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ABSTRACT: Naloxone hydrochloride is an agent capable of antagonizing respiratory depression and analgesic actions which are inherent to the opioid by competitively acting at opioid receptors. It greatly contributed to basic research on antagonistic action of opioid receptors due to its high affinity to opioid receptors, in particular, micro-receptor. Naloxone has been recommended as an analeptic agent at a guideline level for patients with revealed or suspicious opioid addiction. Further, it has also been used as a preventive and treatment agent for spinal cord ischemia. Moreover, even though it has been confirmed in 1980's that naloxone has vasopressor effect in septic shock, further clinical trials are required for its wide clinical application.
Masui. The Japanese journal of anesthesiology 01/2013; 62(1):5-9.
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Advances in experimental medicine and biology 01/2012; 737:239-43. · 1.09 Impact Factor
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ABSTRACT: The pleth variability index (PVI), which is calculated from respiratory variations in the perfusion index (PI), reportedly predicts fluid responsiveness. However, vasomotor tone fluctuations induced by nociceptive stimuli change the PI and may reduce the accuracy of PVI. The aim of this study was to confirm the effects of surgical stimuli on PVI.
Twenty-four patients were examined after the induction of general anesthesia. Heart rate (HR), mean arterial blood pressure (MBP), PI, PVI, stroke volume variation (SVV), and cardiac index (CI) were recorded before and after the skin incision. PI and PVI were calculated using a Radical 7 pulse oximeter, and SVV and CI were calculated using the FloTrac/Vigileo system.
After the skin incision, the PI decreased significantly from 5.3 (4.0-6.2%) to 3.6% (1.8-4.7%), whereas the PVI increased significantly from 9.5 (7.0-12.0%) to 13.5% (9.0-16.0%). A significant negative correlation was observed between the changes in PI and PVI before and after the skin incision. The skin incision did not affect the HR, CI, or SVV but increased the MBP.
This study showed a significant increase in the PVI and a negative correlation between the changes in PVI and PI before and after the skin incision. The PVI can be calculated from the variations in the PI caused not by mechanical ventilation, but rather by fluctuations in vasomotor tone. When using the PVI as an indicator for fluid responsiveness, it is crucial to pay attention to fluctuations in vasomotor tone induced by nociceptive stimuli.
International Journal of Clinical Monitoring and Computing 09/2011; 25(4):215-21.
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ABSTRACT: A 7-month-old girl with acute myeloid leukemia (AML) developed acute respiratory distress syndrome (ARDS) during the pancytopenic period after induction chemotherapy. Respiratory failure did not improve despite intensive treatments. Eventually, hemophagocytic lymphohistiocytosis (HLH) was diagnosed based on hemophagocytosis in bone marrow, and high soluble interleukin-2 receptor (sIL-2R) and ferritin levels. Even after cyclosporin A was started against HLH, she did not recover. Autopsy showed macrophage proliferation in bone marrow and lymph nodes. HLH should be considered, even in the pancytopenic period after chemotherapy, when patients develop ARDS that does not respond to supportive therapies.
Pediatric Hematology and Oncology 11/2010; 28(3):244-8. · 0.89 Impact Factor
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ABSTRACT: The phosphodiesterase III inhibitor olprinone has been confirmed to improve myocardial function and increase cerebral blood flow; therefore, if olprinone exerts direct neuroprotective effects against global cerebral ischemia to the same degree as cilostazol, olprinone could be useful for cerebral resuscitation after cardiac arrest. We examined whether olprinone directly protected neuronal cells from global cerebral ischemia both in vivo and in vitro.
In a rat model of 10-minute global cerebral ischemia induced by 4-vessel occlusion, 0.3, 3, or 30 microg x kg(-1) x min(-1) olprinone or saline was infused for a periischemic period of 40 minutes (n = 6 for each group). Hippocampal CA1 neuronal cells were then counted 3 days after reperfusion, and the phosphorylation of cyclic adenosine 3'5'-monophosphate response element-binding protein was examined using Western blotting analyses of specimens obtained 15 minutes after reperfusion. In vitro, cultured cerebral neurons were exposed to 4 hours of hypoxia and glucose deprivation and then 24 hours of recovery in the absence or presence of olprinone (10(-11)-10(-5) mol x L(-1)). Cell viability was measured using the Cell Counting Kit-8 (Dojindo Molecular Technologies, Gaithersburg, MD).
In the rat model of global ischemia, the number of surviving CA1 neurons counted under a microscopic field in the 30 microg x kg(-1) x min(-1) olprinone-treated group (49.9 +/- 9.2) was significantly higher than that in the saline infusion control group (7.2 +/- 3.4), and olprinone treatment increased the phosphorylation of cyclic adenosine 3'5'-monophosphate response element-binding protein. The survival fraction of the neuronal cells cultured in the presence of olprinone was also significantly higher than that of cells cultured in the absence of olprinone in a dose-dependent manner.
Our study successfully demonstrated, for the first time, that olprinone had a protective effect on neuronal cells in vitro and in vivo, especially against global cerebral ischemia. These results suggest that olprinone might be useful for the treatment of patients experiencing global cerebral ischemia.
Anesthesia and analgesia 03/2010; 110(3):888-94. · 3.08 Impact Factor
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Tetsuaki Hashiguchi, Yasuyuki Kakihana,
Sumikazu Isowaki,
Tamotsu Kuniyoshi,
Tatsuya Kaminosono,
Etsuro Nagata,
Kazumi Tobo,
Masamichi Tahara,
Naoko Okayama,
Yuki Arakawa,
Yoshie Kakihara,
Tsuyoshi Goromaru,
Nobuo Nakanishi,
Hiroe Nakazawa,
Yuichi Kanmura
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ABSTRACT: Using a lipopolysaccharide (LPS)-treated porcine model, we examined: (1) whether nitric oxide (NO), anandamide, and tetrahydrobiopterin (BH4) increased or not in early endotoxic shock; and (2) the location of the major site of production of these molecules, by comparing their concentrations in arteries and the portal and hepatic veins.
Ten pigs received an infusion of LPS at 1.7 microg x kg(-1)x h(-1) via the portal vein for 240 min. Consecutive changes in systemic hemodynamics, hepatosplanchnic circulation, and oxygen delivery were measured. Furthermore, the variable changes in the concentrations of nitrite and nitrate (NOx), anandamide, and BH4 were measured. To access the effects of surgery, anesthesia, and fluid management on BH4, an experiment without LPS infusion was performed in two other animals.
Mean arterial pressure and cardiac index started to decrease at 60 min after LPS infusion. However, systemic vascular resistance remained unchanged. Total hepatic blood flow and hepatic oxygen delivery also decreased significantly. NOx and anandamide did not change during LPS infusion. BH4 values did not change without LPS infusion. However, BH4 values increased significantly in the arterial, portal, and hepatic circulation during LPS infusion, especially in the hepatic vein (from 136.8 +/- 27.5 to 281.3 +/- 123.2 mol/ml; P < 0.01).
Our data suggest that the BH4 values were significantly increased in several organs, especially in the liver during endotoxic shock. Impaired cardiac output and decreased blood pressure appeared in the early phase of porcine endotoxemia. Longer-term observation of these parameters after LPS treatment should be performed as the next step in future studies.
Journal of Anesthesia 01/2008; 22(3):213-20. · 0.83 Impact Factor
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Satoshi Noma,
Wataru Matsuyama,
Hideo Mitsuyama,
Takayuki Suetsugu,
Yoshimizu Koreeda,
Keiko Mizuno,
Ikkou Higashimoto, Yasuyuki Kakihana,
Teruto Hashiguchi,
Ikuro Maruyama,
Mitsuhiro Osame,
Kimiyoshi Arimura
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ABSTRACT: The effect of polymixin B-immobilized fiber column (PMX) hemoperfusion treatment for acute exacerbation of interstitial pneumonia (IP) has been reported. Here, we report 2 cases of acute exacerbation of IP successfully treated with PMX hemoperfusion. One is a 55-year-old woman who was diagnosed as microscopic polyangiitis (MPA) with IP. The other is a 58-year-old man, diagnosed as having idiopathic pulmonary fibrosis. Both cases were treated with PMX hemoperfusion and other therapies. One died on day 44 and the other is still alive. The PMX hemoperfusion treatment decreased the serum levels of several cytokines and activated neutrophil percentage in bronchoalveolar lavage fluid.
Internal Medicine 02/2007; 46(17):1447-54. · 0.94 Impact Factor
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ABSTRACT: We assessed the effects of a neutrophil elastase inhibitor, sivelestat, on respiratory and organ functions as well as on the mortality of patients with acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS).
We retrospectively divided 25 patients who fulfilled the diagnostic criteria for SIRS and ARDS into two groups. One group (S group, n = 12) received a continuous infusion of sivelestat (0.2 mg.kg(-1).h(-1)), and the other did not (C group, n = 13).
Between days 1 and 10, the Pa(O2)/FI(O2) ratio in the S group significantly improved from 119.1 +/- 51.1 to 214.4 +/- 88.2 mmHg (P < 0.05). Furthermore, the S group spent significantly fewer days on a ventilator than the C group (16.7 +/- 5.8 vs 26.6 +/- 14.3 days; P < 0.05). The length of the intensive care unit stay was also significantly shorter for the S group than for the C group (18.7 +/- 4.9 vs 27.5 +/- 13.5 days; P < 0.05). However, the mortality rate at 29 days did not statistically differ between the two groups.
Our results suggested that sivelestat has a beneficial effect only on the pulmonary function of ARDS patients with SIRS.
Journal of Anesthesia 02/2006; 20(1):6-10. · 0.83 Impact Factor
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ABSTRACT: We hypothesized that mitral regurgitation (MR) would be exacerbated, cardiac index (CI) decreased, and mean pulmonary artery pressure (MPAP) increased in patients with coexisting MR during off-pump coronary artery bypass (OPCAB) anastomosis, and that milrinone could ameliorate increases in MR that occur during OPCAB anastomosis. Subjects comprised 140 patients scheduled for elective OPCAB divided into three groups: patients without MR (MR(-) group; n = 57), patients with MR (MR(+) group; n = 41), and patients with MR who received milrinone (M+MR(+) group; n = 42). Patients with grade 1+ or 2+ MR were included, whereas those with grade 3+ or 4+ MR were excluded. Hemodynamic variables were measured after the induction of anesthesia and during anastomosis. IV infusion of milrinone (0.5 microg . kg(-1) . min(-1)) started immediately after the induction of anesthesia in the M+MR(+) group. CI was significantly decreased (P < 0.0001), and MPAP and MR were significantly increased (P < 0.001) during left coronary anastomosis in the MR(+) group compared with the MR(-) group. CI was significantly higher (P < 0.001), and neither MPAP nor MR were increased (P < 0.05) during left coronary artery anastomosis in the M+MR(+) group compared to the MR(+) group. In patients with MR, anastomosis of the left coronary artery branches was associated with decreased CI and increased regurgitation and MPAP. In such patients, treatment with milrinone helps to stabilize hemodynamics during anastomosis.
Anesthesia & Analgesia 08/2005; 101(1):2-8, table of contents. · 3.29 Impact Factor
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Tamotsu Kuniyoshi, Yasuyuki Kakihana,
Sumikazu Isowaki,
Etsuro Nagata,
Kazumi Tobo,
Tatsuya Kaminosono,
Tetsuaki Hashiguchi,
Masamichi Tahara,
Hirokazu Kawamae,
Naoko Okayama,
Yuichi Kanmura
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ABSTRACT: This study was performed in order to assess the effects of olprinone, a phosphodiesterase III inhibitor, on hepatic oxygen delivery (DO2H), oxygen consumption (VO2H), and mitochondrial oxidation in the liver of a porcine endotoxemia model.
Fourteen pigs received continuous infusion of endotoxin via the portal vein for 240 min. From t = 150 to t = 240 min, animals were randomly divided into two groups to receive saline (control [CONT]; n = 7), or olprinone (OLP; n = 7) via the central vein.
In the OLP group, prior to olprinone treatment at 150 min, endotoxin induced significant decreases in the cardiac index (CI; from 120 +/- 31 to 65 +/- 13 ml.kg(-1).min(-1); P < 0.01) and DO2H (from 3.58 +/- 0.81 to 1.55 +/- 0.49 ml.kg(-1).min(-1); P < 0.01), while VO2H was maintained. After administration of olprinone (from t = 150 to t = 240 min), CI was unchanged, while DO2H increased from 1.55 +/- 0.49 to 1.93 +/- 0.38 ml.kg(-1).min(-1) (P < 0.01) and VO(2)H increased from 0.42 +/- 0.28 to 0.69 +/- 0.38 ml.kg(-1).min(-1) (P < 0.01). At t = 240 min, the oxidation level of cytochrome aa3 was significantly higher in the OLP group than in the CONT group (OLP, 66.2 +/- 19.3% vs CONT, 26.4 +/- 17.3%; P < 0.01).
Our data for this porcine endotoxemia model suggest that olprinone may have beneficial therapeutic effects in restoring not only systemic and hepatic circulation but also mitochondrial oxidation in the liver.
Journal of Anesthesia 01/2005; 19(4):295-301. · 0.83 Impact Factor
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ABSTRACT: We used serial measurements of serum S-100B protein to evaluate the time course of serum S-100B protein concentration after cardiovascular surgery and to determine the clinical relevance of its concentration and cerebral damage.
We assessed neurologic function in 149 patients undergoing cardiovascular surgery with cardiopulmonary bypass. The patients were classified into three groups according to their early postoperative outcome: those without complications (group A), those having unconsciousness or convulsion or both but no hemiplegia (group B), and those having unconsciousness and hemiplegia either with or without convulsion (group C). Serum S-100B protein concentrations were measured with a commercially available immunoluminometric assay, Sangtec 100 LIA, at seven time-points: before cardiopulmonary bypass, at the end of cardiopulmonary bypass, and at 5, 12, 24, 48, and 72 hours after cardiopulmonary bypass.
At 5 hours after cardiopulmonary bypass, the S-100B values in groups B and C were significantly higher than the value in group A. Although the S-100B level decreased in group C during the first 5 hours after cardiopulmonary bypass, it increased thereafter (12 through 24 hours) and continued at a high level until the final measurement at 72 hours. At 12 hours after cardiopulmonary bypass, S-100B was significantly higher in group C than in group B. This late increase in S-100B was associated with radiologically detected abnormalities and cerebral damage.
Serial measurement of serum S-100B protein in the initial 12 hours after cardiopulmonary bypass can be used to predict early postoperative brain injury.
The Annals of Thoracic Surgery 07/2003; 75(6):1892-7; discussion 1897-8. · 3.74 Impact Factor
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Yasuyuki Kakihana,
Tamotsu Kuniyoshi,
Sumikazu Isowaki,
Kazumi Tobo,
Etsuro Nagata,
Naoko Okayama,
Kouichirou Kitahara,
Takahiro Moriyama,
Takeshi Omae,
Masayuki Kawakami,
Yuichi Kanmura,
Mamoru Tamura
Advances in experimental medicine and biology 02/2003; 540:71-5. · 1.09 Impact Factor
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Yasuyuki Kakihana,
Tamotsu Kuniyoshi,
Sumikazu Isowaki,
Kazumi Tobo,
Etsuro Nagata,
Naoko Okayama,
Kouichirou Kitahara,
Takahiro Moriyama,
Takeshi Omae,
Masayuki Kawakami,
Yuichi Kanmura,
Mamoru Tamura
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ABSTRACT: Currently, no on-line method of assessing cerebral oxygenation is sufficiently accurate to be clinically helpful. In an attempt to find a good predictor of postoperative cerebral outcome, we retrospectively studied the relationship between the redox behavior of cytochrome oxidase (cyt. ox.) during an operation and the neurological prognosis in 83 patients who underwent thoracic aortic surgery. Our data revealed three patterns of change in the redox behavior of cyt. ox. during the operation; the actual pattern exhibited by a given patient showed a highly significant correlation with the neurological prognosis (p < 0.0001). We conclude that the redox behavior of cyt. ox. during an operation is likely to be a good predictor of postoperative cerebral outcome, which implies that brain tissue oxygen sufficiency can be evaluated by near-infrared measurement of cytochrome oxidase (except for that in local regions far from the monitoring site).
Advances in experimental medicine and biology 01/2003; 530:413-9. · 1.09 Impact Factor
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ABSTRACT: Using near-infrared spectroscopy (NIRS), we have developed a new approach to the measurement of the redox state of cytochrome oxidase (cyt. ox.) in the brain. Our previous animal study showed that oxygen-dependent redox changes in cyt. ox. occur only when oxygen delivery is badly impaired. Therefore, in this study, we retrospectively examined the relationship between the redox behavior of cyt. ox. (measured by NIRS) during an operation and the neurological outcome in patients.
We studied 66 patients undergoing thoracic aortic surgery with cardiopulmonary bypass. Cerebral oxygenation was monitored by NIRS, and relative values for the concentrations of oxy-Hb, deoxy-Hb, and the redox state of cyt. ox. in the brain were calculated using our developed algorithm.
Retrospective assessment revealed three different types of cyt. ox. behavior: (1) no change (type-A) in 34 cases (51.5%), (2) a temporary reduction, with a subsequent return to the pre-surgery baseline level (type-B) in 29 cases (43.9%), or (3) a marked and prolonged reduction (type-C) in only three cases (4.5%). Nine of the 66 patients (13.6%; one type-A, five type-B, and all three type-C patients) showed evidence of postoperative brain injury (in the type-A patient, the injury proved to be localized and far from the monitoring site). The relationship between the occurrence of such an injury and the type of cyt. ox. behavior seen during the operation was highly significant (P<0.0001; chi-square test for independence).
Our data suggest that the redox behavior of cyt. ox. during an operation is a good (though not perfect) predictor of postoperative cerebral outcome, and that overall tissue oxygen sufficiency can be confirmed by near-infrared measurement of cyt. ox.
European Journal of Cardio-Thoracic Surgery 03/2002; 21(3):434-9. · 2.55 Impact Factor
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ABSTRACT: Objective: To investigate the physiologic effects of exogenous vasopressin as a potential alternative to traditional high-dose catecholamine therapy for septic patients with vascular hyporeactivity to catecholamines.
Design: Prospective, case-controlled study.
Setting: Intensive care unit of a university hospital.
Patients: Vasopressin was infused in 16 critically ill septic patients who remained persistently hypotensive despite infusions of pharmacologic doses of catecholamines.
Intervention: Continuous intravenous infusion of vasopressin at 0.04 units/min for 16 hrs, in place of escalating the amount of catecholamines being infused.
Measurements and Main Results : After administration of vasopressin, systemic vascular resistance and mean arterial pressure were immediately and significantly increased in comparison with the values obtained just before vasopressin. When the vasopressin infusions were discontinued, mean arterial pressure decreased immediately and dramatically. We did not detect any obvious adverse cardiac effects during the vasopressin infusions. Vasopressin had no effect on other hemodynamic parameters or any of the metabolic parameters studied, including measures of oxygenation, plasma glucose, or electrolytes. Urine output increased significantly during the administration of vasopressin, although this effect may be nonspecific. Lactate concentrations decreased, particularly in the survival group, but the decreases were not significant. Overall survival was 56%.
Conclusions: Low-dose vasopressin infusions increased mean arterial pressure, systemic vascular resistance, and urine output in patients with vasodilatory septic shock and hyporesponsiveness to catecholamines. The data indicate that low-dose vasopressin infusions may be useful in treating hypotension in these patients.
Critical Care Medicine 02/2001; 29(3):487-493. · 6.33 Impact Factor
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ABSTRACT: Near-infrared spectroscopy (NIRS) is a cerebral monitoring method that noninvasively and continuously measures cerebral hemoglobin oxygenation and the redox state of cytochrome oxidase using highly tissue-permeable near-infrared light. This technique now has wide clinical application, and its usefulness in the measurement of cerebral hemoglobin oxygenation has been confirmed under global cerebral injury and/or hypoxemic hypoxia; however, regional cerebral infarction located far from the monitoring site may not be detected by NIRS. Furthermore, the specificity and accuracy of the measurement of the redox state of cytochrome oxidase remain controversial. We apply NIRS to both animal and clinical investigations. Based on these results, we discuss the significance of the measurement of cerebral hemoglobin oxygenation and cytochrome oxidase in vivo and in clinical medicine. Using our algorithm, cytochrome oxidase signals are unaffected by hemoglobin signals, even when hematocrit values change from 35 to 5% under cardiopulmonary bypass in a dog model. In the clinical study, cytochrome oxidase during surgery is likely to be a good (though not perfect) predictor of postoperative cerebral outcome. NIRS appears to be a promising technology, but additional investigations are required to establish its clinical efficacy and justify its routine use during operative and perioperative periods.
Journal of Biomedical Optics 13(3):033001. · 3.16 Impact Factor
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ABSTRACT: We developed a three-wavelength time-resolved spectroscopy (TRS) system, which allows quantitative measurement of hemodynamics within relatively large living tissue. We clinically evaluated this TRS system by monitoring cerebral circulation during cardiopulmonary bypass surgery. Oxyhemoglobin, deoxyhemoglobin, total hemoglobin and oxygen saturation (SO(2)) were determined by TRS on the left forehead attached with an optode spacing of 4 cm. We also simultaneously monitored jugular venous oxygen saturation (SjvO(2)) and arterial blood hematocrit (Hct) using conventional methods. The validity and usefulness of the TRS system were assessed by comparing parameters obtained with the TRS and conventional methods. Although the changes in SO(2) were lower than those in SjvO(2), SO(2) obtained by TRS paralleled the fluctuations in SjvO(2), and a good correlation between these values was observed. The only exceptions occurred during the perfusion period. Moreover, there was a good correlation between tHb and Hct values (r(2)=0.63). We concluded that time-resolved spectroscopy reflected the conditions of cerebral hemodynamics of patients during surgical operations.
Journal of Biomedical Optics 12(6):062112. · 3.16 Impact Factor
