Biomedical subjects

Jun Mohara

Publications and source records attributed to Jun Mohara.

12 recordsLinked to original sources

PubMed2006

Inhibition of cyclooxygenase-2 improves cardiac function following long-term preservation.

BACKGROUND: Cyclooxygenase (COX) is an intracellular enzyme that converts arachidonic acid to prostaglandin endoperoxide (PGG(2)). There are two isoforms of COX, namely constitutive COX-1 and inducible COX-2. It has been reported that COX-2 plays an important role in ischemia-reperfusion injury and that COX-2 mRNA and protein expression were up-regulated during cardiac allograft rejection. FK3311 is a suppressor of COX-2 activation. The purpose of this study was to evaluate the effectiveness of inhibiting COX-2 with FK3311 for the minimization of ischemia-reperfusion injury and for the improvement of donor heart function following transplantation in a canine model. MATERIALS AND METHODS: Adult mongrel dogs were used. After the measurement of hemodynamic parameters [cardiac output (CO), left ventricular pressure (LVP), and the maximum rates of increase and decrease in LVP (+/-LVdp/dt)], coronary vascular beds were washed out with a hypothermic (4 degrees C) University of Wisconsin (UW) solution following cardiac arrest in response to cold (4 degrees C) glucose-insulin-potassium solution. The heart was then excised and preserved in hypothermic (4 degrees C) UW solution for 12 h. FK3311 (3 mg/kg) was administered intravenously to five dogs prior to reperfusion, while vehicle was administered intravenously to a control group (n = 5). After 3 h of orthotopic transplantation using cardiopulmonary bypass, the hemodynamic parameters were compared with preoperative values of the donor animals under the condition of 10 mm Hg right atrial pressure and 5 mug/kg/min dopamine support. RESULTS: The recovery rates of CO and +/-LVdP/dt were significantly (P < 0.05) higher in the FK-treated dogs than in the controls (CO: 93 +/- 6 versus 66% +/- 4%; +LVdp/dt: 125 +/- 8 versus 77 +/- 10%; and -LVdp/dt: 81 +/- 7 versus 52 +/- 6%; for FK-treated versus control dogs, respectively). The recovery rate of LVP was higher in the FK-treated dogs than in the controls (90 +/- 5 versus 72 +/- 5%), but this difference was not statistically significant. Immunohistochemical staining revealed that COX-2 expression was reduced significantly in the myocardium of FK-treated dogs compared with controls. CONCLUSION: Hemodynamic parameters following transplantation were improved significantly in dogs treated with FK3311. Therefore, the inhibition of COX-2 improves transplanted cardiac function following long-term preservation.

Adenosine↗

PubMed2005

Improved myocardial beta-adrenergic responsiveness and signaling with exercise training in hypertension.

BACKGROUND: Cardiac responses to beta-adrenergic receptor stimulation are depressed with pressure overload-induced cardiac hypertrophy. We investigated whether exercise training could modify beta-adrenergic receptor responsiveness in a model of spontaneous hypertension by modifying the beta-adrenergic receptor desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca2+ cycling proteins. METHODS AND RESULTS: Female spontaneously hypertensive rats (SHR; age, 4 months) were placed into a treadmill running (SHR-TRD; 20 m/min, 1 h/d, 5 d/wk, 12 weeks) or sedentary group (SHR-SED). Age-matched Wistar Kyoto (WKY) rats were controls. Mean blood pressure was higher in SHR versus WKY (P<0.01) and unaltered with exercise. Left ventricular (LV) diastolic anterior and posterior wall thicknesses were greater in SHR than WKY (P<0.001) and augmented with training (P<0.01). Langendorff LV performance was examined during isoproterenol (ISO) infusions (1x10(-10) to 1x10(-7) mol/L) and pacing stress (8.5 Hz). The peak LV developed pressure/ISO dose response was shifted rightward 100-fold in SHR relative to WKY. The peak ISO LV developed pressure response was similar between WKY and SHR-SED and increased in SHR-TRD (P<0.05). SHR-TRD showed the greatest lusitropic response to ISO (P<0.05) and offset the pacing-induced increase in LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) observed in WKY and SHR-SED. Improved cardiac responses to ISO in SHR-TRD were associated with normalized myocardial levels of GRK2 (P<0.05). SHR displayed increased L-type Ca2+ channel and sodium calcium exchanger abundance compared with WKY (P<0.001). Training increased ryanodine receptor phosphorylation and phospholamban phosphorylation at both the Ser16 and Thr17 residues (P<0.05). CONCLUSIONS: Exercise training in hypertension improves the inotropic and lusitropic responsiveness to beta-adrenergic receptor stimulation despite augmenting LV wall thickness. A lower GRK2 abundance and an increased phosphorylation of key Ca2+ cycling proteins may be responsible for the above putative effects.

Adrenergic beta-Agonists↗

PubMed2005

Successful transplantation of an older donor heart with documented myocardial bridging: a case report.

Myocardial bridging, the overlying of myocardial tissue onto epicardial coronary arteries, is an anatomic variant that is widely present in the general population. This condition can be associated with reduced forward coronary flow. Once these hearts are identified in potential donors by either visual inspection or coronary catheterization, they may no longer be considered suitable for transplantation. We present a case study that successfully utilized such a heart explanted from an older donor with "bench" myotomy repair before implantation.

Contraindications↗

PubMed2005

Long-term preservation using a new apparatus combined with suppression of pro-inflammatory cytokines improves donor heart function after transplantation in a canine model.

OBJECTIVE: We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of pro-inflammatory cytokines, improves donor heart function after transplantation in a canine model. METHODS: We used adult mongrel dogs in this study. Coronary vascular beds were washed with University of Wisconsin (UW) solution after arresting hearts with glucose-insulin-potassium solution. The heart was then excised and preserved for 12 hours with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into 2 groups: the coronary perfusion (CP) group (n = 7) and the FR167653 (FR-CP) group (n = 6). In the CP group, we used a 4 degrees C UW solution for immersion and coronary perfusion. In the FR-CP group, we used a 4 degrees C UW solution supplemented with 20 mg/liter of the anti-inflammatory agent FR167653 for immersion and coronary perfusion. At 2 and at 3 hours after orthotopic transplantation, we compared hemodynamic parameters with pre-operative values in donor animals, with right atrial pressure at 10 mm Hg and with 5 microg/kg/min dopamine infusion. We compared serum concentrations of TNF-alpha from the coronary sinus and compared electron microscopic studies between the 2 groups. RESULTS: Three hours after transplantation, cardiac output (CO), left ventricular pressure (LVP), and -LVdp/dt were significantly greater (p < 0.05) in the FR-CP group than in the CP group (CO, 178% +/- 65% vs 93% +/- 40%; LVP, 115% +/- 22% vs 73% +/-26%; -LVdp/dt, 168% +/- 13% vs 61% +/- 17%, respectively). Electron microscopic studies showed that glycogen was well preserved in the FR-CP group compared with the CP group. Serum concentrations of TNF-alpha were decreased significantly in the FR-CP group compared with the CP group at 3 hours after reperfusion (161 +/- 54 pg/dl vs 642 +/- 636 pg/dl, respectively). CONCLUSION: Hemodynamics after transplantation were significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of pro-inflammatory cytokines improves donor heart function after transplantation.

Animals↗

PubMed2005

Potential suitability for transplantation of hearts from human non-heart-beating donors: data review from the Gift of Life Donor Program.

BACKGROUND: Organ availability limits use of heart transplantation for treatment for end-stage heart disease. Hearts are currently obtained from donors declared brain dead (heart-beating donors [HBDs]). Although use of hearts from non-heart-beating donors (NHBDs) could reduce the shortage, they are considered unusable because of possible peri-mortem ischemic injury. METHODS: To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from the Gift of Life Donor Program (GLDP), our local organ procurement organization, from 2001 through 2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross-clamp) of 30 minutes. RESULTS: During the study period, there were 894 HBDs, 334 heart transplants and 119 NHBDs. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (< or =45 years) and 20 were eliminated because of incomplete data. Eighty-two NHBDs were cross-clamped within 30 minutes of care withdrawal. Twenty NHBDs met all cardiac donor criteria, and 14 of these 20 had hypoxic/ischemic times < or =30 minutes. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. CONCLUSIONS: Based on our assumptions, 12% to 18% of NHBDs in the study period (14 to 21 of 119 total) were potential heart donors, representing a 4% to 6% increase over of the number of heart transplants performed during the same time interval.

Adolescent↗

PubMed2005

Mitral regurgitation with an isolated anterior mitral leaflet cleft: a case report.

A 20-year-old man was admitted to hospital because of general fatigue during exercise. He had had a heart murmur since the age of 6 years. Echocardiography showed severe mitral regurgitation (MR, IV), probably caused by an anterior leaflet cleft or tendon rupture. During surgery, a cleft measuring 9 mm in length was found in the center of the anterior leaflet of the mitral valve. The cleft was closed directly, together with annuloplasty using the bilateral Kay's method. A Cosgrove ring (32 mm) was added because the mitral valve annulus was dilated. The patient's postoperative course was uneventful and echocardiography after surgery demonstrated no MR. An isolated cleft of the anterior mitral leaflet is a rare cause of MR and in this case, direct closure of the cleft with additional annuloplasty gave a good functional result.

Adult↗

PubMed2004

Screening cost for abdominal aortic aneurysms: Japan-based estimates.

PURPOSE: The aim of this study was to evaluate the screening procedures in Japan economically focusing on the screening costs and the hospital costs for abdominal aortic aneurysm (AAA) surgery. METHODS: A total of 10,057 residents, 60 years of age or older, including 4 247 men and 5 810 women, participated in the screening test for AAA using ultrasound. RESULTS: Aneurysms were detected in 34 participants, including 32 men and 2 women. The detection rate of AAA was 0.8% in men, 0.03% in women, and 0.3% in total. It cost 8 US dollars to screen each participant, and the cost to detect each aneurysm was thus estimated at 1,250 dollars in men, 23,240 dollars in women, and 2,366 dollars in total. The difference in the mean hospital cost between ruptured and nonruptured AAA was 21,833 dollars in our recent cases. Obesity, male sex, and smoking habits were all significant risk factors for AAA. CONCLUSION: Screening for AAA using ultrasound is useful not only for the early detection of AAA but also for a reduction in the overall medical cost.

Aged↗

PubMed2003

Pericardiectomy to treat constrictive pericarditis in a patient with hyperbilirubinemia: report of a case.

An 18-year-old man was admitted to our hospital with abdominal distension and edema of both legs. His total serum bilirubin level was 5.2 mg/dl. Echocardiography showed impaired left ventricular contraction, and computed tomography showed a thickened pericardium with massive pleural effusion and ascites. Cardiac catheterization showed both a dip and a plateau in the right ventricle pressure curve, based on which we diagnosed constrictive pericarditis. The selected treatment option was a pericardiectomy. We dissected the thickened pericardium, which was about 7-10 mm thick, and removed as much as possible through a median sternotomy without cardiopulmonary bypass. Postoperatively, his hemodynamics and renal dysfunction improved, and the serum bilirubin level gradually decreased. We report this case to show how pericardiectomy was effective not only for improving this patient's hemodynamics, but also for resolving his hyperbilirubinemia. The relevant literature is reviewed following this case report.

Adolescent↗

PubMed2002

The optimal pressure for initial flush with UW solution in heart procurement.

OBJECTIVE: University of Wisconsin (UW) solution is widely used in organ preservation. Some investigators have reported that high pressure during initial flush with UW solution may induce vasoconstriction and endothelial damage, because of its high potassium content and high viscosity. However, using lower pressure during the initial flush may lead to irregular distribution of the solution and incomplete flushing of blood components from coronary vascular beds. This experimental study evaluated the effects of a range of initial flush pressures during heart procurement, followed by orthotopic transplantation of the graft after 12 hours of preservation. MATERIALS AND METHODS: Twelve pairs of adult mongrel dogs, weighing 9 to 14 kg, formed the recipient-donor combinations. After determining hemodynamic status by measuring cardiac output, left ventricular pressure (LVP), and maximum positive and negative change in LVP (+/-LVdP/dt), donor hearts were excised. Coronary vascular beds were flushed with 4 degrees C UW solution at a pressure of 60 mm Hg in the low-pressure group (n = 6) and at 120 mm Hg in the high-pressure group (n = 6). After 12 hours of cold preservation, orthotopic transplantation was performed using cardiopulmonary bypass (CPB). The hemodynamics of the transplanted graft were assessed by comparing recovery rates (%) from donor hearts 2 hours after weaning from CPB. Endothelin-1 (ET-1) levels were measured in the blood obtained from the coronary sinus 30 minutes after reperfusion. The transplanted grafts were then harvested for histologic study and measurement of adenosine triphosphate (ATP) content. RESULTS: Cardiac output, LVP, LVdP/dt and myocardial tissue ATP content were significantly better (p < 0.05) in the high-pressure group than in the low-pressure group. We found no significant differences in ET-1 levels between the groups. Transmission electron microscopic findings revealed that degeneration of the mitochondria was less extensive in the high-pressure group than in the low-pressure group. We observed no obvious ultrastructural damage to the endothelial cells in either group. CONCLUSION: When using UW solution in heart procurement, high pressure is better to completely wash out the blood components and distribute the solution.

Adenosine↗

PubMed2002

Early results and operative considerations of endoventricular circular patch plasty for ischemic cardiomyopathy.

Seven patients with ischemic cardiomyopathy who underwent elective endoventricular circular patch plasty (EVCPP) were included in this study. The mean age of the patients at the time of surgery was 63 years old. All seven patients had anterior left ventricular aneurysms following old myocardial infarction. Two patients were graded NYHA class II, 4 patients class III, and one patient class IV. EVCPP was performed under cardiac arrest with moderate hypothermia in five patients. The two most recent patients underwent EVCPP under on-pump beating and normothermia. Coronary artery bypass grafting was conducted in all cases and the mean number of grafts was 1.8, ranging from one to three. The mitral valve was replaced in one patient. One patient died of myonephrotic metabolic syndrome caused by ischemia of the lower limb. In the follow-up of six patients, the left ventricular end-diastolic volume index (LVEDI) decreased significantly from 128 +/- 31 mL/ m2 to 108 +/- 37 mL/m2. Left ventricular end-systolic volume index (LVESI) decreased in five patients. Left ventricular end-diastolic and end-systolic diameter remained unchanged after surgery. The left ventricular ejection fraction (LVEF) increased from 0.28 +/- 0.08 to 0.321 +/- 0.1. LVESI and LVEF did not improve in one patient with a large residual dyskinetic area at the distal LV septum. A residual dyskinetic area at the distal LV septum was observed in two of four patients who underwent EVCPP under cardiac arrest. This condition, however, was not detected in two patients who underwent EVCPP under on-pump beating conditions. In the follow-up study, the grade of NYHA functional classification improved in all six patients. In conclusion, EVCPP under on-pump beating is a realistic and effective procedure with which to complete ideal LV geometry and promote good results in patients with ischemic cardiomyopathy.

Aged↗

PubMed2001

The Effect of Coronary Perfusion with an Oxygenated Celsior Solution on 12-hour Cardiac Preservation.

Celsior is a new extracellular-type cardiac preservation solution. We recently developed an apparatus for preservation using low-pressure continuous coronary perfusion. The purpose of this study was to investigate the efficacy of coronary perfusion with an oxygenated Celsior solution using the new apparatus for prolonged cardiac preservation. Adult mongrel dogs weighing 9-13 kg were divided into two groups: the coronary perfusion group (CP; n = 5) and the simple immersion group (SI; n = 7). The coronary vascular beds were washed out with a 4 degrees C Celsior solution following cardiac arrest using the same solution, and their hearts were excised. In the CP group, the graft was immersed in a 4 degrees C Celsior solution and perfused with the same oxygenated solution. In the SI group, the graft was simply immersed in a 4 degrees C Celsior solution. beta-adenosine triphosphate (beta-ATP), phosphocreatine (Pcr), inorganic phosphate (Pi) levels and myocardial pH (pHi) were measured immediately after excising the heart, and at 3, 6, and 12 hours after preservation. beta-ATP, Pcr, and Pi values were expressed as a percentage of control values, which were measured immediately after excising the heart. beta-ATP/Pi and Pcr/Pi levels were significantly higher in the CP group than in the SI group at 6 and at 12 hours after preservation. The pHi levels during preservation were significantly higher in the CP group than in the SI group. Low-pressure hypothermic coronary perfusion with an oxygenated Celsior solution is effective for long-term heart preservation. </hea

Journal Article↗

PubMedDate not supplied

Effects of nutrient and hemoglobin enriched cell free perfusates upon ex vivo isolated rat heart preparation.

We evaluated the effects of nutrient enriched medium and hemoglobin based oxygen carrier (HBOC) upon myocardial functional recovery after 15 minutes of warm ischemia in an isovolumic Langendorff rat heart model. Hearts (n = 8/group) were perfused at constant pressure (90 mm Hg) with Krebs-Henseleit buffer or HEPES modified cell culture medium (M199) in the absence and presence of HBOC. Hearts received 15 minutes of normothermic no flow ischemia followed by 60 minutes reperfusion. Hemodynamics, coronary flow, and tissue water content were measured, and microscopic evidence of injury including TUNEL assay was assessed. Preischemic left ventricular performance (left ventricular developed pressure and maximum rate of positive and negative change in systolic pressure) and coronary flow were similar among groups. At 60 minutes of reperfusion, M199 alone provided more stable and complete left ventricular systolic and diastolic functional recovery than any other perfusate. Coronary flow rates reflected left ventricular function observed under each perfusate condition. TUNEL assay showed arterial endothelial cell death in some hearts perfused with HBOC. Tissue water content did not reflect functional recovery. The combination of M199 and HBOC was associated with poor recovery and elevated perfusate methemoglobin. In this system, postischemic dysfunction is prevented by components in M199. Added HBOC does not improve functional recovery and negates the salutary effects of M199, possibly by augmenting methemoglobin formation.

Animals↗