Ichiro Kashima

Heterotopic transplantation of a decellularized and recellularized whole porcine heart

OBJECTIVES One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37°C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically.

Selective perfusion of segmental arteries in patients undergoing thoracoabdominal aortic surgery

BACKGROUND Reattachment of segmental arteries is one method used to prevent paraplegia associated with thoracoabdominal aortic repair. Nevertheless, even when important segmental arteries are reattached, ischemia causing spinal injury may occur during anastomosis. METHODS In 27 patients undergoing thoracoabdominal aortic repair, we attempted to perfuse the segmental arteries to be reattached with catheters connected to the distal bypass circuit. To identify perioperative risk factors for spinal ischemia, we examined changes in spinal somatosensory evoked potentials. RESULTS A median value of four segmental arteries were perfused in 20 (74%) of the 27 patients. Changes in somatosensory evoked potential indicative of spinal ischemia were observed in 13 patients (48%). The only risk factor associated with changes in evoked potentials revealed by a multivariate analysis was prolonged aortic cross-clamp time (> 120 minutes). Of the 2 patients who suffered paraplegia, one had the longest clamp time and the other showed spinal cord necrosis due to embolic shower. CONCLUSIONS Despite selective perfusion of segmental arteries, spinal ischemia associated with aortic cross-clamping may occur when clamping is prolonged over 120 minutes. Most of the changes appear to be reversible, however.

Detection and Management of Concomitant Coronary Artery Disease in Patients Undergoing Thoracic Aortic Surgery

OBJECTIVES No method has been established to detect and manage coronary artery disease in patients undergoing thoracic aortic surgery. METHODS Subjects were 192 patients scheduled for elective thoracic aortic surgery. Selection criteria for coronary angiography included a history of coronary artery disease or a positive dipyridamole myocardial perfusion imaging test. RESULTS Four patients were inoperable due to complications associated with coronary angiography or aneurysm rupture following coronary revascularization. A total of 55 patients with coronary angiography (group A) underwent 57 thoracic aortic operations and 133 patients without coronary angiography (group B) underwent 143 similar operations. Of 13 group A patients with significant coronary stenosis, 9 underwent either preoperative percutaneous transluminal coronary angioplasty (n = 3) or concomitant coronary artery bypass (n = 6). Perioperative myocardial infarction occurred in 3 group A patients (5%) and in 4 group B patients (1%, ns). The incidence of cardiac events--perioperative myocardial infarction or cardiac death--in group A (11%, 6/57) was higher than that in group B (3%, 4/143; p < 0.05). Multivariate analysis demonstrated incomplete revascularization of major coronary arteries with significant stenosis as a risk factor for cardiac events (p = 0.0106). CONCLUSIONS Although dipyridamole myocardial perfusion imaging was useful, additional selection criteria for coronary angiography is needed. Complete revascularization of major coronary arteries with significant stenosis is essential to reduce postoperative cardiac events.

Left Atrial Appendage Insertion for Right Ventricular Outflow Tract Reconstruction

BACKGROUND The left atrial appendage (LAA) may serve as an alternative to the pulmonary arterial wall for right ventricular outflow tract (RVOT) reconstruction without an extracardiac conduit. METHODS Five consecutive patients with pulmonary atresia or severe stenosis underwent corrective (n = 4) or palliative (n = 1) RVOT reconstruction using an LAA insertion. Surgery was performed to treat tetralogy of Fallot, double-outlet right ventricle, or transposition of the great arteries. By inserting the LAA into the obstructed portion, the width of the posterior wall of the RVOT was 20 mm or more. The anterior half of the RVOT was then augmented with pericardial patch. RESULTS There were no early or late postoperative deaths, and no major complications (arrhythmias, thrombo-embolic episodes, infective endocarditis, need for reoperation). The postrepair systolic right ventricular-to-systemic arterial pressure ratio was 0.61 +/- 0.26. Color Doppler flow mapping revealed that the reconstructed RVOT was nonobstructive and had nonturbulent flow. No thrombus or pseudoneointimal formation was observed in the RVOT. CONCLUSIONS LAA insertion in the RVOT is an effective alternative to, or adjunct of, direct anastomosis. It offers several advantages, including fewer early and midterm complications and avoiding the use of an extracardiac conduit.

Surgical treatment for a ruptured thoracic aortic aneurysm.

OBJECTIVE The treatment for a ruptured thoracic aortic aneurysm remains controversial. This study was undertaken to assess the outcome from surgery. METHODS Between 1993 and 1998, we have performed 19 operations for a ruptured thoracic aortic aneurysm. Patients with an impending rupture or a chronic false aneurysm were excluded. There were 11 men and 8 women, with a mean age of 70.5 +/- 6.7 years. The aneurysm was caused by dissection in 8 patients. Of these, 7 were acute (Stanford type A, 6; type B, 1), and the other one was chronic (type B). Aortic rupture occurred into the pericardial cavity (n = 7), into the left lung (n = 6), the mediastinum (n = 3), the pleural cavity (n = 2), or into the esophagus (n = 1). Severely unstable hemodynamics were noted in 12 patients with a rupture into the pericardium, mediastinum, or pleural cavity (Group A). Inotropic support was required in each of these patients. Metabolic acidosis developed all but 1 patient. The 7 patients with a rupture into the lung or esophagus coughed or vomited blood (Group B). The operative approach was anterior (n = 17) or lateral (n = 2). Grafts were placed in the ascending aorta (n = 4), ascending and transverse arch aorta (n = 7), transverse arch aorta (n = 3), or in the descending thoracic aorta (n = 5). Selective cerebral perfusion was used in 13 patients. RESULTS There were 5 hospital deaths (26.3%). The postoperative complications included central nervous system dysfunction (n = 3), low cardiac output syndrome or cardiac arrhythmias (n = 3), respiratory failure (n = 4), acute renal failure (n = 1), and local or systemic infections (n = 4). The perioperative event-free rate was 36.8% overall, 25% in Group A, and 57.1% in Group B. CONCLUSIONS Patients with unstable hemodynamics require prompt operative intervention. Rupture into the esophagus is associated with a high mortality rate. Rupture in a thoracic aortic aneurysm can be successfully treated with emergency surgery.

The use of intra-aortic balloon pump as cerebral protection in a patient with moyamoya disease undergoing coronary artery bypass grafting

We performed coronary artery bypass grafting in an urgent and rare case of acute coronary syndrome with moyamoya disease in a 75-year-old female. Because of collateral dependent severe cerebrovascular obstruction, additional support for brain protection was necessary; we used high pressure pulsatile perfusion assist to maintain cerebral circulation with an intra-aortic balloon pump support throughout the cardiopulmonary bypass, giving a successful outcome.

Mediastinal hematoma: another lethal sign of aortic dissection

Acute compressive hemomediastinum due to type A acute aortic dissection in a 70-year-old man caused acute simultaneous obstruction of pulmonary artery and superior vena cava, leading to sudden death, presenting acute progressive bruising of the upper half of the body and subsequent massive hemoptysis. Computed tomography scanning revealed acute severe stenosis of the superior vena cava and right pulmonary artery by mediastinal hematoma. Mediastinal hematoma combined with simultaneous obstruction of pulmonary artery and superior vena cava is a rare entity and should be recognized as one of the acutely fatal signs of type A dissection.

Surgically created double orifice repair of tricuspid regurgitation in infants with congenital heart disease

Repair of tricuspid regurgitation (TR) in infants with congenital heart disease (CHD) is frequently associated with postoperative morbidity. Annuloplasty is a well-established surgical procedure for TR and is associated with a satisfactory postoperative outcome provided the deformity of the tricuspid leaflet is mild. However, in the presence of severe leaflet deformity, the reparative procedure remains a surgical challenge. The present study describes our experience with the surgically created double orifice repair of the tricuspid valve in infants with CHD and significant TR. Clinical Summary PATIENT 1. A 7-month-old male infant was referred to our hospital at 1 month of age with the diagnosis of double outlet from the right ventricle, pulmonary hypertension, TR, and bronchial stenosis. At 2 months of age, the clinical condition deteriorated progressively due to respiratory tract infection. Although he underwent pulmonary artery banding (PAB) at 3 months of age, weaning from the respirator was unsuccessful. At 7 months of age, he underwent a definitive operation, in which intraventricular rerouting was established with a 0.4-mm Gore-Tex patch (W. L. Gore & Associates, Inc, Flagstaff, Ariz) connecting the left ventricle with the aorta. The tricuspid valve was dilated to 23 mm and showed a diffuse degenerative change with deficient valvar tissue near the commissure between the anterior and septal leaflet (Figure 1, B). Because Reed’s annuloplasty at this area failed to alleviate TR, a double orifice repair was performed wherein the central free edge of the anterior leaflet was approximated to the facing edge of the septal leaflet with a 5-0 polypropylene mattress suture (Figure 1, C). The divided orifices were equal in size, each measuring 10 mm. The patient recovered uneventfully and was weaned from the respirator on postoperative day 5. The mean right atrial pressure ranged from 5 to 9 mm Hg in early postoperative days and was 3 mm Hg at 6 months after surgery. Postoperative Doppler echocardiography demonstrated a divided unobstructed flow through the tricuspid

Efficacy of autologous platelet-rich plasma in thoracic aortic aneurysm surgery

OBJECTIVE Allogenic blood transfusion can transmit viral infection or cause immunological side effects. Recently, improved operative techniques have required less frequent transfusions in thoracic aortic aneurysm surgery. This study examined the efficacy of using autologous platelet-rich plasma in thoracic aortic aneurysm surgery. METHOD Eight patients underwent nine operations using an autologous platelet-rich plasma program. The control group consisted of 15 historic patients matched for operative procedure and age. All operations were performed by the same surgeon. The platelet-rich plasma program required the collection of platelet-rich plasma prior to the infusion of heparin; platelet-rich plasma transfusions were administered following neutralization by heparin. RESULTS The volume of platelet-rich plasma averaged 252 +/- 14.3 ml; total platelets in the platelet-rich plasma were 2.27 +/- 0.20 x 10(11) cells. The median number of homologous red blood cells transfused during the operative day was 0 units (range 0 to 12) in the platelet-rich plasma group and 3 units (range 0 to 25) in the controls. The median number of homologous fresh frozen plasma was 0 units (range 0 to 20) in the platelet-rich plasma group, and 5 units (range 0 to 30) in the controls. The platelet-rich plasma group received significantly fewer transfusions. CONCLUSION Autologous platelet-rich plasma transfusion was an effective way to reduce homologous blood transfusions in thoracic aortic aneurysm surgery.

Effect of storage temperature on cell viability in cryopreserved canine aortic, pulmonic, mitral, and tricuspid valve homografts

We determined how long cryopreserved aortic, pulmonic, mitral, and tricuspid valve homografts could be stored in a deep freezer (-80 degrees C) without compromising fibroblast viability. Valves harvested from 20 anesthetized mongrel dogs were grouped into nonfrozen control, frozen and stored in liquid nitrogen (-196 degrees C), and frozen and stored in a deep freezer (-80 degrees C). Frozen groups were divided into subgroups and stored for 2, 4, 8, or 12 weeks. A leaflet of each valve was divided into three fragments, and fibroblast viability was analyzed by flow cytometry. Cell viability was defined as staining by fluorescent diacetate but not by propidium iodide. The viability of untreated control valves from all four sites was about 70%, decreasing to about 50% when treated with low doses of antibiotics. The viability of frozen valves stored in liquid nitrogen was about 45% without a significant difference among storage periods. The viability of valves frozen and stored in a deep freezer was significantly lower than for the liquid nitrogen group at 2 weeks for the mitral valve and at 4 weeks for other valves. These results suggest that homografts can be stored in a deep freezer for up to 2 weeks without deterioration.