Yoshio Misawa

Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions

Factors controlling the proliferation of vascular smooth muscle cells (SMC) are thought to be key elements in the progression of atherosclerosis. We have previously shown that interleukin 6 (IL-6) stimulates the growth of SMC in vitro and that IL-6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. To understand the involvement of IL-6 in the development of human atherosclerosis, we investigated IL-6 mRNA expression in atherosclerotic arteries from patients undergoing surgical vascularization, utilizing reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization analyses. In RT-PCR analysis, the atherosclerotic arteries showed 10- to 40-fold levels of IL-6 mRNA expression over the non-atherosclerotic artery. In in situ hybridization analysis, IL-6 gene transcripts were observed in the thickened intimal layer of atherosclerotic lesions. These results strongly suggest the involvement of IL-6 in the development of human atherosclerosis.

Repair of Infarcted Myocardium Mediated by Transplanted Bone Marrow–Derived CD34+ Stem Cells in a Nonhuman Primate Model

Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34+ cells were transplanted to the peri‐ischemic zone. To track the in vivo fate of transplanted cells, CD34+ cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline‐treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell–derived, GFP‐positive cells were found incorporated into the vascular structure, and GFP‐positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34+ cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell–derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.

Genome-wide histone methylation profile for heart failure.

Epigenetic alterations are implicated in the development of cardiac hypertrophy and heart failure, but little is known of which epigenetic changes in which regions of the genome play such a role. We now show that trimethylation of histone H3 on lysine‐4 (K4TM) or lysine‐9 (K9TM) is markedly affected in cardiomyocytes in association with the development of heart failure in a rat disease model. High‐throughput pyrosequencing performed with ChIP products for K4TM or K9TM prepared from human left ventricular tissue with retained or damaged function also revealed that protein‐coding genes located in the vicinity of K4TM marks differ between functional and disabled myocytes, yet both sets of genes encode proteins that function in the same signal transduction pathways for cardiac function, indicative of differential K4TM marking during the development of heart failure. However, K9TM mark‐profile was less dependent on the disease status compared to that of K4TM. Our data collectively reveal global epigenetic changes in cardiac myocytes associated with heart failure.

Usefulness of extracorporeal membrane oxygenation for treatment of fulminant myocarditis and circulatory collapse

Prognosis for fulminant myocarditis with cardiogenic shock refractory to conventional therapy is poor. This report describes mechanical circulatory support with extracorporeal membrane oxygenation as an effective alternative for treating fulminant myocarditis with circulatory collapse.

Infectious Mediastinitis After Cardiac Operations: Computed Tomographic Findings

BACKGROUND Infectious mediastinitis after cardiac operations is of great concern to cardiac surgeons because of its poor prognosis. Prompt surgical interventions such as debridement and irrigation are the key to treatment of infectious mediastinitis. METHODS We surveyed retrospectively the cases of 722 consecutive cardiac surgery patients at our hospital. Mediastinitis developed in 21 patients after the cardiac operation. We performed computed tomography in 11 of these patients before resternotomy and in 10 patients as the control 2 to 3 weeks after the cardiac operation. RESULTS Mediastinal soft tissue swelling was seen in 7 patients, bilateral pleural effusion was found in 9 patients, sternal dehiscence or sternal erosion was observed in 8 patients, and subcutaneous fluid accumulation was found in 7 of the mediastinitis group. Unilateral pleural effusion was seen in 6 and bilateral effusion in 1, and mediastinal soft tissue swelling was seen in 1 patient of the control group. CONCLUSIONS Our study showed that mediastinal soft tissue mass combined with bilateral pleural effusion can be a characteristic computed tomography finding in poststernotomy infectious mediastinitis, and that chest computed tomography is more sensitive to detecting sternal dehiscence, sternal erosion, and subcutaneous fluid accumulation.

Platelet aggregation during cardiopulmonary bypass evaluated by a laser light-scattering method

BACKGROUND In regard to postoperative bleeding, the most important consequence of cardiopulmonary bypass (CPB) is the loss of aggregability. However, the mechanism of platelet aggregation loss during CPB is unclear. Newly developed particle-counting methods that use light scattering can be used to quantify changes in the number of platelet aggregates of different sizes after application of an aggregating stimulus. Using a light-scattering method, we investigated changes in platelet aggregation during cardiac operation. METHODS Nineteen patients undergoing CPB were evaluated. Blood samples were obtained before the operation, 1 hour after initiation of CPB, at the end of CPB, at the end of the operation, and on day 1 after the operation. Platelet aggregation after stimulation by 2.5 micromol/L adenosine diphosphate and 2.0 microg/mL collagen was determined; small (9 to 25 microm), medium (25 to 50 microm), and large (50 to 70 microm) aggregates were counted. RESULTS Generation of medium and large aggregates after stimulation with adenosine diphosphate and collagen were significantly decreased with CPB, whereas, in spite of hemodilution, the quantity of the small aggregates was maintained at the elevated level. CONCLUSIONS These results reflect the fact that CPB does not affect the first phase of aggregation. It suggests that platelet dysfunction associated with CPB is mainly caused by an inhibition in the development of small aggregates into larger aggregates.

Saphenous Vein Graft Pseudoaneurysm Rupture After Coronary Artery Bypass Grafting

An elderly woman underwent coronary artery bypass grafting, which was followed 1 month later by pseudoaneurysmal rupture at the distal anastomosis of a saphenous vein graft. Emergency repair of the suture line dehiscence was made, and the postoperative course was uneventful. Pseudoaneurysm formation of a saphenous vein graft after coronary artery bypass grafting is a rare but potentially lethal complication requiring urgent operative intervention.

Conduction disturbances after superior septal approach for mitral valve repair

BACKGROUND The superior septal approach sacrifices the sinus node artery, and it requires more invasive incisions into the right and left atria. Therefore, postoperative rhythm disturbances could be troublesome in patients with SSA. In this study, we evaluated perioperative and midterm conduction disturbances in the cardiac rhythms of patients who had a SSA for mitral valve repair. METHODS Fifty-two patients had mitral valve operations by the superior septal approach, and cardiac rhythm status was assessed. The mean follow-up period was 15 +/- 8 months. In patients with normal sinus rhythms preoperatively, serial changes in PR intervals were also assessed. Holter electrocardiograms were used 6 to 12 months postoperatively. Twelve patients who had mitral valve operations by conventional left atriotomy from the right side of the left atrium served as the control group. RESULTS There were no operative deaths, but one patient in the experimental group died of cerebral hemorrhage 4 months postoperatively. No intractable arrhythmias occurred. Of the 25 patients who maintained sinus rhythms, preoperative PR interval on electrocardiogram was 155 +/- 20 milliseconds. Postoperative PR intervals increased for 1 week, had decreased within 2 weeks postoperatively, and returned to the normal range by 6 months postoperatively. Holter electrocardiograms of 17 patients did not show supraventricular arrhythmias exceeding 3% of the total beats. None of the patients needed pacemaker implantation. The PR intervals of 5 patients with normal sinus rhythms in the control group did not show significant changes perioperatively. CONCLUSIONS The superior septal approach is excellent for mitral valve operations because it overcomes postoperative dysrhythmias.

Mechanical circulatory assist for pulmonary embolism.

Optimal management of acute pulmonary embolism remains controversial, despite advances in thrombolytic therapy. Haemodynamic instability and, in particular, right ventricular dysfunction is associated with poor outcomes. Urgent surgical embolectomy has been the treatment of choice in this category of patients. We present two cases in which percutaneous cardiopulmonary support (PCPS) was used as an adjunct to thrombolytic therapy for progressive circulatory collapse secondary to massive acute pulmonary embolism. This experience suggests that PCPS may offer an attractive option for a condition which continues to carry significant morbidity and mortality.

RIGHT CORONARY ARTERY DISSECTION AND ACUTE INFARCTION DUE TO BLUNT TRAUMA : REPORT OF A CASE

Coronary artery dissection occurring after a nonpenetrating chest trauma is extremely rare. We describe herein the case of a 43-year-old man who suffered traumatic myocardial infarction after an intimal tear of the right coronary artery had been inflicted by a horse stepping on his back.