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Biomedical subjects

M Kusagawa

Publications and source records attributed to M Kusagawa.

At least 37 records · Page 2Linked to original sources

Ca2+(-)dependent and Ca2+(-)independent vasorelaxation induced by cardiotonic phosphodiesterase inhibitors.

Cardiotonic agents that belong to a group of phosphodiesterase inhibitors--vesnarinone, amrinone, enoximone, pimobendan, MS-857 and E-1020--inhibited the 35 mM KCl- and 10(-7) M norepinephrine-induced contractions of helical strips from rat thoracic aorta in a concentration-dependent manner. In the absence of extracellular Ca2+, 10(-7) M phorbol 12,13-dibutyrate caused a sustained contraction of the muscle strip without an increase in intracellular Ca2+ level ([Ca2+]i). The phorbol 12,13-dibutyrate-induced contractions in Ca2+(-)free buffer were also inhibited by the cardiotonic phosphodiesterase inhibitors. A cyclic GMP-inhibited cyclic nucleotide phosphodiesterase was partially purified from rat aorta and the activity of the phosphodiesterase was inhibited by the cardiotonic agents. The inhibitory effect of these agents on the KCl-, norepinephrine-and phorbol 12,13-dibutyrate-induced contractions showed good correlations to the concentrations of the agents producing 50% inhibition (IC50) of cyclic GMP-inhibited cyclic nucleotide phosphodiesterase. Vesnarinone inhibited the norepinephrine-induced contraction with a decrease in [Ca2+]i, but inhibited the phorbol 12,13-dibutyrate-induced contraction in Ca(2+)-free buffer without significant changes in [Ca2+]i. Dibutyryl cyclic AMP and NKH477 also inhibited the phorbol 12,13-dibutyrate-induced contraction in Ca(2+)-free buffer without significant changes in [Ca2+]i. The six cardiotonic phosphodiesterase inhibitors increased the cyclic AMP contents of the muscle strips. These results suggest that the inhibitory actions of these cardiotonic phosphodiesterase inhibitors on cyclic GMP-inhibited cyclic nucleotide phosphodiesterase may cause vasorelaxation through a decrease in [Ca2+]i and an inhibitory effect on a Ca(2+)-independent contractile process (or a decrease in Ca(2+)-sensitivity of contractile elements).

Animals↗

Aneurysm of the inferior mesenteric artery.

The case of a 48-year-old man with an aneurysm of the inferior mesenteric artery is described. This aneurysm was associated with extensive vascular disease characterized by multiple sites of stenosis and occlusion in addition to an upper abdominal aortic aneurysm. Repair of both aneurysms and reconstruction of the left renal artery and inferior mesenteric artery, which supplied all splanchnic circulation, were performed. The aetiology of the disease was thought to involve Takayasu's arteritis.

Aneurysm↗

Measurement of myocardial blood flow in coronary artery bypass surgery.

It is now possible experimentally to measure myocardial blood flow of the beating heart using a helium-neon (He-Ne) laser Doppler flowmeter. A myocardial probe was redesigned to reduce its size and weight, and a method devised of fixing the probe to the beating cardiac surface to allow its clinical application. This modified laser flowmeter was used on 36 patients with ischaemic heart disease to measure myocardial blood flow before and after revascularization. Flow was measured in the right and left ventricles while patients were in a haemodynamically stable state as determined by electrocardiography, heart rate, blood pressure and double product (heart rate x systolic blood pressure). No significant difference was found between the mean(s.e.m.) preoperative and postoperative flow volume at the anterior wall of the right ventricle (77(15) versus 81 (12)ml/min per 100 g), which did not undergo revascularization, but mean(s.e.m.) myocardial blood flow at the ischaemic left ventricle increased significantly (from 68(15) to 88(13) ml/min per 100 g; P < 0.01). There was also no significant difference between preoperative and postoperative values of haemodynamic parameters of coronary blood flow. In conclusion, a means to measure myocardial blood flow with He-Ne laser Doppler flowmetry has been devised which shows coronary artery bypass grafting to increase myocardial blood flow in the ischaemic myocardium.

Adolescent↗

[Selective cerebral perfusion and pharmacological cerebral protection in the patients with aortic arch aneurysm].

We have developed the protocol for selective cerebral perfusion (SCP) and pharmacological cerebral protection, and used it successfully in cases of aortic arch aneurysm. The subjects of the present study were 34 patients (28 males, 6 females) whose aortic arch aneurysm were surgically treated. Preoperative brain CT and brain scintigram showed high incidence of brain ischemia. However only 4 patients experienced a neurological episode. We conclude that our SCP technique and pharmacological cerebral protection are useful component to surgery of the aortic arch.

Adult↗

A new instrument for pulmonary resection: the bipolar Nd-YAG laser dissector.

A bipolar Nd-YAG laser dissector was developed to quickly dissect or resect organs, and the possibility of laser pulmonary dissection without scissors and ligation threads was studied experimentally. Pulmonary tissue was completely and easily divided using a bipolar laser handpiece, and the dissected edge was perfectly sealed. Leakage of air and blood from the edge was not induced and no additional stitching was required. Histological examination of the dissected edge revealed tissue remodeling after laser irradiation. The formation of amorphous layers, including vacuoles, was peculiar to the fusion-coagulation area, and alveolar atelectasis and capillary obstructions were characteristic of the degenerative area. When tissue dissection was performed by laser vaporazation, tissue remodeling seemed to be the most important factor in the prevention of leakage. In conclusion, we can effectively and quickly resect pulmonary tissue using the bipolar Nd-YAG laser dissector without scissors and without ligation threads.

Aluminum↗

Hematological problems during the use of cardiac assist devices: clinical experiences in Japan.

Hematological changes occurring during use of left ventricular assist devices (LVADs) were evaluated in 3 patients suffering from postcardiotomy cardiogenic shock. LVAD treatment ranged from 6 to 9 days. During the procedure, no anticoagulants were used in the first two cases, while in the third case, a protease-inhibiting agent, nafamostat mesilate (FUT-175), was used. In the first two cases without any anticoagulants, fibrinopeptide A (FPA) and thrombin-antithrombin III complex (TAT) increased markedly over the course of LVAD treatment, suggesting the excessive activation of the coagulatory system. The fibrinolytic system also became activated during LVAD treatment as was indicated by a marked increase in FDP-D-dimer and alpha 2 plasmin inhibitor-plasmin complex (PIC). Continual decreases observed in Factor XII and prekallikrein indicate that the coagulofibrinolytic activation occurring during LVAD treatment is presumably the result of contact activation of these factors due to interaction of blood with the internal surface of the LVAD. In the third case with FUT-175, both coagulation and fibrinolysis were successfully maintained at minimum levels as was demonstrated by the extremely low levels of these molecular markers. There was also no significant consumption of any contact factors. FUT-175 looks promising as an anticoagulant during the use of cardiac assist devices.

Aged↗

[Left atrial myxomas: clinical characteristics, evaluation and considerations in classifying tumors].

Eleven patients underwent surgical excision for left atrial myxomas. Clinical symptoms, coronary angiographic findings and operative procedures were evaluated. Myxomas were classified into two types based on macroscopical findings, and clinical characteristics of these two types were analyzed. Seven cases (64%) classified as "lobular-type myxomas" were seen as lobulated, gelatinous and fragile. Four cases (36%) were classified as "round-type myxomas" were round and elastic soft. Primary symptoms included dyspnea on exertion in five cases (45%) and neurological disturbances in six cases (55%). Brain emboli were found in four patients by CT scan, and were classified as lobular-type myxomas. These eleven myxomas successfully removed in all cases. Four of these myxomas, which were pedunculated with fine fibrous stalks, were shaved along the base at the atrial septum or free wall. Others were excised completely along with a portion of the adjacent septum. Microscopic examination of the operative specimens revealed that two lobular-type myxomas with broad-based attachment to left atrial septum had invaded the atrial septum. All patients are doing well and have had no signs of myxoma recurrence at postoperative periods ranging from 10 months to 12 years (mean follow-up 5.3 years). Seven patients underwent selective coronary angiography due to a diagnosis of a coronary artery disease. All coronary angiograms were normal in all cases. In five (71%) of these seven, abnormally dilated atrial branches were seen as supplying the tumor. In two cases with round-type myxomas, neovascularity was evident and was made up of clusters of tortuous vessels with tumor blush.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Reconstructive surgery for mitral regurgitation caused by degenerative disease--indications for expansion and early clinical outcomes].

Between January 1983 and June 1990, there were 48 patients who underwent surgery for mitral regurgitation due to degenerative diseases. Among these, 20 patients received mitral valve repair. Overall operative mortality was 5% for patients who underwent valve repair, and 7.1% for those who underwent valve replacement. We standardized a maneuver for valve repair in August 1988 in an attempt to expand its indications. There were 35 patients who underwent surgery prior to that date (group 1), and 13 patients after that date (group 2). There were nine patients (25.7%) in group 1 and 2 patients (84.6%) in group 2 who underwent valve repair. Among these, one patient (11%) in group 1 died within 30 days after the operation, but there were no surgical deaths for any patients in group 2. In addition, one patient (11%) in group 1 and one (9%) in group 2 required another operation for valve replacement. Doppler echocardiographic studies performed postoperatively in 18 patients who had undergone valve repair showed that 13 (72.2%) had no regurgitation, 4 (22.2%) had trivial regurgitation, and 1 (5.6%) had mild regurgitation. Postoperative valve area as determined by continuous-wave Doppler echocardiography was 3.7 +/- 1.1 cm2 (mean +/- SD) for patients who had undergone reconstruction and 3.1 +/- 0.7 cm2 for those who had undergone replacement.

Adolescent↗

[Clinical evaluation of treatment for prosthetic valve endocarditis and analysis of factors affecting outcome of surgical therapy].

We analyzed the outcome for 18 patients with prosthetic valve endocarditis (PVE) treated between 1965 and 1990, 17 of whom had undergone valve replacement with mechanical prosthetic valves and one of whom had a bioprosthesis. Two patients developed infection within 60 days after surgery, and 16 thereafter. Fifteen patients received combined medical and surgical therapy and three medical therapy. In 14 patients, surgery had been performed during active infection. Mortality rate of those who had received combined medical and surgical therapy was 27%, and that of those who had received medical therapy was 67%. At operation, para-annular abscess was around the mitral prosthesis was found in three patients and around the aortic prosthesis in eight. Seven patients required reoperation for postoperative paravalvular leakage, in six, para-annular abscess had been found at the operation for PVE, and in one para-annular abscess had been noted. One patient who had undergone reoperation had developed reinfection after the first surgery and died due to multiple organ failure after the second operation (Danielson's translocation technique). In one patient who had complete loss of supporting tissue because of severe para-annular abscess, we had performed aortic valve replacement by implanting the aortic valve prosthesis into the left ventricle with Dacron felt-supported sutures placed in the mitral annulus and the muscles of the left ventricular outflow tract. This patient showed no postoperative infection or no paravalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Application and limitation of laser pulmonary resection].

A new type of laser handpiece, bipolar Nd-YAG laser dissector, was experimentally applied for laser pulmonary resection of the dogs. The lung was completely and easily divided by the use of the bipolar laser dissector without scissors. The dissected edge without cartilages was completely sealed and additional stitches by threads was not required. But massive leakage of air was obvious from the dissected bronchus. The cause of unsuccessful sealing of the bronchus was supposed to be an unequal tissue remodeling, because of a very high melting point of cartilages compared with other tissue. We conclude that the bipolar Nd-YAG laser dissector contributes segmental pulmonary resection at the level without bronchi and it should not be applied for pulmonary resection containing bronchial cartilages.

Animals↗

Inactivation of DNA polymerase beta by in vitro phosphorylation with protein kinase C.

The Mr = 38,300 polypeptide of the purified recombinant rat DNA polymerase beta served as an excellent substrate for protein kinase C (PKC) in vitro but not for the catalytic subunit of cAMP-dependent protein kinase. The phosphorylation by PKC resulted in inactivation of DNA polymerase beta activity, and recovery was achieved by dephosphorylation with alkaline phosphatase. Since the phosphorylated DNA polymerase beta was retained with use of a single-stranded DNA-cellulose column, inactivation might occur at a site different from that for the DNA binding. Amino acid sequence analysis of the phosphopeptides revealed that the phosphorylated sites were 2 serine residues at positions 44 and 55 from the NH2 terminus, either or both of which might be involved in the catalytic activity of DNA polymerase beta. Thus, the inactivation of the DNA repair enzyme, DNA polymerase beta, by PKC may be an important process in the modification of DNA metabolism in the nucleus through signal transduction processes.

Alkaline Phosphatase↗

Rupture of a benign mediastinal teratoma into the right pleural cavity.

A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid. The activity of the amylase is thought to be the most likely cause of the rupture. High levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors.

Adult↗

Laser measurement of myocardial blood flow.

A He-Ne laser flowmeter (wavelength: 632.8 nm, power: 2 mW) has already been used to measure blood flow in skin, muscle, and mucosa. However, the application of this flowmeter for the beating heart has been left undeveloped due to its difficulty. For the purpose of establishment of the laser measurement of myocardial blood flow, we redesigned a flow probe to be small and light and used a connecting paste to support the subepicardial flow probe. After resolving many obstacles, the noninvasive and real-time blood flow measurement of the beating heart was made possible. The flow volume in subendocardial myocardium was greater than the volume in subepicardial myocardium, and the average ratio of subendocardial flow to subepicardial flow was 1.62 +/- 0.21.

Animals↗

The enhancement of myocardial protection through an acalcemic storage solution containing nicardipine, a potent calcium channel blocker. A basic study using rat ventricular myocytes.

Adult rat ventricular myocytes were used as a model system for investigating the direct effects of nicardipine, a potent calcium-channel blocker, on preservation of the heart during periods of simple cold storage. Cells were stored at 4 degrees C for 24 hr with an acalcemic storage solution. The superfusate then was exchanged with hypoxic Tyrode solution (1.8 mmol/L CaCl2). After 2 hr of hypoxia at 20 degrees C, cells were reoxygenated and simultaneously warmed to 37 degrees C. The addition of nicardipine to both the storage solution and Tyrode solution resulted in the highest percentage of viable cells (70.5%). Using either the storage solution or Tyrode solution containing the compound, the percentages of viable myocytes were 51.9% and 52.2%, respectively. In the absence of the drug in either solution, the percentage was 38.0%. The effect of diltiazem, another potent calcium-channel blocker, was examined using the same experimental procedure. The addition of diltiazem to Tyrode solution elevated the viability of ventricular myocytes, but addition to the storage solution showed no cardioprotective effect. Moreover, the addition of 8-bromo cyclic GMP to the storage solution resulted in a cardioprotective effect. These results suggested that nicardipine exerts a direct effect on myocardial protection in hypothermic and acalcemic storage solution and that the pharmacological effect of nicardipine depends on a mechanism other than its calcium-channel blocking action.

Animals↗

Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure.

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

Aged↗

[Surgical treatment of the so-called "galloping type" small size carcinoma of the lung].

We experienced twelve cases of non-small cell carcinoma of the lung of the so-called "galloping type" small size carcinoma (less than or equal to 2 cm). Ten cases presented with mediastinal lymph node metastasis and two cases with distant metastasis. Solitary lymph node metastasis observed in almost half of the cases and lymph node metastasis in peculiar lymphatic regions (#3 a) seen in two cases, were the prominent characteristics of the lymphatic pathway dissemination showed by this type of cancer in advanced clinical stage. The prognosis was good, with 3 years and 5 years survival rate of 72.2% and 54.1% respectively. According to these results, we consider that, if the clinical stage is favorable, the surgical treatment must be indicated in all cases of these advanced small size carcinoma of the lung.

Adult↗