Takao Shimanuki

Ibuprofen in the Prevention of Experimentally Induced Postoperative Adhesions

Using a five-dose 70 mg/kg regimen, of ibuprofen significantly reduced both overall adhesion formation and the severity of adhesions when given to rabbits in the immediate postoperative period. This reduction was apparently time- and dose-related, as animals given smaller doses of ibuprofen at subsequent intervals had a tendency toward more adhesions and also more severe adhesions. A positive correlation was found between the severity of adhesions and the formation of new glycosaminoglycans and collagens.

Modulation of leukotaxis by ibuprofen: a quantitative determination in vivo

The purpose of this study was to evaluate the rabbit anterior eye chamber as a quantitative measure of leukotaxis using51Cr-labeled homologous leukocytes and then to determine the effects of ibuprofen onN-formyl-methionyl-leucyl-phenylalanine (FMLP) -induced leukotaxis. Leukocyte accumulation was assessed at various intervals (0–24 h) after instillation of FMLP (10−4 M, 40μl) and at various doses (FMLP 10−6–10−4 M). New Zealand white rabbits (2.6–3.0 kg) were treated with ibuprofen for three days with the following regimens: 8.0, 17.5, 35.0, 70.0 mg/kg/day. Leukocyte quantitation was determined using a direct cell count and recovery of51Cr-labeled leukocytes from anterior eye chamber aspirations 3 h after their injection into the systemic circulation. FMLP induced a dose-dependent accumulation of leukocytes. Leukocyte influx into the anterior eye chamber increased between 2 and 4 h after FMLP instillation, peaking between 4 and 6 h, then resolving after 8 h. Ibuprofen inhibited leukocyte accumulation into the anterior eye chamber in a dose dependent fashion with a maximum (90.0±1.4%, X±SEM) inhibition with 70 mg/kg/day and an ID50 of 8 mg/kg/day. In conclusion, the anterior eye chamber FMLP-stimulated leukotaxis assay is useful to evaluate the role of pharmacologie agents. Here, ibuprofen was found to inhibit leukotaxis in a dose-dependent manner.

A clinical study of postoperative infections following open-heart surgery: occurrence and microbiological findings in 782 cases.

A total 782 consecutive patients underwent open-heart surgery with CPB between January, 1979 and December, 1988, at the Yamagata University Hospital. We assessed the incidence of postoperative infections in relation to age, the duration of surgery and antibiotic prophylaxis, and examined the causative organisms, after which the types of infecting flora were compared between the 1st period, from 1979 to 1983 and the 2nd period, from 1984 to 1988.Postoperative infection occurred in 104 of the 782 patients (13.3 per cent); in the form of a wound infection in 41 (5.2 per cent), pneumonia in 33 (4.2 per cent), urinary tract infection in 9 (1.2 per cent), prosthetic valve endocarditis in 6 (0.8 per cent), and other infections in 15 (1.9 per cent). Patients aged under 12 months or over 60 years showed a higher incidence of infection, being 17.4 per cent and 19.2 per cent, respectively. Patients who underwent an operation of over 8 hours duration also had a significantly higher incidence compared to those whose operation time was less than 4 hours, being 32.9 per cent and 6.3 per cent, respectively (p<0.0001). There was no significant difference in the incidence of postoperative infection between patients given or not given preoperative prophylaxis. A total 123 species of organisms were isolated from the 104 patients, 52.8 per cent being gram-negative bacteria (GNB), and 43.9 per cent grampositive bacteria (GPB), and a remarkable increase in the incidence of GPB was seen in the 2nd period compared to the 1st period from 31.7 per cent to 50.0 per cent.There has been a recent increase in the number of high risk patients compromised by the severity of an underlying disease. Thus, to control infection, the surgical environment and aseptic technique seem more important than antibiotic prophylaxis.

Spontaneous splenic rupture after mitral valve replacement for infective endocarditis

We report a successful treatment of massive bleeding due to spontaneous splenic rupture after mitral valve replacement. A 61-year-old man was admitted to our hospital for intermittent high fever. An echocardiogram demonstrated a large vegetation on the posterior cusp of the mitral valve and mitral regurgitation of moderate degree. Staphylococcus epidermidis was cultured from his arterial blood. He underwent a mitral valve replacement after 3 weeks of antimicrobiological therapy with penicillin G crystalline and minocycline hydrochloeide. The patient fell into hemorrhagic shock on postoperative day 11 after complaining dull pain on his left upper abdomen for 3 days. A computed tomography demonstrated a splenic rupture and massive hematoma in the retroperitoneum. A splenic arterial embolization was done before splenectomy. The blood and clot of 2800 g were sucked from peritoneal and retroperitoneal cavities. There were no mycotic aneurysms nor abscess but the torn capsule on the swelled and partially necrotic spleen. The patient discharged uneventfully on postoperative day 43. Infective endocarditis frequently causes splenic infarction but rarely splenic rupture. Anticoagulation therapy after mitral valve replacement might have emphasized the bleeding in the patient.

Spontaneous rupture of the descending aorta through atherosclerotic plaque: Report of a case

Spontaneous rupture of the thoracic descending aorta is rare, and uniformly fatal without surgery. We report herein the case of a man in whom such a rupture was successfully treated with emergency surgery. We believe that the rupture in this patient was most likely associated with perforation through an atherosclerotic plaque of the descending aorta and was induced by sudden hypertension.

In vivo modulation of leukotaxis by non-steroidal anti-inflammatory drugs

Since non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for inhibition of inflammation, anin vivo assay for leukotaxis would be of use in comparing the biological activity effects of the agents. Here, the effects of 4 different NSAIDs onin vivo leukocyte accumulation was determined by quantitatingN-formyl-methionyl-leucylphenylalanine induced leukotaxis in the rabbit anterior eye chamber. New Zealand white female rabbits were treated for three days with the following regimens: ibuprofen or aspirin, 0.1, 1.0, 10.0 or 100.0 mg/kg/day, indomethacin or flurbiprofen, 0.01, 0.1, 1.0, or 10.0 mg/kg/day. Indomethacin and flurbiprofen significantly reduced leukotaxis in a dose of 10.0 mg/kg/day. Aspirin was associated with a weak inhibition of leukotaxis. Ibuprofen had biphasic effects, 1.0 mg/kg/day potentiated and 10 mg/kg/day inhibited leukotaxis, whereas leukocyte accumulation was uneffected by a high dose (100.0 mg/kg/day). These results suggest that modulation of leukotaxis by NSAIDs may reflect a differential dose-response sensitivity of lipoxygenase and cycloxygenase pathways.

Accelerated myocardial metabolic and functional recovery with terminal nicorandil-Mg cardioplegia in heart transplantation

SummaryCardiac reperfusion injury after heart transplantation or cardiopulmonary bypass has been difficult to control due to the variable degree of myocardial damage with respect to the length of ischemia and the complexity of the surgical procedure. Here, we evaluated the myocardial metabolic and functional recovery of hearts infused with a nicorandil vasodilator-magnesium (Mg) solution just prior to reperfusion (terminal cardioplegia). Donor hearts (20 dogs) were removed and immersed in a 4°C water bath containing 20 mEq/1 KCL-5% glucose for 6 hours, and then were transplanted to recipient dogs. Orthotopically transplanted dog hearts were either reperfused without any further treatment or received a terminal cardioplegic solution containing 8 mg/ 1 nicorandil, 30 mEq/1 Mg, and 50 g/1 glucose, which was infused at a pressure of 75 cm H2O for 2 minutes. During the reperfusion period, myocardial tissue PCO2 (t-PCO2) and calcium ion (t-Ca) were continuously monitored by an ISFET (ion-sensitive field effect transistor) sensor. Myocardial oxygen consumption and lactate flux were calculated/monitored at 5, 10, 20, and 40 minutes of reperfusion. Thereafter, myocardial function was evaluated at 45 minutes of reperfusion using LVSWI. Just after reperfusion, the treatment group (group B, n = 10) had a significantly greater coronary flow than the control group (Group A, n = 10, 35.0 ± 10.1; group B, 47.4 ± 8.5 ml/100 g/min, p < 0.025). Myocardial tissue PCO2 and calcium ion levels in group B were significantly decreased at 5 minutes of reperfusion (A: 110 ± 21 → 88 ± 16; B: 126 ± 24 mmHg → 44 ± 7 mmHg, t-PCO2, p < 0.001; A: 3.5 ± 0.7 → 3.2 ± 0.7; B: 2.7 ± 0.7 mM → 1.7 ± 0.6 mM, t-Ca, p < 0.001). Also, group B had better metabolic recovery, as evaluated by increased myocardial oxygen consumption and increased lactate flux. Thus, terminal nicorandil-Mg cardioplegia improved myocardial blood flow, which in turn markedly improved tissue acidosis, thereby reducing the extent of reperfusion injury.

Quadricuspid aortic valve illustrated by 64-slice multidetector computed tomography: Surgical treatment of a rare cause of severe aortic regurgitation

The quadricuspid aortic valve (QAV) is a rare congenital malformation that usually presents with aortic regurgitation (AR). The first case was reported in 1862. Most cases were diagnosed at the time of surgery or postmortem examination. With advances in imaging techniques, more cases have been diagnosed before surgery. We describe a 59-year-old man whose QAV had not been noted until the current admission. Transthoracic echocardiography revealed dilation of the left ventricle, severe AR, and suspected QAV. The QAV was confirmed by transesophageal echocardiography and 64-slice multidetector computed tomography. This case was a QAV with three equal cusps and one smaller cusp (type B in Hurwitz and Roberts classification). Because the cardiac catheterization and aortography showed severe AR and a QAV, the patient underwent elective surgery. The surgery consisted of replacing the QAV by a mechanical prosthesis. There were no post-operative complications. The patient revealed no symptoms in the post-operative 7 months.

Myocardial tissue pCO2 and calcium content during ventricular fibrillation and reperfusion periods

Forty-one patients who underwent cardiac surgery under conditions of systemic hypothermia and intermittent cold crystalloid potassium cardioplegia were studied, in order to elucidate the effects of ventricular fibrillation and reperfusion on the myocardium, by using the intramyocardial pCO2 and temperature sensor. All patients were assigned to 2 groups, namely; group A (21 cases), in which the time between the aorta declamping and defibrillation was under 10 minutes, and group B (20 cases) in which the time was over 10 minutes. In both groups A and B, myocardial pCO2 increased at the rate of 3.58±1.70 and 2.16±0.62 mmHg/min (p<0.05) after aorta declamping, respectively and the myocardial pCO2 decreased at the rate of 5.59±0.60 and 4.18±0.76 mmHg/min (p<0.05) after defibrillation, respectively. In group A, the myocardial calcium content, pre-CPB (cardio pulmonary bypass) was 10.98±1.62 nmol/mg/dry weight and at the time of aorta declamping it was 15.90±1.81 nmol/mg/dry weight (p<0.05). In group B, the myocardial calcium content, pre-CPB, was 14.62±2.15 nmol/mg/dry weight and at the time of aorta declamping it was 18.23±4.36 nmol/mg/dry weight (p<0.05). At both three and dix hours after the operation, the left ventricular work index per minute (LVWI) in group A showed better cardiac pump function than that in group B. We therefore conclude that when reperfusion is encountered, acidosis can be minimized by prompt defibrillation.

Ceftizoxime Level in the Myocardium (Right Atrial Muscle and Mitral Papillary Muscle) during Open Heart Surgery

We determined the level of sodium ceftizoxime (CZX) in the right atrium and mitral papillary muscle of 22 adults and 6 children undergoing open-heart surgery, 60 and 120 minutes after intravenous administration of this drug at the dosages of 2 grams for adults and 1 gram for children. The CZX level in the right atrial muscle after 60 minutes was 37.0 μg/g in adults and 51.0 μg/g in children. The CZX level in the papillary muscle of the mitral valve, determined at 120 minutes was 16.9 μg/g. In the present study, we measured the level of the antibiotic CZX in the myocardial tissue during open-heart surgery. The purpose of this was to determine the quantity in which the antibiotic is taken into the myocardial tissue.