Makoto Sawano

Beneficial Effects of Cocoa in Perivascular Mato Cells of Cerebral Arterioles in SHR-SP (Izm) Rats

As previously reported, the cerebral arterioles are surrounded by unique perivascular Mato cells. They contain many inclusion bodies rich in hydrolytic enzymes, and have strong uptake capacity. They are thus considered scavenger cells of vascular and neural tissues in steady-state. In this study, employing hypertensive SHR-SP (Izm) rats, the viability of Mato cells was investigated. In hypertensive rats, the capacity for uptake of horse radish peroxidase (HRP) and the activity of acid phosphatase (ACPase) of Mato cells were markedly reduced, and on electron-microscopic examination Mato cells were found to include heterogeneous contents and appeared electron-dense and degenerated. Vascular cells exhibited some signs of pathology. However, in hypertensive rats fed chow containing 0.25% cocoa, the uptake capacity and ACPase activity of Mato cells for HRP were enhanced, and on electron-microscopic examination Mato cells appeared healthy, with mitochondria with nearly normal profiles. Signs of pathology in vascular cells were also decreased. Superoxides may impair Mato cells and vascular cells.

A tracer analysis study on the redistribution and oxidization of endogenous carbon monoxide in the human body.

Past studies have suggested that some carbon monoxide (CO) moves from blood haemoglobin to tissue cells and that mitochondrial cytochrome c oxidase oxidizes CO to carbon dioxide (CO2). However, no study has demonstrated this redistribution and oxidization of CO under physiological conditions. The objective of this study was to trace the redistribution and oxidization of CO in the human body by detecting 13CO2 production after the inhalation of 13CO. In Experiment 1, we asked a healthy subject to inhale 50 ppm 13CO gas. In Experiment 2, we circulated heparinized human blood in a cardio-pulmonary bypass circuit and supplied 50 ppm 13CO gas to the oxygenator. We sequentially sampled exhaled and output gases and measured the 13CO2/12CO2 ratios. In Experiment 1, the exhaled 13CO2/12CO2 ratio increased significantly between 4 to 31 h of 13CO inhalation. In Experiment 2, the output 13CO2/12CO2 ratio showed no significant increase within 36 h of 13CO input. Experiment 1 demonstrated the oxidization of CO in the human body under physiological conditions. Experiment 2 confirmed that oxidization does not occur in the circulating blood and indicated the redistribution of CO from blood carboxyhaemoglobin to tissue cells.

Demonstration and quantification of the redistribution and oxidation of carbon monoxide in the human body by tracer analysis

Numerous studies have confirmed the role of endogenous carbon monoxide (CO) gas as a signal transmitter. However, CO is considered an intracellular transmitter, as no studies have demonstrated the redistribution of CO from the blood to tissue cells. Tracer analyses of 13 CO 2 production following 13 CO gas inhalation demonstrated that CO is oxidized to carbon dioxide (CO 2 ) in the body and that CO oxidation does not occur in the circulation. However, these results could not clearly demonstrate the redistribution of CO, because oxidation may have occurred in the airway epithelium. The objective of this study, therefore, was to definitively demonstrate and quantify the redistribution and oxidation of CO using time-course analyses of CO and 13 CO 2 production following 13 CO-hemoglobin infusion. The subject was infused with 0.45 L of 13 CO-saturated autologous blood. Exhaled gas was collected intermittently for 36 hours for measurement of minute volumes of CO/CO 2 exhalation and determination of the 13 CO 2 / 12 CO 2 ratio. 13 CO 2 production significantly increased from 3 to 28 hours, peaking at 8 hours. Of the infused CO, 81% was exhaled as CO and 2.6% as 13 CO 2 . Identical time courses of 13 CO 2 production following 13 CO-hemoglobin infusion and 13 CO inhalation refute the hypothesis that CO is oxidized in the airway epithelium and clearly demonstrate the redistribution of CO from the blood to the tissues. Quantitative analyses have revealed that 19% of CO in the circulating blood is redistributed to tissue cells, whereas 2.6% is oxidized there. Overall, these results suggest that CO functions as a systemic signal transmitter.

Membranous tracheal stenosis in a patient with anorexia nervosa and self-induced vomiting- challenges in securing the airway

We report a rare case of acquired membranous tracheal stenosis in a patient with anorexia nervosa and a history of self-induced vomiting, but without a history of tracheal intubation or tracheostomy. A 50-year-old woman presented with difficulty in breathing and swallowing, self-expectoration, and impaired consciousness due to acute benzodiazepine intoxication. Bronchoscopic examination was performed after tracheotomy and placement of a tracheostomy tube failed to secure her respiratory tract and ventilation continued to deteriorate. A flap-like membranous structure was identified on the posterior tracheal wall, obstructing the tracheostomy tube. Physical compression of the membranous structure improved ventilation. Bronchoscopic examination is generally recommended prior to performing tracheostomy in patients suspected to have post-intubation tracheal obstruction. Based on our findings, we suggest that these examinations should also be performed in patients with conditions associated with chronic irritation of the respiratory tract, including those with a prolonged history of self-induced vomiting.

Successful early romiplostim use in a case of severe immune thrombocytopenia with critical carotid arterial injury

Thrombopoietin receptor (TPO-R) agonists have been shown to be effective in refractory chronic immune thrombocytopenia (ITP); however, their efficacy in patients under critical care is not known. We report the case of a female patient with a newly diagnosed ITP who experienced severe bleeding from an external wound. The patient was administered the standard treatments for ITP, which are high-dose intravenous immunoglobulin (IVIg) and corticosteroids. However, following failure of these treatments, we administered romiplostim on day 6 after the onset of ITP. On day 6 after the initiation of romiplostim, there was improvement in platelet count and bleeding tendency. We were subsequently able to perform a splenectomy successfully. The efficacy of TPO-R agonists in ITP has been reported in several situations, including before surgery in an ITP patient; however, the use of TPO-R for arterial bleeding with shock has not been reported. To our knowledge, the present article is a rare case report of the use of a TPO-R agonist in a patient with critical artery injury. Our data suggest that the early use of romiplostim is effective in emergency cases of newly diagnosed ITP with life-threatening bleeding, which is refractory to standard treatment.

A case series of pelvic fracture patients who developed lower urinary tract symptoms after transarterial embolization of bilateral internal iliac arteries

Transarterial embolization of bilateral internal iliac arteries (TAE) is a useful hemostatic method for the management of pelvic fracture patients, but its effects on urinary functions remain unclear. In this study, we evaluated the impact of TAE on lower urinary tract symptoms (LUTS) in 10 pelvic fracture patients.

Early administration of fibrinogen concentrates improves the short-term outcomes of severe pelvic fracture patients

Hemorrhage from pelvic fracture is a major cause of mortality after blunt trauma. Several studies have suggested that early fibrinogen supplementation improves outcomes of traumatic hemorrhage. Thus, we revised our massive transfusion protocol (MTP) in April 2013 to include early off‐label administration of fibrinogen concentrate. The objective of this study was to evaluate the impact of the revision on the short‐term outcomes of pelvic fracture patients.

Pre-emptive administration of fibrinogen concentrate contributes to improved prognosis in patients with severe trauma

Background Patients with severe trauma often present with critical coagulopathy, resulting in impaired hemostasis, massive hemorrhage, and a poor survival prognosis. The efficacy of hemostatic resuscitation in correcting coagulopathy and restoring tissue perfusion has not been studied. We assessed a novel approach of pre-emptive administration of fibrinogen concentrate to improve critical coagulopathy in patients with severe trauma. Methods We retrospectively compared blood transfusion volumes and survival prognosis between three groups of patients with trauma, with an Injury Severity Score (ISS) ≥26 over three consecutive periods: group A, no administration of fibrinogen concentrate; group B, administration of 3 g of fibrinogen concentrate after evaluation of trauma severity and a plasma fibrinogen level <1.5 g/L; group C, pre-emptive administration of 3 g of fibrinogen concentrate immediately on patient arrival based on prehospital information, including high-severity injury or assessed need for massive transfusion before measurement of fibrinogen. Results ∼56% of patients with an ISS ≥26 and transfused with red blood cell concentrates ≥10 units, had hypofibrinogenemia (fibrinogen <1.5 g/L) on arrival. Patients who received fibrinogen concentrate in group C showed significantly higher fibrinogen levels after treatment with this agent than those in group B (2.41 g/L vs 1.88 g/L; p=0.01). Although no significant difference was observed in blood transfusion volumes between the groups, the 30-day survival of patients in group C (all, and those with an ISS ≥26) was significantly better than in group A (p<0.05). The 48-hour mortality rate in patients with an ISS ≥26 was significantly lower in group C than in group A (8.6% vs 22.9%; p=0.005). Further, among patients with an ISS ≥41, the overall mortality was significantly lower in group C than in group A (20% vs 50%; p=0.02). Conclusion Pre-emptive administration of fibrinogen concentrate for patients with trauma with critical coagulopathy may contribute to improved survival. Level of evidence Level IV.

Analysis of Breath CO and Application to Hemodynamic Monitoring

Breath tests have replaced more invasive conventional tests in the diagnosis of digestion and absorption disorders or gastrointestinal infection. However, highly invasive techniques are still widely used for hemodynamic monitoring. Although less invasive replacement of these techniques has long been desired, no breath test has succeeded in this field, because of its difficulty in continuous measurement of rapidly fluctuating parameters. Thermodilution using a pulmonary-artery catheter is the gold standard in the estimation of cardiac output. However, recent trials showed an increased mortality in the group of cardiac failure patients treated using a pulmonary-artery catheter. There is no question that cardiac output estimation provides useful information for management of circulatory disorders, undesired outcome should be attributed to high incidence and severity of complications associated with pulmonary-artery catheter placement. Radioisotope-labeled red-cell dilution is the gold standard in estimation of circulating blood volume. Carboxyhemoglobin dilution was developed as a possible replacement of the radioisotope dilution. However, infusion of 100 ml carbon monoxide saturated autologous blood was required and was potentially hazardous to patients under critical conditions. The author developed accurate, noninvasive, continuous carboxyhemoglobin densitometry by expired gas analysis. Application of this technique to low-dose carboxyhemoglobin dilution achieved minimally invasive estimation of cardiac output and circulating blood volume. The only prerequisite for the estimation is the infusion of 20 ml CO-saturated autologous blood via the peripheral vein. Hemodynamic monitoring by expired gas analysis achieved good agreement with conventional methods and is acceptable as an equivalently accurate but low invasive replacement.