Takahiro Katsumata

Implantation of Mesenchymal Stem Cells Overexpressing Endothelial Nitric Oxide Synthase Improves Right Ventricular Impairments Caused by Pulmonary Hypertension

Background— Pulmonary hypertension (PH) is a life-threatening disease. Bone marrow cell transplantation is reported to reduce the development of PH by increasing vascular beds in pulmonary circulation. However, adenoviral overexpression of endothelial nitric oxide synthase (eNOS) in the lung is also known to reduce PH. Because mesenchymal stem cells (MSCs) are potential cell sources for neovascularization, the implantation of MSCs overexpressing eNOS (MSCs/eNOS) may further improve the surgical results. We evaluated the efficacy of MSCs/eNOS implantation in monocrotaline (MCT)-induced PH rats. Methods and Results— MSCs were isolated from rat bone marrow. PH was induced in rats by subcutaneous injection of MCT. One week after MCT administration, the rats received 3 different treatments: MSCs (MSC group), MSCs/eNOS (MSC/eNOS group), or nontreatment (PH group). As the negative control, rats received saline instead of MCT (control group). Right ventricular (RV) hypertrophy and the elevation of RV systolic pressure (RVSP) were evaluated 3 weeks after MCT administration. Moreover, the effects of MSCs/eNOS on survival were investigated in PH induced by MCT 3 weeks earlier. RVSP in both the MSC and MSC/eNOS groups was significantly lower than the PH group. RVSP in the MSC/eNOS group was significantly lower than the MSC group. The RV weight to body weight ratio was significantly lower in the MSC and MSC/eNOS groups than the PH group. The survival time of rats receiving MSCs/eNOS was significantly longer than the nontreatment rats. Conclusion— Intravenous implantation of MSCs/eNOS may offer ameliorating effects on PH-related RV impairment and survival time.

Proximal aortic perfusion for complex arch and descending aortic disease

OBJECTIVEnCannulation of the femoral artery is used routinely for hypothermic circulatory arrest operations on the aortic arch. A two-stage approach is advocated for combined arch and descending aortic disease. These methods are associated with important neurologic injury through embolism or malperfusion. We therefore changed to a central cannulation technique through extended left thoracotomy.nnnMETHODSnEighteen patients with arch or combined pathologic conditions underwent one-stage repair with hypothermic circulatory arrest using ascending aortic cannulation and venous drainage from the pulmonary artery. Emergency operations were performed for bleeding or dissection. Cerebral and myocardial perfusion were restored during descending aortic replacement.nnnRESULTSnOne elderly patient died of gastrointestinal hemorrhage after initial recovery (overall mortality 5.6%, range 0.14% to 27%, p = 0.05). One possible transient monoparesis occurred but without computed tomographic scan evidence of embolism. No other significant events and no morbidity occurred from the surgical methods.nnnCONCLUSIONSnExtended left thoracotomy with central cannulation allows safe one-stage replacement of the arch and descending aorta using anterograde cerebral perfusion. We believe that this method will reduce cerebral complications in arch and descending aortic operations.

Aortic Valve Conservation in Acute Type A Dissection

BACKGROUNDnWe consider operative survival as the primary objective in acute type A dissection and believe that virtually all native aortic valves can be conserved. We sought to answer the question: Does glue repair improve the long-term stability of proximal aortic repair?nnnMETHODSnWe retrospectively studied 64 patients with an acute type A dissection, an ascending aortic tear, and aortic regurgitation operated on by the same surgeon between 1988 and 1996. Three had Marfans syndrome and 2 had a bicuspid valve. The valves in all patients without Marfans syndrome were repaired with gelatin-resorcinol-formol glue. The valve and root were reinvestigated by echocardiography. Some patients underwent nuclear magnetic resonance imaging.nnnRESULTSnThere were four hospital (6%) and three late deaths. Aortic root reoperation was required in 2 of the 60 survivors (3.3%) and operation on the distal aorta in 2. Root reoperations were required within 3 years. The remaining proximal repairs remained stable.nnnCONCLUSIONSnThe native aortic valve can be conserved in most patients, and glue repair is durable. Simple root repair is associated with a low operative mortality.

Jarvik 2000 Heart Potential for Bridge to Myocyte Recovery

BACKGROUNDnMechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We sought to validate the use of a new intracardiac axial flow impeller pump for this purpose.nnnMETHODS AND RESULTSnThe Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability, biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible. Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or vascular graft.nnnCONCLUSIONSnThe Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge to transplantation or long-term support.

ATP regulation of ciliary beat frequency in rat tracheal and distal airway epithelium

Ciliary beat frequency (CBF) was measured by video‐optical microscopy in rat tracheal and distal airway ciliary cells using a slice preparation. In tracheal ciliary cells (tracheal slice), ATP or 2‐methylthio ATP (MeSATP) increased CBF, which was inhibited by suramin (100 μm, an inhibitor of purinergic receptor). Ionomycin (5 μm) or thapsigargin (2 μm) increased CBF similarly. Ca2+‐free solution or addition of Ni2+ (1 mm) decreased CBF gradually by approximately 25% and subsequent stimulation with ATP (10 μm) increased CBF transiently. The purinergic agonist experiments demonstrated that ATP increases CBF in tracheal ciliary cells via both P2X and P2Y receptors. ATP increased the intracellular calcium concentration ([Ca2+]i) in tracheal ciliary cells. However, in distal airway ciliary cells (lung slice), ATP did not increase CBF and [Ca2+]i, although a Ca2+‐free solution decreased CBF, and ionomycin (5 μm) or thapsigargin (2 μm) increased it. Moreover, acetylcholine (100 μm) did not increase CBF in distal airway ciliary cells, although it increased CBF in tracheal ciliary cells. Terbutaline (10 μm), a selective β2‐adrenergic agonist, increased CBF in both tracheal and distal airway ciliary cells. These observations suggest that the Ca2+‐mobilization mechanisms via purinergic or muscarinic receptors of the distal airway ciliary cell may be different from those of the tracheal ciliary cell. In conclusion, the CBF increase is differently regulated in the tracheal and distal airway epithelia of the rat.

Valve replacement with a stentless bioprosthesis: Versatility of the porcine aortic root☆☆☆★

OBJECTIVEnStentless valves convey important hemodynamic benefits but are used selectively depending on aortic root structure. The Freestyle valve (Medtronic, Inc, Minneapolis, Minn) is a versatile device that can be implanted by different methods depending on operating conditions. We aimed to demonstrate that a stentless valve could be used in every patient without increased risk of morbidity or mortality. We documented the effects of this valve on clinical outcome and left ventricular mechanics.nnnMETHODSnThe Freestyle valve was implanted by the modified subcoronary method into 200 consecutive unselected patients who received a tissue valve in the aortic position and by root replacement in 2. Forty-three percent were older than 75 years. Forty percent underwent coronary bypass. Detailed clinical and echocardiographic follow-up (Food and Drug Administration protocol) was used out to 3 years.nnnRESULTSnMean ischemic time was 43+/-6 minutes for isolated aortic valve replacement and 63+/-14 minutes with concomitant procedures. Thirty-day mortality was 6%, none of the deaths being valve related. Hemodynamic function improved progressively with falling valve gradients and increased effective orifice areas. Left ventricular mass fell within normal limits over 2 years, but at 3 years there was a non-valve-related upswing. No instances of valve thrombosis, hemolysis, or paravalvular leak were noted. Less than 5% had mild to moderate aortic regurgitation.nnnCONCLUSIONSnThe Freestyle valve can be used in virtually every patient with aortic valve disease and provides superlative hemodynamic outcome. Hospital mortality and morbidity are similar to those reported for stented valves in an elderly population.

Immunoglobulin G4―related coronary periarteritis in a patient presenting with myocardial ischemia

Recent studies suggest that the cardiovascular system might be a possible target of immunoglobulin G4-related disease. Here we present a 66-year-old man who was admitted to our hospital because of chest symptoms suggestive of acute coronary syndrome. Besides luminal narrowing of the coronary arteries, marked periarterial thickening around the coronary artery was observed by computed tomography coronary angiography. Serum immunoglobulin G4 levels of this patient were elevated (564 mg/dL). The patient underwent coronary bypass surgery. After incision of the pericardium, a glittery white-yellowish, elastic-hard periarterial mass surrounding the left circumflex artery could be seen. Histologic analysis of the biopsy specimen showed the formation of lymphoid follicles and the presence of immunoglobulin G4-positive plasma cells; therefore, the diagnosis was immunoglobulin G4-related coronary periarteritis accompanied by physiologically significant myocardial ischemia.

The significance of chymase in the progression of abdominal aortic aneurysms in dogs.

In this study, we investigated the effect of a specific chymase inhibitor, NK3201, in the progression of abdominal aortic aneurysm in a dog experimental model. Abdominal aortic aneurysms were induced in dogs by injecting elastase into the abdominal aorta. NK3201 (1 mg/kg per day, p.o.) or a placebo was started 3 days before elastase injection and continued for 8 weeks after the injection. On abdominal ultrasound, the aortic diameter was seen to gradually expand in the placebo-treated group, but not in the NK3201-treated group. Eight weeks after elastase injection, the ratio of the medial area to the total area in the placebo-treated group was significantly smaller than that in the normal group, but it was significantly larger than that in the NK3201-treated group. In addition to chymase activity, angiotensin II–forming and matrix metalloproteinase-9 activities were significantly higher in the placebo-treated group than in the normal group; in the NK3201-treated group, all of these activities were significantly decreased. On immunohistochemical analyses, there was a significantly greater number of chymase-positive cells in the placebo-treated group than in the normal group, but the number was significantly smaller in the NK3201-treated group than in the placebo-treated group. Thus, chymase inhibition may become a useful strategy for preventing abdominal aortic aneurysms.

Infected aortic aneurysm and inflammatory aortic aneurysm--in search of an optimal differential diagnosis.

Infected aortic aneurysm and inflammatory aortic aneurysm each account for a minor fraction of the total incidence of aortic aneurysm and are associated with periaortic inflammation. Despite the similarity, infected aortic aneurysm generally shows a more rapid change in clinical condition, leading to a fatal outcome; in addition, delayed diagnosis and misuse of corticosteroid or immunosuppressing drugs may lead to uncontrolled growth of microorganisms. Therefore, it is mandatory that detection of aortic aneurysm is followed by accurate differential diagnosis. In general, infected aortic aneurysm appears usually as a saccular form aneurysm with nodularity, irregular configuration; however, the differential diagnosis may not be easy sometimes for the following reasons: (1) symptoms, such as abdominal and/or back pain and fever, and blood test abnormalities, such as elevated C-reactive protein and enhanced erythrocyte sedimentation rate, are common in infected aortic aneurysm, but they are not found infrequently in inflammatory aortic aneurysm; (2) some inflammatory aortic aneurysms are immunoglobulin (Ig) G4-related, but not all of them; (3) the prevalence of IgG4 positivity in infected aortic aneurysm has not been well investigated; (4) enhanced uptake of 18F-fluorodeoxyglucose (FDG) by 18F-FDG-positron emission tomography may not distinguish between inflammation mediated by autoimmunity and that mediated by microorganism infection. Here we discuss the characteristics of these two forms of aortic aneurysm and the points of which we have to be aware before reaching a final diagnosis.

Oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in children

OBJECTIVEnSildenafil is a strong pulmonary vasodilator that increases the intracellular cyclic guanosine monophosphate concentration through inhibition of phosphodiesterase-5. We assessed the benefit of oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in paediatric patients.nnnMETHODSnSildenafil was administered at a starting dose of 0.5 mg kg(-1) following admission to the intensive care unit. With careful monitoring of haemodynamics, the dose was increased stepwise by 0.5 mg kg(-1) every 4-6 h up to a maximum of 2 mg kg(-1). After successful weaning from a ventilator and from other vasodilators, sildenafil was gradually discontinued over the next 5-7 days.nnnRESULTSnA retrospective review of medical records showed an age distribution of <1 month (n=26), > or = 1-<6 months (n=36), > or = 6-<12 months (n=19), 1-3 years (n=8), 4-9 years (n=9) and >10 years (n=2) at the time of surgery. The surgeries were performed for ventricular septal defect closure (n=17), arterial switch (n=30), truncus arteriosus repair (n=10), complete atrioventricular septal defect repair (n=12), total anomalous venous drainage repair (n=9), and other open-heart surgery (n=22). The aforementioned concomitant inhaled nitrous oxide treatment was performed in 66 patients. Pulmonary arterial pressure decreased in 28, was unchanged in five and elevated in one patient out of the total of 34 cases for which data from continuous pressure monitoring were available. Bosentan was added in three cases with persistent symptoms due to pulmonary hypertension despite sildenafil treatment. After sildenafil administration, modest oxygen desaturation occurred in seven cases, but no rebound pulmonary hypertension occurred. There were no significant adverse events during sildenafil treatment.nnnCONCLUSIONSnOur results suggest that oral sildenafil is a safe and effective alternate for persistent pulmonary hypertension following congenital heart surgery in children.