Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Safety and efficacy of bariatric surgery in patients with advanced fibrosis.

BACKGROUND: Bariatric surgery is performed safely in non-alcoholic fatty liver disease (NAFLD) patients with minimal fibrosis (stage 1-2). However, the safety and potential benefits of bariatric surgery for NAFLD with advanced fibrosis (stage 3-4) remain unclear. This study was designed to compare the safety and efficacy of bariatric surgery in patients with biopsy proven advanced fibrosis to those with minimal fibrosis. METHODS: All patients who underwent bariatric surgery between 2005 and 2014 and had evidence of NAFLD with fibrosis score 3-4 (advanced fibrosis) based on the staging system defined by Kleiner et al. on intraoperative liver biopsy were included and compared with patients who had fibrosis score 1-2 (minimal fibrosis). The groups were compared for length of hospital stay after bariatric surgery and incidence of postoperative complications over a follow-up period of 1 year. An improvement in hepatic function tests before and 1 year after surgery was used as a parameter to evaluate for NAFLD improvement. RESULTS: Ninety-nine patients with F3-4 (group 1) and 198 patients with F1-2 (group 2) were included. Mean age (51.9 vs 50.1 years) and body mass index (46.4 vs 46.5 kg m-2) were similar in the two groups. Median serum aspartate aminotransferase (43 vs 30 U l-1; normal 10-40 U l-1) and alanine aminotransferase (40.5 vs 34 U l-1; normal 10-50 U l-1) were significantly higher in group 1 and improved 1 year after surgery. Median length of hospital stay after surgery was higher in group 1 than that in group 2 (4 days vs 3 days; P-value=0.002). The proportion of patients developing postoperative complications over 1 year was similar in both groups (36.4% vs 32.8%; P-value=0.54). CONCLUSIONS: Advanced fibrosis does not increase the risk of developing postoperative complications in medically optimized patients undergoing bariatric surgery. Improvement in serum transaminase levels suggests a reduction in hepatic necroinflammatory activity following bariatric surgery.

How safe is metabolic/diabetes surgery?

Although recent studies have shown the impressive antidiabetic effects of laparoscopic Roux-en-Y gastric bypass (LRYGB), the safety profile of metabolic/diabetes surgery has been a matter of concern among patients and physicians. Data on patients with type 2 diabetes who underwent LRYGB or one of seven other procedures between January 2007 and December 2012 were retrieved from the American College of Surgeons National Surgical Quality Improvement Program database and compared. Of the 66 678 patients included, 16 509 underwent LRYGB. The composite complication rate of 3.4% after LRYGB was similar to those of laparoscopic cholecystectomy and hysterectomy. The mortality rate for LRYGB (0.3%) was similar to that of knee arthroplasty. Patients who underwent LRYGB had significantly better short-term outcomes in all examined variables than patients who underwent coronary bypass, infra-inguinal revascularization and laparoscopic colectomy. In conclusion, LRYGB can be considered a safe procedure in people with diabetes, with similar short-term morbidity to that of common procedures such as cholecystectomy and appendectomy and a mortality rate similar to that of knee arthroplasty. The mortality risk for LRYGB is one-tenth that of cardiovascular surgery and earlier intervention with metabolic surgery to treat diabetes may eliminate the need for some later higher-risk procedures to treat diabetes complications.

Altered glycosylation in donor mice causes rejection of strain-matched skin and heart grafts.

Differential protein glycosylation in the donor and recipient can have profound consequences for transplanted organs, as evident in ABO-incompatible transplantation and xenotransplantation. In this study, we investigated the impact of altered fucosylation on graft acceptance by using donor mice overexpressing human α1,2-fucosyltransferase (HTF). Skin and heart grafts from HTF transgenic mice were rapidly rejected by otherwise completely matched recipients (median survival times 16 and 14 days, respectively). HTF skin transplanted onto mice lacking T and B cells induced an natural killer cell-mediated innate rejection crisis that affected 50-95% of the graft at 10-20 days. However, in the absence of adaptive immunity, the residual graft recovered and survived long-term (>100 days). Experiments using "parked" grafts or MHC class II-deficient recipients suggested that indirect rather than direct antigen presentation plays a role in HTF skin graft rejection, although the putative antigen(s) was not identified. We conclude that altered glycosylation patterns on donor tissue can trigger a powerful rejection response comprising both innate and adaptive components. This has potential implications for allotransplantation, in light of increasing recognition of the variability of the human glycome, and for xenotransplantation, where carbohydrate remodeling has been a lynchpin of donor genetic modification.

Tropisetron diminishes demyelination and disease severity in an animal model of multiple sclerosis.

Tropisetron, a selective 5-HT3 receptor (5-HT3R) antagonist, has been widely used to counteract chemotherapy-induced emesis. New investigations described the immunomodulatory properties of tropisetron which may not be 5HT3R mediated. In the present study, we assessed the potential effects of tropisetron on an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice by myelin oligodendrocyte glycoprotein peptide (MOG35-55) immunization. Animals were treated with tropisetron (5 mg/kg/day); m-chlorophenylbiguanide (mCPBG), a selective 5-HT3R agonist (10 mg/kg/day); tropisetron (5 mg/kg/day) plus mCPBG (10 mg/kg/day), and granisetron (5 mg/kg/day) intraperitoneally on days 3-35 post-immunization. Treatment with tropisetron and granisetron markedly suppressed the clinical symptoms of EAE (p<0.001) and reduced leukocyte infiltration as well as demyelination in the spinal cord (p<0.05). In addition, in vivo tropisetron, granisetron or tropisetron plus mCPBG therapy greatly reduced in vitro MOG35-55-stimulated proliferation of mononuclear cells from spleens, and MOG35-55-induced IL-2, IL-6 and IL-17 production by splenocytes isolated from EAE-induced mice (p<0.05). Concurrent administration of tropisetron and mCPBG did not significantly alter the histological damage in the spinal cord. mCPBG had no effect on the mentioned parameters. Taken together, these findings indicate that tropisetron has considerable immunoregulatory functions in EAE and may be promising for the treatment of MS or other autoimmune and inflammatory diseases of the CNS. Furthermore, beneficial effects of tropisetron in this setting seem to be both receptor dependent and receptor independent in the early phase of the disease.

Randomized clinical trial of subcutaneous versus interfascial bupivacaine for pain control after midline laparotomy.

BACKGROUND: Although patient-controlled analgesia for pain management after abdominal surgery is common, efforts to find alternative effective methods to control postoperative pain are continuing. The aim of this study was to compare postoperative pain levels following intermittent regional administration of bupivacaine via a catheter placed in the rectus sheath or subcutaneously at abdominal surgery through midline incisions. METHODS: Consecutive patients undergoing elective midline laparotomy were assigned randomly to a group with two catheters placed over the fascia (suprafascial group) before surgical wound closure or to a group with catheters placed between the two sheaths of each rectus muscle (interfascial group). Pain levels were determined every 12 h, both at rest and with movement, by means of a standard visual analogue scale (VAS) for 72 h after surgery. The amounts of administered opioid were recorded. RESULTS: Sixty patients were enrolled in the study (30 patients in each group).The median VAS score 36 h after surgery, both at rest and with movement, was significantly lower in the interfascial group than in the suprafascial group (P<0·050). Repeated-measures ANOVA also showed a significant difference in the postoperative VAS scores (P<0·007). The amount of self-administered morphine was significantly lower in the interfascial group, overall (P = 0·001) as well as on postoperative day 1 (P = 0·001) and day 2 (P = 0·016). Bowel sounds returned more quickly in the interfascial group (P = 0·040). CONCLUSION: Locoregional catheter administration of bupivacaine following midline laparotomy is more effective when the catheter is placed in the rectus sheath compared with suprafascial delivery. REGISTRATION NUMBER: IRCT138810142982N1 (http://www.irct.ir).

Correlation of serum alkaline phosphatase with clinicopathological characteristics of patients with oesophageal cancer.

Oesophageal cancer is endemic in some regions of the Islamic Republic of Iran and efforts have made to find factors that play a role in its prognosis. We retrospectively examined the correlation of serum alkaline phosphatase (ALP) levels with several clinicopathological characteristics of 207 cases of oesophageal carcinoma. The mean ALP level in patients with lymph node involvement was significantly higher [141 (SD 77) U/L] than with node negative cancers [116 (SD 63) U/L]. Patients with ALP levels 165 U/L were 3.29 times more likely to have lymph node involvement than patients with ALP levels < or = 165 U/L. There was no statistically significant correlation between ALP level and sex, age, tumour histological type, site and size of tumour, depth of penetration, distant metastasis, degree of differentiation, presence of lymphatic invasion and presence of simultaneous multiple cancers. Elevated ALP in patients with oesophageal cancer may predict lymph node involvement.

Correlation of serum alkaline phosphatase with clinicopathological characteristics of patients with oesophageal cancer

Oesophageal cancer is endemic in some regions of the Islamic Republic of Iran and efforts have been made to find factors that play a role in its prognosis. We retrospectively examined the correlation of serum alkaline phosphatase [ALP] levels with several clinicopathological characteristics of 207 cases of oesophageal carcinoma. The mean ALP level in patients with lymph node involvement was significantly higher [141 [SD 77] U/L] than with node negative cancers [116 [SD 63] U/L]. Patients with ALP level > 165 U/L were 3.29 times more likely to have lymph node involvement than patients with ALP level </= 165 U/L. There was no statistically significant correlation between ALP level and sex, age, tumour histological type, site and size of tumour, depth of penetration, distant metastasis, degree of differentiation, presence of lymphatic invasion and presence of simultaneous multiple cancers. Elevated ALP in patients with oesophageal cancer may predict lymph node involvement

Influence of splenectomy on morbidity of esophageal cancer surgery.

BACKGROUND AND AIM: During esophagectomy, splenic injury may occur due to unintentional operative trauma, caused by excessive traction on the splenic ligaments or misplacement of re-tractors. The role of spleen in immune system is well recognized and the addition of splenectomy to esophagectomy may increase the rate of complications. The goal of this study was to determine the influence of splenectomy on postoperative morbidity and mortality after esophageal resection for esophageal cancer. MATERIALS AND METHODS: Between January 2001 and April 2006, 420 cases with esophageal cancer underwent esophagectomy in a referral cancer institute. In 14 patients (3.3%) splenectomy was added because of unwanted splenic injury during operation. In-hospital morbidities and mortality and hospital stay were compared between patients with and without concomitant splenectomy. RESULTS: Although the overall complication rate in splenectomized patients was higher than other patients (43% vs. 30%), this figure was not statistically significant (P value: 0.3). Cervical anastomotic leakage occurred in 35.7% of splenectomized patients in comparison to 12.2% of control group (P value: 0.01, Odds Ratio: 3.93, CI95%: 1.27-12.2). There were no significant differences in cardiac and pulmonary complications, and in-hospital mortality rate between patients with and without splenectomy (P value > 0.05). Splenectomy did significantly affect post operative hospital stay (19 +/- 13 vs. 13 +/- 7 days, P value: 0.004). CONCLUSIONS: During esophagectomy, unplanned splenectomy may increase the incidence of anastomotic leakage and hospital stay. Therefore, whenever possible preservation of the spleen should be considered. An unexpected relationship between splenectomy and anastomotic leaks needs further investigation.Key words: Esophageal cancer; esophagectomy; splenectomy; esophagus; leakage; morbidity; mortality; complication.

Protective effects of recombinant human antithrombin III in pig-to-primate renal xenotransplantation.

Delayed rejection of pig kidney xenografts by primates is associated with vascular injury that may be accompanied by a form of consumptive coagulopathy in recipients. Using a life-supporting pig-to-baboon renal xenotransplantation model, we have tested the hypothesis that treatment with recombinant human antithrombin III would prevent or at least delay the onset of rejection and coagulopathy. Non-immunosuppressed baboons were transplanted with transgenic pig kidneys expressing the human complement regulators CD55 and CD59. Recipients were treated with an intravenous infusion of antithrombin III eight hourly (250 units per kg body weight), with or without low molecular weight heparin. Antithrombin-treated recipients had preservation of normal renal function for 4-5 days, which was twice as long as untreated animals, and developed neither thrombocytopenia nor significant coagulopathy during this period. Thus, recombinant antithrombin III may be a useful therapeutic agent to ameliorate both early graft damage and the development of systemic coagulation disorders in pig-to-human xenotransplantation.

Standards in anterior spine surgery in pediatric patients with neuromuscular scoliosis.

The authors reviewed 111 patients with neuromuscular disease who underwent anterior spine surgery for correction of scoliosis. An overall complication rate of 44.1% was found, 21.6% major and 22.5% minor. Pulmonary complications were the most common major complications, urinary tract infections the most common minor complications. The rate of complications was greater in patients with cerebral palsy, thoracoabdominal and transthoracic approaches, staged procedures, operative blood loss >1,000 mL, or previous spine surgery. In addition, statistical analysis confirmed that curve magnitude >100 degrees degrees was a risk factor for complications.

Tooth preparation techniques for porcelain laminate veneers.

OBJECTIVE: The purpose of this study was to determine the effect that two guides to tooth preparation had on an operator's ability to appropriately and consistently prepare teeth for porcelain laminate veneers. STUDY DESIGN: In-vitro study. MATERIALS AND METHODS: Thirty typodont central incisor teeth were randomly allocated into three groups and a general dental practitioner was asked to prepare the teeth for porcelain laminate veneers. Group A were prepared freehand while Groups B and C were prepared with the assistance of a silicone index and depth preparation bur respectively. Images of the prepared teeth were used to calculate the mean labial depth of preparation and incisal reduction of teeth in each group. RESULTS: The mean labial reduction for Groups A, B and C was 0.37 mm (SD 0.13), 0.62 mm (SD 0.17) and 0.61 mm (SD 0.15) and the mean incisal reduction for Groups A, B and C was 1.0 mm (SD 0.28), 1.0 mm (SD 0.38) and 1.03 mm (SD 0.26) respectively. CONCLUSION: It is suggested that consideration be given to the use of a silicone index or depth gauge bur when teeth are prepared for porcelain laminate veneers.

The pig analogue of CD59 protects transgenic mouse hearts from injury by human complement.

BACKGROUND: It has been proposed that hyperacute rejection (HAR) of pig-to-primate vascularized xenografts is due in large part to ineffective regulation of recipient complement by pig complement regulatory proteins (CRPs), and indeed transgenic expression of human CRPs in pigs can prevent hyperacute rejection. However, at least one pig CRP (CD59) efficiently regulates human complement in vitro, suggesting that it is the level of expression of a particular CRP(s) rather than cross-species incompatibility that explains the HAR of porcine xenografts. We investigated the relative effectiveness of transgenically expressed pig and human CD59 in providing protection of mouse hearts from human complement in an ex vivo setting. METHODS: Transgenic mice expressing pig CD59 or human CD59 under the control of the human ICAM-2 promoter, which restricts expression in tissues to vascular endothelium, were used. Hearts from mice expressing similar levels of pig CD59 or human CD59 were perfused ex vivo with 10% human plasma and heart function was monitored for 60 min. Sections of perfused hearts were examined for deposition of the membrane attack complex (MAC). RESULTS: Control nontransgenic hearts (n=5) were rapidly affected by the addition of human plasma, with mean function falling to less than 10% of the initial level within 15 min. In contrast, hearts expressing either pig CD59 (n=6) or human CD59 (n=8) were protected from plasma-induced injury, maintaining 31 and 35% function, respectively, after 60 min of perfusion. MAC deposition was markedly reduced in both pig CD59 and human CD59 transgenic hearts compared to nontransgenic control hearts. CONCLUSIONS: When highly expressed on endothelium in transgenic mice, pig CD59 provided equivalent protection to human CD59 in a model of human complement-mediated xenograft rejection. Thus supranormal expression of endogenous porcine CRPs may be a feasible alternative to the expression of human CRPs in preventing HAR of pig-to-primate xenografts.

Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but cause coagulopathy in non-immunosuppressed baboons.

BACKGROUND: The genetic modification of pigs is a powerful strategy that may ultimately enable successful xenotransplantation of porcine organs into humans. METHODS: Transgenic pigs were produced by microinjection of gene constructs for human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2-fucosyltransferase (H-transferase, HT), which reduces expression of the major xenoepitope galactose-alpha1,3-galactose (alphaGal). Kidneys from CD55/HT and CD55/CD59/HT transgenic pigs were transplanted into nephrectomised, nonimmunosuppressed adult baboons. RESULTS: In several lines of transgenic pigs, CD55 and CD59 were expressed strongly in all tissues examined, whereas HT expression was relatively weak and did not significantly reduce alphaGal. Control nontransgenic kidneys (n=4) grafted into baboons were hyperacutely rejected within 1 hr. In contrast, kidneys from CD55/HT pigs (n=2) were rejected after 30 hr, although kidneys from CD55/CD59/HT pigs (n=6) maintained function for up to 5 days. In the latter grafts, infiltration by macrophages, T cells, and B cells was observed at days 3 and 5 posttransplantation. The recipients developed thrombocytopenia and abnormalities in coagulation, manifested in increased clotting times and an elevation in the plasma level of the fibrin degradation product D-dimer, within 2 days of transplantation. Treatment with low molecular weight heparin prevented profound thrombocytopenia but not the other aspects of coagulopathy. CONCLUSIONS: Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.

High-level co-expression of complement regulators on vascular endothelium in transgenic mice: CD55 and CD59 provide greater protection from human complement-mediated injury than CD59 alone.

High-level endothelial expression of the human complement regulatory factor CD59 has been shown to protect transgenic mouse hearts from human complement-mediated injury in an ex vivo perfusion model. In this study we examine whether co-expression of CD55 provides additional protection. CD55/CD59 double-transgenic mice were generated by co-injection of CD55 and CD59 expression constructs driven by the human intercellular adhesion molecule 2 (ICAM-2) promoter. A line was established from one mouse that exhibited strong expression of CD55 and CD59 on vascular endothelium in the heart and other transplantable organs. An ex vivo perfusion model was used to compare hearts from these CD55/CD59 mice with hearts from a previously established line, which expressed CD59 at a similar level to the double transgenic line. CD59 hearts displayed prolonged survival compared to wild-type hearts during perfusion with 40% human plasma and maintained approximately 20% maximum work after 60 min. CD55/CD59 hearts were further protected, with work maintained at 35% of the maximum level after 60 min. The data demonstrate that high-level endothelial co-expression of CD55 and CD59 provides greater protection from human complement-mediated injury in this model than expression of CD59 alone.

Expression and functional analysis of glycosyl-phosphatidyl inositol-linked CD46 in transgenic mice.

BACKGROUND: Complement activation plays a pivotal role in hyperacute xenograft rejection. In humans, activation of complement is regulated by a number of cell surface regulatory proteins. Membrane cofactor protein (CD46) is one such regulator that protects cells by acting as a cofactor for the factor I-mediated cleavage of C3b and C4b. Transgenic animals expressing human CD46 may provide organs that are resistant to complement attack. However, attempts to generate mice expressing human CD46 using cDNA-based constructs have been largely unsuccessful. METHODS: Transgenic mice expressing a glycosylphosphatidyl inositol (GPI)-linked form of CD46 were generated by microinjection of a hybrid CD46/CD55 cDNA under the control of the human intercellular adhesion molecule-2 promoter. Expression of CD46-GPI on the vascular endothelium was determined by immunohistochemistry. The ability of CD46-GPI to protect mouse tissues from human complement attack was determined using an ex vivo isolated perfused heart model. RESULTS: Three founder animals expressing CD46-GPI were identified. Histological analysis showed strong and uniform expression of CD46-GPI on the vascular endothelium of all organs examined. Ex vivo perfusion of transgenic mouse hearts with human plasma showed a reduction in C3c deposition and a slightly prolonged function compared with controls. CONCLUSIONS: High-level expression of CD46-GPI was achieved in transgenic mice by using a modified cDNA-based construct. The CD46-GPI was functional, providing some protection from complement-mediated damage in the ex vivo model, and may be useful in xenotransplantation if expressed in combination with CD55 and CD59.

Knock out of alpha1,3-galactosyltransferase or expression of alpha1,2-fucosyltransferase further protects CD55- and CD59-expressing mouse hearts in an ex vivo model of xenograft rejection.

BACKGROUND: Organs from transgenic animals with high-level endothelial expression of the human complement regulatory factors CD55 and CD59 are significantly protected from human complement-mediated injury. Elimination or reduction of the major xenoepitope alphaGal, achieved by knocking out the alpha1,3-galactosyltransferase gene (Gal KO) or expressing human alpha1,2-fucosyltransferase (H transferase or HTF), also affords protection, although to a lesser degree. In this study, we examined whether the protection provided by strong CD55 and CD59 expression can be augmented by the Gal KO or HTF modifications. METHODS: Hearts from four groups of mice (wild type, CD55/CD59, CD55/CD59/HTF, and CD55/CD59/Gal KO) were perfused ex vivo with 40% human plasma. Mean heart work for each group was compared over a 60-min period. RESULTS: Wild-type hearts ceased to function effectively within 15 min of plasma addition. CD55/CD59 hearts displayed prolonged survival and maintained approximately 10% maximum work at the end of perfusion. Introduction of Gal KO or HTF onto the CD55/CD59 background resulted in a further prolongation, with work maintained at 20-30% of the maximum level. CONCLUSIONS: We used an ex vivo model to demonstrate that eliminating alphaGal expression further prolongs the function of mouse hearts expressing high levels of CD55 and CD59. In addition, we showed that reducing alphaGal by expressing HTF is equally as effective in prolonging CD55/CD59 heart function as knocking out Gal transferase, thus providing a feasible strategy for translating these advances to the pig.

High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection.

BACKGROUND: Hyperacute rejection of discordant xenografts is dependent on activation of the complement system of the recipient. Transgenic expression of recipient complement regulatory factors in donor tissue has proved to be a promising approach to dealing with hyperacute rejection, although the relationship between the level of complement regulatory factor expression and the degree of protection is not well established. Here, we examine this relationship using CD59 transgenic mouse hearts in an ex vivo model of xenograft rejection. METHODS: The level of expression of CD59 in two lines of transgenic mice, in which CD59 is expressed under the control of either the murine H2Kb (MHC class I) promoter (line CA-17) or the endothelium-specific human intercellular adhesion molecule-2 promoter (line 237-7), was compared by immunohistochemistry and flow cytometry. Hearts from both groups and wild-type controls were perfused ex vivo with human plasma, and mean heart work for each group was compared over a 60-min period. RESULTS: CD59 expression on cardiac endothelial cells isolated from homozygous CA-17 mice was 25- to 30-fold lower than that on cardiac endothelial cells from heterozygous 237-7 mice. CA-17 hearts perfused with 6% human plasma exhibited a reduction in deposition of the membrane attack complex, but not a prolongation of function, compared with nontransgenic mouse hearts. In contrast, 237-7 hearts showed significantly prolonged function during perfusion with 20% plasma. CONCLUSIONS: High-level endothelial-specific expression of CD59 was effective in prolonging the function of mouse hearts perfused with 20% human plasma, whereas low-level, broader expression did not provide protection from 6% plasma.