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Biomedical subjects

D Wheeldon

Publications and source records attributed to D Wheeldon.

9 recordsLinked to original sources

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

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

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

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

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

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