[Emergent Endovascular Treatment of Spontaneous Rupture of the Thoracic Aorta].

Spontaneous rupture of the thoracic aorta is a rare disease with a poor prognosis without obvious trauma, aortic aneurysm and aortic dissection. We report 2 cases of successful endovascular aortic repair for spontaneous rupture of the thoracic aorta. Case 1:A 79-year-old man was referred to our hospital complaining of general fatigue. He returned home without any obvious abnormalities in blood tests and computed tomography (CT). The patient was aware of dizziness and fluttering in the early morning the next day, and was transported to the hospital by shock vital. CT showed rupture of descending aorta, so we performed emergent thoracic endovascular aortic repair (TEVAR). Postoperatively, the patient progressed without paraplegia and was transferred to other hospital on the 15th day of hospital for the purpose of rehabilitation. Case 2:A 87-year-old woman was admitted to hospital with suspected pyelonephritis, but his respiratory status was gradually exacerbated. CT showed a rupture of the thoracic aorta at the distal arch. Ten days ago, CT showed no findings suggestive of aneurysm and dissection at the same site of aorta. We performed emergency TEVAR. She was removed from mechanical ventilation on the 4th postoperative day. We are continuing rehabilitation treatment now.

Use of a novel drainage flow servo-controlled CPB for mitral valve replacement in a Jehovah's Witness.

We developed a novel open cardiopulmonary bypass (CPB) system, a drainage flow servo-controlled CPB system (DS-CPB), in which rotational speed of the main roller pump is servo-controlled to generate the same amount of flow as the systemic venous drainage. It was designed to safely decrease the priming volume while maintaining a constant reservoir level, even during fluctuations of the drainage flow. We report a successful use of a novel DS-CPB system in an elderly Jehovah's Witness patient with dehydration who underwent mitral valve replacement.

[Concomitant Atrial Septal Defect Closure and Repair of Pectus Excavatum in a 50-year-old Patient;Report of a Case].

We report a case of atrial septal defect (ASD) with severe pectus excavatum. A 50-year-old female had a stroke due to paradoxical embolism from deep vein thrombosis thorough ASD. Her preoperative computed tomography(CT) revealed a severe pectus excavatum (Haller CT index 28.6). The patient underwent ASD closure and repair of the pectus excavatum concomitantly. Median full sternotomy was performed for ASD closure. And we adopted sterno-costal elevation for pectus excavatum repair. Cartilages of the 3rd to the 7th rib were segmentally resected and the remainders were re-sutured to the sternum. The operation was performed uneventfully. The postoperative echocardiogram revealed no residual shunt. And the deformity of the anterior chest wall was remarkably lessen.

Pericoronary pseudotumor caused by helicobacter cinaedi.

Cardiac tumors and tumor-like lesions are uncommon; most are true neoplasms. We here report a case of a pericoronary tumor-like lesion surrounding the right coronary artery in a 39-year-old man who presented with fever and chest pain. Although clarithromycin was administered for 1 week, his fever persisted. Helicobacter cinaedi (H. cinaedi) was isolated from blood cultures and found to be sensitive to ceftriaxone. A computed tomography scan showed a tumor-like lesion with no (18)F-fl uorodeoxyglucose uptake surrounding the right coronary artery. After administration of ceftriaxone, the tumor-like lesion diminished in size according to meticulous computed tomography examinations. We therefore concluded that it was caused by H. cinaedi infection. The patient has been followed up closely for 1 year and remains asymptomatic.

Plasma neutrophil gelatinase-associated lipocalin in acute kidney injury superimposed on chronic kidney disease after cardiac surgery: a multicenter prospective study.

INTRODUCTION: Plasma neutrophil gelatinase-associated lipocalin (NGAL) is reportedly useful for post-cardiac surgery acute kidney injury (AKI). Although chronic kidney disease (CKD) is a strong risk factor for AKI development, no clinical evaluation of plasma NGAL has specifically examined AKI occurring in patients with CKD. This study evaluated plasma NGAL in AKI superimposed on CKD after cardiac surgery. METHODS: This study prospectively evaluated 146 adult patients with scheduled cardiac surgery at 2 general hospitals. Plasma NGAL was measured before surgery, at ICU arrival after surgery (0 hours), and 2, 4, 12, 24, 36, and 60 hours after ICU arrival. RESULTS: Based on the Kidney Disease Improving Global Outcomes (KDIGO) CKD guideline, 72 (49.3%) were diagnosed as having CKD. Of 146 patients, 53 (36.3%) developed AKI after surgery. Multiple logistic regression analysis revealed that preoperative plasma NGAL, estimated glomerular filtration rate (eGFR), and operation time are significantly associated with AKI occurrence after surgery. Plasma NGAL in AKI measured after surgery was significantly higher than in non-AKI irrespective of CKD complication. However, transient decrease of plasma NGAL at 0 to 4 hours was observed especially in AKI superimposed on CKD. Plasma NGAL peaked earlier than serum creatinine and at the same time in mild AKI and AKI superimposed on CKD with increased preoperative plasma NGAL (>300 ng/ml). Although AKI superimposed on CKD showed the highest plasma NGAL levels after surgery, plasma NGAL alone was insufficient to discriminate de novo AKI from CKD without AKI after surgery. Receiver operating characteristics analysis revealed different cutoff values of AKI for CKD and non-CKD patients. CONCLUSIONS: Results show the distinct features of plasma NGAL in AKI superimposed on CKD after cardiac surgery: 1) increased preoperative plasma NGAL is an independent risk factor for post-cardiac surgery AKI; 2) plasma NGAL showed an earlier peak than serum creatinine did, indicating that plasma NGAL can predict the recovery of AKI earlier; 3) different cutoff values of post-operative plasma NGAL are necessary to detect AKI superimposed on CKD distinctly from de novo AKI. Further investigation is necessary to confirm these findings because this study examined a small number of patients.

Microbial biodegradation of a novel fluorotelomer alcohol, 1H,1H,2H,2H,8H,8H-perfluorododecanol, yields short fluorinated acids.

The accumulation of perfluorooctanoic acid (PFOA) has been detected in wildlife, soil, and water. Further, 8:2 fluorotelomer alcohol (8:2 FTOH) is used for the industrial synthesis of other fluorotelomer compounds, surfactants, and polymeric materials; however, it was recently found to be a potential source of PFOA contamination in the environment. 1H,1H,2H,2H,8H,8H-perfluorododecanol (degradable telomer fluoroalcohol (DTFA)), which is a newly developed fluorotelomer, contains the -CH2- group in the fluorinated carbon backbone, making it potentially degradable through biological reactions. In this study, we investigated the biodegradation of DTFA in a mixed bacterial culture obtained from activated sludge. Optimized quantitative liquid chromatography-mass spectrometry analysis of the predicted metabolites generated in the culture revealed accumulations of the transformation products from DTFA to 2H,2H,8H,8H-PFDoA and 2H,8H,8H-2-PFUDoA via multiple processes. Furthermore, the production of short fluorinated compounds, perfluorobutanoic acid, perfluoropentanoic acid, and perfluoropentanedioic acid, which are believed to have lower accumulation potential and toxicity toward organisms than PFOA, was determined.

Endovascular treatment for mycotic aneurysm using pyoktanin- applied devices.

BACKGROUND: Mycotic thoracic aortic aneurysm is an extremely rare but serious disease because it can easily rupture and has a high mortality rate. The standard therapy for it comprises graft replacement and debridement using systemic antibiotics; nonetheless, this has a high mortality rate and complications. Endovascular aortic repair is considered a bridging therapy before open surgery. However, we have used it at our institution for the radical treatment of mycotic thoracic aortic aneurysm utilizing pyoktanin (methylrosanilide chloride)-applied devices. Thus, the aim of this study was to report our clinical experience with pyoktanin-applied thoracic endovascular aortic repair for the treatment of mycotic thoracic aortic aneurysm, including its effects. METHODS: From April 2017 to July 2019, we performed thoracic endovascular aortic repair using pyoktanin for eight cases of mycotic thoracic aortic aneurysm using Valiant®. During device preparation before insertion, pyoktanin was flushed from the side port instead of saline containing heparin. RESULTS: There were no operative deaths, recurrences of infection, or major complications. Two cases died from pneumonia and cancer; the other six cases were alive during the follow-up period. CONCLUSIONS: Pyoktanin-applied thoracic endovascular aortic repair for mycotic thoracic aortic aneurysm treatment is effective. However, the appropriate use of antibiotics and bundled therapy is necessary at present.

Endovascular Repair for Kommerell's Diverticulum and Right-Sided Aortic Arch.

A 74-year-old man with hoarseness was diagnosed with a right-sided aortic arch and Kommerell's diverticulum by computed tomography (CT). The diverticulum had a maximum diameter of 33 mm, and surgical intervention was chosen because of the possibility of rupture. A right common carotid to right subclavian artery bypass was constructed, stent-graft was placed after the branching of the right common carotid artery, and coil embolization of the diverticulum was performed via left brachial artery. No leaks were found on postoperative CT. Symptoms disappeared and the diverticulum became smaller soon after surgery. Thoracic endovascular aortic repair (TEVAR) for Kommerell's diverticulum was safe and effective.

Impact of concomitant cardiac procedure on coronary artery surgery in hemodialysis-dependent patients.

OBJECTIVE: Coronary artery bypass grafting (CABG) in hemodialysis-dependent patients is associated with high mortality and morbidity rates. This retrospective study was undertaken to identify the risk factors for in-hospital mortality for hemodialysis-dependent patients. METHODS: Subjects included 87 consecutive hemodialysis-dependent patients (81 men and 6 women), aged 47-82 years (mean age, 65 years), who underwent CABG. Operative procedures included CABG alone (n=77) and CABG with valve replacement, repair, or the Dor procedure (n=10). Thirty-one perioperative risk factors were subjected to univariate and multivariate analyses to identify the risk factors for hospital death. RESULTS: The overall in-hospital mortality rate, including operative death, was 14.9% (13/87). Univariate analysis showed the following 7 risk factors to be statistically significant predictors of hospital death: age > or = 70 years, a concomitant cardiac procedure, left ventricular ejection fraction <30%, left ventricular end-systolic volume index >70 ml/m2, a left main lesion, emergency/urgent surgery, and anemia (hemoglobin <10 mg/dl) (p<0.05 for each predictor). Multivariate logistic regression analysis confirmed that a concomitant cardiac procedure (chi-squared = 17.080, p=0.013) and age > or = 70 years (chi-squared = 9.112, p=0.019) are statistically significant independent risk factors for hospital death. CONCLUSION: A concomitant cardiac procedure and age > or = 70 years were identified as significant independent risk factors for hospital mortality after CABG for hemodialysis-dependent patients. These preoperative risk factors may help in predicting operative risks and improving clinical outcomes in hemodialysis-dependent patients undergoing CABG.

Cyclosporine treatment of high dose and long duration reduces the severity of graft coronary artery disease in rodent cardiac allografts.

BACKGROUND: Graft coronary artery disease (GCAD) limits allograft survival after cardiac transplantation. The objective of this study was to correlate GCAD with the level of immunosuppression in an established allogeneic rodent cardiac chronic rejection model to better understand the mechanisms of GCAD in this system. METHODS: Donor PVG hearts were transplanted into the abdomen of ACI rats. Six recipient groups received either 10, 7.5 or 5 mg/kg/day of oral cyclosporine (CsA), for 90 (10 mg/90 d, 7.5 mg/90 d, 5 mg/90 d) or 10 days (10 mg/10 d, 7.5 mg/10 d, 5 mg/10 d; n = 10 all groups), and grafts procured on Day 90. GCAD was assessed by histology for percent luminal narrowing (%LN), percent affected vessels (%AV) and intima/media ratio (I/M ratio). Sections were stained for ED1-positive macrophages and MHC Class II-positive cells. RESULTS: The 10 mg/90 d treatment group showed significantly reduced GCAD compared with the 5mg/10d treatment group (%LN = 4.3 +/- 3.1% vs 39 +/- 11.9%, p < 0.05). The 7.5 mg/90 d group had a reduced %LN and I/M ratio compared with the 5 mg/10 d group (%LN = 8.0 +/- 3.5% vs 39 +/- 11.9%, p < 0.05; I/M ratio = 0.06 +/- 0.02 vs 0.41 +/- 0.14, p < 0.05). There was a trend toward reduction of GCAD with both increasing the dose of CsA as well as the duration of treatment. Continuous treatment with CsA reduced perivascular macrophage and MHC II cell infiltration. Macrophage infiltrates correlated strongly with GCAD (R(2) > 0.90, p < 0.01), and MHC II infiltrates showed a weak correlation, although not statistically significant (R(2) > 0.56, p = NS). CONCLUSIONS: This study further defines the effect of cyclosporine on GCAD in this cardiac transplantation model. In this system, higher dose and longer duration of treatment with CsA markedly reduces macrophage and MHC II infiltration, correlating with diminished GCAD. However, increasing dose and duration of CsA did not completely eliminate the development of GCAD. Non-immunologic factors could contribute to this occurrence.

Aortobronchial fistula resulting from a mycotic pseudoaneurysm after treatment of an aortoesophageal fistula due to a thoracic aortic aneurysm.

A 58-year-old man was admitted for an aortoesophageal fistula (AEF) resulting from a thoracic aortic aneurysm. He underwent immediate in-situ prosthetic graft replacement, primary esophageal repair and wrapping of the aneurysm. Postoperative upper gastrointestinal endoscopy and computerized tomography (CT) findings were unremarkable. He was discharged on postoperative day (POD) 25. Three months after surgery, he was readmitted with complaints of worsening cough and hemoptysis. CT showed a thrombosed aneurysm adjacent to the left bronchus. Aortobronchial fistula due to mycotic pseudoaneurysm was suspected. The patient underwent immediate resection of the infected graft and prosthetic graft replacement positioned to avoid the infected area. The graft was wrapped with omentum. On POD 7, pleural empyema developed, and esophagography revealed a residual leak. Staged reconstruction of the esophagus was performed successfully. We conclude that even if the fistulous opening is small, simultaneous esophageal resection should be performed during the initial treatment of AEF.

Pitfalls of sutureless repair of a blow-out type left ventricular free wall rupture.

A 55-year-old man was admitted for acute myocardial infarction. Cardiac catheterization revealed total occlusion of the left circumflex artery. During catheterization, he suffered cardiogenic shock. Percutaneous cardiopulmonary support was established, and the patient was transferred to the operating room. A blow-out left ventricular free wall rupture (LVFWR) with an epicardial tear, 1 mm in diameter, was found, and sutureless repair with a collagen hemostat (TachoComb) was performed. However, on postoperative day 7, echocardiography revealed an echo-free space resembling a pseudoaneurysm. A second operation was performed immediately for impending re-rupture. An epicardial tear, 2 x 10 mm in diameter, was found at the previous bleeding point where hemostasis had been achieved with only one sheet of TachoComb. The defect was closed with mattress sutures buttressed with Teflon felt. We conclude that even if the risk of re-rupture is low, sutureless repair with a collagen hemostat alone should be avoided in treating blow-out LVFWR.

Superoxide dismutase mimetic m40401 reduces ischemia-reperfusion injury and graft coronary artery disease in rodent cardiac allografts.

BACKGROUND: The oxidative stress associated with ischemia-reperfusion (I/R) of cardiac allografts leads to production of injurious cytokines and expression of proinflammatory adhesion molecules. This is one of the most important alloantigen-independent factors associated with graft coronary artery disease (GCAD). M40401 is a newly developed cell permeable superoxide dismutase mimetic, which has been shown to scavenge superoxide anion with highly specific and enhanced catalytic activity. We hypothesized that M40401 would exert a protective effect in I/R injury of cardiac allografts and ameliorate the progression of GCAD. METHODS: Recipient ACI rats were pretreated with M40401 or vehicle control. PVG donor hearts were heterotopically transplanted into the abdomen of ACI recipients. Cardiac allografts were analyzed for adhesion molecule mRNA expression and tumor necrosis factor-alpha expression after 4 hr of reperfusion. Neutrophil infiltration was detected by myeloperoxidase activity. Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 mRNA were detected by reverse-transcriptase polymerase chain reaction. Immunohistochemical analysis of adhesion molecule expression was also performed. Additional grafts were procured 90 days after transplantation and assessed for the development of GCAD by computer-assisted image analysis. RESULTS: In the M40401-treated group, adhesion molecule expression was significantly less than in the vehicle control group. Treated grafts also had lower myeloperoxidase activity and tumor necrosis factor-alpha concentration compared with controls. Neointimal proliferation and intima to media ratios in M40401-treated allografts were significantly decreased compared with controls. CONCLUSIONS: Selective removal of superoxide anion by M40401 results in inhibition of I/R injury. Furthermore, M40401 treatment decreases the development of oxidative stress-associated GCAD. This treatment strategy may have broad cardioprotective applications for all cardiac operations in addition to cardiac transplantation.

Effects of adenoviral up-regulation of bcl-2 on oxidative stress and graft coronary artery disease in rat heart transplants.

BACKGROUND: Bcl-2 has been shown to have antioxidant properties. Early oxidative stress is an important antigen-independent factor that contributes to the development of graft coronary artery disease (GCAD). We hypothesized that adenoviral up-regulation of bcl-2 would decrease early oxidative stress and inhibit GCAD after heart transplantation. METHODS: PVG rat hearts were treated with adenovirus carrying the human bcl-2 gene (AdvBcl-2) or null adenovirus (AdvNull) then transplanted into the abdomens of PVG recipients. After 4 days of reperfusion to allow adenoviral gene expression, grafts were retransplanted into ACI rat recipients and reperfused for 4 or 8 hours or 90 days (cyclosporine A 7.5 mg/kg on postoperative day [POD] 0-9). Production of tumor necrosis factor (TNF)-alpha after 4 hours and oxidized glutathione (GSSG) after 8 hours indicated development of oxidative stress. 90-day allografts were assessed for GCAD by way of computerized morphometry. RESULTS: Over-expression of bcl-2 at the time of allograft reperfusion was confirmed by Western blotting. Whereas AdvNull-treated hearts demonstrated elevated TNF-alpha levels after 4 hours and increased GSSG after 8 hours of reperfusion, AdvBcl-2-treated hearts were no different from nontransplanted hearts. AdvBcl-2 treatment also resulted in decreased luminal narrowing and intima-to-media ratio at POD 90. CONCLUSIONS: Bcl-2 over-expression interrupts the development of oxidative stress in reperfused rat-heart allografts. Early up-regulation of bcl-2 also decreases GCAD, indicating the importance of early oxidative stress and the role that bcl-2 may play in the long-term function of heart transplants.

Effects of AGI-1096, a novel antioxidant compound with anti-inflammatory and antiproliferative properties, on rodent allograft arteriosclerosis.

BACKGROUND: AGI-1096 is a novel phenolic intracellular antioxidant with anti-inflammatory and antiproliferative properties. In vitro, AGI-1096 inhibited the inducible expression of vascular cell adhesion molecule (VCAM)-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 in endothelial cells and tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells. It also inhibited serum-stimulated proliferation of aortic smooth-muscle cells. In vivo, AGI-1096 demonstrated anti-inflammatory properties in a murine delayed-type hypersensitivity model. Given these antioxidant, anti-inflammatory and antiproliferative properties, we reasoned that AGI-1096 may be able to prevent chronic allograft arteriosclerosis. This hypothesis was tested in a rodent aortic transplantation model. METHODS: Donor descending aortas from August-Copenhagen-Irish rats were heterotopically transplanted into Lewis rat abdomens in end-to-end fashion. Animals were assigned to six groups as follows: AGI-1096 0 mg/kg per day (vehicle, n = 10), 10 mg/kg per day (n = 10), 20 mg/kg per day (n = 10), 40 mg/kg per day (n = 10), positive control (cyclosporine A 10 mg/kg per day by oral gavage, n = 10), and isograft negative control (Lewis-to-Lewis, n = 5). AGI-1096 was administrated subcutaneously to recipient animals three days before the surgery and for 90 days thereafter. On day 90, the paraffin-embedded allograft sections were stained with Elastin-van Gieson's stain, and the intima/media (I/M) ratio and luminal narrowing (1%LN) was assessed by digital morphometry. RESULTS: AGI-1096 demonstrated dose-dependent lowering of the I/M ratio and %LN when compared with vehicle controls. CONCLUSION: This is the first study to show that treatment of allograft recipients with AGI-1096 decreases the incidence of transplant arteriosclerosis. These data suggest that AGI-1096 may be a promising new therapeutic agent for use in clinical transplantation.

L-Arginine polymers enhance coronary flow and reduce oxidative stress following cardiac transplantation in rats.

BACKGROUND: Hearts treated with l-arginine polymers have demonstrated upregulated production of nitric oxide. The current study examined whether these polymers improved coronary flow and reduced myocardial oxidative stress after rat heart transplantation. METHODS: PVG donor hearts were incubated ex vivo with either 100 mumol/L l-arginine polymers 9 amino acids in length (R9) (n = 7) or phosphate-buffered saline (n = 7) for 30 minutes after arrest and then transplanted heterotopically into the abdomen of ACI recipient rats. Coronary flows were assessed using fluorescent microspheres both at baseline (30 minutes after reperfusion) and at 6 hours and compared using the paired Student t test. Evidence of oxidative stress was assessed in a separate cohort of similarly treated animals by enzyme-linked imunosorbent assay for rat tumor necrosis factor-alpha at 6 hours. RESULTS: Histochemistry with biotinylated l-arginine polymers demonstrated uptake of R9 into the vascular walls of treated allografts. Although all hearts experienced deterioration in coronary flow between baseline and 6 hours, the R9-treated group had a smaller reduction (29.9%, P =.10) than the phosphate-buffered saline control group (58.0%, P =.003). Tumor necrosis factor-alpha levels were also significantly reduced in the R9 treatment group compared with the phosphate-buffered saline category (160 +/- 30 versus 205 +/- 38, P =.007). CONCLUSION: Rat cardiac allografts treated with R9 at the time of procurement exhibited less deterioration in coronary flow and a reduction in myocardial oxidative stress than the phosphate-buffered saline control group in the perioperative period. The use of arginine polymers may thus provide important myocardial protection against ischemia-reperfusion injury in both transplant and routine cardiac surgery cases.

Up-regulation of Bcl-2 through hyperbaric pressure transfection of TGF-beta1 ameliorates ischemia-reperfusion injury in rat cardiac allografts.

BACKGROUND: Oxidative stress after ischemia-reperfusion of cardiac allografts leads to activation of cardiomyocytes and production of cytokines. Bcl-2, an inhibitor of the apoptotic pathway, also has strong antioxidant properties. Ischemia-reperfusion injury after transplantation leads to decreased bcl-2 and increased tumor necrosis factor (TNF)-alpha levels. Transforming growth factor (TGF)-beta1 is known to attenuate ischemia-reperfusion injury and inhibits apoptosis of myofibroblasts. We hypothesize that TGF-beta1, prevents bcl-2 cleavage and increased TNF-alpha production. METHODS: Rat PVG donor hearts were heterotopically transplanted into ACI recipients. Donor hearts were procured and assigned to groups: (1) intracoronary TGF-beta1 (200 ng/ml) perfusion and pressure at 78 psi for 45 minutes (n = 4); (2) intracoronary TGF-beta1 perfusion and incubation for 45 minutes without pressure (n = 4), (3) saline perfusion and incubation for 45 minutes without pressure (n = 4). Hearts were procured 4 hours after transplantation and analyzed by reverse transcriptase-polymerase chain reaction for bcl-2 mRNA expression, ELISA for TNF-alpha, and for myeloperoxidase activity (MPO). RESULTS: Bcl-2 decreased in untreated animals (bcl-2:G3PDH ratio = 0.85 +/- 0.73 vs 1.16 +/- 0.11, not significant [NS]), whereas TNF-alpha increased to 669.99 +/- 127.09 vs 276.84 +/- 73.65 pg/mg total protein in controls (p < 0.003). In TGF-beta(1) pressure-treated hearts, bcl-2 was up-regulated (2.49 +/- 0.6 vs 1.16 +/- 0.11, controls, p < 0.005), whereas TNF-alpha was unchanged (396.1 +/- 100.38 vs 276.84 +/- 73.65 pg/mg, NS). Hearts treated with TGF-beta1 and pressure showed significant up-regulation of bcl-2 compared with hearts treated with TGF-beta1 without pressure (2.49 +/- 0.6 vs 1.17 +/- 0.6, p < 0.02). MPO showed no differences. CONCLUSIONS: Bcl-2 is down-regulated and TNF-alpha up-regulated in this model of ischemia-reperfusion injury. Furthermore, TGF-beta1 is linked to this process and ameliorates reperfusion injury by up-regulating bcl-2 and inhibiting TNF-alpha. Therapeutic overexpression of myocardial TGF-beta1 may be clinically useful to control ischemia-reperfusion injury associated with cardiac transplantation.

Elevated cyclic adenosine monophosphate ameliorates ischemia-reperfusion injury in rat cardiac allografts.

BACKGROUND: Oxidative stress after ischemia and reperfusion leads to leukocyte activation, the production of injurious cytokines, and increased expression of inflammatory adhesion molecules. This initial event is one of the most important alloantigen-independent factors associated with graft coronary artery disease (GCAD). Cyclic adenosine monophosphate (cAMP) is an important second messenger that inhibits the expression of tumor necrosis factor alpha (TNF-alpha), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1) in vitro. Its levels decrease during organ preservation. We hypothesized that augmenting allograft cAMP levels with the water-soluble adenylate cyclase activator, NKH477, could decrease ischemia-reperfusion injury and inhibit the progression of GCAD. METHODS: PVG to ACI rat heterotopic cardiac allografts, treated with NKH477 solution or vehicle, were reperfused for 4 hours or 90 days after 60 minutes of ischemia. We analyzed grafts for intracellular adhesion molecule 1 (ICAM-1), VCAM-1, and ELAM-1 mRNA expression; TNF-alpha and interleukin-6 (IL-6) protein expression; and myeloperoxidase activity. We also performed immunohistochemical analysis for ICAM-1 and VCAM-1 protein expression. At post-operative Day 90, the progression of GCAD had increased morphometrically. RESULTS: NKH477-treated grafts had significantly decreased levels of myeloperoxidase activity compared with controls. In this group, TNF-alpha, IL-6, and VCAM-1 protein expression was inhibited; however, ICAM-1 and ELAM-1 expression did not alter. We found no differences in the degree of development of GCAD between groups. CONCLUSION: Although augmented intracellular cAMP prevented acute reperfusion injury, it was insufficient to prevent the development of GCAD. Intracellular adhesion molecule 1 and ELAM-1, whose expression NKH477 does not inhibit, may play important roles in the development of GCAD.

Bcl-2-mediated inhibition of apoptosis in rat cardiac allografts worsens development of graft coronary artery disease.

BACKGROUND: We hypothesized that adenovirally mediated Bcl-2 transfection of donor hearts would reduce the apoptosis that occurs during acute rejection while worsening the development of chronic graft coronary artery disease (GCAD). METHODS: PVG donor hearts were treated with either AdvBcl-2 or AdvNull virus before heterotopic transplantation into ACI rats. Bcl-2 expression was assessed on post-operative day 4 (POD) 4 by western blot. Apoptosis was measured using (99m)Technetium-bound-annexin V imaging and caspase 3 activity assay. Allograft survival was determined in a separate cohort of animals. Long-term-treated animals were then assessed for measures of GCAD on POD 90. RESULTS: Western blot analysis showed upregulation of Bcl-2 expression in AdvBcl-2-treated hearts. (99m)Tc-annexin V images demonstrated decreased uptake in the AdvBcl-2 group (1.41 +/- 0.33% vs 1.94 +/- 0.37%, p = 0.026). Caspase 3 activity was also significantly lower in this treatment group (0.112 +/- 0.032 vs 0.204 +/- 0.096, p = 0.049). Allograft survival was similar in both groups, respectively (7.7 +/- 1.2 vs 6.8 +/- 1.5 days, p = 0.340). GCAD, as determined by percent luminal narrowing (5.9 +/- 6.1% vs 1.6 +/- 1.5%, p = 0.039), intima-to-media ratio (5.1 +/- 5.1% vs 1.5 +/- 1.7%, p = 0.040) and percent of affected vessels (15.1 +/- 9.9% vs 5.3 +/- 4.4%, p = 0.009), was higher for the AdvBcl-2 group. CONCLUSION: Treatment of cardiac allografts with AdvBcl-2 resulted in a reduction of apoptosis that did not significantly improve short-term graft survival, but worsened chronic GCAD.

Coronary malperfusion due to type A aortic dissection: mechanism and surgical management.

BACKGROUND: Coronary malperfusion associated with aortic dissection is relatively rare, but when it occurs, it is fatal to the patient. To salvage such moribund patients, aggressive coronary revascularization concomitant with aortic repair is essential. We review the surgical results and mechanism of malperfusion in a group of 12 patients with coronary malperfusion caused by type A aortic dissection, and we discuss our surgical approach. METHODS: Between March 1990 and March 2003, 12 patients (6.1%) from a total of 196 consecutive patients with acute type A aortic dissection undergoing surgery suffered coronary malperfusion associated with the dissection. There were 4 men and 8 women (mean age, 60.8 +/- 8.3 years). Nine patients had acute myocardial infarction due to dissection before surgery, and 3 patients suffered coronary malperfusion after aortic declamping. RESULTS: Hospital mortality rate was 33.3% (4 patients). The mortality rate was higher than that in patients without coronary malperfusion (33.3% vs. 8.2%, p = 0.019). Three patients could not be weaned from cardiopulmonary bypass, and 1 patient died of heart failure in the intensive care unit. Involved coronary arteries included the right coronary artery (8 patients), left coronary (2 patients), and both (2 patients). Mechanisms of coronary obstruction were compression (2 patients), coronary dissection (7 patients), and coronary disruption (3 patients). Coronary artery bypass grafting was performed concomitant with aortic repair. CONCLUSIONS: Acute type A aortic dissection with coronary involvement is associated with high mortality rate, aggressive coronary revascularization and early aortic repair with simple techniques are necessary to salvage these critically ill patients.