We examined late results of 30 patients who underwent a Blalock-Taussig (BT) shunt in the neonatal period from 1982 through 1991. Original BT shunt was performed in 19 patients and modified BT shunt ...in 11 patients; In 9 of the 11 patients, an expanded polytetrafluoroethlence (EPTFE) tube was used. There was no significant difference in the size of pulmonary artery at anastomosis between original shunt group and modified shunt group, respectively. The obstruction of shunt did not occur in the early post-operative period within one month after operation, but occured in one patient (5%) of the original shunt group and 2 patients (22%) of the modified shunt group in the postoperative period. Pulmonary angioplasty at total repair was required in one patient in each group, and percutanous angioplasty was attempted in one patient in the original shunt group. In conclusion, late results of BT shunt in enonates is satisfactory, and the modified BT shunt utilizing an EPTFE tube could be a palliative procedure of a choice when additional palliation or total repair is considered in appropriate time.
Clinical Survey of Cell Therapy in Japan Katsuda, Yousuke; Takeshita, Yoshiaki; Arima, Ken ...
Cardiovascular Regeneration Therapies Using Tissue Engineering Approaches
Book Chapter
Background: Therapeutic angiogenesis by using cells is being performed in Japan. However, it is unknown in how many centers and how these therapies are performed. The efficacy and side effects are ...also unknown. Thus, we conducted the survey by mailing questionnaire within Japan. Methods and results: Two surveys were performed in 2003. The first survey unveiled that cell therapy was performed in 32 facilities until October 2003. The second survey unveiled the followings. (1) The total number of performed cases was 221. 153 patients (69.2%) had arterio-sclerosis obliterance (ASO), 56 patients (25.3%) thromboangitis obliterans (TAO, Burger’s disease), and 12 patients (5.4%) other conditions. (2) The sources of cells were bone marrow-mononuclear cells (61.5%), peripheral-mononuclear cells (9.5%), and peripheral CD34+ cells (22.1%). A few patients (6.7%) were treated with a cytokine only (granulocyte-colony stimulating factor: G-CSF). (3) Inclusion criteria were the same for most facilities, such as patients with PAOD, especially with critical limb ischemia with rest pain, non-healing ischemic ulcers and non-candidates for non-surgical or surgical revascularization. All facilities excluded patients with histories of malignant disorder during the past 5 years, proliferative diabetic retinopathy, pregnancy, proliferative blood disease, uncontrolled ischemic heart disease, rheumatic arthritis, or psychiatric disease. (4) Subjective improvement was observed in 138 of 199 patients (69%). Objective improvements for ABI, TcO2 or angiographic findings were observed in 98 of 182 patients (53.8%). (6) Three of 221 patients (1.4%) died after cell therapy. One died from cerebro-vascular attack (thrombo-embolizm), and two died from acute myocardial infarction (AMI). Conclusion: Our clinical survey has shown that cell therapy is being performed in many medical centers in Japan. It seems to be safe and effective for patients with PAOD with no surgical options
The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte ...adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia.
Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic arrest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 micrograms/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70 +/- 4% in control versus 77 +/- 2% in group P-sel, P < 0.01), maximum positive first derivative of pressure (dP/dt) (64 +/- 7% in control versus 73 +/- 5% in group P-sel, P < 0.05), and maximum negative dP/dt (61 +/- 6% in control versus 70 +/- 6% in group P-sel, P < 0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135 +/- 40% in control versus 205 +/- 43% in group P-sel, P < 0.05). Myocardial myeloperoxidase activity was significantly lower (P < 0.05) in group P-sel (4.7 +/- 3.2) versus control (16.0 +/- 10.1). (Units are change in absorbance/min/g tissue.)
The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion.
Prior studies indicate that immature myocardium has a greater tolerance to ischemia. Prior studies from our laboratory have shown that impaired postischemic endothelial function was correlated with ...reduced ventricular contractility, and that coronary endothelium has an important role in ischemia and reperfusion injury in neonatal hearts.
We examined the differences of endothelial function as well as ventricular function between immature and mature hearts in isolated blood-perfused lamb and sheep hearts after 2 hours of 15 °C cardioplegic ischemia. Three groups were defined according to age: neonatal (<1 week) hearts (n = 8), infant (1 month) hearts (n = 8), and adult (1 year) hearts (n = 6). Each of the three groups underwent a similar protocol including ischemic time, myocardial temperature, and cardioplegic solution. Based on earlier work, all had low perfusion pressures during the first 10 minutes of reperfusion. Thereafter the perfusion pressure was constant at 60 mm Hg in the neonatal hearts, 80 mm Hg in the infant hearts, and 100 mm Hg in the adult hearts to match the mean arterial pressure at each age in this species.
At 30 minutes of reperfusion, the neonatal and infant hearts achieved significantly improved recovery of left ventricular systolic (maximum developed pressure and positive first time derivative of pressure, and volume normalized developed pressure and first time derivative of pressure) and diastolic (negative maximum first time derivative of pressure) functions and coronary blood flow. The postischemic endothelial function determined by the coronary vasodilator response to acetytlcholine was better in the neonatal and infant hearts compared with the adult hearts (
p < 0.05).
These results show that the immature hearts had better recovery of endothelial function and coronary blood flow as well as ventricular function compared with adult hearts after hypothermic ischemia and reperfusion. These results combined with previous studies add further support to the concept that events in the coronary vascular bed play an important role in reperfusion injury in both immature and mature hearts.
Prior studies indicate that immature myocardium has a greater tolerance to ischemia. Prior studies from our laboratory have shown that impaired postischemic endothelial function was correlated with ...reduced ventricular contractility, and that coronary endothelium has an important role in ischemia and reperfusion injury in neonatal hearts.
We examined the differences of endothelial function as well as ventricular function between immature and mature hearts in isolated blood-perfused lamb and sheep hearts after 2 hours of 15°C cardioplegic ischemia. Three groups were defined according to age: neonatal (<1 week) hearts (n = 8), infant (1 month) hearts (n = 8), and adult (1 year) hearts (n = 6). Each of the three groups underwent a similar protocol including ischemic time, myocardial temperature, and cardioplegic solution. Based on earlier work, all had low perfusion pressures during the first 10 minutes of reperfusion. Thereafter the perfusion pressure was constant at 60 mm Hg in the neonatal hearts, 80 mm Hg in the infant hearts, and 100 mm Hg in the adult hearts to match the mean arterial pressure at each age in this species.
At 30 minutes of reperfusion, the neonatal and infant hearts achieved significantly improved recovery of left ventricular systolic (maximum developed pressure and positive first time derivative of pressure, and volume normalized developed pressure and first time derivative of pressure) and diastolic (negative maximum first time derivative of pressure) functions and coronary blood flow. The postischemic endothelial function determined by the coronary vasodilator response to acetytlcholine was better in the neonatal and infant hearts compared with the adult hearts (p < 0.05).
These results show that the immature hearts had better recovery of endothelial function and coronary blood flow as well as ventricular function compared with adult hearts after hypothermic ischemia and reperfusion. These results combined with previous studies add further support to the concept that events in the coronary vascular bed play an important role in reperfusion injury in both immature and mature hearts.
Between January 1985 and October 1998, 169 of 372 patients who underwent a modified Fontan procedure had atrioventricular valve regurgitation (AVVR) that ranged in degrees from 1 to 4. Concomitant ...repair for AVVR was performed in the majority of cases. All but 12 patients had the AV valve repaired, mainly by circular annuloplasty; none had valve replacement. Although mortality was significantly higher in the AVVR cases (21 of 169 12%) than in the cases without AVVR (eight of 203 3.9%; P < .007, chi-square), actuarial survival in the AVVR cases was 83% at 5 years, 81% at 10 years, and 73% at 12 years. The degree of AVVR before surgery was 1.62 ± 0.73 on average; 82 cases had more than grade 2 regurgitation. There was a significant decrease to 0.54 ± 0.61 (P < .0001) after surgery in long-term survivors. Cases with AVVR can be treated with reasonable risk provided proper repair of the valve is performed. Circular annuloplasty is a simple and uniformly effective method with which to control regurgitation, even for the common AV valve.
Quantitative elastic modulus measurements of tissue- engineered (TE) vascular wall are useful for in vivo clinical follow-up because the elastic modulus is closely related with the biocompatibility, ...maturity and structural intensity of the vascular wall. While we have presented an in vitro measurement system for the TE vessel prior to grafting it in the previous study, we present a novel and specified method for in vivo assessment and follow-up of the TE vascular wall in this paper. Moreover, the regeneration score for in vivo assessment are also presented based on the measured quantitative elastic modulus. The effectiveness of the proposed assessment method was validated by in vivo experiment using canines.
