Prone Position Impairs Oxygen Supply-Demand Balance During Systemic Hypoxia in Rabbits.

Ventilation in the prone position improves the prognosis of patients with severe acute respiratory distress syndrome (ARDS). Contraindications to ventilation in this position include unstable systemic circulation. Only a few reports exist on the effects of prone ventilation in respiratory failure on systemic circulation. This animal study compared systemic hemodynamic changes between supine and prone positions in anesthetized rabbits under acute systemic hypoxia (breathing 15% O2). Cardiac output and the systemic O2 extraction ratio increased under the hypoxia, but only in the supine group. Besides, the rate pressure product was higher in the prone group than in the supine group. This study showed that prone ventilation increases myocardial O2 consumption and suppresses compensatory mechanisms to maintain aerobic metabolism during systemic hypoxia. First of all, it will be necessary to examine the effect of prone ventilation on the O2 supply-demand balance in the ARDS model.

The Effects of Volatile Anesthetics on Lung Ischemia-Reperfusion Injury: Basic to Clinical Studies.

Case reports from as early as the 1970s have shown that intravenous injection of even a small dose of volatile anesthetics result in fatal lung injury. Direct contact between volatile anesthetics and pulmonary vasculature triggers chemical damage in the vessel walls. A wide variety of factors are involved in lung ischemia-reperfusion injury (LIRI), such as pulmonary endothelial cells, alveolar epithelial cells, alveolar macrophages, neutrophils, mast cells, platelets, proinflammatory cytokines, and surfactant. With a constellation of factors involved, the assessment of the protective effect of volatile anesthetics in LIRI is difficult. Multiple animal studies have reported that with regards to LIRI, sevoflurane demonstrates an anti-inflammatory effect in immunocompetent cells and an anti-apoptotic effect on lung tissue. Scattered studies have dismissed a protective effect of desflurane against LIRI. While a single-center randomized controlled trial (RCT) found that volatile anesthetics including desflurane demonstrated a lung-protective effect in thoracic surgery, a multicenter RCT did not demonstrate a lung-protective effect of desflurane. LIRI is common in lung transplantation. One study, although limited due to its small sample size, found that the use of volatile anesthetics in organ procurement surgery involving "death by neurologic criteria" donors did not improve lung graft survival. Future studies on the protective effect of volatile anesthetics against LIRI must examine not only the mechanism of the protective effect but also differences in the effects of different types of volatile anesthetics, their optimal dosage, and the appropriateness of their use in the event of marked alveolar capillary barrier damage.

Marathoners' Breathing Pattern Protects Against Lung Injury by Mechanical Ventilation: An Ex Vivo Study Using Rabbit Lungs.

BACKGROUND: Breathing during a marathon is often empirically conducted in a so-called "2:2 breathing rhythm," which is based on a four-phase cycle, consisting of the 1st and 2nd inspiratory and the 1st and 2nd expiratory phases. We developed a prototype ventilator that can perform intermittent positive pressure ventilation, mimicking the breathing cycle of the 2:2 breathing rhythm. This mode of ventilation was named the marathoners' breathing rhythm ventilation (MBV). We hypothesized that MBV may have a lung protective effect. METHODS: We examined the effects of the MBV on the pulmonary pre-edema model in isolated perfused rabbit lungs. The pulmonary pre-edema state was induced using bloodless perfusate with low colloid osmotic pressure. The 14 isolated rabbit lung preparations were randomly divided into the conventional mechanical ventilation (CMV) group and MBV group, (both had an inspiratory/expiratory ratio of 1/1). In the CMV group, seven rabbit lungs were ventilated using the Harvard Ventilator 683 with a tidal volume (TV) of 8 mL/kg, a respiratory rate (RR) of 30 cycles/min, and a positive end-expiratory pressure (PEEP) of 2 cmH2O for 60 min. In the MBV group, seven rabbit lungs were ventilated using the prototype ventilator with a TV of 6 mL/kg, an RR of 30 cycles/min, and a PEEP of 4 cmH2O (first step) and 2 cmH2O (second step) for 60 min. The time allocation of the MBV for one cycle was 0.3 s for each of the 1st and 2nd inspiratory and expiratory phases with 0.2 s of intermittent resting between each phase. RESULTS: Peak airway pressure and lung wet-to-dry ratio after 60 min of ventilation were lower in the MBV group than in the CMV group. CONCLUSION: MBV was considered to have a lung-protective effect compared to CMV.

Peripartum myocardial infarction associated with coronary spasm and acquired protein S deficiency: A case report.

RATIONALE: Coronary angiography (CAG) findings of acute myocardial infarction (AMI) in pregnant women are characterized by a high incidence of normal coronary arteries. This is the first report of AMI with normal coronary arteries during pregnancy, showing coronary spasm and pregnancy-related acquired protein S (PS) deficiency. PATIENT CONCERNS: A 30-year-old Japanese woman was admitted to an emergency department. One hour before admission, she developed sudden onset of precordial discomfort, back pain, and dyspnea. She was a primigravida at 39 weeks' gestation and had no abnormality in the pregnancy thus far. She had no history of heart disease, diabetes, hypertension, dyslipidemia, deep vein thrombosis (DVT), smoking, or oral contraceptive use and no family history of ischemic heart disease, hemostasis disorder, or DVT. She did not take any medication. DIAGNOSIS: Electrocardiography showed ST-segment elevations in leads II, III, aVF, and V2-V6. Heart-type fatty acid-binding protein was positive. Echocardiography showed hypokinesis of the anterior interventricular septum and inferior wall. Continuous intravenous infusion of isosorbide dinitrate was initiated. Coronary computed tomography angiography revealed diffuse narrowing of the apical segment of the left anterior descending coronary artery. Three hours after admission, troponin T became positive, and the following enzymes reached their peak levels: creatine kinase (CK), 1,886 U/L; CK-muscle/brain, 130 U/L. She was diagnosed with transmural AMI due to severe coronary spasm and administered benidipine hydrochloride. Five hours after admission, premature membrane rupture occurred. INTERVENTIONS: Emergency cesarean section was performed. There were no anesthetic or obstetrical complications during the operation. On postpartum day 1, the free PS antigen level was low (29%). On postpartum day 18, she was discharged with no reduction in physical performance. OUTCOMES: Four months after the infarction, CAG showed normal coronary arteries. Acetylcholine provocation test showed diffuse vasospasm in the coronary artery. She was advised that her next pregnancy should be carefully planned. Two years after delivery, free PS antigen level was within normal range, at 86%. She had not experienced recurrence of angina during the 2-year period. Her child was also developing normally. LESSONS: In addition to coronary spasm, pregnancy-related acquired PS deficiency may be involved in AMI etiology.

Unintended retention of a ruptured radiopaque thread extending from the corner of a gauze during laparoscopy.

Small gauze is used in laparoscopy; therefore, retention of gauze can occur. We experienced a case of retention of a radiopaque thread that ruptured from a piece of gauze and moved into the peritoneum during a scheduled laparoscopy. The patient was a 65-year-old woman who underwent laparoscopic-assisted transverse colon resection for transverse colon cancer. A commercial gauze commonly used for laparoscopy was used during the surgery. To more easily identify the gauze during surgery, radiopaque threads extending up to 3.0 cm from the two diagonal corners of the gauze body were attached. After wound closure, radiography showed a radiopaque thread-like substance in the abdomen. Minor laparotomy was performed, and part of the radiopaque thread was discovered. On postoperative day 22, the patient was in remission and discharged.

Desflurane inhalation before ischemia increases ischemia-reperfusion-induced vascular leakage in isolated rabbit lungs.

BACKGROUND: Isoflurane and sevoflurane protect lungs with ischemia-reperfusion (IR) injury. We examined the influence of desflurane on IR lung injury using isolated rabbit lungs perfused with a physiological salt solution. METHODS: The isolated lungs were divided into three groups: IR, desflurane-treated ischemia-reperfusion (DES-IR), and ventilation/perfusion-continued control (Cont) groups (n = 6 per group). In the DES-IR group, inhalation of desflurane at 1 minimum alveolar concentration (MAC) was conducted in a stable 30-min phase. In the IR and DES-IR groups, ventilation/perfusion was stopped for 75 min after the stable phase. Subsequently, they were resumed. Each lung was placed on a balance, and weighed. Weight changes were measured serially throughout this experiment. The coefficient of filtration (Kfc) was determined immediately before ischemia and 60 min after reperfusion. Furthermore, bronchoalveolar lavage fluid (BALF) was collected from the right bronchus at the completion of the experiment. After the completion of the experiment, the left lung was dried, and the lung wet-to-dry weight ratio (W/D) was calculated. RESULTS: The Kfc values at 60 min after perfusion were 0.40 ± 0.13 ml/min/mmHg/100 g in the DES-IR group, 0.26 ± 0.07 ml/min/mmHg/100 g in the IR group, and 0.22 ± 0.08 (mean ± SD) ml/mmHg/100 g in the Cont group. In the DES-IR group, the Kfc at 60 min after the start of reperfusion was significantly higher than in the other groups. In the DES-IR group, W/D was significantly higher than in the Cont group. In the DES-IR group, the BALF concentrations of nitric oxide metabolites were significantly higher than in the other groups. In the DES-IR group, the total amount of vascular endothelial growth factor in BALF was significantly higher than in the Cont group. CONCLUSIONS: The pre-inhalation of desflurane at 1 MAC exacerbates pulmonary IR injury in isolated/perfused rabbit lungs.

Phosphoenolpyruvate administration protects ischemia-reperfusion injury in isolated rabbit lungs.

Phosphoenolpyruvate (PEP) is an intermediate metabolite of the glycolytic pathway and an in vivo high-energy phosphate compound. We have examined the protective effects of PEP on ischemia-reperfusion lung injury in isolated rabbits lungs perfused with a physiological salt solution. The lungs were divided into three treatment groups: (1) ischemia-reperfusion (IR), (2) ischemia-reperfusion with PEP treatment (PEP-IR), in which 1 mM PEP was pre-administered into the perfusate during the stable period, and (3) ventilation-perfusion continued without interruption (Cont). In the IR and PEP-IR groups, ventilation-perfusion was discontinued for about 60 min after a 30-min stable period and then restarted. The capillary filtration coefficients (K fc) and pyruvate concentration in the perfusate were determined immediately before ischemia and 30 and 60 min after reperfusion. The left lungs were dried at the end of the experiment to calculate the tissue wet-to-dry weight ratio (W/D). The K fc values after reperfusion were significantly higher in the IR group than in the other two groups. Pyruvate concentrations were significantly higher at three time-points in the PEP-IR group than in the other two groups. The W/D was significantly higher in the IR group than in the other two groups. Based on these results, we conclude that the administration of PEP prior to lung ischemia alleviates lung ischemia-reperfusion injury.

Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esophageal cancer in the ICU: a case control study.

BACKGROUND: We previously reported that measuring circulating serum mRNAs using quantitative one-step real-time RT-PCR was clinically useful for detecting malignancies and determining prognosis. The aim of our study was to find crucial serum mRNA biomarkers in esophageal cancer that would provide prognostic information for post-esophagectomy patients in the critical care setting. METHODS: We measured serum mRNA levels of 11 inflammatory-related genes in 27 post-esophagectomy patients admitted to the intensive care unit (ICU). We tracked these levels chronologically, perioperatively and postoperatively, until the two-week mark, investigating their clinical and prognostic significance as compared with clinical parameters. Furthermore, we investigated whether gene expression can accurately predict clinical outcome and prognosis. RESULTS: Circulating mRNAs in postoperative esophagectomy patients had gene-specific expression profiles that varied with the clinical phase of their treatment. Multivariate regression analysis showed that upregulation of IL-6, VWF and TGF-ß1 mRNA in the intraoperative phase (p = 0.016, 0.0021 and 0.009) and NAMPT and MUC1 mRNA on postoperative day 3 (p < 0.01) were independent factors of mortality in the first year of follow-up. Duration of ventilator dependence (DVD) and ICU stay were independent factors of poor prognosis (p < 0.05). Therapeutic use of Sivelestat (Elaspol®, Ono Pharmaceutical Co., Ltd.) significantly correlated with MUC1 and NAMPT mRNA expression (p = 0.048 and 0.045). IL-6 mRNA correlated with hypercytokinemia and recovery from hypercytokinemia (sensitivity 80.9%) and was a significant biomarker in predicting the onset of severe inflammatory diseases. CONCLUSION: Chronological tracking of postoperative mRNA levels of inflammatory-related genes in esophageal cancer patients may facilitate early institution of pharamacologic therapy, prediction of treatment response, and prognostication during ICU management in the perioperative period.

[Preliminary report: observation by video laryngoscope of glottal narrowing due to cricoid pressure].

BACKGROUND: When the applied cricoid pressure is too strong, or the place or direction of the pressure application is not appropriate, glottal closure may occur, but its details are unclear. METHODS: We evaluated possible changes in the size of the rima glottides due to backward pressure on the cricoid cartilage or backward pressure or backward, upward, and rightward pressure (BURP) on the thyroid cartilage using a video laryngoscope (Fine View' Laryngoscope, Tray Medical, Tokyo) in 6 adult males and 6 females with Cormack and Lehane grade 1. RESULTS: The right-to-left distance of the rima glottides was 5.1 +/- 1.2 mm without pressure application but was reduced to 3.8 +/- 1.7, 3.5 +/- 1.8, 2.8 +/- 1.9, 2.4 +/- 1.8, and 2.6 +/- 1.2 mm by 20 N and 30 N backward pressure on the cricoid cartilage and 20 N and 30 N backward pressure and BURP on the thyroid cartilage, respectively. Compared with the absence of pressure application, 20 N and 30 N backward pressure and BURP on the thyroid cartilage significantly reduced it. It was reduced to 1 mm by 30 N backward cricoid pressure in 1 patient while glottal closure occurred due to 30 backward thyroid pressure in 1 patient. CONCLUSIONS: The right-to-left distance of the rima glottides was significantly reduced by backward pressure or BURP on the thyroid cartilage, and was also markedly reduced by cricoid pressure in 1 of the 12 patients.

[Augmentation of hypoxic pulmonary vasoconstriction in isolated rabbit lungs with phosphoenolpyruvate].

BACKGROUND: Phosphoenolpyruvate (PEP) is a glycolytic substrate which can be metabolized to pyruvate with concomitant formation of ATP. We examined the effects of PEP on hypoxic pulmonary vasoconstriction (HPV). METHODS: Isolated rabbit lungs (n = 6) were reperfused at a flow rate of 40 ml x kg(-1) body weight x min(-1) with a mixture of the physiological salt solution and autologous blood. They were ventilated with a mixture of 21% O2, 5% CO2, and balance N2. The HPV response was induced by reduction of inspired O2 concentration from 21 to 3% for 5 min and was evaluated by an increase of the pulmonary arterial pressure (PAP) with inhalation of nitric oxide (NO) at concentration of 0, 10, 20 ppm in random order. Next, PEP with the final concentration of 10 mM was added to the reservoir. After 30-min equilibration, the above protocol of hypoxic stimulations was repeated. RESULTS: PEP did not alter the basal PAP, but augmented the HPV response. Without and with PEP, inhaled NO depressed the HPV response in a dose-related manner and the half inhibition values (ED50) were 9.4 +/- 2.2, 14.9 +/- 10.3 ppm (mean +/- SD), respectively. CONCLUSIONS: The combination of intravenous PEP and inhaled NO may improve PaO2 without increasing PAP in acute respiratory failure.

[Four cases of extrapyramidal reactions to epidural droperidol administration].

Continuous epidural administration of droperidol at 2.5 mg x day(-1) or less was performed in 837 patients after surgery. In 4 of these patients, an extrapyramidal reaction occurred. Patient 1 was a 10-year-old girl who developed the symptom 29 hours after the start of administration, with a total dose of 3.0 mg. Patient 2 was a 16-year-old girl in whom the symptom occurred 24 hours after the start, with a total of 5.3 mg. Patient 3 was a 22-year-old female with the symptom occurring 26 hours after the start, with a total of 5.2 mg. Patient 4 was a 74-year-old female in whom the symptom occurred 24 hours after the start, with a total of 1.3 mg. With respect to the age distribution, the total of 837 patients consisted of 16 patients aged 10 to 19 years, 85 patients aged 20 to 29 years, 91 patients aged 30 to 39 years, 90 patients aged 40 to 49 years, 77 patients aged 50 to 59 years, 148 patients aged 60 to 69 years, 240 patients aged 70 to 79 years, 97 patients aged 80 to 89 years, and 9 patients aged 90 to 99 years. Extrapyramidal reactions related to epidural administration may readily develop at younger ages.

[Preliminary report: effects of artificial blood on hypoxic pulmonary vasoconstriction].

BACKGROUND: We examined the effects of artificial blood on hypoxic pulmonary vasoconstriction (HPV). METHODS: Pump-perfused rabbit lungs were reperfused and ventilated with a mixture of 21% O2, 5% CO2, and balance N2. HPV was induced by reduction of O2 concentration from 21 to 3% for 5 min. Pulmonary arterial pressure (PAP) was measured using a low-pressure transducer. Two perfusion solutions, (1) a mixture of autologous red blood cells and physiological salt solution supplemented with 5% albumin and (2) artificial red blood cells (liposome-encapsulated hemoglobin) and physiological saline supplemented with 5% albumin, were made. Using each solution, HPV was evaluated by PAP increase with and without inhalation of nitric oxide (NO). RESULTS: (1) With both autologous and artificial perfusion solutions, hypoxic stimulation (HS) increased PAP. (2) With the autologous solution, NO inhalation suppressed the HS-induced PAP increase, but with the artificial solutions no such a phenomenon was observed. CONCLUSIONS: NO inhalation failed to suppress HPV with the artificial solution, probably since the liposome-encapsulated hemoglobin strongly inactivated NO.