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Biomedical subjects

D Wheeldon

Publications and source records attributed to D Wheeldon.

At least 19 recordsLinked to original sources
PubMed2000

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device.

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.

Heart Septal Defects, Atrial↗
PubMed2000

Structural changes in porcine bioprosthetic valves of a left ventricular assist system in human patients.

BACKGROUND AND AIM OF THE STUDY: Porcine, specially manufactured bioprosthetic valves regulate blood flow from the left ventricle to pump sac (inflow valve) and from the pump to the aorta (outflow valve) in a wearable, electrically powered left ventricular support system (LVAS, Novacor). The increased need for long-term circulatory assistance requires information on the evolution of these valves when exposed to specific hemodynamic conditions and inflammatory reactions in the device. The study aim was to examine structural changes in valves from explanted LVASs. METHODS: Thirteen patients (11 males, two females; mean age 42 years (range: 17-64 years) were supported for a mean of 285 days (range: 37-1,293 days) with LVAS. Histologic sections from explanted inflow and outflow valves were studied immunohistochemically using peroxidase-labeled antibodies and avidin-biotinylated peroxidase complex for detection. RESULTS: In the macroscopically normal inflow valves (11/13), the outflow surface (facing the pump) was covered with a discontinuous deposit of fibrin, macrophages and granulocyte elastase. Fibrinogen, IgG, complement proteins C1q and C3 had infiltrated the extracellular matrix (ECM) between 37 and 1,293 days. The crevices were enlarged during circulatory support, and fibrinogen/fibrin insudations were detected in the spongiosa. The collagen layers in the fibrosa were disrupted after 293 days, and eroded on the inflow surface in the ventricularis after 1,293 days. In a deteriorated valve from a patient with endocarditis, Gram-positive bacteria and metalloproteinases were concentrated in the ECM. In the macroscopically normal (11/13) outflow valves, fibrin and complement proteins had penetrated the ECM from the inflow side (facing the pump), while macrophages and granulocytes were localized mainly on the outflow surface. IgG and complement proteins were detected on and beneath the cusp surface up to 200 days and covered the disrupted ECM as implant time progressed. CONCLUSIONS: Structural changes appear to progress more rapidly in the inflow than in the outflow of bioprosthetic valves. This difference indicates that the effects of biological factors are modulated by mechanical stress.

Adolescent↗
PubMed1999

The contribution of donor management and modified cold blood lung perfusate to post-transplant lung function.

BACKGROUND: Donor organ availability remains the major limiting factor in the treatment of patients with end-stage lung disease by lung transplantation. Maximising the use of available organs is therefore crucial. Details available at the time of organ referral may give a misleading impression of their quality. Intensive donor management may improve the quality of the organs thereby improving the quality of the outcome. METHODS: We performed 56 heart-lung and 5 double lung transplants between November 1990 and September 1993; 49 had adequate documentation for analysis. All organs were preserved with modified cold blood solution with an ischemic time of 197 (117-297) minutes. Assessment of lung function post-implantation was performed using an acute lung injury score as this gives a more accurate indication of overall lung function. Donors were treated intensively by bronchoscopy, optimal fluid management and appropriate lung expansion. RESULTS: Careful management improved donor quality so that the alveolar-arterial oxygen gradient fell significantly from 185 (+/-20) mmHg at arrival to 80 (+/-11) mmHg (p < .0001) immediately prior to harvesting 190 minutes later. This improvement was maintained following harvesting using the modified cold blood preservation solution so that lung injury was assessed as "mild" according to the acute lung injury criteria post-transplantation. There was one instance of primary lung failure following transplantation which was neither related to the quality of the organ at harvesting nor to the method of lung preservation. CONCLUSIONS: Intensive donor management significantly improves the quality of donor organs, providing an improvement in immediate post-transplantation lung function. This improvement is maintained using modified cold blood lung preservation solution.

Adolescent↗
PubMed1991

Thoracic organ preservation.

Clinical heart transplantation began in December 1967 when Cristiaan Barnard performed the first human to human heart transplant on a 57 year old man with ischaemic heart disease, in Cape Town. This ushered in a bout of enthusiastic heart transplantations world-wide over the subsequent few years which soon waned as the problems of acute rejection and infection became apparent to those who had embarked on this venture without fully understanding the complications. The importance of a well functioning donor heart cannot be overemphasized. Early donor heart failure accounts for approximately 26% of the deaths of heart transplant recipients today and there is also a steep rise in acute mortality associated with storage times in excess of two hours (9.8% less than 2 hours rising to 17.6 greater than 4 hours), although satisfactory function has been reported in a few hearts stored for up to 6 hours. Careful selection and meticulous management of the donor, followed by optimal storage, are therefore essential to a satisfactory outcome. There is evidence that some of the problems of organ preservation are related to metabolic changes in the donor consequent upon brain death and recent ongoing studies by our own group show some benefit from hormone replacement therapy in the donor. There are essentially two major approaches to the problem of organ storage; metabolic inhibition resulting in reduced substrate requirements, and the supply of metabolic requirements, or a combination of both. Although nonperfusion methods currently predominate, the simplicity of these methods are overshadowed by the short safe time interval which they allow and the variable functional quality which results. The author believes that perfusion preservation methods will predominate in the future and may also allow expansion of the donor pool by whole donor and/or ex vivo thoracic organ resuscitation.

Equipment Design↗
PubMed1989

Effect of donor heart damage on survival after transplantation.

Evaluation of the functional condition of the heart prior to its removal from the donor or after transport to the recipient is difficult. Biopsies of the myocardium allow serial assessments to be made throughout this period, but suffer from the disadvantage that the average analysis of biopsies has only a tenuous connection with physiological function. Quantitative birefringence measurements (QBM), on the other hand, assess the ability of myocardial fibres to respond to ATP and calcium and have been shown to correlate well with measurements of cardiac function (P less than 0.001). A prospective study of myocardial biopsies before excision, after transport and again after transplantation, using quantitative birefringence measurement of biopsies of the heart has recently been completed. These studies have shown evidence of impaired myocardial function in 73 (43%) of 172 donor hearts studied prior to excision, with a further 27% showing significant deterioration during storage and transport to the recipient. Biopsy assessments therefore indicated that at the moment of implantation, only 30% of the donor hearts were normal. Functional assessment of the biopsies by QBM correlated with early clinical outcome of transplantation (P less than 0.001). Longer term follow-up of the recipients (up to 5 years) has shown that the mortality of recipients of hearts with impaired function before transplantation is significantly increased (44% of 120) compared with that of recipients of undamaged hearts (6% of 52, P less than 0.001).

Biopsy↗
PubMed1988

Three solutions for preservation of the rabbit heart at 0 degree C. A comparison with phosphorus-31 nuclear magnetic resonance spectroscopy.

Phosphorus-31 nuclear magnetic resonance has been used to measure changes in tissue adenosine triphosphate and pH that occur during hypothermic preservation of rabbit hearts. Three potential preservation solutions were studied: the St. Thomas' Hospital no. 1 cardioplegic solution, Bretschneider's HTP solution, and a solution originated in our laboratory, CP5, which we have previously studied in the rabbit heart with functional assessment by Langendorff perfusion. After being flushed with one of these solutions, each heart was stored at 0 degrees C for 12 hours, during which time it was subjected to repeated phosphorus-31 nuclear magnetic resonance scans. It was shown that adenosine triphosphate levels decayed more slowly with CP5 than with either of the other solutions or in the control experiments. Adenosine triphosphate decay was also slower with Bretschneider's HTP than with St. Thomas' Hospital solution, but pH was somewhat better maintained with Bretschneider's HTP than with either other solution or in the control hearts, although the pH did not decrease drastically in any group. CP5 was designed to prevent cell swelling and to reduce the uptake of calcium during storage, for which reasons it contains 30 mmol/L glucose and 0.1 mmol/L calcium. The potassium content is somewhat higher and the sodium and magnesium content somewhat lower than in St. Thomas' Hospital solution, with the objective of stabilizing intracellular concentrations of these ions during storage.

Adenosine Triphosphate↗
PubMed1987

Cardiac output and oxygen consumption in exercising Thoroughbred horses.

This study characterizes the effects of exercise on the cardiac output (Q) and the metabolic rate (VO2) of trained Thoroughbred racehorses. Heart rate, Q, and arteriovenous (a-v)O2 difference were measured at rest and at three levels of submaximal treadmill exercise (1.6 m/s walk and 3-4 m/s trot at 6% incline, and 6.5 m/s horizontal canter). Heart rate and (a-v)O2 difference were also measured during maximal exercise (12.5 m/s gallop, 5% incline) to obtain an estimate of maximum O2 uptake (VO2max). The walk, trot, and canter represented 25, 45, and 55% VO2max. Mean heart rate went from 48.9 (rest) to 197 beats/min (gallop). Q ranged from 106 (rest) to 571 ml.min-1.kg-1 (canter), and stroke volume went from 1.34 (rest) to a maximum of 1.58 liters (walk). Thoroughbreds were able to bring hematocrit from 38 (rest) to 63% (gallop), and this adjustment allowed them to reach an impressive (a-v)O2 difference of 23 vol%, which represents a fivefold increase over resting values. These outstanding athletes probably support an aerobic scope of 40-fold.

Animals↗
PubMed1987

Biopsy assessment of fifty hearts during transplantation.

The aim of the study was to evaluate myocardial protection during the transportation of human donor hearts stored at 4 degrees C in crystalloid cardioplegic solution. Biopsies were performed on 50 donor hearts before excision and at four subsequent time intervals during transplantation. Quantitative birefringence measurements on cryostat sections of the left ventricular biopsy specimens were used to assess myocardial function. Fifteen donor hearts had poor birefringence assessments before excision, and 67% received inotropic support after implantation; 22 deteriorated during transportation, and 50% received inotropic support; 13 were unchanged throughout the procedure, and none required inotropic support. This study demonstrates the need for improved protection of donor hearts during transportation and recommends the use of rigorous criteria in the selection of these hearts.

Adolescent↗
PubMed1985

Haemodialysis and haemofiltration on cardiopulmonary bypass.

Over a three year period we have used haemodialysis and haemofiltration in parallel with cardiopulmonary bypass in 26 patients. Impaired renal function and excessive fluid retention have been the main indications. Patients on haemodialysis programmes for end stage renal failure did not require further dialysis until at least the third postoperative day, when they could tolerate the haemodynamic disturbance of dialysis. In the other patients these techniques proved valuable in reversing the effects of haemodilution and in controlling the concentration of serum potassium. Our experience has confirmed that haemodialysis and haemofiltration in parallel with cardiopulmonary bypass are useful adjuncts in the perioperative management of patients with impaired renal function undergoing open heart surgery. The techniques are also effective in correcting the fluid retention and biochemical imbalance in patients with congestive cardiac failure, including those with heart transplants.

Adolescent↗
PubMed1984

Selection and procurement of hearts for transplantation.

The success of orthotopic heart transplantation depends wholly on satisfactory function of the new heart on completion of the operation. This in turn depends on the quality of the donor heart before its removal, the effectiveness of the methods used to preserve it during transport from the donor to the recipient hospital, and the accuracy of the operative procedure. From January 1979 to December 1983, 62 donor hearts were transplanted into 61 recipients at Papworth Hospital. These hearts were selected from 250 offered for consideration. The most common reasons for not proceeding with an initial inquiry were failure of the donor to meet the medical criteria for selection (77 cases) and lack of intensive care facilities or staff shortages such that a transplant could not be accommodated at the time of inquiry (80). Eight early deaths occurred, of which three were due to primary failure of the donor heart. Actual one and three year survivals for the whole programme were 58% and 50% respectively, the current actual one year survival being 70%. Forty per cent of patients selected for transplantation died while waiting for a heart to become available. Their average survival time was 46 days. The number of donor hearts referred for transplantation depends on public attitudes towards organ transplantation, the willingness of doctors looking after brain dead patients to seek permission from relatives for the heart to be donated, and the cooperation of local kidney transplant surgeons. A larger number of suitable donor hearts to choose from would enable more patients to be treated, as transplant operations could be arranged so that existing facilities were used to their maximum capacity.

Adolescent↗
PubMed1979

Use of partial cardiopulmonary bypass during the anhepatic phase of orthotopic liver grafting.

Femoro-femoral partial cardiopulmonary bypass has been used in two patients under going orthotopic liver allografting who had severe cardiovascular disturbances on trial clamping of their venae cavae. Flows of 2-3 litres/min resulted in satisfactory cardiovascular control during the anhepatic phase in each ase. A third patient who tolerated caval clamping withstood the grafting without bypass. Having bypass available for use in critical cases could increase the safety of orthotopic liver transplantation.

Adult↗
PubMedDate not supplied

Donor heart preservation survey.

A questionnaire requesting information on donor heart preservation technique and outcomes during the first 6 months of 1990 was circulated to heart transplantation centers worldwide. Seventy-nine usable replies representing 1371 clinical transplant operations were received. Twenty-seven percent of the respondents reported using some form of donor pretreatment. Most (90%) used single flush cardioplegic induction with the use of eight different types of cardioplegic solutions, only 5% of which were oxygenated. Six different types of storage media were used, and the coolant was melting ice in 66% of the centers. Storage temperatures between 0 degrees C and 7 degrees C were reported, with 78% of the respondents using 4 degrees C storage. Fifty-five percent of the centers used some form of reperfusion modification. No statistically significant associations were noted between outcome and technique, apart from the use of storage medium in which the use of cardioplegic solution conferred a 2.5 times increase in deaths compared with cold saline. The results of this questionnaire provide evidence for the diversity of techniques currently used for donor heart preservation, reflecting the lack of any one optimal method.

Cardioplegic Solutions↗