Postoperative administration of landiolol hydrochloride for patients with supraventricular arrhythmia: the efficacy of sustained intravenous infusion at a low dose.

The purpose of this study was to investigate the efficacy of landiolol hydrochloride, a short-acting beta(1) blocker, by initiating its administration at a low dose (5 microg kg(-1) min(-1)) in patients with postoperative supraventricular arrhythmia. The efficacy of landiolol was evaluated in 38 patients who, after developing postoperative atrial flutter or fibrillation, with sinus tachycardia and two patients who had a history of paroxysmal atrial fibrillation with frequent atrial extrasystole. The heart rate and blood pressure before and 2 h after the administration of landiolol were compared. A return to the sinus rhythm from supraventricular arrhythmia was noted in 89%. The heart rate was reduced from 137+/-26 bpm (before landiolol administration) to 93+/-18 bpm (2 h after the start of the medication, P<0.01). As an agent to correct an arrhythmic condition, landiolol successfully raised the systolic blood pressure from 108+/-24 mmHg (before medication) to 120+/-19 mmHg (2 h after the medication was started, P<0.05). Continuous intravenous infusion of landiolol at a low dose was found to be effective for postoperative supraventricular arrhythmia.

Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression.

Dissolved organic matter (DOM) in seawater can be defined as the fraction of organic matter that passes through a filter of sub micron pore size. In this study, we have examined the effect of DOM of deep seawater (DSW) from Pacific Ocean on platelet aggregation and atherosclerosis progression. DSW was passed through a series of filters and then through an Octadecyl C18 filter; the retained substance in ethanol was designated as C18 extractable DOM (C18-DOM). Our studies showed that C18-DOM treatment inhibited platelet aggregation, P-selectin expression and activity of COX-1 significantly. C18-DOM increased the expression of anti-atherogenic molecule namely heme oxygenase-1 in endothelial cells and all these data showed that C18-DOM is exhibiting aspirin-like effects. Moreover our in vivo studies showed that C18-DOM feeding slowed remarkably the progression of atherosclerosis. Our study demonstrated a novel biological effect of oceanic DOM, which has several important implications, including a possible therapeutic strategy for atherosclerosis.

Biphasic elevation of bilirubin oxidation during myocardial ischemia reperfusion.

BACKGROUND: The time course of oxidative stress involving nitric oxide (NO) after myocardial ischemia reperfusion (MIR) has not been elucidated in detail, so the present study was designed to assess the dynamics of oxidative stress after MIR, urinary excretion of oxidized bilirubin metabolites (ie, biopyrrins) and their generation in various organs. METHODS AND RESULTS: Rat models of MIR were created by occluding the left coronary artery for 30 min followed by 48 h of reperfusion. Levels of urinary biopyrrins increased biphasically at 8 h and 24 h after MIR. Biopyrrins were upregulated in the lungs at 8 h after MIR, according to immunohistochemistry and ELISA, and at 24 h biopyrrin expression was increased in the heart and lungs. The NO synthase inhibitor, NG-monomethyl-L-arginine, significantly diminished biopyrrin synthesis in the heart and lungs at 24 h, but not in the lungs at 8 h after MIR. Hemodynamic assessment revealed increased left ventricle end-diastolic pressure, suggesting that lung congestion influences pulmonary biopyrrin formation. CONCLUSIONS: The dynamics of urinary biopyrrins might reflect earlier biopyrrin generation in the lungs and delayed formation in both the lungs and heart when NO is involved. Therefore, urinary biopyrrins can serve as a useful marker of systemic oxidative stress after MIR.

The local injection of peritoneal macrophages induces neovascularization in rat ischemic hind limb muscles.

Macrophages play a pivotal role in the development of newly formed vascular networks, in addition to their normal immunological functions. This research focuses on peritoneal macrophages as a novel source in cell implantation therapy for ischemic diseases. In this study, production of angiogenic growth factors by peritoneal macrophages and its in vivo effect of neovascularization were evaluated. Mononuclear cells from the peritoneal cavity (P-MNCs) enriched with macrophages were isolated and stimulated with hypoxia and interleukin-1beta (IL-1beta) to mimic an ischemic tissue environment in vitro. Expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) of mRNA in P-MNCs was apparently enhanced by hypoxic stimulation, and the production of VEGF protein was also augmented by hypoxia and IL-1beta. A rat ischemic hind limb model was created and P-MNCs (8 x 10(6)/limb) were injected into the ischemic muscles. The blood flow, which was assessed using the colored microsphere method, showed that the percentage blood flow was significantly increased by P-MNCs injection 4 weeks after surgery (48.3 +/- 16.8% in noninjected ischemic limb vs. 84.3 +/- 13.0% in the P-MNCs-injected limb). A histological analysis revealed that the number of capillaries detected by alkaline phosphatase staining was increased in the P-MNCs group 4 weeks after injection. Furthermore, the number of alpha-smooth muscle actin-positive vessels also showed a significant increase following P-MNC injection. The injected P-MNCs labeled with fluorescence were detected in the interstitial space of ischemic muscles, and VEGF protein expression of the implanted cells was confirmed by immunohistochemistry. These results indicate that peritoneal macrophages stimulate capillary formation and arteriogenesis in the ischemic limbs, possibly through the production of angiogenic growth factors. These findings suggest that the physiological angiogenic property of peritoneal macrophages could therefore be utilized for neovascularization in cell implantation therapy.

Inhibition of neointimal hyperplasia development by MCI-186 is correlated with downregulation of nuclear factor-kappaB pathway.

BACKGROUND: Atherosclerosis is a progressing inflammatory response mediated by various signaling molecules among which nuclear factor kappaB (NF-kappaB) is thought to have a pivotal role. This study demonstrated the efficacy of antioxidant MCI-186 in preventing the progression of atherosclerosis by inhibiting signaling molecules such as NF-kappaB. METHODS AND RESULTS: Balloon injury of intima was performed in the right common carotid artery of Japanese male white rabbits, which were then fed a 1% high cholesterol diet for 4 weeks, after assigning them to either the control (n=7) or MCI-186 (0.5 mg .kg(-1) . day(-1), n=7) group. Histological analysis revealed a reduction in neointimal thickness and lipid deposition in the subendothelial area of the MCI-186 group. Immunohistochemical analysis revealed attenuation of E-selectin expression, macrophage migration and proliferation of smooth muscle cells in the MCI-186 treated group. In in vitro studies, rabbit aorta smooth muscle cells were incubated with rIL-1betain either the presence or absence of MCI-186. MCI-186 significantly inhibited rIL-1beta-induced proliferation of smooth muscle cells from rabbit aorta, as well as the activation of NF-kappaB. Moreover, western blot analysis showed the inhibitory action of MCI-186 on the nuclear translocation of NF-kappaB in human umbilical vein endothelial cells under rIL-1betastimulation. CONCLUSIONS: MCI-186 could provide a novel therapeutic strategy for atherosclerosis by inhibiting the NF-kappaB pathway.