Yasuhide Iwao

Cardiac output and circulating blood volume analysis by pulse dye-densitometry.

Objective. Pulse dye-densitometry (PDD) is a newly developed methodfor monitoring the indocyanine green (ICG) concentration in an artery withwhich cardiac output (CO) and circulating blood volume (CBV) can bedetermined. We evaluated its accuracy for clinical use. Methods. In 7patients under general anesthesia, ICG-sensitive optical probes (805 and 890nm) were attached to a finger. Following injection of ICG, the arterialconcentration of dye was recorded optically by the non-invasive testinstrument and sampled arterial blood ICG concentration was also measuredphotometrically for comparison. In order to validate the PDD analysis, CO wasalso measured by both the dye dilution cuvette method and by thermodilutionin 8 patients scheduled for coronary artery bypass grafting. In 30 otherpatients, CBV assessed by PDD was compared with its value estimated from bodysize. Results. The blood dye concentration correlated well with thevalues obtained by PDD (r = 0.953, p < 0.01). Meanbias for the test PDD CO was +0.15 ± 0.72 minl−1 (not significant (n.s.)) compared with the cuvette methodwhile the mean bias of the thermodilution method vs thecuvette method was +0.79 ± 0.84 min l−1 (p < 0.0001.). The average value of CBV obtained by PDD was 3.81± 1.39 L compared with that estimated value, 3.72 ± 0.77 L (n.s.).Conclusions. CO determined by PDD agrees wellwith cuvette densitometry, and somewhat less well with CO by thermodilution.The new method, by not requiring a pulmonary arterial catheter, is lessinvasivethan either older method, and yields in addition a value of CBV.

Anesthesia‐related mortality and morbidity over a 5‐year period in 2,363,038 patients in Japan

Background:  Statistical data of mortality and morbidity related to anesthesia have not been reported in Japan since World War II. The need to comprehensively examine the events of cardiac arrest as well as mortality prompted the first national study in Japan.

The epileptogenic properties of the volatile anesthetics sevoflurane and isoflurane in patients with epilepsy.

No study comparing epileptogenicity of sevoflurane to other volatile anesthetics has been performed. We compared the epileptogenic properties of sevoflurane to isoflurane in patients with epilepsy. In 24 mentally and/or physically disabled patients, 12 with epilepsy and 12 without epilepsy, electroencephalograms were recorded under anesthesia with 1.0 minimum alveolar anesthetic concentration (MAC), 1.5 MAC, and then 2.0 MAC sevoflurane or isoflurane under three ventilatory conditions: (A) 100% oxygen, and end-tidal CO2 partial pressure (ETco2) = 40 mm Hg, (B) 50% oxygen, 50% nitrous oxide, ETco2 = 40 mm Hg, and (C) 100% oxygen, ETco2 = 20 mm Hg. Spike activity was evaluated as a spike-and-wave index (% durations of spike and wave). The spike-and-wave index increased (P < 0.05) from 1.99% ± 0.96% during 1.0 MAC sevoflurane to 6.14% ± 4.45% during 2.0 MAC sevoflurane in (A) in the epilepsy group, while no spike activity was observed in the nonepilepsy group. Only a few spikes were observed under isoflurane anesthesia, 0.04% ± 0.04% in (A), with no spikes in (B) and (C). Supplementation with 50% nitrous oxide or hyperventilation (P < 0.05) suppressed the occurrence of spikes. Sevoflurane has a stronger epileptogenic property than isoflurane, but nitrous oxide or hyperventilation counteracts this specific epileptogenic property. Implications The stronger epileptogenicity of sevoflurane than isoflurane was confirmed in a controlled study in patients with epilepsy. Hyperventilation and supplementation of nitrous oxide under sevoflurane anesthesia suppressed epileptogenicity. A combination of sevoflurane and nitrous oxide may be a safer method for seizure-prone patients than the use of sevoflurane alone.

Circulating Blood Volume Measured by Pulse Dye-Densitometry Comparison with131I-HSA Analysis

Background Pulse dye‐densitometry (PDD) is a newly developed technique for monitoring the arterial concentration of indocyanine green. Using this method, circulating blood volume (CBV) can be calculated without using radioisotopes. In this study, the CBV value obtained by PDD was validated by comparison using the human serum albumin (131) I‐HSA) dilution method. Methods Eleven healthy volunteers underwent placement of cannulae into the radial artery and antecubital vein for withdrawal of blood samples and injection of indicator. Probes for PDD were attached to the right nostril and the right index finger. Indocyanine green (20 mg), dissolved in 4 ml water, and 25 [micro sign]Ci131 I‐HSA in 1 ml distilled water were injected simultaneously into the left antecubital vein. Blood samples were withdrawn 3, 6, 10, 20, 30, and 45 min after injection, then processed for spectrophotometric measurement of indocyanine green and scintillation counting. Results The blood dye concentration correlated well with the values obtained by PDD (r = 0.986, imprecision 0.04 +/− 0.11 mg/l, 10.0 +/− 31%. The imprecision of the CBV value obtained by PDD (nose probe) and by the131 I‐HSA dilution method was 3.99 +/− 10.54%, 0.259 +/− 0.593 l. The imprecision of the CBV obtained by in vitro spectrophotometry compared with PDD was 2.47 +/− 9.00%, 0.100 +/− 0.446 l. Conclusions This newly developed, less invasive method can measure CBV with an imprecision of 3.99 +/− 10.54%, 0.259 +/− 0.593 l (nose probe), and thus is also as accurate as the conventional radioisotope method

Mitochondrial hyperpolarization after transient oxygen-glucose deprivation and subsequent apoptosis in cultured rat hippocampal neurons

Mitochondrial membrane potential (MMP) regulates the production of high-energy phosphate and apoptotic cascade, both occurring after ischemic impact. The timed profile of MMP differing from grading ischemic impact has to be determined. Primary rat hippocampal cultures were exposed to oxygen-glucose deprivation (OGD) for 30, 60, and 90 min and then were reoxygenated. MMP was expressed as a voltage-dependent dye, JC-1 fluorescence, under confocal microscopy. Cell viability was assessed by calcein AM and ethidium homodimer, each at 3 hours and 24 hours after 30, 60, and 90 min of OGD. The appearance of apoptosis was also evaluated by the TUNEL method at 24 hours. Hyperpolarization of MMP (2.31+/-0.94 normalized JC-1 fluorescence ratio between red and green) was observed during reoxygenation after 30 min OGD, while 60 min OGD induced depolarization (0.66+/-0.22, Valinomycin (potassium ionophore)-induced depolarization: 0.53+/-0.19). The fluorescence of mitochondria became weak after 90 min OGD. Most of the neurons were shrunken after 90 min and neurons were TUNEL-positive 24 hours after 30 min OGD, although most neurons were viable at 3 hours. A longer period of OGD induced necrosis, and most neurons remained viable after only 3 hours. Our data present that the short (30 min) OGD induced hyperpolarization of MMP during reoxygenation, while a longer OGD (60 or 90 min) induced depolarization and acute necrosis. Neurons were still viable even during hyperpolarization of mitochondria, but this hyperpolarization appears to be linked to subsequent apoptotic change.

Mitochondrial membrane potential and intracellular ATP content after transient experimental ischemia in the cultured hippocampal neuron.

Ischemia limits the delivery of oxygen and glucose to cells and disturbs the maintenance of mitochondrial membrane potential (MMP). MMP regulates the production of high-energy phosphate and apoptotic cascading. Thus, MMP is an important parameter determining the fate of neurons. Differences in the time course of MMP according to the grading of the ischemic impact have not been clarified. MMP and intracellular ATP contents were monitored before and after short-term oxygen-glucose deprivation. A primary hippocampal culture seeded in a 35 mm fenestrated dish for fluorescence microscopy was mounted in a sealed chamber for an anaerobic incubation. A continuous flow of 100% nitrogen into the chamber and a replacement of glucose-free medium allowed the condition of oxygen-glucose deprivation (OGD), thereby extrapolating ischemia. MMP was evaluated by the fluorescence of a voltage-dependent dye, JC-1, under fluorescence microscopy. The intracellular ATP content was evaluated in a hippocampal culture seeded in a 96-well plate by the luciferin-luciferase reaction after a designated period of OGD. During OGD, MMP decreased to 0.72+/-0.03 (normalized JC-1 fluorescence), then increased to the hyperpolarized level 1.99+/-0.12 during 60 min reoxygenation after 30 min OGD. MMP after 60 min OGD decreased and recovered occasionally during reoxygenation. After 90 min OGD and reoxygenation, MMP was reduced and never recovered. The intracellular ATP content was 8.1+/-6.6 and 3.2+/-1.9% after 30 min OGD and 30 min reoxygenation following 30 min OGD, respectively; 60 min OGD did not significantly change these levels (7.1+/-5.8, 2.6+/-0.5%). Hyperpolarization after OGD did not accompany ATP production. This observation suggests the inhibition of electron reentry into an inner membrane during reoxygenation and the disturbance of FoF1-ATP synthase. This pathological finding of an energy-producing system after OGD may provide a clue to explain post-ischemic energy failure.

Impact of fresh-frozen plasma from male-only donors versus mixed-sex donors on postoperative respiratory function in surgical patients: a prospective case-controlled study

BACKGROUND: To reduce the risk of transfusion‐related acute lung injury (TRALI), plasma products are mainly made from male donors in some countries because of the lower possibility of alloimmunization; other countries are considering this policy. The advantage of male‐only fresh‐frozen plasma (FFP) should be examined in a prospective case‐control study.

Neuroprotective effect of propofol on necrosis and apoptosis following oxygen–glucose deprivation—Relationship between mitochondrial membrane potential and mode of death

Mitochondrial membrane potential (MMP) appears to play an important role in apoptotic cascade and has been proposed as an index for apoptosis or necrosis. We examined the neuroprotective effect of propofol on mode of death, focusing on MMP. Hippocampal cell culture was divided into three groups: control, oxygen-glucose deprivation for 30 min (30OGD), 90 min (90OGD). Propofol was added to each culture group at a concentration of 0 microM (Vehicle), 0.1 microM (Pro0.1) or 1.0 microM (Pro1.0). MMP was expressed as normalized JC-1 fluorescence. ATP content was assayed using the luciferin-luciferase reaction. Neuronal viability and appearance of apoptosis were also assessed. ATP content was decreased after OGD (0.276 +/- 0.115 microM/microg (control), 0.172 +/- 0.125 microM/microg (30OGD) and 0.096 +/- 0.092 microM/microg (90OGD)). Propofol did not alter ATP content. MMP was hyperpolarized after 30OGD (1.26 +/- 0.23 (vehicle), 1.29 +/- 0.13 (Pro0.1) and 1.18 +/- 0.06 (Pro1.0)) but was depolarized after 90OGD (0.77 +/- 0.04 (vehicle), 0.89 +/- 0.04 (Pro0.1), but Pro1.0 prevented depolarization (1.03 +/- 0.15 (P < 0.05)). Viability of cells significantly decreased to 50.3 +/- 5.7% (vehicle), 46.1 +/- 7.5% (Pro0.1), but Pro1.0 significantly salvaged neurons 65.1 +/- 6.2% (higher than vehicle and Pro0.1 value, P < 0.05) after 90OGD. At 24 h after OGD, TUNEL-positive cells were increased to 34.5 +/- 6.2% (vehicle), 26.7 +/- 7.9% (Pro0.1) and 30.4 +/- 7.1% (Pro1.0) in the 30OGD group. No pharmacological effect of propofol on the incidence of apoptosis was found. Propofol inhibited acute neuronal death accompanied with the maintenance of MMP but did not prevent subsequent apoptosis. Propofol induces a moratorium on neuronal death, during which pharmacological intervention might be able to prevent cell death.

Anesthesia-related mortality and morbidity in Japan (1999).

1 Department of Anesthesiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan 2 Department of Anesthesiology and Critical Care Medicine, Jichi Medical School, Tochigi, Japan 3 Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine and Dentistry, Okayama, Japan 4 Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 5 Department of Anesthesiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan 6 Department of Anesthesiology, School of Medicine, Keio University, Tokyo, Japan 7 Department of Anesthesiology and Intensive Care Medicine, Kanazawa University, Graduate School of Medical Science, Kanazawa, Japan 8 Sapporo Ichijyo Clinic, Sapporo, Japan 9 Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Gifu, Japan

Relationships between glutamate release, blood flow and spreading depression: real-time monitoring using an electroenzymatic dialysis electrode

Spreading depression (SD) in a flow-restricted area of the brain may be prolonged and may become potentially harmful by releasing glutamate. We induced SD in an oligemia model and examined the subsequent glutamate release. In 18 anesthetized male Fischer rats, a laser Doppler flowmeter, an electroenzymatic electrode for continuous measurement of glutamate, and a calomel electrode for measuring DC potential were placed through a cranial window positioned 3 mm away from a second window where KCl-soaked cotton was placed to initiate SD. The left carotid artery or both the common carotid arteries were ligated to suppress reactive hyperemia of SD. SD produced an increase in glutamate from 24.8 +/- 13.8 to 33.5 +/- 25.3 microM (peak value) (P < 0.0001). After ligation of both carotid arteries, the duration of SD increased from 1.5 +/- 0.6 min (before ligation) to 6.4 +/- 5.1 min (P < 0.05). Glutamate reached a peak level of 63.9 +/- 72.3 microM, then quickly returned to the control value. However, there was no positive correlation between the duration of SD and glutamate concentration. It is concluded that prolonged SD is not accompanied by a progressive increase in glutamate. Therefore, glutamate release induced by SD may not exert harmful effects on neurons.