Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation.

BACKGROUND: The coagulation process in hyperacute and delayed xenograft rejection is essential and depends upon platelet adhesion and aggregation. The initial binding of platelets to the damaged endothelium is due to the interaction of the platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is present on activated endothelial cells and bound to the subendothelial matrix. We hypothesized that the use of organs from animals with homozygous von Willebrand disease (vWD), severely deficient in vWF, might prevent the thrombosis encountered in delayed xenograft rejection. METHODS: Ten baboons were treated by extracorporeal immunoadsorption of xenoreactive natural antibodies (XNA) through the donor pig liver to inhibit hyperacute rejection and received heterotopic vWD or control pig kidney xenografts. XNA levels, coagulation, and platelet activation markers were studied, and specimens of rejected kidneys were analyzed histologically. RESULTS: Although XNA depletion was comparable in both groups, neither kidney function nor survival times of control (n=5) or vWD (n=5) porcine kidneys showed any difference. Platelet and coagulation activation was evidenced in both groups after surgery and at rejection time. Immunohistochemical analysis revealed a weak endothelial vWF immunostaining in the rejected vWD kidneys, whereas it was undetectable in the nongrafted vWD kidneys, suggesting the deposition of baboon plasma vWF on the porcine vessels. CONCLUSIONS: The use of vWD organs did not improve the survival time of grafted kidneys in this xenotransplantation model. Further studies on the use of vWD organs, in association with other therapeutic approaches, such as complement inhibition, are nevertheless necessary to evaluate the usefulness of vWF deficiency as an adjunctive therapy to decrease the coagulation process during xenograft rejection.

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Albumin-impregnated prosthetic graft for infrarenal aortic replacement: effects on the incidence and volume of perioperative blood transfusion.

We retrospectively reviewed 290 cases in which an albumin-impregnated polyester prosthetic graft was used for surgical management of aortic bifurcation disease between November 1987 and December 1990. The purpose of this review was to determine the incidence and volume of blood transfusion and to evaluate the rate of patency and the incidence of infection achieved using this type of prosthesis. The indication for surgery was abdominal aortic aneurysm (AAA) in 218 cases (190 elective procedures and 28 emergency procedures) and occlusive disease of the aortic bifurcation (ODAB) in 72 cases. Mean follow-up was 25.5 +/- 13.4 months (range: 1 and 50 months). The incidence of blood transfusion for elective AAA and ODAB surgery was 30.2% and 32.3% intraoperatively, 21.3% and 12.9% postoperatively, and 40.4% and 42.6% overall. The mean number of red cell packs transfused for elective AAA and ODAB surgery was respectively 1 and 0.8 intraoperatively, 0.4 and 0.6 postoperatively, and 1.4 and 1 overall. No immediate or late graft infection prosthesis was observed in any patient in this series. Primary and secondary patency was 95.5% and 97.5% at 6 months with no graft thrombosis during further follow-up. The fact that use of an impregnated graft in management of aortic bifurcation disease was accompanied by a high incidence and volume of blood transfusion suggests that these grafts do not reduce perioperative blood loss. Use of an impregnated prosthesis had no effect on the rate of patency and the incidence infection.

The pig as a model in liver xenotransplantation.

Xenotransplantation is considered to be the best solution to the critical shortage of human donors. Despite its phylogenetic distance, the pig appears to be the most appropriate source of organs for transplantation in humans. Its anatomy and physiology are similar to that of man, it can be raised in specific pathogen free environments and it is available in large quantities. The immunological barrier remains to be overcome, however. Considerable progress in the pathogeny of xenogenic rejection has led to the development of therapeutic strategies and the prospect of clinical xenografting appears realisable in the near future.

[An original case of simultaneous cardiac, pancreatic and renal transplantation. Results over 6 years]. / Observation princeps de transplantation associée cardiaque pancréatique et rénale. Résultat à 6 ans.

Combined transplantation is actually performed on specific and rare indications. We are presenting here the results of a combined heart-kidney and pancreatic graft. It was performed in a patient presenting an idiopathic cardiomyopathy in end-stage failure and a post-diabetic nephropathy on dialysis. Today, organs function is quite satisfactory with a 6 year follow-up. Only one isolated heart rejection episode was observed at the 15th post-operative day. The patient has recovered a full-time professional activity at one year. This successful graft was obtained by an "homogeneous multiorgan approach" during all the pre-peri and postoperative time.

[Evaluation of a new technique of extracorporeal perfusion of the swine liver on a swine-primate model]. / Evaluation d'une nouvelle technique de perfusion extracorporelle de foie de porc sur un modèle porc-primate.

With the increasing success of liver transplantation there is an urgent need for developing an artificial liver support system to be used in patients with liver failure. An extracorporeal porcine liver perfusion machine was successfully tested in animals with experimental liver failure. Livers were flushed, removed from 35 kg pigs and placed in a heated sterile cassette. The portal vein and the hepatic artery of the graft were connected to the arterial system of the animals. The perfusion pressure of the hepatic artery was regulated via a pressure-flow computerized feed-back device. The venous flow was reinfused from the hepatic veins of the graft to the jugular vein of the animals. The experimental work consisted in two steps: 1. evaluation of clinical and biological consequences of liver perfusion in healthy animals (Group A = pigs, n = 3; group B = primates, n = 3); 2. evaluation of the efficiency of the liver perfusion in animals with ischemic liver failure (Groupe D = pigs, n = 6). The control group (Group C = pigs, n = 7) consisted of pigs with ischemic liver failure without hepatic support. No major clinical or biological adverse effects are reported in groups A and B excepted a thrombocytmia and a marked increase in serum transaminases levels in group B. Liver function as assessed by the bile flow was good in both groups. Comatose pigs with ischemic hepatic failure (group D) recovered a subnormal neurological status in five out of six cases. Serum ammoniemia level were significantly decreased (from 1076 +/- 163 to 255 +/- 32 umol/l). A decrease in serum bilirubine levels and an improvement in the coagulation profile were observed in the perfused animals. Pigs and primates tolerated the perfusion procedure well and beneficial effects were observed in perfused pigs with experimental liver failure.

Evolution of carotid restenosis after endarterectomy.

Some 176 consecutive carotid endarterectomies performed during 1987 were assessed after 11.5 and 44 months. There were four perioperative deaths. At mean follow-up of 32.5 months the 50% restenosis rate progressed from 9.7% to 11.9%. Of the 168 carotid arteries with a normal patency at discharge, 36 showed progression of stenoses as judged by duplex scanning during the observation period of 44 months. Twenty-nine stenoses were present within 1 year and seven developed between 12 and 44 months. Successive assessments revealed marked differences in the evolution of restenoses which usually depended on the degree of severity reached at the end of the first year: 44% progressed, 28% regressed and only 28% remained stable. The risk of late occlusion in vessels with a < 50% restenosis at 1 year was below 1% and the risk of progressing to a stenosis > 50% was 3.3%. Assessment at 56 months was limited to patients who had a restenotic lesion during the first 44 months. It confirmed that the disease was still unstable with progression in 7% of cases and regression in 10%. This study did not demonstrate any significant restenosis after 20 endarterectomies using the eversion technique compared with an incidence of 13.4% after 156 standard endarterectomies.

Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?

Two hundred twelve eversion endarterectomies of the internal carotid artery and reimplantation in the common carotid artery were performed between January 1985 and July 1990. A total of 206 patients with stenosis of 75% or more and with redundancy and tortuosity of the internal carotid artery underwent this procedure. Cumulative mortality and neurologic morbidity were 2.4%. Forty patients died during the course of follow-up, seven of neurologic causes (17.1%). Duplex scans of 107 operated carotid arteries were obtained an average of 27.1 months after surgery. Restenosis of > 50% was encountered in three patients (1.9%), two asymptomatic patients (1.3%) with > 75% restenosis and one symptomatic patient with occlusion (0.6%). These results contrast with a 13.5% rate of restenoses > 50% (including 5.9% of restenoses > 75% and 1.7% occlusions) observed after 156 consecutive endarterectomies performed and closed by direct suture by the same surgical team in 1987 at a mean follow-up of 44 months. We believe that this technique can be used more often because the the operative and long-term risks are not any greater than those of the other methods of carotid revascularization. Eversion endarterectomy associated with reimplantation is especially indicated when the internal carotid artery is elongated, is < 4 mm wide, and occurs in women.

[Transesophageal echography and peripheral arterial embolism. A new etiologic approach. Apropos of 87 cases]. / Echographie transoesophagienne et embolies artérielles périphériques. Nouvelle approche étiologique. A propos de 87 cas.

This prospective study (September 1989 to November 1990) was undertaken to evaluate the utility of transesophageal echocardiography in acute peripheral ischaemic syndromes. After embolectomy or thrombolysis, 87 patients with an average age of 69.7 years underwent not only the usual investigations (conventional echocardiography, abdominal ultrasonography and Holter monitoring) but also transesophageal echocardiography within 2 days of the ischaemic events (lower limb 84%, multiple embolism 11%, recurrent embolism 13%). Atrial fibrillation was documented in 44 patients (50.5%), 19 patients had chronic arterial disease (22%), 8 patients had valvular heart disease (9%) and 2 patients had a blood disorder (2%). Transthoracic echocardiography only demonstrated one left ventricular apical thrombus whereas transesophageal echocardiography showed residual thrombus in 22 patients (25%) mainly in the left auricle but also in the descending thoracic aorta (8 patients) as a mobile, pediculated thrombus or lining an aortic aneurysm, thereby opening up new therapeutic possibilities. In addition, double aortic dissection was diagnosed in a patient who was not echogenic, isolated spontaneous contrast in 20 patients (23%) and other abnormalities in 7 patients (8%). Statistical analysis showed a significant relationship between the presence of thrombus and/or spontaneous contrast in the left atrium and/or left auricle and the size of the left atrium (Fisher test - p = 0.0073), and the presence of a supraventricular arrhythmia (chi 2 test).

Traumatic lesions of the thoracic aorta. A report of 73 cases.

In a 24 year period we treated 73 traumatic lesions of the thoracic aorta; 36 of these were acute ruptures and 37 post traumatic pseudo-aneurysms. All these cases were associated with violent, sudden deceleration and in 68 instances the cause of this was a traffic accident. Fifty two patients (70%) had severe associated lesions involving the cranium, abdomen, thorax or leg fractures and dislocations but in 5 patients the aortic rupture was the only injury observed. Thirty four patients with acute aortic lesions were operated upon; 30 with extracorporeal circulatory assistance (CA) and 4 with aortic cross clamping alone. Twenty one were repaired by direct suture, 13 by prosthetic graft interposition and there were 8 deaths (23.5%) and one case of post-operative paraplegia. Thirty six traumatic aneurysms were operated upon; 34 with CA and 2 with cross clamping. Only two were repaired by direct suture, 5 by prosthetic angioplasty and 29 required prosthetic interposition grafts; there were no deaths or paraplegias in this group. Aortic rupture demands early diagnosis and immediate surgery. Associated abdominal injuries are easily missed and therefore exploratory laparotomy should be considered after every acute aortic repair.

What is the place of pulmonary embolectomy today?

From 1.1970 to 31.12.1989, 134 patients with pulmonary embolism were treated by pulmonary embolectomy (74 women and 60 men) of mean age 55 years (23-78 years); 93 (69%) of these patients developed embolism during the postoperative period following surgery for another condition. In 12 cases the embolectomy was performed without circulatory assistance by a modified Trendelenburg operation after an average delay time of 2 hours. In 122 cases, extracorporeal circulation (ECC) was used, preceded in 64 cases, by a femoral-femoral bypass (the average delay interval of operation being 16.9 hours). At operation, 23 patients were in complete circulatory failure needing external cardiac massage, 34 were in cardiogenic shock with systolic arterial pressures (SAP) less than 60 mmHg, 42 maintained their arterial pressure between 60 and 100 mmHg, and only 35 were seen with SAP higher than 100 mmHg under vasopressive drugs. No haemodynamic and angiographic investigations could be undertaken in 31 patients because of their dramatic clinical state. In the other 103 patients who had invasive angiographic investigations performed the pulmonary bed was obstructed from 65% to 90% (mean 79.4%) according to Miller's index. The mean arterial pulmonary pressure was 51.2 mmHg. The survival rate at the 30th postoperative day showed 113 patients were alive (84.3%) with 7 among the 12 operated by the Trendelenburg's modified method and 106 among the 122 operated under ECC. The main causes of the 21 deaths were: peroperative 8, neurological 4, cardiac 4, respiratory 1, recurrent embolism 1, acute thrombosis of the IVC 1. Our results of pulmonary embolectomy can be compared favorably to those obtained by thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgery of gastrointestinal vessels, selective indications for revascularization in a syndrome suggestive of chronic small intestinal ischemia]. / Chirurgie des vaisseaux digestifs, indications électives de revascularisation face à un syndrome évoquant une ischémie chronique de l'intestin grêle.

The authors present a critical review of the indications for revascularization of intestinal arteries in the presence of chronic ischaemia of the small intestine. They stress the extreme lability of the "chronic" clinical stage and emphasize the fundamental importance of establishing the diagnosis before the development of acute complications. Based on a personal experience of 92 intestinal revascularizations with a follow-up of one to 26 years, they stress the good quality of the results obtained after isolated revascularization of the superior mesenteric artery by direct or indirect reimplantation into the infrarenal aorta. However, they do not challenge the current tendency towards multiple revascularizations, but consider that the essential prerequisite for a correct result is the early surgical treatment of a disease which is still poorly understood and frequently disappointing.

Percutaneous atherectomy with the Kensey catheter: early and midterm results in femoropopliteal occlusions unsuitable for conventional angioplasty.

Forty-six femoropopliteal occlusions in 44 patients (aged 45-95 years) were recanalized with the percutaneous rotating tip atherectomy catheter completed by balloon dilatation. Thirty-one patients had tight intermittent claudication of the lower limbs, five had resting pain and 10 had skin disorders. The length of the occlusion ranged from 2 to 24 cm. Of 46 procedures, 40 (87%) were immediately successful (increase of mean Doppler systolic ankle-arm index from 0.44 to 0.89) and six (13%) were failures. In two it was impossible to pass through the lesion and in four arterial perforation occurred without any clinical consequences. Of the six failures, five occurred in calcified arteries. Five recanalizations (11%) reoccluded within 48 hours, bringing the total number of early failures to 11. Of these 11 failures, nine were treated by femoropopliteal vein bypass and two by medical treatment only. Two postoperative asymptomatic posterior tibial artery embolisms were treated medically, and one popliteal artery embolism was treated using a Fogarty catheter. At the present time, 25 of 35 primary successes had been followed for six months, and 20 for 12 months with primary patencies 18 of 25 (72%) and 14 of 20 (70%), respectively. If massively calcified lesions are excluded, femoropopliteal recanalization with the percutaneous rotary Kensey atherectomy catheter followed by balloon catheter dilatation is efficacious and reliable with an 80% primary success rate and a 70% patency rate at one year.

Superior mesenteric artery embolism: eighty-two cases.

Eighty-two consecutive patients with superior mesenteric artery embolism were treated between 1966 and 1988. Abdominal pain was atypical or absent in 19 (23%) patients. Except for two instances of intraoperative embolism, emergency mesenteric arteriography was diagnostic in all cases. Seventeen patients were treated medically either because the site of embolism was peripheral, or because there were no life-threatening signs. Sixty-five patients underwent surgery, 31 for mesenteric infarction, and 34 for acute mesenteric ischemia without intestinal necrosis. Surgical treatment included 34 isolated embolectomies, 20 embolectomies associated with intestinal resection, two short segmental resections for limited necrosis of the small intestine, and nine exploratory laparotomies. Of the 34 patients operated on for acute mesenteric ischemia, 12 (35%) died. Of the 31 remaining patients operated on for intestinal infarction, 21 (68%) (p less than 0.05) died. The mean duration of ischemia before operation was 13 hours 20 +/- 6 min and 21 hours 24 +/- 24 min, respectively (p less than 0.05). Two patients (12%) receiving medical treatment died. This study confirms that survival is directly related to early diagnosis based on emergency mesenteric arteriography. Treatment is determined by clinical and roentgenographic criteria. Medical treatment is indicated in certain circumstances.

Aortic reimplantation of the superior mesenteric artery for atherosclerotic lesions of the visceral arteries: sixty cases.

We report the results of a series of patients who had isolated or associated reimplantation of the superior mesenteric artery directly into the infrarenal aorta. Between 1967 and 1988, a total of 91 revascularizations for atheromatous lesions of the visceral arteries were performed in 89 patients. The superior mesenteric artery was reconstructed in 87 instances, 60 of which were direct or indirect reimplantations into the juxtarenal aorta. The procedure was isolated in 51 cases, and associated with the revascularization of another visceral artery in nine cases. These 60 patients were divided into three groups: Group A--seven patients undergoing emergency operation for acute intestinal ischemia; Group B--30 patients operated upon for chronic intestinal angina; and Group C--22 asymptomatic patients who underwent prophylactic revascularization. Two patients died in the immediate postoperative period (3.5%). Although most of the 29 late deaths were due to vascular disorders, only one was secondary to intestinal infarction. Twenty-one patients followed had good functional results; six patients had relapse of abdominal pain. Three of these underwent repeat revascularization of the superior mesenteric artery 12 days, 18 months, and 22 months, postoperatively. Follow-up ranged from six months to 18 years. Two patients were lost to follow-up. Overall actuarial survival at five years was 69.60 +/- 15%. In our experience, isolated reimplantation of the superior mesenteric artery on the anterior aspect of the infrarenal aorta is a simple and reliable technique which affords good long-term results.