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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.

Purpose: 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., Methods: 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., Results: 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)., Conclusion: 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.

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.

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.

Purpose: 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)., Methods: 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)., Results: 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., Conclusion: Our results suggested that sivelestat has a beneficial effect only on the pulmonary function of ARDS patients with SIRS.

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.

Purpose: 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., Methods: 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., Results: 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)., Conclusion: 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.

Background: 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., Methods: 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., Results: 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., Conclusions: Serial measurement of serum S-100B protein in the initial 12 hours after cardiopulmonary bypass can be used to predict early postoperative brain injury.

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).

Unlabelled: Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by endotoxin, result in hepatic metabolic deterioration followed by liver dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors, only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous infusion (1.7 microg. kg(-1). h(-1)) of endotoxin (lipopolysaccharide [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 microg. kg(-1). min(-1)) via a central vein from t = 150 min to t = 240 min, whereas the eight remaining pigs served as LPS controls. Continuous infusion of LPS caused significant reductions in hemodynamic variables and a significant increase in arterial lactate. After the administration of olprinone during the LPS infusion, portal venous flow and hepatic oxygen delivery were increased and were higher than in the LPS group. Furthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia., Implications: Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.

Disturbances in tissue perfusion and oxygenation are known to occur during shock. To treat shock properly, it is necessary to have a good understanding of its pathophysiological characteristics. By monitoring cardiac output and oxygen delivery, we can assess the systemic oxygen transport to the tissues, while mixed venous oxygen saturation provides an index of the systemic oxygen balance between oxygen delivery and consumption. However, because a redistribution of blood volume and flow occurs in shock, the use of systemic monitoring alone does not allow an assessment of regional oxygenation in the various organs. Monitoring of hepatic and jugular venous oxygen saturation enables us to assess the adequacy of regional tissue oxygenation in the liver and brain, respectively, while monitoring intramucosal pH (pHi) is useful not only to assess regional oxygenation in the splanchnic organs, but also to predict complications and to evaluate the clinical outcome. The use of near-infrared spectroscopy may allow simultaneous, noninvasive monitoring of regional tissue oxygenation and energy levels. There exists a wide variety of viable options for the monitoring of shock, both systemically and regionally. This increases the chances of successful treatment.

The effects of ligustrazine on hepatic oxygenation in the isolated rat liver were investigated during prolonged perfusion and following the injection of norepinephrine. After injection of erythrocytes into the perfusate, the hemoglobin spectra in the liver were measured by Erlangen microlightguide spectroscopy, and the hemoglobin oxygenation (HbO2) in the liver was calculated on the basis of the Kubelka-Munk theory. During artificial perfusion, the HbO2 value was decreased from 59.3 +/- 6.4% (after one hour's perfusion) to 25.5 +/- 19.5% (n = 441; after six hours' perfusion). However, when ligustrazine was injected into the perfusate after six hours' perfusion, the HbO2 values recovered to 56.4 +/- 9.7% (n = 441). After injection of norepinephrine, HbO2 in the liver decreased from 48.8 +/- 10.4% to 25.2 +/- 18.4% (n = 961), while subsequent administration of ligustrazine caused a recovery to 62.9 +/- 6.0% (n = 961). Our results suggested that ligustrazine is a powerful hepatic vasodilator for improving hepatic oxygenation.

To evaluate microvascular regulation in human skin, changes in intracapillary hemoglobin oxygen saturation (HbO2) were studied in human finger skin following an abrupt change in local ambient temperature. In the first series of experiments, we assessed the heterogeneity of HbO2 in the skin by using a 2-D scanning system and a rapid micro-lightguide spectrophotometer at each of two near-normal skin temperatures. The data showed that heterogeneous oxygenation exists in human skin even at near-normal temperatures (although the pattern is different at different skin temperatures). In a second series of experiments, the performance of the microcirculation of the skin was continuously examined in a selected area with initially different oxygenation levels during an abrupt change in local ambient temperature (5, 15, 25, 35, and 45 degrees C). At very low (5 degrees C) or very high (45 degrees C) temperatures, oxygenation in tissues within the low HbO2 area increased greatly, but there was no such change within the high HbO2 area. Our data indicate that different types of capillary supply units exist in human skin (indicated by the initially different oxygenation levels). These different capillary supply units may operate to produce a local redistribution of flow between the various capillary supply units. This effect may be initiated by heat sensors and oxygen sensors when temperature of the skin is varied., (Copyright 1998 Academic Press.)

Using near-infrared spectroscopy, we developed a new approach for measuring the redox state of cytochrome oxidase in the brain under normal blood-circulation conditions. Our algorithm does not require the absorption coefficient of cytochrome oxidase, which differs from study to study. We employed this method for evaluation of effects of changes in oxygen delivery on cerebral oxygenation in rats. When fractional inspired oxygen was decreased in a stepwise manner from 100 to <10%, at which point the concentration of oxygenated hemoglobin ([HbO2]) decreased by approximately 60%, cytochrome oxidase started to be reduced. Increases in arterial PO2 under hyperoxic conditions caused an increase in [HbO2], whereas further oxidation of cytochrome oxidase was not observed. The dissociation of the responses of hemogloblin and cytochrome oxidase was also clearly observed after the injection of epinephrine under severely hypoxic conditions; that is, cytochrome oxidase was reoxidized with increasing blood pressure, whereas hemoglobin oxygenation was not changed. These data indicated that oxygen-dependent redox changes in cytochrome oxidase occur only when oxygen delivery is extremely impaired. This is consistent with the in vitro data of our previous study.

Purpose: We retrospectively analyzed prognostic factors for local control in hypopharyngeal cancer., Patients and Methods: Twenty-five patients with hypopharyngeal cancer treated with radical irradiation were entered into analyses. Local control according to clinical T stage and subsites of hypopharynx were analyzed. For 8 clinical T2 patients, local control according to findings assessed by pretreatment CT was also evaluated., Results: The 2-year local control rates were 40% for all, 1/2 for T1, 8/11 (73%) for T2, 1/8 (12%) for T3, and 0/4 for T4. Two-year local control rates were 28% for pyriform sinus cancer and 66% for pharyngeal wall cancer. Local control analysis according to CT findings for patients with T2 hypopharyngeal cancer showed that patients without specified involvement beyond the hypopharynx or in the apex had good local control., Conclusion: Our preliminary analysis suggested that clinical T2 hypopharyngeal cancer patients without invasion beyond the hypopharynx or in the apex demonstrated on CT had favorable local prognosis when treated with radical irradiation.

Locally advanced cervical cancer has a dismal prognosis, with a high local failure rate and a poor survival rate. To improve the cure rate for advanced carcinoma of the cervix, we initiated a study of intra-arterial (I-A) chemotherapy with cisplatin via the uterine artery prior to definitive radiotherapy. I-A chemotherapy via the internal iliac artery has been used to treat advanced cervical cancer; however, access by way of the uterine artery has not been tested for this purpose. Thirty-four patients with central tumor > or = 5 cm in anteroposterior diameter observed on CT scans were treated with I-A chemotherapy. I-A chemotherapy consisted of unilateral catheterization of the uterine artery using 120 mg/m2 cisplatin. After assessment of I-A chemotherapy, all but 3 patients were treated with a combination of whole-pelvis external irradiation and intracavitary irradiation. The 3 patients underwent external radiotherapy alone. Twenty-seven of 34 patients treated were evaluable for response to I-A chemotherapy. Eleven patients (41%) experienced a partial response. Seventy-six percent of the 34 patients treated with I-A chemotherapy followed by radiotherapy exhibited a complete response by the end of treatment. Toxicity was well tolerated and no death due to treatment occurred. The 2- and 5-year actuarial survival rates were 64 and 55%, respectively. The crude incidences of pelvic recurrence and distant metastasis observed at a median follow-up of 54 months were both 47%. This study for locally advanced cervical cancer suggests there is benefit to be derived from our I-A chemotherapy followed by radical radiotherapy.

A Shimazu OM-100A near infrared spectrophotometer was used to monitor the cerebral oxygenated hemoglobin (Oxy-Hb), deoxygenated hemoglobin (Deoxy-Hb) and total hemoglobin (Total-Hb) in 3 patients with a) massive hemorrhage, b) ruptured aneurysm in the abdominal aorta, or c) hypercapnia. The hematocrit value of the patient with massive hemorrhage decreased rapidly to 18 %; the Total-Hb and Oxy-Hb also decreased significantly. Red blood cell transfusion raised the Oxy-Hb level, indicating an improvement in cerebral oxygenation. In the patient with a ruptured aneurysm, changes in blood flow brought about by clamping or declamping of the abdominal aorta were immediately reflected by corresponding changes in Total-Hb and Oxy-Hb. Oxy-Hb increased significantly and correlated well with the PETCO2 value in the patient with hypercapnia. Thus, NIR spectrophotometry is a useful non-invasive tool which can monitor metabolic and hemodynamic changes in the brain in various pathological conditions.

Purpose: To determine the efficacy of intraoperative radiation therapy (IORT) for patients with advanced or recurrent head and neck cancer., Methods and Materials: Intraoperative radiation therapy was given at 30 sites in 25 patients using a 6-18 MeV electron beam with or without conventional external beam irradiation. A single dose of 10-30 Gy was delivered after surgical resection. Sites treated with IORT were classified into three types after surgical resection: gross residual disease (GR, n = 7), microscopic residual disease (MR, n = 12), and close margin (CM, n = 11). Local control rate, patterns of recurrence, survival rate, and complications were analyzed., Results: The 2-year cumulative local control rate within the IORT port was 54.1% for all cases, 0% for GR, 54.5% for MR, and 81.8% for CM. There were significant differences between GR and MR (p < 0.05), and GR and CM (p < 0.01). The majority of the failures inside the IORT port were associated with recurrence outside the port. Distant metastases occurred in five patients. Four of these had GR. The 2-year cumulative survival rate was 45.1% for all, 0% for GR, 33.0% for MR, and 70.0% for CM. Five patients (22%) experienced late complications. The 2-year cumulative complication rate was 32.8%. Four sites developed osteoradionecrosis and three developed carotid artery blowout. Incidence of complications increased when patients received over 20 Gy with a single dose of IORT., Conclusions: Considering both therapeutic ratio and patterns of failure, it is not suitable to treat patients with gross residual disease with IORT. We could not firmly determine the therapeutic value of IORT for patients with microscopic residual disease and close margin. For this subset, further study of moderate dose (less than 20 Gy) IORT combined with adequate postoperative irradiation is needed.

Purpose: Analysis of the therapeutic value of radical irradiation for patients with uterine cervical adenocarcinoma with special reference to pelvic disease control., Patients and Methods: 20 patients with uterine cervical adenocarcinoma were treated with a combination of external beam and intracavitary irradiation (four patients stage IB, one stage IIA, three stage IIB and twelve patients stage IIIB). Seven patients were treated with high dose-rate (HDR) intracavitary irradiation, eleven with low dose-rate (LDR) intracavitary irradiation and two with HDR and LDR., Results: Six out of the 20 patients experienced pelvic recurrence (all stage IIIB patients). Analysis of the relation between pelvic recurrence and dose rate of intracavitary irradiation revealed that LDR showed a higher pelvic disease control rate than HDR (6/7 vs. 0/4) in stage IIIB patients. Intracavitary irradiation doses of LDR were 1.2 to 1.5 times higher than those of HDR. Three out of the 20 patients developed rectal complication grade 2 (two patients treated with HDR, one with LDR). The five-year cumulative survival rate was 67.2% for all, 100% for stage I and II, and 43.3% for stage IIIB patients., Conclusion: These results suggest that locally advanced uterine cervical adenocarcinoma should be treated with a higher dose using LDR intracavitary irradiation. If adequate total doses can be delivered, pelvic disease control of uterine cervical adenocarcinoma is comparable with that achieved for squamous cell carcinoma.

The mutual relationship of the redox state of cytochrome oxidase in both cardiac and brain tissues were examined by the simultaneous optical measurement. The oxygenation states of cardiac and brain tissues behaved in a same manner during progressive hypoxia. We concluded that the oxygenation state of brain completely depends on the oxygenation state of cardiac tissue which determines the cardiac output.