Biomedical subjects

Shigeaki Ohtake

Publications and source records attributed to Shigeaki Ohtake.

14 recordsLinked to original sources

PubMed2004

Peroxynitrite, a product between nitric oxide and superoxide anion, plays a cytotoxic role in the development of post-bypass systemic inflammatory response.

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to induce post-bypass systemic inflammatory response. Peroxynitrite (ONOO-) is a potent oxidant formed by a rapid reaction between nitric oxide (NO) and superoxide anion. We hypothesized that ONOO- plays a role in the development of post-bypass systemic inflammatory response and examined the efficacy of ONOO- scavenger in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60 min of CPB (100 ml/kg per min, 34 degrees C). Group-P (n = 10) received 50 mg/kg of ONOO- scavenger, quercetin, intraperitoneally 24 h before the initiation of CPB, and Group-C (n = 10) served as controls. RESULTS: There were significant time-dependent changes in plasma nitrate+nitrite (NOx), the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr: an indicator of ONOO- formation), interleukin (IL)-6, IL-8, and respiratory index (RI). There were significant differences in %NO2-Tyr between the groups both at CPB termination (Group-P vs C; 0.26+/-0.07 vs 0.55+/-0.11%, P < 0.01) and 3 h after CPB termination (0.65+/-0.14 vs 1.46+/-0.25%, P < 0.01); whereas there were no significant differences in NOx between the groups at any sampling point ((at CPB termination) Group-P vs C; 31.6+/-4.3 vs 32.7+/-4.1 micromol/l, (3 h after CPB termination) Group-P vs C; 47.8+/-4.9 vs 51.7+/-5.3 micromol/l). Group-P showed significantly lower plasma IL-6 (176.8+/-44.3 vs 302.4+/-78.1 pg/ml, P < 0.01), IL-8 (9.45+/-1.78 vs 16.42+/-2.53 ng/ml, P < 0.01) and RI (1.07+/-0.19 vs 1.54+/-0.25, P < 0.01) 3 h after CPB termination, though there were no significant differences between the groups at CPB termination. CONCLUSIONS: These results suggest that ONOO- plays a crucial role in the development of post-bypass systemic inflammatory response and the pretreatment with quercetin has a potential benefit to avoid deleterious effects of ONOO-.

Animals↗

PubMed2004

Early result of heart transplantation in Japan: Osaka University experience.

Since the new organ transplantation law was established in 1997, 17 heart transplantations have been performed in Japan, 7 of which were carried out at Osaka University Hospital. Recipient diagnosis was dilated cardiomyopathy in 2, dilated phase of hypertrophic cardiomyopathy in 4, and post-myocarditis cardiomyopathy in 1. Ages ranged from 8 to 49 years with a mean of 35.3 years. Five patients were bridged with a left ventricular assist device. The waiting period was 182-977 days (mean, 643 days). There was no early or late death during follow-up of 1-4.8 years. Under a standard triple-drug regimen using mycophenolate, there were 3 rejection episodes greater than grade 3 in 2 patients, and humoral rejection requiring plasmapheresis in one. A young boy whose donor was a hemodynamically compromised adult developed neurological sequelae after resuscitation following ventricular tachycardia. All patients were discharged and went back to work or their regular daily life. Although the donor shortage is still severe in Japan, the resumption of heart transplantation has been satisfactory, and left ventricular assist devices have played a crucial role.

Adult↗

PubMed2003

The clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery.

BACKGROUND: Minimally invasive cardiac surgery is now becoming standard in the correction of simple congenital cardiac malfbrmations. We introduced a clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery, and assessed the function of the pathway in children with atrial or ventricular septal defects, comparing minimally invasive surgery to repair through a conventional full sternotomy. METHODS: We studied 15 children of school age who underwent repair of an atrial or ventricular septal defect through a lower midline sternotomy, and 10 children undergoing repair through a full sternotomy. The clinical pathway was for extubation to take place in the operating room, echocardiographic evaluation on the 5th postoperative day, and discharge home on the 7th postoperative day, with return to school within 2 weeks, and resumption of all gymnastic activity within 6 weeks of the minimally invasive surgery. RESULTS: In those having a lower midline sternotomy, postoperative hospital stay was 7.4 +/- 0.8 days, with return to school 8.0 +/- 2.4 days after discharge. They resumed gymnastics 41 +/- 11 days after the minimally invasive surgery. In those having a full sternotomy, in contrast, these parameters were 13.5 +/- 2.7, 23.1 +/- 8.4, and 95 +/- 43 days, respectively. Of the 15 children undergoing a minimally invasive approach, 12 (80%) fulfilled the criterions of our clinical pathway. CONCLUSIONS: We conclude that minimally invasive cardiac surgery can safely be performed in children. In addition to its cosmetic role, the technique has added value in promoting early return to normal school life, including gymnastics.

Adolescent↗

PubMed2003

Participation of caspase-3-like protease in necrotic cell death of myocardium during ischemia-reperfusion injury in rat hearts.

This experimental study was designed to determine if caspase-3-like protease is activated during a short period of ischemia - reperfusion (I-R) that did not induce apoptosis, and whether protease-3-protease inhibitor could prevent myocardial I-R injury, especially necrotic cell death. The subjects were 20 isolated rat hearts; 10 were pretreated for 20 min with 100 micromol/L of the protease-3-protease inhibitor, peptide antagonist Asp-Glu-Val-Asp-CHO (DEVD) (Group D), and compared with the 10 no-pretreated hearts (Group C). The hearts were then subjected to 20, 30, 45, and 60 min of normothermic global ischemia followed by 30 min of reperfusion. Caspase-3-like protease was significantly elevated after 45 min and 60 min in ischemic hearts. Group D had reduced levels of caspase-3-like protease activity after 45 min and 60 min (302+/-58%, 378+/-69% of pre-ischemic control, respectively), as compared with Group C (542+/-74%, 689+/-85%, respectively) (p<0.05, p<0.05, respectively). Histological analysis also demonstrated a decrease in cellular damage in Group D, as the count ratio of necrotic cells with total cardiomyocytes was 38%, as compared with 78% in the control group (p<0.05). Caspase-3-like protease participated in I-R injury in rat hearts and inhibition of this protease resulted in a reduction of necrotic cell death.

Animals↗

PubMed2002

Beating coronary bypass with right-heart bypass. A safer option in patients at high risk for stroke.

Two patients with bilateral obstructive carotid artery disease underwent beating heart coronary bypass including revascularization of the circumflex branch using right-heart bypass in a stable hemodynamic state. Without this mechanical support, lifting the left ventricle for the exposure of the posterior wall could impair the hemodynamic state of the patient. Right-heart bypass in addition to aortic no-touch technique can be a safer option for complete coronary revascularization in patients at high risk for neurological complications.

Aged↗

PubMed2002

Simultaneous repair of stenosis in coronary and vertebral arteries and aortic regurgitation secondary to Takayasu's aortitis.

We report a case of severe stenosis in the ostium of both the coronary artery and the proximal left vertebral artery and severe aortic regurgitation secondary to Takayasu's aortitis. A 47-year-old woman underwent simultaneous repair consisting of aortic valve replacement, triple coronary artery bypass grafting, and aorto-left vertebral artery bypass. Saphenous vein grafts to 3 coronary arteries and the left vertebral artery were proximally anastomosed on a bovine pericardial patch in the ascending aorta. Since the patient had severe preoperative ischemic symptoms from vertebral-basilar insufficiency, we clamped the vertebral artery during reconstruction under deep hypothermic circulation. The postoperative course was uncomplicated. Simultaneous repair of such multiple lesions requires meticulous planning of surgical procedures and circulatory assist systems.

Anastomosis, Surgical↗

PubMed2002

Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation.

BACKGROUND: In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma. METHODS: Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups. RESULTS: Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis. CONCLUSIONS: Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.

Adult↗

PubMed2002

Arch-first technique for aortic arch aneurysm repair through median sternotomy.

We describe a modified arch-first technique for total arch replacement through median sternotomy. This technique involves a short period of circulatory arrest (less than 30 minutes) and subsequent anterior cerebral perfusion. It does not require cannulation of the carotid vessels, which can cause cerebral thromboembolism, and it enables anterior cerebral perfusion to be resumed after a relatively short period of circulatory arrest. This appears to be a useful technique to reduce cerebral complications in complicated arch reconstruction operation for patients with severely atherosclerotic carotid vessels.

Aorta, Thoracic↗

PubMed2002

Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats.

BACKGROUND: As one of the future strategies of advanced pulmonary hypertension, intrinsic prostacyclin drug delivery using gene therapy may be useful. We investigated whether transfer of the prostacyclin synthase gene into the liver could ameliorate monocrotaline-induced pulmonary hypertension in rats. METHODS: The human prostacyclin synthase gene was transfected into the liver of rats with monocrotaline-induced pulmonary hypertension. Hemodynamic indices, blood samples, lung tissues, and survival curves were evaluated between rats receiving the gene and control rats. RESULTS: High levels of prostacyclin synthase gene expression were found in the hepatocytes of the prostacyclin synthase group. The level of 6-keto-prostaglandin F(1alpha) was significantly higher in the prostacyclin synthase group (prostacyclin synthase, 35.4 +/- 4.4 ng/mL; control, 22.3 +/- 3.3 ng/mL; P =.0436). The right ventricular/femoral artery pressure ratio was significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 0.60 +/- 0.039; control, 0.88 +/- 0.051; P =.0036). The endothelin-1 levels in the lung tissues were significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 10.42 +/- 2.01 pg/mg protein; control, 19.94 +/- 2.82 pg/mg protein; P =.0176). The survival ratio was significantly higher in the prostacyclin synthase group than the control group (P =.0375). CONCLUSION: This drug delivery system using gene transfer can be considered as an alternative for continuous intravenous prostacyclin infusion for pulmonary hypertension.

Animals↗

PubMed2002

Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor.

OBJECTIVE: We investigated the efficacy of directly injecting a plasmid with complementary DNA encoding human hepatocyte growth factor into ischemic canine myocardium to induce angiogenesis. METHODS: Four weeks after ligation of the left anterior descending coronary artery, 125 microg of a complementary DNA plasmid encoding the gene for either hepatocyte growth factor (n = 8) or LacZ (transfection control group, n = 8) was injected directly into the myocardium at the border between the normal tissue and the infarction. Eight other dogs were used as a sham control group. Regional thickening fraction, which indicated contractile function, and blood flow in the normal (circumflex branch territory) and ischemic areas were evaluated under dobutamine administration just before and 4 weeks after transfection. The animals were killed, and capillary numbers in both areas were assessed. These data in the ischemic area were evaluated as the percentage of those in the normal. RESULTS: The number of myocardial capillaries in the ischemic area was successfully increased to approximately 140% of usual in the hepatocyte growth factor group, whereas no change was observed in the other groups (P =.0017 by analysis of variance). Furthermore, regional thickening fraction and blood flow in the ischemic area, which had deteriorated after coronary ligation, showed significant improvement in the hepatocyte growth factor group relative to the other groups (thickening fraction P <.0001 by analysis of variance, blood flow P =.0005 by analysis of variance). CONCLUSIONS: These results support the efficacy of the direct injection of plasmid complementary DNA encoding human hepatocyte growth factor to induce therapeutic angiogenesis in the ischemic myocardium.

Animals↗

PubMed2002

Emergency operation for spontaneous coronary artery dissection in young female.

Emergency coronary artery bypass grafting using a composite graft of the right internal thoracic artery and the radial artery was successfully performed for impending myocardial infarction secondary to spontaneous dissection of the right coronary artery in a 46-year-old woman. As spontaneous coronary artery dissection frequently presents as myocardial infarction or sudden death, timely diagnosis and intervention are required.

Aortic Dissection↗

PubMed2002

Right heart assist during beating bypass for severe left ventricular dysfunction.

Three patients with triple-vessel disease and severe left ventricular dysfunction underwent successful revascularization on a beating heart, using a right ventricular assist system. Heparin-coated circuits with a centrifugal pump provided 2.5 to 3.5 L x min(-1) of flow to maintain good hemodynamics and enable easy access to the posterior vessels during vertical displacement of the heart.

Blood Pressure↗

PubMedDate not supplied

Improvement of bypass circuit biocompatibility: comparison and combination of heparin-coated circuit and nitric oxide gas infusion.

OBJECTIVES: Nitric oxide (NO) gas infusion to the oxygenator, as well as heparin-coated bypass circuits, have been reported to attenuate blood activation induced by the interaction with the artificial surfaces of an extracorporeal bypass circuit. Using a mock circulation model, we compared the effect of each and also evaluated the effect of their combination on attenuating bypass-induced blood activation. METHODS: A miniature closed bypass circuit was primed with diluted fresh human blood and perfused for 180 minutes using a centrifugal pump. NO gas (0, 50, or 100 ppm) was infused to the oxygenator sweep gas of either a non-heparin-coated or a heparin-coated circuit. Platelet counts, beta-thromboglobulin, platelet factor 4, complement-3 activation products and granulocyte elastase were measured at 0, 30, 60, 120, and 180 minutes after starting the perfusion. RESULTS: One hundred ppm of NO was statistically equivalent to the heparin-coated circuit for attenuating bypass-induced blood activation, and a combination of the two significantly surpassed the results of either modification alone. Fifty ppm of NO alone provided only a slight attenuation of blood activation as compared with the non-heparin-coated circuit, though the difference was not significant. A combination of 50 ppm NO and the heparin-coated circuit did not significantly enhance the effects of the heparin-coated circuit alone. CONCLUSIONS: The combination of NO gas infusion and heparin-coated circuits appears to be a useful and promising modification for enhancing the attenuation of bypass-induced blood activation, though the optimal dose of NO infusion in terms of effectiveness and adverse effects to the whole body remains to be established.

Anticoagulants↗

PubMedDate not supplied

Avoidance of full-sternotomy: effect on inflammatory cytokine production during cardiopulmonary bypass in rats.

BACKGROUND AND AIM OF THE STUDY: Although open heart operations via a mini-sternotomy or mini-thoracotomy are considered "less invasive" cosmetically and are hopeful for early social recovery, clinical experiences have not shown less invasiveness toward systemic inflammatory response, because of the wide variety of patients and operative procedures encountered. We examined the effect of a mini-sternotomy on an inflammatory response during a cardiopulmonary bypass (CPB) procedure performed in rats. METHODS: Thirty-two adult Sprague-Dawley (SD) rats, each of which underwent a 120-minute CPB, were randomly divided into four groups according to the method of exposing the pericardial cavity; no sternotomy (Group N [0 cm], n = 8), right para-sternal thoracotomy (Group P [2 cm], n = 8), lower mini-sternotomy (Group M [2 cm], n = 8), and full-sternotomy (Group F [4 cm], n = 8). Blood samples were obtained (1) just prior to the initiation of CPB, and then (2) 30, (3) 60, and (4) 120 minutes after the initiation of CPB. RESULTS: Thirty minutes after the initiation of CPB, there were significant differences in plasma interleukin [IL]-6 levels between groups, except for Groups P and M; whereas at 60 minutes the only significant difference occurred between Groups N and F, and at 120 minutes there were no significant differences between any of the groups. Further, plasma IL-8 levels were not significantly different at each sampling point between all of the groups. CONCLUSIONS: These results first demonstrate experimentally that the avoidance of a full-sternotomy can be considered a less invasive strategy in terms of reducing the systemic inflammatory response that accompanies a shorter CPB duration.

Animals↗