at risk in both groups). Airway complication was not affected by steroids, pre-operative diagnosis, presence of a wrap (34 with pericardium or omentum, 89 with peribronchial tissue alone) or any other variable. There was a higher incidence of dehiscence (2/36) with continuous rather then interrupted (0/87) suture, but this was not statistically significant. There was one airway-related death. Two patients who required anastomotic stenting remain alive and well. CONCLUSIONS: A very low complication rate can be achieved without recourse to bronchial wrapping, telescoping anastomoses or steroid avoidance. Combined heart-lung transplantation or bronchial revascularisation are not required to achieve reliable bronchial healing.

Adolescent↗
PubMed1996

Role of glycosaminoglycans (GAGs) in regulation of the immunogenicity of human vascular endothelial cells.

Heparan sulphate is a common glycosaminoglycan component of proteoglycans present on the luminal surface of vascular endothelium. It has been proposed that an important function of these molecules is the sequestration of a range of proinflammatory and proadhesive cytokines. Such cytokines play a vital role during lymphocyte recruitment from the blood at sites of inflammation. In this study it is shown that the effects of interferon-gamma (IFN-gamma), but not of tumour necrosis factor-alpha (TNF-alpha), are inhibited by treatment with soluble heparin. Specifically, heparin was shown to inhibit the induction of class II MHC antigens and the up-regulation of intercellular adhesion molecule-1 (ICAM-1) produced by treatment of cultured human endothelial cells with IFN-gamma. Furthermore, it was shown that heparin blocked the enhanced adhesion of T lymphocytes to IFN-gamma-treated endothelial cells. Investigation of the inhibitory effects of other GAG molecules demonstrated a requirement for heparin-like structural domains as chondroitin sulphate was unable to inhibit the function of IFN-gamma. These results may explain reported immunosuppressive properties of heparin, and are consistent with the model that heparin may compete with cell surface GAGs to bind IFN-gamma, thereby reducing effective biological activity.

Cell Adhesion↗
PubMed1996

Reproducibility of electrophysiological measurements in cardiac transplant recipients.

The clinical usefulness of certain electrophysiological measurements, particularly those of sinus node function, is limited by variation in autonomic tone resulting in poor reproducibility. The denervated transplanted heart is not susceptible to direct autonomic control and, therefore, electrophysiological measurements may be more reproducible in this group. To our knowledge, this hypothesis has not previously been systematically evaluated. Ten adult recipients underwent serial electrophysiological studies between 10-18 days after cardiac transplantation. Five studies were performed at 2-hour intervals during a single day, between 9:00 a.m. and 5:00 p.m. Spontaneous cycle length (SCL) was recorded. Sinus node recovery time (SNRT), sinoatrial conduction time (SACT), and atrioventricular (AV) Wenckebach cycle length were measured using standard techniques. The effective refractory periods of the complete AV conducting system (AVERP), atrium (AERP), and ventricle (VERP) were measured. Corrected maximal SNRT was normal in all subjects. Mean coefficients of variation (Cv) for SCL, corrected maximal SNRT, and SACT were 2.8%, 7.4%, and 3.5%, respectively. AVERP was less than AERP in seven subjects, limiting further analysis. The mean Cv for AV Wenckebach cycle length was 2.1%. The mean coefficients of variation for AERP were 3.6% and 3.7%, and for VERP 3% and 3.3%, at 600- and 400-ms drive cycle lengths, respectively. Previous studies report much greater variation in innervated subjects particularly of indices of sinus node function. Thus, the reproducibility of electrophysiological measurements of sinus and AV node function in the transplanted heart is better than in normal subjects. This may have important implications for the reliability of electrophysiological testing in transplant recipients.

Atrioventricular Node↗
PubMed1996

Exercise response after cardiac transplantation: correlation with sympathetic reinnervation.

OBJECTIVE: To investigate the relation between sympathetic efferent reinnervation and chronotropic competence during exercise testing after cardiac transplantation. PATIENTS: Twenty five long-term cardiac transplant recipients and 11 normal controls. SETTING: Regional cardiothoracic centre. METHODS: Intracoronary tyramine was given to the transplant recipients and the per cent heart rate change measured. Exercise tests were performed in patients and controls according to the chronotropic assessment exercise protocol, and the per cent heart rate reserve measured at peak exercise and 6 min afterwards to estimate the recovery rate. RESULTS: The mean (SD) percentage heart rate change after intracoronary tyramine was 15.7 (15.4). Heart rate reserve achieved at peak exercise was 68.3 (20.6)% compared with 102.7 (9.3)% in the controls (P < 0.001). Heart rate recovery at 6 min was 41.7 (20.1)% compared with 79.5 (9.0)% in the controls (P < 0.001). Total workload was 69.0 (33.0) METS.min compared with 117.2 (41.9) METS.min in the controls (P < 0.01). There was a positive correlation between heart rate reserve achieved at peak exercise and response to tyramine (r = 0.66, P < 0.01), between heart rate recovery and response to tyramine (r = 0.69, P < 0.001), and between total workload and response to tyramine (r = 0.63, P = 0.04). CONCLUSION: Functional sympathetic efferent reinnervation of the sinus node occurred in some patients after transplantation, and was associated with improved heart rate response during and recovery after exercise, as well as with increased total workload.

Adult↗
PubMed1996

Permanent pacemaker use after cardiac transplantation: completing the audit cycle.

OBJECTIVE: To determine the effects of delaying permanent pacemaker implantation in cardiac transplant recipients from less than tree weeks to three weeks or more post transplantation-a change prompted by an earlier audit. DESIGN: Retrospective review of resting 12 lead electrocardiograms and prospective 24 hour ambulatory electrocardiograms. Comparison of pacemaker usage before (period 1) and after (period 2) the policy change in November 1990. SETTING: Outpatient department, supra-regional cardiopulmonary transplant unit. PATIENTS: All 30 consecutive orthotopic cardiac transplant recipients who received a permanent pacemaker within one month of transplantation between May 1985 and August 1995. MAIN OUTCOME MEASURES: Presence of pacing on the 12 lead electrocardiogram and during 24 hour ambulatory electro-cardiogram monitoring (pacemaker programmed to 50 beats per minute). RESULTS: 16/152 (10.5%) cardiac transplant recipients received permanent pacemakers in period 1 compared with 14/180 (7.8%) in period 2 (P = NS). Evidence of pacing was seen on 12 lead electrocardiograms at three months in 37.5% recipients in period 1 compared with 78.6% in period 2 (P = 0.03). At six months pacemaker usage had declined to 18.8% in period 1 and 35.7% in period 2 and at three years to 13.3% in period 1 and 40% in period 2 (P = NS for both). 21% patients in period 1 paced on ambulatory 24 hour monitoring compared with 38.5% in period 2 (P = NS). CONCLUSIONS: Delaying permanent pacemaker implantation to three weeks or more after cardiac transplantation reduced the proportion of permanent pacemaker implantations, slightly but not significantly. There was a significant increase in permanent pacemaker usage at three months post transplantation with trends towards increased usage at later times, suggesting more appropriate selection of patients for permanent pacing.

Clinical Protocols↗
PubMed1996

Permanent pacemaker implantation after cardiac transplantation: extra cost of a conservative policy.

OBJECTIVE: To determine the costs of a change in permanent pacemaker implantation policy to later implantation (day 21+) after cardiac transplantation. DESIGN: Retrospective review of patient records including duration of temporary pacing, timed of permanent pacemaker implantation, and length of hospital stay for every patient surviving > or = 14 days from November 1990 to August 1995 (period 2) and for all patients in whom permanent pacemakers were implanted between May 1985 and November 1990 (period 1). SETTING: Supra-regional cardiopulmonary transplant unit. PATIENTS: 335 consecutive adult cardiac transplant recipients at Freeman Hospital between May 1985 and August 1995. MAIN OUTCOME MEASURES: The cost of the policy change was calculated by subtraction of the overall saving in pacemaker implantations from the overall cost of the extra inpatient stay in period 2 due to delayed implantation. RESULTS: Mean inpatient stay per patient following cardiac transplantation of permanent pacemaker recipients in period 1 was 13.8 days compared with 23.9 days in period 2 (P < 0.001). The cost of this extended hospital stay is 60,095 pounds. Had the implantation policy not been changed, a further seven patients would have received a permanent pacemaker in period 2. A saving in pacemaker hardware of 16,275 pounds was made. Overall, however, the new permanent pacemaker implantation policy increased expenditure by 43,820 pounds, assuming that permanent pacemaker implantation was the only reason for the extended hospital stay. CONCLUSION: The change in policy from early to later permanent pacemaker implantation has markedly increased expenditure.

Clinical Protocols↗
PubMed1995

Evolution of the chronotropic response to exercise after cardiac transplantation.

The chronotropic response to exercise is abnormal in cardiac transplant recipients as a result of autonomic denervation. Differences in the response between recent transplant recipients and longer-term survivors have been described in previous cross-sectional studies. These changes have not been assessed directly using serial studies. The effect of sinus node dysfunction on the chronotropic response has not previously been determined. Thirty-one transplant recipients underwent serial treadmill exercise tests using the chronotropic exercise assessment protocol 3 and 6 weeks and 3 and 6 months after transplantation. Sinus node function was assessed using standard electrophysiologic techniques. The chronotropic response increased between 3 and 6 weeks after transplantation in all subjects. Six months after transplantation, there was a further marked increase in the response in a subgroup of 5 subjects. These subjects also had a dramatic decrease in heart rate on cessation of exercise. Three subjects had abnormal sinus node function. Although heart rates and chronotropic response were below average in these subjects, 2 other subjects with normal sinus node function on electrophysiologic testing had lower heart rates and worse chronotropic responses. Thus, the chronotropic response to exercise evolves over the first 6 weeks after cardiac transplantation in all subjects. In a number of recipients (16%), there is a marked increase in chronotropic response between 3 and 6 months, which suggests efferent sympathetic reinnervation. There was no clear difference in chronotropic response between subjects with and without evidence of sinus node dysfunction.

Adult↗
PubMed1995

Use of low dose arginine vasopressin to support brain-dead organ donors.

In a prospective study, we documented the hemodynamic effects of conventional donor maintenance in 24 brain-dead organ donors. Patients were then randomized to receive either saline or a low dose arginine vasopressin (AVP) infusion. In the AVP group (n = 11), plasma hyperosmolality decreased (P < 0.05), blood pressure increased (P < 0.01), inotrope use decreased (P < 0.01), and cardiac output was maintained. In the control group (n = 13), plasma hyperosmolality increased (NS); no significant change in blood pressure, cardiac output, or inotrope infusion rate occurred. Myocardial ATP levels were higher in the AVP than the control group (NS). Early organ function was similar in the 2 groups. We conclude that the use of a low dose AVP infusion enables inotrope use to be reduced and recommend consideration be given to the use of a low dose AVP infusion in potential thoracic organ donors.

Adenosine Triphosphate↗
PubMed1995

Donor-acquired fat embolism causing primary organ failure after lung transplantation.

Technically successful bilateral sequential lung transplantation in a 40-year-old man was complicated by the immediate development of pulmonary edema on reperfusion of the allograft. Death resulted within 12 hours and was caused by the fat embolism syndrome confirmed on premortem open-lung biopsy. The donor had satisfied current selection criteria but had sustained a femoral and multiple rib fractures. This case highlights the potential risks of transplanting lungs from traumatic donors and the deficiencies in current methods of donor assessment.

Adult↗
PubMed1995

Mechanical ventricular assistance for the failing right ventricle after cardiac transplantation.

Right ventricular failure secondary to elevated pulmonary vascular resistance (PVR) following orthotopic cardiac transplant is a complication with a high mortality; and patients with high resistance are often not accepted on transplant waiting lists. We describe six cases of right ventricular failure after cardiac transplant managed by right ventricular assist device (RVAD), four of whom died and two patients who survived following life-threatening complications.

Adult↗
PubMed1995

The economics of transplantation.

Transplantation continues to be a popular solution for a number of end-stage diseases and survival rates continue to increase. It is, however, an expensive therapeutic option, with the costs persisting throughout a patient's lifetime. It is therefore important to keep sight of these costs in relation to the quality of patient outcome and the emergence of alternative therapies.

Cost-Benefit Analysis↗
PubMed1994

Sinus node function after cardiac transplantation.

OBJECTIVES: This study aimed to examine changes over time in sinus mode function after cardiac transplantation; to determine the incidence, natural history and etiology of sinus node dysfunction in transplant recipients; and to identify any early predictors of long-term sinus node function. BACKGROUND: Bradyarrhythmias caused by sinus node dysfunction are common immediately after cardiac transplantation. Existing electrophysiologic studies have been limited by small numbers and have reported an unexpectedly high incidence of sinus node dysfunction (approximately 50%) compared with the incidence of bradyarrhythmias in other studies. There have been no previous studies reporting serial electrophysiologic data. Thus, the natural history of sinus node dysfunction after transplantation has not been adequately described. METHODS: Serial electrophysiologic studies of sinus node function and 24-h ambulatory electrocardiographic recordings were performed at 1, 2, 3 and 6 weeks and 3 and 6 months after transplantation in 40 adult recipients. RESULTS: The overall incidence of sinus node dysfunction was 17.5% (7 of 40). Six patients (15%) had sinus node dysfunction from week 1; one developed sinus node dysfunction at 3 months. Sinus node recovery time returned to normal by 6 weeks in all six patients with early sinus node dysfunction, but abnormalities of sinoatrial conduction persisted in two. Two patients who required pacing during ambulatory monitoring at 2 weeks after transplantation (temporary pacemaker 50 beats/min, demand) received a permanent pacemaker. One patient required pacing at 3 weeks and continued to require pacing 6 months after transplantation. CONCLUSIONS: The incidence of sinus node dysfunction after cardiac transplantation is lower than has been previously reported in electrophysiologic studies. Sinus node automaticity improves with time, although abnormalities of sinoatrial conduction may persist. The best predictor of permanent pacing requirements is the temporary pacing requirements during 24-h Holter monitoring 2 and 3 weeks after transplantation, with temporary pacing set at 50 beats/min on demand.

Arrhythmia, Sinus↗