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Biomedical subjects

A Kadner

Publications and source records attributed to A Kadner.

At least 19 recordsLinked to original sources
PubMed2002

Endoscopic saphenous vein harvesting for CABG -- a randomized, prospective trial.

BACKGROUND: The saphenous vein is an established conduit for coronary revascularization. Disadvantages of traditional harvest technique are significant pain and morbidity. We compared the endoscopic harvest technique with the traditional method. METHOD: 140 coronary artery bypass graft (CABG) patients were randomized into 2 groups: endoscopic vein harvesting (EVH; n = 80) and traditional open vein harvesting (OVH; n = 60). Analysis included preoperative risk factors for wound complication, harvesting time, graft injury, and intraoperative and postoperative complications. Patient follow-up lasted 3 months. RESULTS: The preoperative risk profiles of the groups were comparable. In the EVH group, 5 patients (7.1 %) had to be switched to the open technique. EVH time was 45 +/- 6.2 min vs. 31.1 +/- 6.5 min. Two patients (2.5 %) had to be revised because of bleeding complication vs. 6 (10 %) in the OVH group. No local infections or wound complications were observed in the EVH group vs. 11 (18 %) cases in the OVH group. Two OVH cases (3.6 %) were readmitted for wound debridement. All EVH patients reported less pain and were completely satisfied by the cosmetic results. CONCLUSION: EVH is a safe and efficient technique for CABG. Morbidity was significantly lower, with reduced pain and better cosmetic results. EVH time was significantly longer compared to the traditional harvesting technique.

Aged↗
PubMed2001

Artificial mitral valve chordae replacement made simple.

Mitral valve repair techniques are now widely applied in patients with myxomatous valve disease. The use of artificial chords to achieve correct height adjustment of the prolapsing anterior leaflet segment can often be challenging. We describe a simple method of artificial chord reconstruction performed after annuloplasty, which allows for easy identification of functional prolapse and accurate chordal height adjustment.

Bioprosthesis↗
PubMed2001

Hemograft crossmatching is unnecessary due to the absence of blood group antigens.

BACKGROUND: Homograft valves are subject to calcification and structural degeneration in the long term. Blood group matching is performed in many centers, and it remains controversial whether immunologic responses associated with potential blood group incompatibility contribute to the degeneration of unmatched homografts. We studied the expression of carbohydrate blood group antigens on valve endothelium of thawed aortic homograft valves and freshly harvested human cardiac valves. METHODS: Cryopreserved human aortic homograft valves and freshly harvested human aortic, pulmonary, mitral, and tricuspid valves were incubated with antibodies to A, B, and O blood group antigens. RESULTS: Cardiac microvascular endothelium stained positively with antiendothelial CD31 antibody in both cryopreserved and fresh tissue. Cryopreserved valve endothelial lining rarely stained positively for CD31, in contrast to fresh valves, which always stained positive. Cryopreserved or fresh cardiac microvascular endothelium strongly expressed A, B, or H antigens. In contrast, ABH antigens were not detectable on homograft or fresh cardiac valve endothelium. CONCLUSIONS: The absence of expression of carbohydrate antigen on valvular endothelium suggests that blood group incompatibility does not play a significant role in homograft degeneration.

Cryopreservation↗
PubMed2001

Anaesthetic management of baboons undergoing heterotopic porcine cardiac xenotransplantation.

A detailed anaesthetic technique for baboons (Papio anubis) undergoing heterotopic abdominal cardiac xenotransplantation is described. Twenty-two baboons served as transplant recipients. Donors were either crossbred farm pigs (Sus scrofa) (n = 4) or transgenic pigs (Sus scroefa) (n = 18) expressing human complement regulatory proteins on the endothelium. Intra-operative management was complicated by the physiological consequences of infrarenal. abdominal aortic cross-clamping, in addition to the immunological sequelae related to cross-species transplantation. In choosing anaesthetics for this procedure, we considered the need for maximal cardiac stability throughout a long surgical procedure that required abdominal aortic cross-clamping to facilitate the implantation of an oversized porcine cardiac graft. Baboons received a balanced anaesthetic consisting of inhaled isoflurane in oxygen, intravenous fentanyl and intravenous pancuronium. The pharmacological techniques employed were found to be safe and reliable and were well tolerated by our recipients without any significant side-effects.

Anesthesia↗
PubMed2001

Human membrane cofactor protein (MCP, CD 46) protects transgenic pig hearts from hyperacute rejection in primates.

Recently, we and others have shown the prolongation of xenograft survival with the use of transgenic pigs bearing human CD 59 and DAF complement regulatory proteins (CRP). We now report heart transplantation using a new line of transgenic pigs bearing a different human CRP, membrane cofactor protein (MCP, CD 46). We transplanted three MCP transgenic and three wild-type porcine hearts into baboons suppressed with cyclosporine, methylprednisone, and rapamycin or cyclophosphamide. In addition, recipients were treated with extracorporeal plasma perfusion to remove alpha-Gal reactivity. The wild-type grafts were rapidly rejected at 60 to 80 min. Two functioning MCP hearts were removed after 5 and 46 h for histological examination. One MCP heart showed vigorous function until postoperative day 16. Immunohistochemistry of both wild-type and MCP-transgenic hearts showed strong deposition of IgM. In contrast, there was less MAC deposition in the transgenic graft as compared to the wild-type control. MCP is another CRP capable of decreasing the features of hyperacute rejection of cardiac xenografts in baboon recipients.

Animals↗
PubMed2000

Mechanism of delayed rejection in transgenic pig-to-primate cardiac xenotransplantation.

BACKGROUND: Pig-to-primate cardiac xenografts undergo hyperacute rejection (HAR), in which primate IgM bind to porcine endothelial alpha-Gal molecules and activate membrane attack complex (MAC) deposition. Prolonged graft survival can be achieved by using transgenic pig donors, which express human complement regulatory proteins (hCRP) to inhibit MAC. However, these xenografts invariably fail from delayed xenograft rejection (DXR). We sought to investigate the poorly understood DXR process. MATERIALS AND METHODS: Wild-type (n = 3) and transgenic (n = 3) porcine hearts were heterotopically transplanted into baboons. Biopsies were analyzed by histology and by immunohistochemistry for porcine endothelial markers (vWF, alpha-Gal, and beta-Gal) and primate IgM and MAC deposition. RESULTS: Wild-type xenografts survived 60-80 min but succumbed to rapid IgM/MAC deposition and microvascular thrombosis. Transgenic xenografts avoided HAR but showed increasing IgM/MAC deposition before rejection on days 5, 7, and 11. Serum from baboons after transgenic xenograft rejection showed increased activity against porcine endothelial cells, and in vitro incubation of untransplanted porcine cardiac sections with sensitized baboon serum showed elevated microvascular IgM binding. Increased IgM deposition appeared specific to alpha-Gal, since it competes specifically with alpha-Gal-specific GS-4 lectin, but not with beta-Gal-specific RCA-1 lectin. Competition with GS-4 was not seen if naïve baboon serum was used. CONCLUSION: DXR may be mediated by increasing baboon IgM binding on porcine microvascular endothelial alpha-Gal molecules.

Acute Disease↗
PubMed2000

Cardiac xenotransplantation: clinical experience and future direction.

The shortage of human organs has focused research on finding an animal source of replacement organs. The immunological barriers to xenotransplantation are now more clearly defined, allowing retrospective interpretation of past clinical experience in humans. Due to physiological compatibilities as well as ethical and infectious considerations, pigs have now emerged as the most likely source of future xenografts. The introduction of transgenic pigs expressing human complement regulatory proteins and new immunosuppressive regimens have shown early promise in the laboratory, although further advancements are needed to advance to clinical trials. Additional clarification of infectious risks and patient strategies are remaining obstacles to application in the clinical arena.

Animals↗
PubMed2000

Heterotopic heart transplantation: experimental development and clinical experience.

Heterotopic heart transplantation was initially developed in the laboratory for experimental transplantation. While it was more widely utilized in the pre-cyclosporine era to provide adjunct circulatory support in combination with the native heart, associated complications as well as improved long-term graft survival have now established orthotopic transplantation as the procedure of choice. Heterotopic heart transplantation is currently reserved for highly selected patients. The technique is only performed at selected transplantation centers, and indications include significant donor recipient size mismatch or irreversible recipient pulmonary hypertension. The foreseeable introduction of clinical porcine xenotransplantation may lead to renewed interest in the technique of heterotopic heart transplantation as a bridge to potential native heart recovery or allotransplantation in selected patients.

Adolescent↗
PubMed2000

Monitoring pig-to-primate cardiac xenografts with live Internet images of recipients and xenograft telemetric signals: histologic and immunohistochemical correlations.

BACKGROUND: Monitoring pig-to-primate cardiac xenografts is often difficult in awake and uncooperative primates. We investigated the possibility of monitoring xenotransplantation through Internet broadcasting of (1) continuous video images of transplant recipients and (2) xenograft telemetric signals detected by an implanted device. The telemetric readings were later compared with histology and immunohistochemistry for signs of rejection. METHODS: Heterotopic baboon-to-baboon (n = 2) and transgenic pig (human complement regulatory proteins CD59/DAF, n = 3; MCP, n = 1)-to-baboon transplants were performed with serial biopsies for hematoxylin-and-eosin staining and immunohistochemical detection of immunoglobulin M (IgM) and complement membrane attack complex (MAC) deposition. Baboon recipients were continuously monitored with a QuickCamPro digital camera, whereas grafts were monitored with a Data Science International implantable telemetric system. Video images and telemetric signals were broadcast over the Internet through a laptop computer. RESULTS: Baboon allografts remained healthy until explant on Day 14, whereas pig xenografts were rejected on Day 5, 6, 7, and 11. Telemetry of allografts and xenografts documented regular rhythm with an average heart rate of 80 to 120, but xenografts developed bradycardia and widened/dampened QRS complexes 24 to 48 hours before graft loss. Continuous video monitoring of recipient activities was vital in differentiating between graft arrhythmias and telemetric artifacts. Allograft biopsies showed little cellular infiltrate, whereas xenograft biopsies showed increasing IgM and MAC deposition, with extensive thrombi and myocardial damage 24 hours before cessation of cardiac activities. CONCLUSIONS: Combined video surveillance of recipient activities and graft telemetric signals is a useful method to continuously monitor abdominal cardiac grafts in large, uncooperative, awake primates. QRS-complex widening associated with progressive bradycardia correlated with histologic and immunohistochemical evidence of xenograft rejection.

Animals↗
PubMed2000

Fresh porcine cardiac valves are not rejected in primates.

OBJECTIVE: Transplanted porcine hearts are hyperacutely rejected by human immunoglobulin M antibodies against a porcine vascular endothelial molecule, galactose alpha-1,3-galactose, with ensuing human complement activation and membrane attack complex deposition. It is unclear, however, whether porcine valve endothelium triggers a similar immune response. We sought to investigate whether fresh porcine valves implanted into primates are rejected. METHODS: Wild-type porcine hearts before (n = 6) and after (n = 3) heterotopic transplantation into baboons underwent sectioning and were examined by hematoxylin and eosin staining and immunohistochemistry for galactose alpha-1,3-galactose, primate immunoglobulin M, and membrane attack complex. RESULTS: Examination of untransplanted porcine hearts showed that although cardiac microvascular endothelium strongly expressed the galactose alpha-1, 3-galactose antigen, galactose alpha-1,3-galactose was not detected on the endothelium of porcine aortic and pulmonary valves. Porcine hearts transplanted into baboon recipients were hyperacutely rejected 60 to 80 minutes after implantation. Despite dramatic tissue damage associated with extensive immunoglobulin M and membrane attack complex binding on the microvascular endothelium, the aortic and pulmonary valves were entirely spared. Valves remained morphologically intact at explant and showed no signs of immunoglobulin M- and membrane attack complex-mediated damage. CONCLUSIONS: The absence of galactose alpha-1,3-galactose expression may protect unfixed porcine valves from xenograft rejection in primates. Further investigation of viable porcine valves appears warranted.

Animals↗
PubMed2000

Lack of ABH-antigen expression on human cardiac valves.

BACKGROUND AND AIM OF THE STUDY: Seeding of heart valve prostheses with human umbilical vein endothelial cells (HUVEC) and human saphenous vein endothelial cells (HSVEC) has been applied to create a viable valve surface and improve valve performance. HUVEC and HSVEC are well characterized and have been used as a model of endothelial antigenicity, but antigenicity of the valve endothelium is less well characterized. To clarify this issue, we studied the expression of blood group antigens by human valvular endothelium, HSVEC and HUVEC. METHODS: Human aortic and mitral valves and myocardial tissue were freshly harvested from explanted hearts of patients undergoing heart transplantation (blood group A, n = 4; group O, n = 4) or valve replacement (blood group B, n = 4). After fixation in Carnoy's or formalin solution, paraffin sections were stained with anti-A (blood group A), anti-B (blood group B), and anti-H (blood group O) antibodies. Human umbilical cords were freshly harvested postpartum, and human saphenous veins were obtained from patients undergoing coronary bypass grafting (each blood group, n = 2) and similarly fixed and stained to detect ABO antigens. The preservation of endothelium was confirmed by staining with anti-CD 31 monoclonal antibody. All sections were examined by light microscopy. RESULTS: CD 31 staining demonstrated vascular and valve endothelial preservation. Human umbilical cords, saphenous vein and myocardium showed strongly expressed A, B and H blood group antigens on vascular endothelium. However, no A, B and H antigens were detected on the valvular endothelium. CONCLUSIONS: Valve endothelial cells appear to be a class of specialized endothelial cells that does not express the ABO antigens. Due to the strong expression of A, B and H antigens by HUVEC and HSVEC blood group cross-matching should be considered for non-autologous endothelialization of valve prostheses.

ABO Blood-Group System↗
PubMed1999

Technique for heterotopic pig heart xenotransplantation in primates.

The primate is a commonly utilized model for the human immune response after heart transplantation. This report describes our experience with heterotopic abdominal transplantation of porcine hearts into primate recipients. Abdominal graft placement was surprisingly well tolerated, and we found this approach to be particularly useful in the setting of significant donor-recipient size mismatch. Continuous monitoring with an implantable monitoring system facilitated assessment of graft viability in awake recipients; progressive graft bradycardia and decreasing QRS amplitude were predictive of ensuing graft failure.

Abdomen↗
PubMed1999

Impact of small prosthetic valve size on operative mortality in elderly patients after aortic valve replacement for aortic stenosis: does gender matter?

OBJECTIVE: Ideal management of the elderly patient with a small aortic root remains controversial. This retrospective analysis was performed to determine whether small prosthetic valve size is related to outcome in patients 70 years of age or older undergoing aortic valve replacement for aortic stenosis. METHODS: Between December 1991 and July 1998, 366 patients 70 years of age or older (median age 77 years, range 73-81 years, 49% male) underwent isolated aortic valve replacement or aortic valve replacement with coronary bypass grafting with standard Carpentier-Edwards bovine pericardial valves (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) (n = 277; 76%) or St Jude Medical mechanical valves (St Jude Medical, Inc, St Paul, Minn) (n = 89; 24%). Propensity scoring and multivariable regression models were used to evaluate the risks associated with implantation of 19-mm valves. RESULTS: Operative mortality was 16.7% (17/102) in patients who received 19-mm valves and 3% (8/264) among those receiving >/=21-mm valves (P </=.0005). The univariable odds ratio for operative death for 19-mm versus >/=21-mm valves was 6.4 (95% CI 2.7, 15.4; P </=.0005). In the final multivariable model, receipt of a 19-mm valve alone was not a statistically significant predictor of operative death (odds ratio 2. 1; 95% CI 0.7, 6.4; P =.21). However, the combination of male sex and 19-mm valve resulted in a significant risk of operative death (4/9 patients; odds ratio 17.5; 95% CI 2.2, 139; P =.007). Use of a 19-mm valve was not related to late death in either the univariable (hazard ratio 1.0; 95% CI 0.5, 2.0; P =.95) or the multivariable analysis (hazard ratio 0.7; 95% CI 0.3, 1.8; P =.51). CONCLUSIONS: Implantation of a standard 19-mm aortic valve in elderly men with aortic stenosis may be associated with an increased risk of operative mortality. A higher performance valve and/or a root enlargement procedure should be considered in men with a measured 19-mm anulus.

Aged↗
PubMed1999

Differential galactose alpha(1,3) galactose expression by porcine cardiac vascular endothelium.

Galactose alpha(1,3) galactose (Gal) is the terminal carbohydrate moiety recognized by xenoreactive natural antibodies during hyperacute rejection (HAR). Binding of these antibodies in HAR triggers rapid microvascular thrombosis. We examined the distribution of Gal on the endothelium of porcine hearts before and after heterotopic xenotransplantation into baboons. We found that Gal is strongly expressed on the endothelium of porcine capillaries with less expression on the endothelium of larger vessels. The distribution of Gal staining remains unchanged after xenotransplantation and correlates with the intensity of IgM and membrane attack complex (MAC) deposition. Thus, the Gal epitope is differentially expressed in the pig vasculature, which affects the pattern of xenoreactive antibody and MAC deposition and directs the distribution of vascular thrombosis.

Animals↗