[Lactic Acidosis after Cardiac Surgery Treated by Continuous Renal Replacement Therapy in a Patient on Metformin;Report of a Case].

Lactic acidosis is a common condition observed in a patient after cardiac surgery. It is important to identify the pathogenesis of lactic acidosis since the delay of an appropriate treatment leads to high mortality. Metformin overdose has been known as a risk of lactic acidosis, and previous reports have demonstrated that continuous renal replacement therapy(CRRT) is effective. However, it has yet to be known if metformin-related lactic acidosis after cardiac surgery is treatable with CRRT. We, herein, report a case of 64-year-old diabetic male who had been on metformin treatment until 1 day before surgery. He presented lactic acidosis postoperatively and was successfully treated with CRRT. This case suggests that it is necessary to discontinue metformin no later than 2 days before surgery and that CRRT is of use for perioperative lactic acidosis in a patient on metformin.

[Perioperative Risk Management for Extensively Atheromatous Aortic Disease].

Extensive atheromatous disease of the thoracic aorta is a significant risk factor of lethal complications and remains an unsolved issue in patients undergoing cardiovascular surgery. The disease condition has been documented to be associated not only with high operative risk but also with relatively poor prognosis especially in patients with aortic replacement, due to the susceptibility to potential embolic events such as neurological deficits. To achieve favorable outcomes after surgical intervention, precise preoperative evaluation and meticulous surgical planning are important. 3-dimensional computed tomography (CT) can reveal detailed aortic lesions, graftable anastomotic sites, suitable cannulation sites, risk score related to thoracic endovascular aortic repair (TEVAR). Despite the tendency that atheromatous lesions are extensive and multiple, a selected treatment would better be targeted only for clinically significant pathologic site to minimize the risks associated with surgical intervention. In addition, realistic anticipation and subsequent preparation for potential second operation should also be planned. As for a representative aortic surgery, total aortic arch replacement has been the most frequently performed procedure in Japan. When extensive atheromatous lesions are encountered around the arch and supra-aortic branches, rapid switching over to isolation of neck vessels and selective cerebral perfusion is recommended rather than solely relying on the right axillar artery perfusion. Retrograde cerebral perfusion may also be employed in a case with hostile cervical arterial lesions. Besides surgical strategy, peri-operative managements including preservation of renal and gastrointestinal functions are of paramount importance, and definitely influence the post-operative quality of life in patients with extensive atheromatous disease.

[Surgical Treatment of Giant Coronary Artery Aneurysm Presented as Acute Coronary Syndrome].

Coronary artery aneurysm is rare disease, usually asymptomatic and is often found by chance by echocardiography, computed tomography(CT) and coronary angiography. However, its rupture or thrombotic obstruction to the periphery of the coronary artery leads to cardiac tamponade, angina pectoris, or myocardial infarction. We describe 2 cases of giant coronary artery aneurysm presented as acute coronary syndrome. Surgical resection of the aneurysm and coronary artery bypass grafting were successfully carried out under cardiopulmonary bypass. Postoperative courses of both cases were uneventful, and the patients were free of symptoms.

[Traumatic type A dissection with acute pericarditis 6 weeks after blunt trauma; report of a case].

A 38-year-old man presented with typical symptom of acute pericarditis and chronic cardiac tamponade 6 weeks after blunt trauma. Follow-up computed tomography after 2 weeks revealed a localized dissection at the proximal part of the ascending aorta. This is a rare case of chronic Stanford type A aortic dissection after blunt trauma, a diagnosis of which was established later with consistent suspicion and repeated examination by computed tomography.

[Coronary artery spasm induced by neuroleptic malignant syndrome during off-pump coronary artery bypass grafting; report of a case].

A 61-year-old woman with a left main lesion and coronary spastic angina was scheduled for off-pump coronary artery bypass grafting (OPCAB). She had been orally receiving selective serotonin reuptake inhibitor( SSRI) for the treatment of depression. OPCAB to left anterior discending artery( LAD) and left circumflex branch (LCX) was performed using the bilateral internal thoracic arteries assisted by intra-aortic balloon pumping. When the sternotomy was going to be closed, ST elevation of electrocardiogram (ECG) occurred and was followed by complete atrio-ventricular (AV) block. After returning to intensive care unit (ICU), the patient showed rapid elevation of the body temperature, excessive sweating, progressive metabolic acidosis, and abnormal high levels in white blood cell count and creatine phosphokinase. On suspicion of neuroleptic malignant syndrome(NMS) onset, dantrolene sodium hydrate was administered, resulting in marked improvement of the symptoms. We have concluded that this case was an NMS combined with coronary artery spasm during OPCAB treated successfully with dantrolene sodium hydrate.

[Distal aortic repair after aortic arch replacement].

BACKGROUND: It is crucial to expose the proximal aorta in distal aortic repair, i.e., replacement of the descending thoracic aorta (DTA) or the thoracoabdominal aorta (TAA), after aortic arch replacement. With the elephant trunk (ET), it is usually easy to expose and clamp it. On the other hand, without the ET, it may be difficult or impossible to expose the proximal aorta and deep hypothermic circulatory arrest (DHCA) will be required. METHODS: Between April 1989 and March 2007, 17 patients underwent distal aortic repair after aortic arch replacement. Five patients underwent replacement of DTA and 12 of TAA. Five patients without the ET needed DHCA and open proximal anastomosis [OP (+) group], while in 12 patients, the ET or proximal aorta was successfully clamped [OP (-) group]. RESULTS: The mean extracorporeal circulation time in OP (+) group was significantly longer than that in OP (-) group (415 +/- 131 min v.s. 267 +/- 109 min, p < 0.05). There was no hospital death, cerebral infarction, fatal arrhythmia or low output syndrome in either group, and paraplegia in 2 patients and renal failure requiring hemodialysis in one were found only in OP (+) group. CONCLUSION: The ET procedure enables to avoid DHCA and may contribute to improving operative results in distal aortic repair after aortic arch replacement.

[Aortic root surgery in patients with previous aortic root or valve operations].

OBJECTIVES: To assess the operative indication, risk factors, procedures, and outcomes of aortic root surgery in patients with previous aortic root or valve surgery. PATIENTS AND METHODS: Between 1995 and 2007, aortic root surgery was performed in 137 patients. Thirty-five of those, who had previous root replacement, root remodeling or aortic valve surgery, were evaluated retrospectively. RESULTS: Indications for redo surgery included lesions at coronary artery reconstruction site after root procedures, aneurysmal formation or dissection of sinus Valsalva after aortic valve procedures, and prosthetic material infection. Two cases with prior graft infection died of sepsis, and one case with extended aortic dissection died of esophageal bleeding. Hospital mortalities were, hence, 8.6% in redo cases, which was comparable to 5.0% in primary root surgery cases. Multivariate risk factor analysis of root surgery revealed that preceding infective aortic root lesion was the only significant independent risk factor for postoperative mortality, whereas redo procedure per se was not a significant risk. CONCLUSIONS: Redo aortic root surgery can be performed with a reasonably low operative risk. Graft infection in patients with previous aortic root surgery remains a challenging lesion.

Enhanced perigraft angiogenesis prevents prosthetic graft infection.

BACKGROUND: Prosthetic vascular graft infection is an unsolved fatal complication after aortic surgery. We hypothesized that increased vascularity around a prosthetic graft may exert a preventive role against bacterial infection. METHODS: Eighty-three Fischer rats were divided into five groups according to the types of subcutaneously implanted prosthetic graft and granulocyte-colony stimulating factor (G-CSF) treatment. The groups G and C had gelatin hydrogel microspheres-incorporated graft (gel graft) with or without concomitant systemic administration of G-CSF (50 microg/kg), respectively. The groups FG and F had the gel graft impregnated with 100 mug of basic fibroblast growth factor (bFGF) with or without systemic G-CSF. The group N received untreated grafts. Seven days after graft implantation, broth containing methicillin-sensitive Staphylococcus aureus (4.0 x 10(3) colony-forming units) was inoculated onto the graft. All the grafts and the surrounding tissues were explanted 2 days later. Quantitative culture for methicillin-sensitive Staphylococcus aureus from the grafts and histologic assessment for capillary number in the tissue were performed. RESULTS: Positive infection rates in the groups N, C, and G were 34.7%, 30.4%, and 15.3%, respectively; whereas those were zero in the F and FG groups. Tissue around the grafts demonstrated significantly higher number of capillaries in the groups F and FG compared with the groups C and G. The number of bacterial colonies inversely correlated with the number of capillaries around the implanted graft (r = -0.32, p < 0.05). CONCLUSIONS: Basic fibroblast growth factor incorporated into a prosthetic graft with or without systemic G-CSF can induce angiogenesis around the graft and prevent prosthetic graft infection.

Successful management of esophagoparaprosthetic fistula after aortic surgery.

Aortoesophageal fistula is a relatively rare but highly fatal condition, especially in the case of secondary aortoesophageal fistulas after previous thoracic aortic surgery in which the aortic prosthetic graft itself may be involved in the infection, resulting in an esophagoparaprosthetic fistula. In this report, we describe a complicated case of esophagoparaprosthetic fistula arising after descending thoracic aortic replacement and endovascular pseudoaneurysm repair that was successfully treated by surgical resection and in situ aortic graft replacement using a homograft completely covered with an omental flap, combined with subtotal esophagectomy and staged reconstruction of the alimentary tract. The patient has been doing well for 24 months without signs of recurrent infection.

Redo total aortic arch replacement using an extended homograft for graft infection.

A 65-year-old man developed graft infection 3 years after total aortic arch replacement for a chronic dissecting aneurysm. Redo total aortic arch replacement was performed using an extended homograft following 2 days of open drainage of the mediastinum. The patient has been free from a recurrent mediastinitis over the last 3 years.

Surgical treatment of a retrosternal pseudoaneurysm arising from the posterior aortic root.

We report a case of a 60-year-old male with a retrosternal pseudoaneurysm arising from the posterior aortic root. He had undergone replacement of the aortic root and ascending aorta for an acute aortic dissection. His postoperative course was complicated with composite graft infection. During a redo surgery, femoro-femoral bypass was established prior to sternotomy via the right femoral artery and vein, and ten French cannulas were directly inserted into both carotid arteries through separate skin incisions for brain perfusion. When the sternum was divided, an occlusion balloon catheter introduced through the left femoral artery was inflated to maintain somatic perfusion without compromising clear vision of the operative field. Combined procedures with direct cannulation into both common carotid arteries and balloon occlusion of the distal aortic arch allowed us to safely perform replacement of the aortic root and ascending aorta in the patient with a retrosternal pseudoaneurysm.

Successful treatment of intraoperative heart failure caused by ampulla cardiomyopathy by intra-aortic balloon pumping and percutaneous cardiopulmonary support: report of a case.

An 82-year-old woman underwent total gastrectomy for advanced gastric cancer with invasion to the lower esophagus. Her blood pressure dropped alarmingly during the operation, which was performed via the transabdominal and left-side transthoracic approach. Using echocardiography, we diagnosed intraoperative-onset reversible heart failure caused by ampulla cardiomyopathy. Because the infusion of catecholamines is associated with secondary heart failure, we gave her calcium antagonists and nicorandil, then started intra-aortic balloon pumping (IABP) and the percutaneous cardiopulmonary support system (PCPS). On postoperative day (POD) 7, the IABP and PCPS were removed and on POD 12, she was extubated successfully. The patient was discharged on POD 54 and has remained well. The factors predisposing her to ampulla cardiomyopathy were left-side thoracotomy, hypoxia caused by one-lung ventilation, and the infusion of high-dose catecholamines. Prompt diagnosis and timely treatment of the heart failure with IABP and PCPS prevented any further complications.

Widespread and early myocardial gene expression by adeno-associated virus vector type 6 with a beta-actin hybrid promoter.

Gene therapy for acute cardiac events such as myocardial infarction requires early gene expression over an entire region of myocardium, which has not been possible using adeno-associated virus (AAV) vectors to date. Here we demonstrate marked improvement in the distribution and rapidity of gene expression in myocardium using the AAV pseudotype 6 (AAV6) vector, compared to the standard serotype 2 (AAV2) vector. An alkaline phosphatase (AP) reporter construct driven by the chicken beta-actin promoter was packaged in either AAV6 or AAV2 capsids and delivered to rat hearts in vivo by direct injection. AP expression was evident in both AAV6 and AAV2 vector-treated hearts as early as 1 day after injection, but increased rapidly in AAV6 vector-treated hearts during the first 7 days. The amplitude of AP activity produced by the AAV6 vector was 5-fold greater than that produced by the equivalent AAV2 vector at both 3 and 7 days postinjection. Additionally, the AAV6 vector transduced a myocardial volume that was 10-fold larger than the AAV2 vector. These results indicate the significant potential of AAV6 serotype vectors for early gene expression and widespread regional transduction of myocardium, both auspicious results for in vivo applications in acute cardiac disease.

A CMV-actin-globin hybrid promoter improves adeno-associated viral vector gene expression in the arterial wall in vivo.

BACKGROUND: Adeno-associated virus (AAV) vectors are attractive tools for direct intralumenal arterial gene transfer in interventional cardiology or cardiovascular surgery, but clinical application has been constrained by poor gene expression in this setting. METHODS: To improve arterial wall gene expression, a hybrid promoter consisting of a cytomegalovirus (CMV) immediate-early enhancer, a chicken beta-actin transcription start site, and a rabbit beta-globin intron (CAG promoter) was substituted for the Rous sarcoma virus (RSV) promoter in an AAV type 2 vector with an alkaline phosphatase (AP) reporter gene. RESULTS: Intralumenal transduction of rabbit carotid arteries by an AAV2 vector containing a CAG promoter resulted in gene expression in a mean of > or = 80% of the lumenal area at 14 days following exposure, compared to < or = 25% gene-expressing area with the RSV promoter-based control vector. The high prevalence of gene expression was maintained at 3, 7, 14, and 28 days. Importantly, in carotid arteries transduced with the CAG promoter, gene product expression was readily visible by the third day following transduction whereas gene expression was rarely seen before day 10 using the RSV promoter in the same animal model. On histology, AP gene expression was predominantly in vascular smooth muscle cells although some endothelial cell expression was also present. CONCLUSIONS: Substituting the CAG for the RSV promoter results in widespread gene expression, demonstrating efficient arterial wall transduction by AAV2 vectors. This finding plus the early time to gene expression hold promise for AAV vectors as agents for direct intralumenal arterial wall gene delivery during cardiovascular interventions.

Anterior spinal artery syndrome after minimally invasive direct coronary artery bypass grafting under general combined epidural anesthesia.

A 65-year-old patient with ischemic heart disease and severe diabetes mellitus underwent minimally invasive direct coronary artery bypass grafting under general combined with epidural anesthesia. Paraplegia developed after surgery and the diagnosis of anterior spinal artery syndrome was made based on the patient's neurological condition and magnetic resonance imaging findings. Paraplegia following epidural anesthesia is a rare but recognized complication and this complication should be taken into account, especially in patients at risk, when considering epidural analgesia techniques in the minimally invasive cardiac surgery.

Aortic root replacement with a stentless bioprosthesis in a patient with giant cell arteritis.

A 66-year-old woman was diagnosed with severe aortic regurgitation. Blood studies constantly showed positive C-reactive protein. Aortic valve replacement using a mechanical valve was carried out. Four months after the operation, echocardiogram showed aortic regurgitation due to paravalvular leakage. Reoperation was performed using a stentless aortic root bioprosthesis. The pathological specimen from the aortic wall was consistent with giant cell arteritis. The patient was treated with prednisone with dramatic improvement of systemic symptoms.

Successful weaning from inhaled nitric oxide using dipyridamole.

A 33-year-old woman with an atrial septal defect associated with severe pulmonary hypertension underwent suture closure of the defect after assessment of operability by lung biopsy. Postoperative course was complicated by suprasystemic refractory pulmonary hypertension, and she became dependent upon treatment with inhaled nitric oxide. After multiple attempts to withdraw nitric oxide, dipyridamole was administered and blunted the rebound pulmonary hypertension after subsequent nitric oxide withdrawal.

Gene gun-based co-immunization of merozoite surface protein-1 cDNA with IL-12 expression plasmid confers protection against lethal Plasmodium yoelii in A/J mice.

The carboxyl-terminal region of the merozoite surface protein-1 (MSP1) is a leading candidate for a vaccine against malaria in the erythrocytic stage. In this study, we investigated the utility of interleukin-12 (IL-12) cDNA as an adjuvant for malaria DNA vaccine in a mouse challenge model. We found that co-immunization of expression plasmids encoding a C-terminal 15-kDa fragment of MSP1 (MSP1-15) with the IL-12 gene using a gene gun significantly increased the protective immunity against malaria as compared with MSP1-15 DNA immunization alone. Co-immunization of IL-12 DNA potentiated MSP1-15-specific T helper (Th)1-type immune responses as evaluated by in vivo antibody (Ab) responses and in vitro cytokine profiles. After the Plasmodium yoelii challenge, mice immunized with MSP1-15 plus IL-12 DNA showed a higher level of interferon gamma (IFN-gamma) production than did other groups of mice. In vivo neutralization of IFN-gamma or depletion of CD4(+) T cells completely abolished this protective immunity. Macrophages, but not nitric oxide (NO), were found to play an important role in this effector mechanism. The sera from mice in which the infection had been cleared by the vaccination showed strong protection against P. yoelii infection. Thus, in addition to cellular immune responses, Abs against parasites induced in the course of infection are essential for protection against P. yoelii. The results indicate that combined vaccination with DNA encoding antigenic peptides plus IL-12 DNA provides a strategy for improving the prophylactic efficacy of a vaccine for malaria infection.

A convenient cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid using gene gun technology after priming with irradiated carcinoma cells.

We studied interleukin (IL)-12 gene therapy using a gene gun as a new autologous vaccination strategy for cancer. In the first experiment, BALB/c mice were inoculated with syngeneic murine renal cancer cells (Renca) intradermally in the abdomen. This was followed by an injection of IL-12 expression plasmid using the gene gun. About 40% of the mice exhibited rejection of the tumor after the treatment and these mice also acquired immunological resistance against a secondary challenge with Renca cells. Based on these results, we examined whether antitumor activity can be potentiated when mice undergo combination treatment with intradermal inoculation of irradiated Renca cells and transfection with IL-12 gene. Inoculation of irradiated Renca cells alone was partially effective in inducing antitumor immunity, whereas the combined treatment remarkably intensified this effect. Moreover, this combined treatment inhibited tumor establishment and enhanced survival of the mice with tumor infiltration by CD4(+) and CD8(+) T cells, even when the treatment was started after tumor-implantation at a distant site. This antitumor effect was antigen specific and we confirmed the induction of antitumor cytotoxic T cells by this treatment. These results show that local cutaneous transfer of IL-12 expression plasmid using gene gun technology enhances systemic and specific antitumor immunity primed by irradiated tumor cells.