Hideki Tatewaki

Extracorporeal Cardiac Shock Wave Therapy Markedly Ameliorates Ischemia-Induced Myocardial Dysfunction in Pigs in Vivo

Background—Prognosis of ischemic cardiomyopathy still remains poor because of the lack of effective treatments. To develop a noninvasive therapy for the disorder, we examined the in vitro and vivo effects of extracorporeal shock wave (SW) that could enhance angiogenesis. Methods and Results—SW treatment applied to cultured human umbilical vein endothelial cells significantly upregulated mRNA expression of vascular endothelial growth factor and its receptor Flt-1 in vitro. A porcine model of chronic myocardial ischemia was made by placing an ameroid constrictor at the proximal segment of the left circumflex coronary artery, which gradually induced a total occlusion of the artery with sustained myocardial dysfunction but without myocardial infarction in 4 weeks. Thereafter, extracorporeal SW therapy to the ischemic myocardial region (200 shots/spot for 9 spots at 0.09 mJ/mm2) was performed (n=8), which induced a complete recovery of left ventricular ejection fraction (51±2% to 62±2%), wall thickening fraction (13±3% to 30±3%), and regional myocardial blood flow (1.0±0.2 to 1.4±0.3 mL · min−1 · g−1) of the ischemic region in 4 weeks (all P<0.01). By contrast, animals that did not receive the therapy (n=8) had sustained myocardial dysfunction (left ventricular ejection fraction, 48±3% to 48±1%; wall thickening fraction, 13±2% to 9±2%) and regional myocardial blood flow (1.0±0.3 to 0.6±0.1 mL · min−1 · g−1). Neither arrhythmias nor other complications were observed during or after the treatment. SW treatment of the ischemic myocardium significantly upregulated vascular endothelial growth factor expression in vivo. Conclusions—These results suggest that extracorporeal cardiac SW therapy is an effective and noninvasive therapeutic strategy for ischemic heart disease.

Transfection With a Dominant-Negative Inhibitor of Monocyte Chemoattractant Protein-1 Gene Improves Cardiac Function After 6 Hours of Cold Preservation

Background—Monocyte chemoattractant protein-1 (MCP-1), a potent chemotactic factor for monocytes, is induced during ischemia-reperfusion. As monocytes might play an important causative role in reperfusion injury, we investigated if inhibition of monocyte activation could attenuate ischemia-reperfusion injury and thereby improve cardiac preservation. To inhibit monocyte activation, we transfected a dominant-negative inhibitor of MCP-1 (7ND) gene in an animal model. Methods and Results—We used an isolated rabbit heart preparation perfused with support-rabbit blood and transfected 7ND genes to skeletal muscle of the support rabbits (n=7) using electroporation technique; causing an elevation of serum 7ND level to 20±7 pg/mL at 5 days after transfection. Animals receiving empty plasmid served as controls (n=7). Five days after transfection, hearts from other rabbits were excised, stored in UW solution for 6hours, and perfused with blood from transfected support rabbits. The 7ND group showed better cardiac output (128.7±17.9 versus 81.6±19.8 mL/min; P <0.01), lower serum CK-MB levels (5.0±1.8 versus 11.1±2.9 ng/mL; P <0.01), lower serum IL-1&bgr; levels (257.2±23.2 versus 311.2±37.4pg/mL; P <0.05), and lower serum TNF-&agr; levels (19.0±8.4 versus 35.1±13.0pg/mL; P <0.05). The numbers of infiltrating cells in myocardium were significantly reduced in the 7ND group. Conclusions—Inhibition of MCP-1 with 7ND gene transfection reduced cytokine activation, attenuated myocardial damage, and improved cardiac function after 6 hours of preservation. These results show that MCP-1 plays an important role in ischemia-reperfusion injury.

Surgical application for a prolapse of the anterior mitral leaflet by replacing artificial chordae with polytetrafluoroethylene grafts.

PurposeThere are an increasing number of reports concerning mitral valve repair by a reconstruction of the chordae tendinae using expanded polytetrafluoro-ethylene (PTFE) sutures. However, little information is available about extended application or results of this technique for an extended prolapse of the anterior mitral leaflets.MethodsBetween July 1991 and August 2003, 28 patients with moderate to severe mitral regurgitation as a result of a prolapse of anterior leaflets (age range, 15–73 years) underwent mitral valve repair by reconstruction of the artificial chordae with 4-CV expanded polytetrafluoroethylene sutures without a leaflet resection. Either Kay’s suture technique or ring annuloplasty was also performed to correct annular dilatation in all patients.ResultsNo operative death or late mortality was observed. The prolapsed segment, which was successfully repaired, was within 33% of the anterior mitral leaflet (AML) in 6 patients, from 33% to 50% in 5, from 50% to 99% in 11, and 100% in 6 patients. Before discharge, immediate postoperative echocardiography showed less than moderate mitral regurgitation in 28 of 28 patients. The follow-up, consisting of a clinical examination and serial echocardiograms, was complete in all cases and the mean follow-up period was 80.6 months (range, 12–146). There were two failures that required a reoperation because of a worsening mitral regurgitation and hemolytic anemia (elongation of anchored side of papillary muscle). The other two patients required mitral valve replacement due to a progressive regression of the left ventricular function, although the regurgitation worsened from a mild level to a moderate one. When the reoperated patients were excluded from the following data, the degree of mitral regurgitation, estimated by echocardiography performed at recent follow-up period, was none in 10 patients, trivial in 13 patients, and mild in 1 patient. In addition, the systolic and diastolic dimensions of the left ventricle decreased significantly (P < 0.01).ConclusionsThe replacement of artificial chordae was not complicated and it seemed to help to preserve a good relationship among leaflet tissues, chordae, and papillary muscles. We therefore suggest that the extensive use of PTFE artificial chordae appears to be a promising procedure for the repair of all kinds of mitral lesions causing mitral regurgitation.

Cardiopulmonary bypass, steroid administration, and surgical injury synergistically impair memory T cell function and antigen presentation

Previous reports showed that cardiac surgery with cardiopulmonary bypass (CPB) impair cell-mediated immunity by using antigen-non-specific responses. This study elucidated the effects of cardiac surgery with CPB on antigen-specific immunity. Twenty patients who underwent elective cardiac surgery using CPB were randomly divided into two groups: group A (n=10) and group B (n=10) with and without steroid administration, respectively. Group C patients underwent off-pump CABG (n=8). Peripheral blood mononuclear cells (PBMCs) were taken before and after surgery. Proliferation responses to pure protein derivative antigen were measured. The effects of CPB and steroid on T cell response and antigen-presentation were assessed by cross-stimulation between the preoperative and the postoperative PBMCs. Antigen-specific T cell responses decreased to about 5% of the preoperative values immediately after surgery with CPB, regardless of steroid administration. The T cell response in group B on POD 7 was significantly higher than that in group A. CPB impaired mainly T cell responses, and steroid administration enhanced impairment of T cell response and antigen-presentation. Open-heart surgery with CPB severely impaired antigen-specific immunity. Steroid administration enhanced the impairment of antigen-presentation as well as T cell function, and retarded the recovery of antigen-specific immunity.

Long-Term Comparison of Three Types of Aortic St. Jude Medical Mechanical Prosthesis in Japanese Patients

BACKGROUND The long-term results achieved with aortic St. Jude Medical (SJM) mechanical prostheses in various age groups of Japanese patients have not been previously compared or reported. METHODSANDRESULTS Since 1981, a total of 240 SJM valves were implanted in 79 patients using the Standard model, in 58 patients with the Hemodynamic Plus model, and in 103 patients with the Regent model for aortic valve replacement (AVR). Follow-up was completed for 2,397 patient-years in 97.5% of the patients, among whom the effect of age was compared, and the subjects were divided into younger (<65 years) and older (≥65 years) groups. Hospital mortality rate was 2.5%. No structural valve deterioration was observed during the follow-up period. In addition, no significant differences were observed in long-term survival between the 3 models. In contrast, significantly better rates of freedom from all-cause death (P<0.0001), valve-related death (P=0.0018) and valve-related morbidity (P=0.0021), including bleeding events (P=0.0007), were observed in the younger group (n=157, 50.6±1.0 years old) than in the older group (n=83, 72.5±0.7 years old). CONCLUSIONS All types of SJM valve used for single AVR achieved satisfactory early and long-term results in each age group even 25 years after surgery. When selecting this prosthesis for elderly patients, however, relatively worse performance may be expected compared with that observed in younger patients.

Pulmonary valve replacement after repaired Tetralogy of Fallot

In this review article, we describe pulmonary valve replacement (PVR) late after repaired Tetralogy of Fallot (TOF). Since the introduction of surgical intervention for patients with TOF in 1945, surgical management of TOF has dramatically improved early survival with mortality rates, less than 2–3%. However, the majority of these patients continue to experience residual right ventricular outflow tract pathology, most commonly pulmonary valve regurgitation (PR). The patients are generally asymptomatic during childhood and adolescence and, however, are at risk for severe PR later which can result in exercise intolerance, heart failure, arrhythmias, and sudden death. While it has been shown that PVR improves symptoms and functional status in these patients, the optimal timing and indications for PVR after repaired TOF are still debated. This article reviews the current state of management for the patient with PR after repaired TOF.

Comparison of cardiac energetics after transcatheter and surgical aortic valve replacements

OBJECTIVES The effect of transcatheter aortic valve replacement (TAVR) on cardiac energetics has not been described. We compared changes in cardiac energetics after TAVR with those after surgical aortic valve replacement (SAVR). METHODS We retrospectively estimated end-systolic elastance (Ees) and effective arterial elastance (Ea) using blood pressure and left ventricular (LV) volume obtained from echocardiography. LV efficiency [ventriculoarterial coupling (Ea/Ees) and the stroke work to pressure-volume area ratio (SW/PVA)] was calculated. Measurements were taken before, 1 week after and 1 year after bioprosthetic aortic valve replacement (TAVR, n = 56; SAVR, n = 61) in patients with severe aortic stenosis and preserved ejection fraction. RESULTS Patients with TAVR had a lower aortic valve pressure gradient and larger stroke volume 1 week after the procedure than those with SAVR. Ea was more markedly decreased, and LV efficiency was significantly improved 1 week after TAVR (SW/PVA 68.1% ± 8.4% to 72.0% ± 8.5%, P < 0.001), but LV efficiency was unchanged 1 week after SAVR (SW/PVA 70.1% ± 7.4% to 69.1%  ±  8.0%). LV efficiency was improved 1 year after both procedures (SW/PVA 75.5% ± 6.1% in TAVR; 74.7% ± 6.4% in SAVR). CONCLUSIONS TAVR decreases the transvalvular pressure gradient further without deteriorating stroke volume in the early postoperative period, which is accompanied by early improvement in afterload and LV efficiency compared with SAVR. Improvement in LV efficiency at mid-term follow-up is satisfactory after both procedures.

Axillo-iliac artery bypass for recurrent aortic coarctation to reduce cardiac afterload

A 13-year-old girl, who had undergone interrupted aortic arch repair with an 8-mm graft as a neonate and Fontan completion in childhood, developed ventricular fibrillation due to long-QT syndrome. Cardioverter defibrillator implantation was planned. Preoperative catheterization showed a 45-mmHg aortic pressure gradient and ventricular end-diastolic pressure of 11 mmHg. This indicated that recurrent coarctation had adversely affected ventricular function. After consideration of the patients age, symptoms and anatomical/surgical complexities, axillo-iliac bypass with cardioverter defibrillator implantation was performed. Postoperative ventricular end-diastolic pressure was 6 mmHg. Axillo-iliac bypass is a surgical option for coarctation that can reduce cardiac afterload.