Noriyoshi Kajihara

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.

Surgical Results of Anomalous Origin of the Right Pulmonary Artery From the Ascending Aorta Including Reoperation for Infrequent Complications

BACKGROUND We evaluated the results of surgery for an anomalous origin of the right pulmonary artery from the ascending aorta. METHODS From August 1986 to December 2005, 8 children (6 neonates) aged 7 to 180 days (mean, 35 +/- 59 days) with anomalous origin of the right pulmonary artery from the ascending aorta underwent surgical repair at our institute. All except one child, who had the distal form, had the proximal form. Cardiac catheterization showed that the left pulmonary artery to systemic pressure ratio was 1.0 or more. Surgery was performed by direct anastomosis in 7 patients and by graft interposition in 1. RESULTS There were no operative or late deaths. All patients postoperatively underwent cardiac catheterization that showed decreased left pulmonary artery to systemic pressure ratio ranging from 0.2 to 0.6. Follow-up periods ranged from 2 months to 13 years. We undertook reoperations for two infrequent postoperative causes. One patient exhibited significant supravalvar aortic stenosis and required patch enlargement of the ascending aorta 3 years after operation. The other patient (with the distal form) needed a reoperation after 1 month because of progressive stenosis at the anatomic site. Graft interposition was performed, and histopathologic examination showed that the tissue from the stenotic region looked like that of a ductus. CONCLUSIONS We undertook surgical repair for anomalous origin of the right pulmonary artery from the ascending aorta. Pulmonary hypertension was improved in all patients. Careful follow-up was necessary to detect supravalvar aortic and anastomotic stenosis early and late after operation.

Pulmonary Artery Banding for Functionally Single Ventricles: Impact of Tighter Banding in Staged Fontan Era

BACKGROUND In this study, we assessed our surgical strategy, tighter pulmonary artery banding (PAB) during the neonatal period, as an initial step followed by early application of bidirectional cavopulmonary shunts (BCPS) in infancy, to treat functionally single ventricles with unobstructed pulmonary blood flow. METHODS On the basis of our surgical strategy, 68 consecutive patients underwent PAB and were divided into two groups, group 1 (January 1990 to June 2003; n = 30) and group 2 (July 2003 to August 2008; n = 38). The median age at PAB was 45 days in group 1 and 9 days in group 2. The circumference of the bands was significantly shorter in group 2 than in group 1, corresponding to the patients weight in kg plus 19.0 +/- 0.6 mm in group 1 or 17.0 +/- 0.3 mm in group 2 (p = 0.003). RESULTS Cardiac catheterization before the right heart bypass operation showed that the pulmonary artery index (group 1, 322 +/- 29; group 2, 283 +/- 27 mm(2)/m(2); p = 0.01), pulmonary resistance index (group 1, 2.4 +/- 0.2; group 2, 1.9 +/- 0.1 U x m(2); p = 0.03), and ventricular end-diastolic volume (group 1, 212 +/- 19%; group 2, 166 +/- 9%; p = 0.04) were significantly different between the two groups. The rates for achievement of right heart bypass at 12 months (group 1, 19%; group 2, 81%; p < 0.01) and survival at 3 years (group 1, 70%; group 2, 87%; p = 0.04) were significantly higher in group 2 than in group 1. CONCLUSIONS Our present strategy could prevent volume overload and improve the achievement and survival rates of right heart bypass operations.

Impairment of coronary flow reserve and left ventricular function in the brain-dead canine heart.

OBJECTIVE The mechanisms of cardiac dysfunction after brain death, which are thought to be mainly associated with massive catecholamine release, have not been fully elucidated, especially with respect to the coronary circulation. The aim of this study was to investigate the changes in function of the coronary artery and its contribution to hemodynamic deterioration in a canine brain death model. METHODS Brain death was induced by rapid inflation of a subdurally placed balloon catheter. Hemodynamic measurements including assessment of left ventricular contractility using pressure-volume relations and biochemical analyses of blood samples were performed in seven dogs. Coronary flow reserve in the same brain death model was assessed by changes in coronary flow and resistance induced by administering a vasodilator directly into the coronary artery in another eight dogs. RESULTS A hyperdynamic response was transiently observed after induction of brain death, followed by decreases in arterial pressure, cardiac output, and coronary blood flow. Parameters of left ventricular contractility as measured by pressure-volume relations had significantly deteriorated by 60 min after brain death. Percent changes in coronary flow by administration of acetylcholine and sodium nitroprusside were 272 and 209%, respectively, before brain death; these were decreased to 178 and 145% at 30 min after brain death, and to 192 and 153% at 60 min. Coronary resistance ratios were also significantly increased at 30 and 60 min after brain death. CONCLUSIONS Impairment of coronary flow reserve was found in the brain-dead canine heart. This impaired coronary circulation may constitute a disadvantage of prevention and recovery of cardiac dysfunction after induction of brain death.

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.

Rapid Two-Stage Starnes Procedure for a Symptomatic Neonate With Ebstein Anomaly

We present a rapid two-stage Starnes procedure for a seriously symptomatic neonate with the prenatal diagnosis of Ebstein anomaly. At 16 hours after birth, we performed an emergency operation consisting of main pulmonary artery ligation, plication of the right atrial and right ventricular wall, modified Blalock-Taussig shunt, and patent ductus arteriosus ligation, without cardiopulmonary bypass. At age 12 days, we then performed the Starnes procedure using a glutaraldehyde-treated autologous pericardial patch with a 4-mm fenestration to close the tricuspid valve orifice. The infants postoperative course was excellent. A rapid two-stage Starnes procedure is useful for treating a seriously symptomatic neonate with Ebstein anomaly.

Early and late results of total correction of congenital cardiac anomalies in infancy

OBJECTIVE We evaluated long-term results of surgical correction of congenital cardiac anomalies in infancy. METHODS We reviewed cases of 856 patients who underwent complete correction of major cardiac anomalies in the first year of life during last 24 years at our institution, and analyzed results. Surgery involved ventricular septal defect (n = 453), tetralogy of Fallot (n = 92), atrioventricular canal defect (n = 93), and complete transposition of the great arteries (n = 218). RESULTS Operative mortality was 2.2% in ventricular septal defect, 0% in tetralogy of Fallot, 8.6% in atrioventricular canal defect, and 4.1% in complete transposition of the great arteries. Freedom from reoperation at 20 years was 96.5 +/- 2.0% and actuarial survival was 94.2 +/- 1.3% in ventricular septal defect. Freedom from reoperation at 15 years was 90.5 +/- 3.9% in tetralogy of Fallot and 86.6 +/- 4.4% in atrioventricular canal defect. Actuarial survival at 15 years was 97.8 +/- 1.6% in tetralogy of Fallot, 85.7 +/- 3.7% in atrioventricular canal defect, and 89.9 +/- 2.2% in complete transposition of the great arteries. Actuarial survival in complete transposition of the great arteries was significantly better in arterial than in atrial switch operations. CONCLUSIONS Total correction of ventricular septal defect, tetralogy of Fallot, atrioventricular canal defect, and complete transposition of the great arteries in infancy was conducted safely, but the incidence of reoperation in late follow-up must be reduced.

Surgical Experience of Cardiac Tumors : Early and Late Results

PurposeCardiac tumors include benign and malignant neoplasms that arise within the cardiac chambers or myocardium. This study summarizes our surgical experiences with cardiac tumors.MethodsBetween 1975 and 2003, 51 patients with cardiac tumors were surgically treated.ResultsMyxomas. Forty-seven cardiac myxomas were excised in 46 patients with an average age of 51.7 ± 18 years. The preoperative symptoms included congestive heart failure (37%) and embolism (30%). The incidence of preoperative embolization was significantly higher in the gelatinous and lobated myxomas than in the solid and smooth form (P = 0.017). The early mortality rate was 2.2%. Although the late mortality rate was 9.7%, no patients died from cardiological causes (mean follow-up, 11.2 years). Only 1 patient required surgery for recurrence. Benign nonmyxomatous tumors. Three patients with a mean age of 26.3 ± 19.0 years showed benign nonmyxomatous tumors. There were no perioperative or late deaths. Malignant tumors. Two patients were diagnosed to have malignant tumors and although there was no perioperative death, both died postoperatively within 6 months.ConclusionsCardiac myxomas and nonmyxomatous benign cardiac tumors show excellent results after a surgical excision, with a low morbidity and mortality. A surgical resection should thus be considered as a treatment option for patients with malignant tumors.

A novel electron paramagnetic resonance spin-probe technique demonstrates the relation between the production of hydroxyl radicals and ischemia–reperfusion injury

OBJECTIVE Many previous studies have suggested an increase in hydroxyl radical (OH) production after myocardial ischemia-reperfusion; however, traditional techniques have not been able to conclusively prove this phenomenon. We investigated whether the production of OH was increased during myocardial reperfusion using a novel electron paramagnetic resonance (EPR) technique using an OH-specific spin probe. An OH scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was used to examine the relationship between OH production and post-ischemic functional recovery or the degree of myocardial injury. METHODS We used an isolated rabbit-heart preparation perfused with support-rabbit blood, and the heart was reperfused after normothermic global ischemia. Heart samples were reacted with the OH-specific spin probe, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxyl-TEMPO). The rate of decay of the EPR signal showed OH production. We investigated the rate of EPR signal decay and cardiac function. RESULTS The rate of signal decay was significantly increased just after reperfusion compared with that of pre-ischemia (2.00×10(-2)±0.77×10(-2)min(-1) vs 0.11×10(-2)±0.02×10(-2)min(-1), p<0.01). Administration of MCI-186 reduced the rate of decay to 0.86×10(-2)±0.14×10(-2)min(-1) just after reperfusion (p<0.01). Cardiac function was significantly improved 60 min after reperfusion using MCI-186 compared without MCI-186 (left ventricular developed pressure was 95±9 mm Hg vs 60±6 mm Hg and the first derivative of the left ventricular pressure (dP/dt) was 1843±200 mm Hg s(-1) vs 1182±127 mm Hg s(-1)). CONCLUSIONS A novel EPR spin-probe technique demonstrated the relation between the production of OH and ischemia-reperfusion injury. We confirmed that OH production influenced cardiac function and myocardial ischemia-reperfusion injury.

Surgical treatment of an infant with myocardial ischemia due to an anomalous origin of the right coronary artery from the main pulmonary artery: report of a case.

An anomalous origin of the right coronary artery from the main pulmonary artery (ARCAPA) is a rare cardiac malformation, and only three cases of isolated ARCAPA in patients younger than 2 years of age have been reported. This report describes the surgical treatment of a 12-month-old girl with myocardial ischemia due to ARCAPA. The diagnosis was made by echocardiography. A reimplantation of the aberrant coronary artery was performed, and the patient had a successful postoperative course.