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Biomedical subjects

C N Barnard

Publications and source records attributed to C N Barnard.

At least 55 records · Page 3Linked to original sources

Twenty-four-hour preservation of the pig heart by a portable hypothermic perfusion system.

A portable hypothermic perfusion system for storage of hearts has been developed. The system uses the airlift pump principle, whereby the flow of gas maintains circulation of the perfusate through the heart; no other energy source is required. Performance on ex vivo functional testing of 10 pig hearts stored for 20 to 24 hr using this system (group 3) was compared with that of freshly excised hearts (group 1) and hearts stored simply in the perfusate under hypothermic conditions, but not perfused (group 2). Group 2 hearts performed less well on functional testing than those of groups 1 and 3 which showed little statistical difference, suggesting good preservation by hypothermic perfusion. This has been confirmed by orthotopic transplantation of similarly preserved baboon hearts with survival until rejection at a mean of 27 days. The importance of the various constituents of the perfusate and the significance of weight gain during the storage and reperfusion periods are discussed.

Animals↗

Technique, complications, and clinical value of endomyocardial biopsy in patients with heterotopic heart transplants.

A review of 157 consecutive biopsies of donor endomyocardium in patients with heterotopic heart transplants is reported. The technique of percutaneous transvenous endomyocardial biopsy after this operation is described; manipulation of the catheter and bioptome into the junction of the donor superior vena cava and right atrium can be difficult when this anastomotic junction is small, as a result either of operative surgical technique or of subsequent contraction. The complication rate was 4%, but one patient may have died from infection resulting from biopsy when the bioptome had to be introduced at the groin. The histopathological changes seen in the biopsy specimens have been graded according to a scoring system to give the clinician a guide to the severity of rejection. Histopathological assessment was of clinical value in 96% of cases, but was inaccurate on two occasions, once because an opinion was given on what was in retrospect an inadequate sample. In patients undergoing persistent low-grade acute or chronic rejection there was difficulty in detecting or appreciating the true extent of myocardial fibrosis; this led to inadequate immunosuppressive treatment in two patients. Attention is drawn to the fact that ischaemic fibrosis resulting from the vascular changes of chronic rejection may spare the endomyocardium, which is kept viable by intracavitary blood, and that this may lead to a misleading histopathological report.

Biopsy↗

Changes in indications for heart transplantation. An additional argument for the preservation of the recipient's own heart.

The 1 year survival rate after heart transplantation since 1967 from +/-30% to +/-70%, and the 5 year survival rate is now +/-50%. This improvement has brought renewed interest in this procedure, now done in about twenty centers in eight countries, and increased confidence has widened the indication to patients who are less than terminally ill, to restore quality of life. This trend is illustrated by the Cape Town series, which can be divided into two parts: 10 patients treated by orthotopic heart transplantation (OHT), from 1967 to 1973, and 40 patients treated by heterotopic heart transplantation (HHT), from 1974 to 1981. The HHT group was younger (mean 37 +/- 10 years versus 51 +/- 9 years, p less than 0.001), had been ill for a shorter length of time (mean 3.6 +/- 0.7 years versus 6.6 +/- 1.4 years, p less than 0.091), and were in a lower New York Heart Association (NYHA) class (mean 3.45 +/- 0.11 versus 3.9 +/- 1.0, p less than 0.006). The improved survival is linked to patient selection, progress in management, and switch to HHT, but not to progress in matching between donor and recipient. Since there is no means to predict tolerance of the donor heart, HHT limits the risks from unforseeable mismatch. The recipient's heart is a built-in assist device, maintaining life when the donor heart fails acutely at operation or during acute [three cases] or chronic [two cases] rejection. Had these patients undergone OHT they would have died. Comparing the 10 oldest HHT patients with the OHT series, no difference in pretransplant parameters was found. However, survival of HHT recipients was longer during the critical post-HHT period: at 3 months, p less than 0.011; at 6 months, p less than 0.05. Larger series will separate the effects of progress in management from the intrinsic advantages of HHT. Retaining the recipient's heart is logical and has brought few complications. Survival rate of 40 HHT patients was 73% at 6, 65% at 12, and 51% at 36 months; 85% of survivors are in NYHA Class I. In patients in less than desperate condition, but who refuse to remain cripples, HHT eliminates the growing ethical problem of removing a recipient's heart that may still support the patient.

Adolescent↗

Orthotopic transplantation of the baboon heart after 20 to 24 hours' preservation by continuous hypothermic perfusion with an oxygenated hyperosmolar solution.

Baboon hearts were rapidly excised after being flushed with 500 ml of cardioplegic solution at 4 degrees C and then immersed in cold 4 degrees C saline or cardioplegic solution for 2 minutes. The hearts were then perfused at 8 to 10 cm H2O pressure for 20 to 24 hours under refrigeration with a hyperosmolar clear fluid maintain perfusate at 6 to 8 degrees C, through which 95% oxygen and 5% carbon dioxide were continually bubbled to maintain the perfusate pH between 7.2 and 7.4. Myocardial temperature remained at approximately 6 to 8 degrees C. The hearts were then orthotopically transplanted into recipient baboons matched for size and AB blood group. Two groups (A and B) were studied, differing significantly only with respect to the constitution of the cardioplegic solution and perfusate used. The cardioplegic agent used in Group B contained a higher concentration of magnesium than that used in Group A and included the calcium antagonist verapamil. Perfusate B had higher osmolality than perfusate A, largely due to the inclusion of sucrose. A preliminary group of 10 baboons in Group A received no immunosuppression. Five of the remaining six immunosuppressed baboons in this group survived more than 48 hours to rejection or until killed at 2 to 29 days. All six of the baboons in Group B survived to rejection between 6 and 33 days, with mean survival 19.5 days. Cardiac catheterization was performed in six surviving baboons (Group A, four; Group B, two) between postoperative days 6 and 10 and showed good hemodynamic function. Histologic examination of hearts after death has shown only minor ischemic changes in those hearts which functioned well.

Animals↗

Mitral valve replacement in children.

Mitral valve replacement (MVR) is associated with higher mortality and morbidity rates in children than in adults, and the use of heterograft valves has been encouraged. The results of MVR in 56 consecutive patients, aged 2 to 12 years, presenting between January, 1972, and January 1979, were reviewed to test these beliefs. The etiology of mitral valve disease was rheumatic in 46, congenital in eight, and acute bacterial endocarditis in two. All children were seriously disabled (NYHA Classes III and IV). Cardiac catheterization in 36 patients revealed mixed valve disease in 26, pure mitral regurgitation in seven, and pure mitral stenosis in three. Seventeen Starr-Edwards (SE), five Lillehei (L), Björk-Shiley (BS), eight Hancock (H), and 25 Carpentier-Edwards (CE) mitral prosthesis were inserted. Operative mortality was 2% (1 BS) and late mortality was 10% (three SE, one L, two CE). Serious late complications occurred in 30% of survivors, including 11 instances of calcific valve stenosis (five H, six CE), one case of valve thrombosis (1 L), and two embolic episodes (1 SER, 1 H). Survival curves were similar for patients with heterograft and mechanical valves (92% and 77% at 5 years). Event-free curves showed heterograft valves to have a far higher complication rate than mechanical valves (10% complication free at 4 years compared to 84% free at 5 years). Early operative results in children are excellent, and the overall mortality (10%) compares favorably with figures for MVR in adults. However the long-term durability and choice of prostheses remain problematical, since less than 10% of heterograft valves survive beyond 5 years.

Acute Disease↗

Ex vivo functional evaluation of pig hearts subjected to 24 hours' preservation by hypothermic perfusion.

A system has been developed for the ex vivo functional testing of isolated hearts. Three groups, each of 10 pig hearts, have been studied: group 1--freshly excised hearts; group 2--heart hypothermically perfused for 20 - 24 hours with Krebs-Henseleit solution; group 3--hearts similarly perfused with a clear fluid hyperosmolar solution. Group 2 hearts performed poorly on functional testing and would clearly have been unsuitable for transplantation. Haemodynamic observations on group 3 hearts showed little statistical difference from those of group 1, suggesting good preservation. The value of the ex vivo testing system as a reliable means of assessing myocardial function is discussed, and has been confirmed by subsequent successful orthotopic transplantation of baboon hearts stored under identical conditions.

Animals↗

An investigation of the immunosuppressive effects of niridazole and metronidazole in rat and baboon heterotopic cardiac allograft models.

Niridazole alone (at 50 mg/kg/day) and particularly in combination with azathioprine and prednisolone showed potent immunosuppressive activity, far surpassing that produced by conventional agents, in the rat heterotopic cardiac allograft model. Benzoylmetronidazole or metronidazole (at 50 mg/kg/day) either alone or in combination with azathioprine and prednisolone demonstrated little immunosuppressive activity. The potent immunosuppression obtained with niridazole in the rat could not be reproduced in the baboon heterotopic cardiac allograft model in the doses used; niridazole at 50 mg/kg/day seems to be toxic in this animal.

Animals↗

[The aorto-coronary by-pass. Personal clinical experience (author's transl)].

The surgical treatment of coronary artery disease still remains controversial, despite the fact that the surgical indications are widely recognized and so the efficacy of the aortocoronary bypass in relieving angina and in improving the prognosis of the patients with left mainstem lesions. However, one gets the impression that the criteria for surgery not always are correctly applied, with the consequence that the bypass is often performed on patients that could still benefit from proper medical treatment. At Groote Schuur Hospital, during the period 1976-78, we have bypassed a total of 395 coronary arteries in 204 patients. All the patients were in NYHA class III and IV. The peculiarity of this rather small series is based on the conservatism of the selection criteria, the operation being offered only to candidates with a very long history of angina uncontrolled by adequate medical treatment. The early mortality rate has been 1.47%, the late mortality rate 3.5% and the perioperative infarction rate 10.8%. All the patients have been followed up for 12-48 months (mean follow up 30.3 months). 80% of the patients returned in class I and 13.5% in class II. 80 out of 112 patients operated during 1976-77 have had routine coronary angiography one year post-surgery: the graft patency rate in this group has been 71%. The majority of the obstructed grafts were related to small vessels of 1 mm in diameter. On the basis of these clinical results we conclude that no controversy is justified once and adequate trial with proper medical treatment has already failed.

Angina Pectoris↗

The present status of heterotopic cardiac transplantation.

In the period November, 1974 to May, 1980, 30 patients underwent heterotopic heart transplantation at Groote Schuur Hospital. One patient subsequently underwent retransplantation for rejection. There were no operative deaths. Fifteen patients are alive 4 months to almost 5 1/2 years after transplantation. The 1 year survival rate has been 61%. Three of six patients have survived for more than 4 years. Eight of nine patients whose initial transplant operation was performed during the past 18 months remain alive. Seven patients died from infection, five from rejection, and three from other causes. The advantages of heterotopic over orthotopic heart transplantation, in particular in allowing patients survival even after graft destruction by irreversible rejection, are discussed.

Adult↗

Clinical transplantation of the heart: a review of 13 years' personal experience.

The results of the heart transplantation operations performed personally by one surgeon (CNB) at Groote Schuur Hospital between 1967 and 1980 are reviewed. Of 9 orthotopic transplants performed between 1967 and 1973, 4 survived for more than one year and 2 remain alive today twelve and ten years later. Of 11 heterotopic transplants performed since 1974, one-year patient survival has been 82%, though one patient survived on his own heart after irreversible graft rejection. Three of the original 4 patients remain alive over five years later. These results are rather better than the overall results of our unit, where a total of 37 heterotopic transplants has been performed; the possible reasons for this are discussed. One patient, previously unreported, who underwent transplantation of the heart and both lungs in 1971, died after 23 days from pulmonary complications. Heterotopic transplantation using a xenograft (baboon or chimpanzee heart) has been performed on two occasions as a means of temporary circulatory support in patients with acutely failing hearts when no human donor was available. The chimpanzee heart supported the circulation satisfactorily for four days.

Adolescent↗

Long-term survival after orthotopic and heterotopic cardiac transplantation.

Five long-term survivors of heart transplantation were reinvestigated. Two patients had undergone orthotopic heart transplantation over 11 and 9 years earlier and constitute two of the world's longest-surviving patients after this procedure. Three patients had undergone heterotopic heart transplantation (one left heart bypass alone and two biventricular bypass) four to six years earlier. Four of the five patients had had only one or no documented acute rejection episodes. Three had been given blood transfusions. None had had particularly good tissue matching in relation to the donor on HLA typing. All five patients were leading full and active lives. At review two patients had significant coronary artery disease, one severe, presumably due to chronic immune-complex deposition. Heart transplantation remains a major undertaking, but it can offer the patient many years of good-quality life.

Adult↗

Morphological changes in 49 chacma baboons after cardiac allografts.

The morhpological changes in 49 chacma baboons after cardiac transplantation were studied by light and electron microscopy. Non-immunosuppressed grafts were tolerated for an average of 10 days and immunosuppressed grafts for 18 days. Serial biopsy specimens of non-immunosuppressed grafts showed a progression in severity of rejection changes. Electron microscopy mirrored the light microscopic changes. Rejection changes in the baboon appear similar to those encountered in human and canine allografts. Heterotopic transplants showed more severe grades of rejection than would be compatible with life in orthotopic transplants.

Animals↗

The pathology of human cardiac transplantation: an assessment after 11 years' experience at Groote Schuur Hospital.

Over a period of 11 years, commencing in December 1967, 31 cardiac transplants, 10 orthotopic and 21 heterotopic, were performed at Groote Schuur Hospital. Two patients with orthotopic transplants have a long survival, 1 for 7 1/2 and 1 for 9 1/2 years, and 1 with a heterotopic transplant for 4 years. Eighteen patients have died, and autopsy was performed from 13 to 623 days postoperatively. Rejection of the donor heart was found in 61,1% and was the cause of death in 44,4% of cases. Infection, attributable to immunosuppression, was a common finding and consisted of extensive pneumonia, usually due to Klebsiella aerogenes and Pseudomonas aeruginosa (38,8%), herpesvirus infection (38,8%), cytomegalic virus infection (37,5%), aspergillosis and other opportunistic infections. A combination of cardiac rejection and infection accounted for most of the deaths. The cardinal microscopic features of acute rejection were interstitial lymphocytic infiltration and myocytolysis, while chronic rejection was typified by obliterative myo-intimal proliferation of coronary arteries, with concurrent lipid deposition in the major coronary arteries. These lesions resembled atherosclerosis and caused graft failure due to myocardial ischaemia. Ultrastructurally, severe myofibre damage was reflected in extensive loss of cytoplasmic myofilaments. The advantages of heterotopic over orthotopic transplantation are discussed.

Adult↗

Annular subvalvular idiopathic left ventricular aneurysms in the black African.

The case of a Black African patient with an annular subvalvular left ventricular aneurysm of unknown origin is described, and the pathological findings in this condition together with a review of the literature is presented. We have operated on 12 patients with this condition between 1958 and 1978. Ventricular aneurysm in the Black African is extremely rare; aneurysms resulting from ischemic heart disease have not been encountered in this racial group, and contrary to earlier reports in the literature, syphilis is not the most common cause of left ventricular aneurysms in this group. The aneurysms arise in the fibrous rings below either the aortic or the mitral valve, extend around the valves in this situation, and may occur either singly or in both positions in the same heart. After various etiological factors are excluded, it is probable that in this group of patients the aneurysms develop initially as pulsion diverticula through a congenital weakness in the ventricular wall in the region of the atrioventricular groove.

Adult↗

Heterotopic versus orthotopic heart transplantation.

Since November 1974, heterotopic cardiac transplants have been performed at this unit in preference to orthotopic transplants. A number of reasons have led us to prefer this technique, namely donor malfunction in the immediate postoperative period and during rejection; right ventricular failure of the donor heart in the orthotopic position in patients with pulmonary hypertension; the ease of patient management; and the use of the donor heart as a temporary method of cardiac support. Disadvantages are the later recognition of rejection and the difficulty in performing transvenous endomyocardial biopsies. The results are satisfactory giving a 1, 2, and 3-year survival rate of 62%, 58%, and 50%, respectively.

Graft Rejection↗

A review of experience with cardiac transplantation.

Despite the hazards of rejection and the complications of immunosuppression, cardiac transplantation is the only available treatment for myocardial disease that is refractory to medical therapy and in which no other form of surgery can be offered. There are disadvantages to orthotopic cardiac transplantation, which have led to the development by this department of the heterotopic cardiac transplant, which functions as a natural left-heart and right-heart assist device. The results of 19 cases are presented.

Adult↗