Surgical management of pediatric renovascular hypertension and midaortic syndrome at a single-center multidisciplinary program.

OBJECTIVE: To evaluate the outcomes of various surgical approaches in the treatment of renovascular hypertension and midaortic syndrome (MAS) in children. METHODS: We performed a retrospective medical record review of patients who had undergone surgery for renovascular hypertension from 2010 to 2018 at our center under the care of a multidisciplinary team. The operative interventions included mesenteric artery growth improves circulation (MAGIC), tissue expander-stimulated lengthening of arteries (TESLA), aortic bypass using polytetrafluorethylene, renal artery reimplantation, and autotransplantation. The MAGIC procedure uses the meandering mesenteric artery as a free conduit for aortic bypass. The TESLA procedure is based on lengthening the normal distal aorta and iliac arteries by gradual filling of a retroaortic tissue expander for several weeks, followed by resection of the stenotic aorta and subsequent primary reconstruction. RESULTS: A total of 39 patients were identified, 10 with isolated renal artery stenosis, 26 with MAS, and 3 with systemic inflammatory vasculitis. The median age at presentation and surgery was 6.4 years (range, 0-16.3 years) and 9.3 years (range, 0-9.2 years), respectively. The MAS-associated syndromes included neurofibromatosis type 1 (15.4%) and Williams syndrome (5.1%), although most cases were idiopathic. At surgery, 33.3% had had stage 1 hypertension (HTN), 53.8% stage 2 HTN, and 12.8% normal blood pressure with a median of three antihypertensive medications. Follow-up of 37 patients at a median of 2.5 years demonstrated normal blood pressure in 86.1%, stage 1 HTN in 8.3%, and stage 2 HTN in 5.6%, with a median of one antihypertensive medication for the entire cohort. CONCLUSIONS: The patterns of vascular involvement leading to renovascular hypertension in children are variable and complex, requiring thoughtful multidisciplinary planning and surgical decision-making. The MAGIC and TESLA procedures provide feasible approaches for aortic bypass and reconstruction using autologous tissues and will result in normalization of blood pressure in 85% of children 2.5 years after surgery.

Modified Paul-Mikulicz ileostomy in a Swine model of isolated small bowel transplantation.

BACKGROUND: Intestinal transplantation (ITx) is a life-saving procedure for patients with intestinal failure. The poorer outcome of ITx than of other organ transplantation, however, warrants more clinical and basic research on ITx. Herein, we developed a modified Paul-Mikulicz ileostomy procedure in a swine model of ITx, and investigated its feasibility for obtaining intestinal samples of both the graft and the recipient. MATERIALS AND METHODS: We performed ITx in 10 pairs of piglets, each weighing 15-20 kg. Procurement included an isolated segment of the small bowel, constituting a model of a living, related donor surgery. The recipient procedures included end-to-end anastomosis of vascular stumps, a proximal jejuno-jejunal anastomosis, and a distal modified Paul-Mikulicz ileostomy. The procedure differed from the classic Paul-Mikulicz ileostomy in that a common channel was created in a side-to-side fashion. RESULTS: Vascular thrombosis occurred in three pigs, resulting in immediate loss of the graft. All other pigs underwent ITx successfully and survived for at least 1 wk (7-180 d). No pig experienced anastomotic leaks, ileus, or stoma-related complications. Moreover, this technique enabled us to obtain tissue samples of both the graft and the native ileum without disturbing the natural bowel conduit. CONCLUSIONS: The modified Paul-Mikulicz ileostomy was feasible in a swine model of ITx. It facilitated the collection of intestinal samples of both the graft and the recipient.

HLA class I antibodies provoke graft arteriosclerosis in human arteries transplanted into SCID/beige mice.

Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.

Reconstitution of immunodeficient SCID/beige mice with human cells: applications in preclinical studies.

Experimental studies of the in vivo behaviour of human cells and tissues have become possible with the development of immunodeficient mice strains. Such mice accept readily allogeneic or xenogeneic grafts, including grafts of human cells or tissues, without rejection. In this review we describe different immunodeficient mouse strains that have been used for reconstitution by human immune cells. We subsequently go through the experience that we and others have had with reconstitution, and mention the adverse effects, in particular xenogeneic graft versus host reactions. The use of haematopoietic stem cells avoids such reactions but the immunological reconstitution may take several months. We then report the use of immunodeficient mice for the study of chronic vascular rejection of human mesenteric arteries due to cellular or humoral alloreaction. We have shown that SCID/beige mice grafted with a human artery at the place of the aorta developed a thickening of the intima of the human artery after 5-6 weeks, when they were reconstituted with spleen cells from another human donor. The thickening is mainly due to a proliferation of smooth muscle cells. The same type of lesion developed if they received injection of antibodies towards HLA class I antigens. The arteries of the mouse did not develop any lesion. The arterial lesions closely resembled those seen after clinical organ transplantation. Mice that received spleen cells from the same human donor developed little or no lesions. An important aspect of this experimental transplantation model is the possibility to test drugs that may be used in clinical transplantation. In recent experiments we have shown that novel immunosuppressive drugs can inhibit the hyperproliferation of smooth muscle cells in vitro. Preclinical testing in reconstituted SCID/beige mice grafted with human arteries will permit the evaluation of the potential use of these drugs to prevent chronic vascular rejection. The model also allows pharmacodynamic studies that give information on the biological impact of different drugs that may be used in experimental or clinical transplantation.

Multiple human mesenteric arterial grafts from the same donor to study human chronic vascular rejection in humanized SCID/beige mice.

BACKGROUND: Chronic vascular rejection (CVR) is a major problem in clinical transplantation. Studies in experimental animals have been important to understand some of its mechanisms, but they are hampered by the difficulty of extrapolating the results into clinical practice. METHODS: We created a new experimental model for the study of human CVR by grafting multiple human mesenteric arteries from the same human donor into different SCID/beige mice in the infrarenal aortic position. Twenty-seven different mice were successfully grafted with a human artery from 6 donors. One week later, 23 of the mice received an intraperitoneal injection of 40 million human spleen cells, either from the same donor (autologous) or from another donor (allogeneic). RESULTS: In 81% of the mice an immune reconstitution was obtained, shown by the presence of human T, B and NK cells and IgG in circulating blood. At the time of sacrifice, 5 weeks after the arterial transplantation, a typical CVR with infiltration of human immune cells and deposit of human immunoglobulin was observed in the reconstituted mice that received allogeneic cells, whereas only minor lesions were noted in autologous combinations. No CVR was observed without injection of human splenocytes. We did not observe lymphoma or graft-vs-host reactions during the experiment. CONCLUSIONS: We show that it is feasible to graft multiple human arteries from the same donor into SCID/beige mice, and that a specific and typical CVR is observed after reconstitution with allogeneic spleen cells. Our method allows for pre-clinical testing of new therapeutics in controlled series.

Human immune reconstitution with spleen cells in SCID/Beige mice.

BACKGROUND: We developed an original experimental model to study chronic vascular rejection (CVR) consisting of a graft of human mesenteric artery followed by human immune reconstitution into CB.17 SCID/Beige mice. Human immune reconstitution achieved after human PBMC injection has often been variable and incomplete. The aim of this work was to develop an alternative method to achieve a complete, functional human immune reconstitution. METHOD: After institutional authorizations, spleen cells were recovered from cadaveric organ donors. Single intraperitoneal injections of various doses of spleen cells were made into 70 CB.17 SCID/Beige mice. Reconstitution of the human immune system was monitored by flow cytometry (circulating human cells) and ELISA (human IgG). Colonization of murine lymphoid organs by human cells was studied by immunohistochemistry and flow cytometry. Evaluation of the immune function consisted of examination of CVR lesions in human arterial grafts. The animals were humanely killed at day 28. RESULTS: After injection of 30 to 40 x 10(6) spleen cells, the mice showed significant human CD3(+), CD19(+), and CD56(+) populations in peripheral blood. The mean human cells levels were, respectively, 8.2% +/- 5.4%, 2.9% +/- 1.2%, and 5.3% +/- 5.1%. Murine spleen and mesenteric lymph nodes were colonized by human T and B cells, while the murine thymus was only colonized by human T cells. Human IgG was detected in murine serum (65.9 +/- 63.3 mg/L) and typical CVR lesions were observed within the allogeneic grafts. CONCLUSION: Intraperitoneal injection of 30 to 40 x 10(6) human spleen cells into CB.17 SCID/Beige mice induces complete and functional human immune reconstitution allowing the study of CVR under human allogeneic conditions.

Use of human mesenteric arteries to study chronic vascular rejection in SCID/beige mice reconstituted with human spleen cells.

We wanted to establish a preclinical model of chronic vascular rejection (CVR) by transplanting small arteries from the mesentery of cadaveric organ donors by the rapid "sleeve" technique into SCID/beige mice reconstituted with human allogeneic spleen cells. After institutional authorization and with informed consent from relatives, we obtained tissues and cells from cadaveric organ donors. A piece of mesentery was recovered from the donor and kept in buffered solution at 4 degrees C until use. After dissection of the mesentery, small arteries of suitable size were transplanted in place of the infrarenal aorta of the mice. Cells for the immunological reconstitution of the mice were spleen cells from the same or other organ donors. Twenty-three suitable arterial segments were obtained from the mesentery of three cadaveric donors. Ten of the mice received 3 x 10(7) human spleen cells intraperitoneally 1 week after the arterial graft and they all showed circulating human CD3+ and CD19+ cells 2 weeks after injection. The mice were sacrificed 5 weeks after the arterial graft. SCID/beige mice reconstituted with allogeneic spleen cells showed a typical CVR, whereas mice that received no cells had a normal vascular anatomy. We believe our model is well suited for the study of treatment of CVR under human allograft conditions.

Use of cadaveric superior mesenteric artery as interpositional vascular graft in orthotopic liver transplantation.

BACKGROUND: Hepatic artery thrombosis remains the most common technical complication that causes graft failure following orthotopic liver transplantation. The development of split liver and living related liver transplantation has led to the use of shorter and smaller arteries for arterial reconstruction to the graft. The present aim was to assess the effectiveness of the superior mesenteric artery as an interpositional graft in arterial reconstruction during liver transplantation. METHODS: Cadaveric superior mesenteric artery was used to reconstruct small and short or multiple hepatic arteries in 35 liver transplants including 29 split, three living related, two whole liver transplants and one emergency revascularization post-transplantation. RESULTS AND CONCLUSION: A low incidence of hepatic artery thrombosis (one of 35 patients) was achieved utilizing cadaveric superior mesenteric artery as an interpositional vascular graft in liver transplantation.

Exclusion of internal iliac arterial aneurysm concomitant with abdominal aortic aneurysm repair.

BACKGROUND: To study the long-term outcomes after exclusion of internal iliac arterial aneurysm performed concomitantly with abdominal aortic aneurysm repair in patients with ruptured aortic aneurysm or other high-risk conditions. METHODS: The 31 patients who participated in this study underwent emergency (N = 9) or elective surgery (N = 22). The abdominal aortic aneurysm and the common iliac artery were excluded together with the internal iliac aneurysm in 7 patients. Forty-three (12 bilateral and 19 unilateral) internal iliac aneurysms were excluded: 35 by proximal ligation only, 5 by proximal and distal ligation, and 3 by partial resection of the proximal part of the aneurysm. The platelet count and fibrinogen level were evaluated pre- and postoperatively. Pelvic organ ischemia, classed as ischemic colitis, buttock claudication and sexual dysfunction, was examined. RESULTS: The inferior mesenteric artery was reimplanted in 21 patients. The platelet count dropped significantly postoperatively, but the fibrinogen level increased and no bleeding tendency was noted. Ischemic colitis occurred in 7 patients, resulting in colonic infarction in 2 patients. The operative mortality was 16%, and the postoperative observation periods ranged from 4 days to 217 months (mean, 60 months). The incidence of buttock claudication and sexual dysfunction was 12% and 39%, respectively. The excluded aneurysms were all thrombosed at discharge, and no late rupture was noted. The 5- and 10-year survival rate after surgery was 56% and 51%, respectively. CONCLUSIONS: Exclusion of the internal iliac aneurysm concomitant with abdominal aortic aneurysm repair shows acceptable outcome when performed in patients with high-risk conditions.

Functional recovery of human mesenteric and coronary arteries after cryopreservation at -196 degrees C in a serum-free medium.

PURPOSE: Long-term patency of cryopreserved vascular grafts is determined by maintained cellular and tissue viability, which implies preservation of various biochemical, smooth muscle, and endothelial functions. Therefore, it was investigated whether the presence of fetal calf serum (FCS) in the cryomedium improves the postthaw contractile and endothelial function of human arteries. METHODS: Rings from human mesenteric (HMA) and left circumflex coronary arteries (HCA) obtained from organ donors were randomized into three groups and studied either unfrozen or after storage for 3 to 6 weeks at -196 degrees C while suspended in Krebs-Henseleit solution without or with 20% FCS as the vehicles and 1.8 mol/L dimethyl sulfoxide and 0.1 mol/L sucrose as cryoprotecting agents. The samples were slowly frozen to -70 degrees C and then stored in liquid nitrogen. Before use, the tissues were thawed within 3 minutes in a 40 degrees C water bath. RESULTS: After thawing the sensitivity to various agonists and maximal responses to the endothelium-independent relaxing agent sodium nitroprusside were unchanged. However, after cryopreservation of HMA was performed without and with FCS, maximal contractile responses to noradrenaline were significantly reduced to 10.1 +/- 0.7 gm and 9.9 +/- 0.9 gm compared with 13.3 +/- 0.6 gm in unfrozen HMA (mean +/- SEM, n = 15). After cryopreservation of HCA was performed without and with FCS, maximal contractile responses to prostaglandin F2 alpha (6.9 +/- 0.4 gm in unfrozen HCA) were significantly reduced to 4.3 +/- 0.3 gm and 3.8 +/- 0.2 gm (mean +/- SEM, n = 6). In both types of arteries cryopreservation also attenuated significantly the endothelium-dependent relaxant responses to bradykinin during U46619 (10 nmol/L)-induced tone. In HMA the maximal bradykinin-induced relaxation (85% +/- 4%) was significantly diminished to 29% +/- 7% and 38% +/- 9% after cryopreservation without and with FCS (mean +/- SEM, n = 6). In HCA maximal bradykinin-induced relaxation (88% +/- 4%) was significantly diminished to 26% +/- 10% and 36% +/- 11% after cryopreservation without and with FCS (mean +/- SEM, n = 6). This result was reflected by a marked endothelial denudation in all groups of cryopreserved arteries. Neither functional nor morphologic preservation of the endothelial cell lining was significantly improved by FCS supplementation of the cryomedium. CONCLUSIONS: Cryopreservation diminished contractile and endothelium-dependent relaxant responses of human arteries. The presence of FCS in the cryomedium did not modify these changes.

Hepatic artery anatomy in relation to reconstruction in liver transplantation: some unusual variations.

The anatomy of the hepatic artery and its variations were studied in 70 donor livers harvested for liver transplantation in the Austin Hospital. Forty three (61.5%) had a 'normal' vascular anatomy and 27 (38.5% had anomalous anatomy. The anomalies were single in 13 instances and multiple in 14 and involved the origin of the right or left hepatic arteries or the coeliac axis. The hepatic artery was reconstructed most frequently by end-to-end anastomosis of the donor to the recipient common hepatic artery (79%). A Carrel patch, an interposition aortic graft and the donor superior mesenteric artery were other techniques used for reconstruction. Two patients (3%) had a postoperative hepatic artery thrombosis, with one of those patients having a further reconstruction. When one vascular anomaly is found, there is a high probability of others being present. The authors' experience confirms that safe hepatic arterial anastomosis can be performed even in the presence of abnormalities of the vascular arterial system.

[Indications for reimplantation of the inferior mesenteric artery in the course of prosthetic substitution for the subrenal aorta]. / Le indicazioni al reimpianto dell'arteria mesenterica inferiore in corso di sostituzione protesica dell'aorta sottorenale.

The authors report their experience relative to 8 patients who underwent IMA revascularization during infrarenal AAA repair. The Carrel patch technique was employed in all cases operated. With this procedure no ischemic intestinal complication occurred. Two cases of ischemic colitis were observed in a second group of 40 patients operated for AAA in whom the IMA wasn't reimplanted into the aortic graft. The overall incidence of acute intestinal ischemia was 4%.

Estimating blood supply of the skin and intestine with the fluorescence camera.

We used fluorescein dye to evaluate the vascularity of flaps in 73 patients and of the left colon in 23 individuals after resection and replacement of the abdominal aorta. Instant photographs of the dye pattern were taken in the light using a specially modified Polaroid camera. All areas of skin and bowel that showed adequate staining with the dye survived, and all but one of ten areas that were nonfluorescent became necrotic unless they were excised or revascularized. The intraoperative use of fluorescein dye with the fluorescence camera is a useful technique for all surgeons who need to evaluate the vascularity of tissue.

Monitoring free vascularised jejunum grafts.

A reliable method of monitoring free vascularised jejunum to the head and neck region has been used in six patients. Preliminarily, the jejunum island flap is subdivided into major and minor segments. Transferred to the neck, the major part is used to reconstruct the oesophageal or pharyngeal defect, while the minor part supplied by the same segmental mesenteric artery is exteriorised through the neck incision. After five days direct monitoring, the marker segment is clamped, tied and excised before suturing the neck wound under local anaesthesia. No failures of the graft occurred. The effectiveness of this technique has surpassed all previously published and unpublished methods.

An examination of the arterial media in transplanted arteries of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY).

The hypothesis that arterial medial hypertrophy occurs in the SHR due to genetic factors inherent to the arterial wall, was examined in jejunal arteries cross transplanted between four-week-old SHR and WKY rats as a shunt between the femoral artery and vein. Four weeks after transplant, the arteries were removed and processed for embedding in resin and measurement of wall parameters by light microscopy. It was determined that irrespective of the origin of the transplanted artery, the wall thickness of transplants was higher in SHR hosts than in WKY hosts. Taken with results from other studies, this suggests that genetic factors inherent to the arterial wall are not the cause of arterial hypertrophy in the SHR.

A simplified technique of small intestinal transplantation in the rat.

A technique is described of experimental intestinal transplantation in the rat in which, using microsurgical technique, the superior mesenteric artery and vein distal to the right colic artery are dissected free. The ends of the supplied bowel segment are divided and the lumen irrigated with 0.5% neomycin. The divided superior mesenteric artery is perfused with iced heparinized lactated Ringer's solution, the vessels are then anastomosed to the recipient's aorta and inferior vena cava in end-to-side fashion, and the bowel ends are exteriorized as cutaneous stomas. Seven of 13 recipients of syngeneic grafts survived, and grafts were patent though atrophic up to 12 months later.