Biomedical subjects

Kazuhiro Mizoguchi

Publications and source records attributed to Kazuhiro Mizoguchi.

4 recordsLinked to original sources

PubMed2004

[Ruptured non-dissection thoracic aortic aneurysms].

The number of patients with thoracic aortic aneurysm has been increasing in Japan. The annual report by the Japanese Association for Thoracic Surgery 2001 demonstrated that 4,133 patients underwent surgery for thoracic aortic aneurysm. Among them, ruptured cases consisted of 11% (460 patients) and its early mortality was 32%. At the emergency room, initial accurate diagnosis, using echocardiography and computed tomography (CT), is mandatory for the next step and catastrophic shock status should be corrected if possible, such as pericardiocentesis or transfusion. For patients with ruptured descending or thoracoabdominal aortic aneurysms, the endovascular stent-grafting should be first choice of treatment. Otherwise, patients should be sent for the operation room as quickly as possible for initialing cardiopulmonary bypass and for controlling bleeding. Special attention should be paid for not injuring the left lung after left thoracotomy. Mycotic false aneurysms, including the aorto-esophageal fistula and prosthetic graft infection, remained as one of challenging entities in aortic emergency. The standard treatment for this fatal disease resection of the infected both aneurysm and esophagus, and has been reconstruction with an extra-anatomical bypass, however, recent advancement of technologies, including allograft and tissue engineering might enable to have in situ reconstruction of the aorta.

Aortic Aneurysm, Thoracic↗

PubMed2002

Intestinal ischemia preconditions myocardium: role of protein kinase C and mitochondrial K(ATP) channel.

OBJECTIVE: The present study was designed to test the hypothesis that intestinal ischemia results in an early preconditioning against myocardial infarction and that the mechanism of the early preconditioning involves the activation of protein kinase C-mitochondrial K(ATP) channel signaling pathway in anesthetized rats. METHODS: Rats were either preconditioned with a 25-min occlusion of the superior mesenteric artery followed by 15 min of reperfusion or underwent a 40-min sham period. Subsequently, all rats were subjected to a sustained 30 min of coronary occlusion and 180 min of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. RESULTS: In sham-operated rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was 73+/-4% and 31+/-2%, respectively, and these were significantly reduced to 44+/-4% and 23+/-1% (P<0.01) after intestinal ischemia preconditioning. Intravenous injection of protein kinase C inhibitors chelerythrine (5 mg/kg) and staurosporine (50 microg/kg) or a specific mitochondrial K(ATP) channel inhibitor 5-hydroxydecanoate (5 mg/kg) 5 min before sustained myocardial ischemia abolished the preconditioning afforded by intestinal ischemia. However, hexamethonium, a ganglion blocker, did not attenuate the preconditioning. CONCLUSIONS: These data provide pharmacological evidence that protein kinase C and mitochondrial K(ATP) channel are involved in the mechanism of the early preconditioning induced by intestinal ischemia.

Alkaloids↗

PubMed2002

Amelioration of myocardial global ischemia/reperfusion injury with volume-regulatory chloride channel inhibitors in vivo.

BACKGROUND: Recently, the apoptotic volume decrease was suggested to be regulated by volume regulatory Cl- channels in cultured cell lines. We thus examined whether inhibition of volume-regulatory Cl- channels is cardioprotective, like caspase inhibition, by hindering the apoptosis of cardiomyocytes induced by global ischemia/reperfusion (I/R) in vivo. METHODS: We performed global ischemia for 8 min at 37 degrees C or 4 degrees C in isolated rat hearts, followed by 24-hr reperfusion via heterotopic heart transplantation. The heart tissue was examined by means of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, genomic DNA electrophoresis, and caspase-3 activity. Two blockers of volume-regulatory Cl- channels, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), and a broad-spectrum caspase inhibitor, benzoyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-Asp-DCB), were administered intravenously. Triphenyltetrazolium chloride (TTC) staining and ultrasound cardiography were performed to examine myocardial viability. The TTC-unstained region was assessed by means of horseradish peroxidase (HRP) infiltration and the TUNEL method. RESULTS: The transplanted hearts showed TUNEL-positivity and DNA laddering with a peak at 24 hr during reperfusion after ischemia at 37 degrees C, but not at 4 degrees C. NPPB and DIDS were as potent as Z-Asp-DCB for recovery of cardiac function and for blocking the appearance of TUNEL-positivity, DNA laddering, caspase 3 activity, and a TTC-unstained area. TTC-unstained areas were composed of either TUNEL- and slightly HRP-positive or TUNEL-negative and strongly HRP-positive cardiomyocytes. CONCLUSION: The present results demonstrated that myocardial DNA fragmentation, caspase activation, and loss of cardiac function after global I/R were blocked by NPPB and DIDS, similar to in the case of Z-Asp-DCB. These results suggest that inhibition of volume-regulatory Cl- channels is also effective for preventing cardiac I/R injury.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2002

Lipopolysaccharide triggers late preconditioning against myocardial infarction via inducible nitric oxide synthase.

OBJECTIVE: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) as a trigger in lipopolysaccharide (LPS)-induced late preconditioning against myocardial infarction. METHODS: Rats were pretreated intraperitoneally with two different doses of LPS (0.5 or 2.5 mg/kg) or normal saline (control) 24 h prior to lethal myocardial ischemia. Subsequently, all rats were subjected to a sustained 30-min coronary occlusion followed by 180-min reperfusion. In the second study, total RNA and protein were extracted from myocardium of the control and LPS-treated rats (after 4, 6 and 24 h of treatment) for reverse transcription-polymerase chain reaction and Western blot analysis. RESULTS: In LPS (2.5 mg/kg, but not 0.5 mg/kg)-treated rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was significantly reduced to 42+/-4 and 24+/-2% (P<0.01) compared with the control group. The cardioprotection was abolished by injection of dexamethasone (4 mg/kg x 2, i.p.) or the selective iNOS inhibitor aminoguanidine (300 mg/kg x 2, s.c.) before LPS treatment. The expression of iNOS mRNA and the iNOS protein significantly increased 4 and 6 h after administration of LPS (2.5 mg/kg), respectively. The increases in iNOS mRNA and protein were eliminated by dexamethasone. But the iNOS mRNA and protein were not detectable 24 h after administration of LPS (2.5 mg/kg). CONCLUSIONS: These data provide molecular and pharmacological evidence that LPS-induced late preconditioning against myocardial infarction is triggered by iNOS.

Analysis of Variance↗