Tomoyuki Tomita

Nitrosyl hemoglobin in blood of normoxic and hypoxic sheep during nitric oxide inhalation

During nitric oxide (NO) inhalation therapy, NO combines with deoxyhemoglobin to form nitrosyl hemoglobin (HbNO). We used electron spin resonance (ESR) spectroscopy to measure HbNO in arterial and mixed venous blood of normoxic and hypoxic sheep during NO inhalation. Our aim was to quantitatively measure HbNO levels in the blood during NO inhalation, because large amounts of HbNO reduce the oxygen capacity of blood, particularly in hypoxia. Another aim was to investigate the transfer of exogenous NO to the alpha-heme iron of hemoglobin. Thirteen sheep were anesthetized with pentobarbital sodium, and 60 parts per million (ppm) NO were administered for 1 h in the presence of normoxia and hypoxia. Two-way analysis of variance revealed that the HbNO level was dependent on the oxygen level (normoxia vs. hypoxia) and NO inhalation, and there was a significant negative correlation between the HbNO level and arterial O2 saturation (SaO2). Although the HbNO level increased during NO inhalation in hypoxia, the HbNO level at SaO2 > 60% was < 11 mumol/l monomer hemoglobin (0.11% of total 10 mmol/l monomer hemoglobin). The peak of the HbNO ESR spectrum in arterial blood is located in almost the same position in mixed venous blood with an asymmetric HbNO signal, indicating that the NO in beta-heme HbNO molecules had been transferred to alpha-heme molecules. The three-line hyperfine structure of HbNO on ESR spectra was distinct in venous blood in hypoxia during NO inhalation, indicating pentacoordinate alpha-NO heme formation in hypoxic blood. In conclusion, the amount of HbNO during 60 ppm NO inhalation did not considerably reduce the oxygen capacity of the blood even in the presence of hypoxia, and the NO of HbNO was transferred to the alpha-heme iron of hemoglobin, forming pentacoordinate alpha-NO heme in mixed venous blood in hypoxia.During nitric oxide (NO) inhalation therapy, NO combines with deoxyhemoglobin to form nitrosyl hemoglobin (HbNO). We used electron spin resonance (ESR) spectroscopy to measure HbNO in arterial and mixed venous blood of normoxic and hypoxic sheep during NO inhalation. Our aim was to quantitatively measure HbNO levels in the blood during NO inhalation, because large amounts of HbNO reduce the oxygen capacity of blood, particularly in hypoxia. Another aim was to investigate the transfer of exogenous NO to the α-heme iron of hemoglobin. Thirteen sheep were anesthetized with pentobarbital sodium, and 60 parts per million (ppm) NO were administered for 1 h in the presence of normoxia and hypoxia. Two-way analysis of variance revealed that the HbNO level was dependent on the oxygen level (normoxia vs. hypoxia) and NO inhalation, and there was a significant negative correlation between the HbNO level and arterial O2 saturation ([Formula: see text]). Although the HbNO level increased during NO inhalation in hypoxia, the HbNO level at[Formula: see text] >60% was <11 μmol/l monomer hemoglobin (0.11% of total 10 mmol/l monomer hemoglobin). The peak of the HbNO ESR spectrum in arterial blood is located in almost the same position in mixed venous blood with an asymmetric HbNO signal, indicating that the NO in β-heme HbNO molecules had been transferred to α-heme molecules. The three-line hyperfine structure of HbNO on ESR spectra was distinct in venous blood in hypoxia during NO inhalation, indicating pentacoordinate α-NO heme formation in hypoxic blood. In conclusion, the amount of HbNO during 60 ppm NO inhalation did not considerably reduce the oxygen capacity of the blood even in the presence of hypoxia, and the NO of HbNO was transferred to the α-heme iron of hemoglobin, forming pentacoordinate α-NO heme in mixed venous blood in hypoxia.

Respiratory muscle electromyogram and mouth pressure during isometric contraction.

When extra-diaphragmatic muscles are activated progressively under approximately isometric conditions, we expect a corresponding increase in respiratory muscle output. Therefore, we examined relative recruitment shown as the latency to onset of EMG activity, and the relationship between mouth pressure and electromyogram activity of the neck accessory and transversus abdominis (TRANS) muscles during respiratory maneuvers against occlusion. Fine wire electrodes were inserted into the scalene (SCLN), sternocleidomastoid (STERNO), trapezius (TRAPZ) and TRANS in six awake, healthy subjects. Mouth pressure, raw and moving average EMG signals were recorded during gradual production of expiratory or inspiratory mouth pressure to maximum (MPmax) at FRC in the standing posture. Group mean linear regression lines of EMG activity versus mouth pressure were strongly significant for SCLN and TRANS, less for STERNO, and least for TRAPZ. The SCLN and STERNO showed EMG activities with low, and TRAPZ showed EMG activity only with high, mouth pressure. At 90% MPmax, TRAPZ was much less active compared with TRANS, SCLN, or STERNO. These results suggest that over a wide range of respiratory effort there is a significant difference in the relationship between mouth pressure and EMG activity in the accessory muscles, with differential recruitment of individual respiratory muscles.

NOVEL FORM OF ATRIAL TACHYCARDIA ORIGINATING AT THE ATRIOVENTRICULAR ANNULUS

We report two patients with reentrant atrial tachycardia that originated at the AV annulus. Atrial tachycardia originated in the posterior portion of mitral annulus in one patient (case 1) and the posterolateral portion of tricuspid annulus in one patient (case 2). Tachycardia was successfully eliminated by RF catheter ablation in both patients, with the catheter placed underneath the mitral valve in case 1 and on the tricuspid annulus in case 2. Spiky potentials were recorded in the diastolic phase of the atrium during tachycardia at the sites of successful ablation. Spiky potentials were also recorded after atrial electrogram during sinus rhythm, and showed decremental properties during atrial pacing. An accelerated atrial rhythm was observed during RF application, and tachycardia could not be induced after ablation in either patient. Tachycardia in these patients seemed to be due to reentrant tachycardia originating in the accessory AV node (Mahaim fiber) without ventricular connection.

Differential function of the costal and crural diaphragm during emesis in canines.

In six mongrel dogs under thiopental anesthesia, piezoelectric transducers and bipolar electromyographic (EMG) wires were installed onto left costal, medial crural and lateral crural segments of the diaphragm. During CO2 rebreathing, shortening and EMG activity increased significantly in all three regions of the diaphragm compared to resting breathing. During emesis, (1) both shortening and EMG activity significantly increased compared to resting in costal segment; however, (2) lateral crural shortening was not increased in spite of significant increase in EMG activity; furthermore, (3) the medial crural segment lengthened without any increased EMG activity. These results demonstrate a differential recruitment of costal and crural diaphragm segments, and an additional differential activity within the crural segment between medial and lateral crural regions, during emesis. This activity of the canine diaphragm is consistent with a central influence of emesis upon individual regions of the diaphragm.

Worsening of hypoxemia with nitric oxide inhalation during bronchospasm in humans

In some COPD patients, in contrast to those with ARDS, inhaled NO reportedly worsens hypoxemia. The issue examined in this study was whether inhaled NO improves or worsens hypoxemia in humans during bronchoconstriction induced by methacholine (MCh) nebulization. Five healthy subjects and six asthma patients were recruited, and during 80 ppm NO inhalation gas exchange parameters 10 min after MCh nebulization were compared with the values obtained while breathing NO-free air. During NO inhalation, the drop in PaO2 10 min after MCh, from 95.1 +/- 5.5 (baseline; mean +/- SD) to 68.9 +/- 6.2 Torr, was greater than that under the same conditions but breathing NO-free air (from 92.6 +/- 5.3 to 79.5 +/- 11.1 Torr), and the increase in AaDO2 (from 8.9 +/- 5.4 to 29.8 +/- 5.4 Torr) was greater than that during NO-free air breathing (from 8.5 +/- 7.6 to 15.4 +/- 9.2 Torr). The SaO2 dose-response reached a plateau at 5 ppm of NO. Our results show that NO inhalation worsens desaturation during bronchospasm in humans after MCh nebulization.

Hepatopulmonary syndrome associated with autoimmune liver cirrhosis.

A 46‐year‐old woman presented for evaluation of liver dysfunction and dyspnoea. Laboratory examination showed high levels of γ‐globulin, immunoglobulin (Ig)G, and antinuclear antibodies. Laparoscopy demonstrated hepatic cirrhosis. Despite normal spirometry, hypoxaemia (which was worse in standing position) and a low diffusing capacity were present. The shunt ratio calculated using arterial blood gas was 6.4%, but was 40% when measured using 99mTc‐macroaggregated albumin scanning. The discrepancy between the ratios indicated that hypoxaemia was caused by intrapulmonary vascular dilatation. The patient was diagnosed with hepatopulmonary syndrome associated with autoimmune liver cirrhosis.

Valor Diagnóstico do Aumento dos Eosinóftlos e Linfocitos no Lavado Bronco-Alveolar em Doentes com Insuficiência Respiratória Aguda e Infiltrados Pulmonares Difusos

RESUMO Os autores analisaram de 1983 a 199 1, a utilidade da contagem diferencial de celulas no Lavado Bronco-Alveolar (LBA) em doentes com Insuficiencia Respiratoria Aguda (IRA) e Infiltrados Pulmonares Difusos (IPD) , com particular interesse nos que apresentavam niveis elevados de eosinoflos ou de linfocitos no LBA . Foram estudados 118 doentes com insuficiencia respiratoria para aguda e com PaO 2 2 /FiO 2 Infiltrados Pulmonares Difusos (IPD) na radiografia de torax. A doenca pulmonar foi avaliada em bases clinicas, resultados dos exames Bacteriologicos das Secrecoes Bronquicas recolhidas por Broncofibroscopia, por Biopsia Pulmonar Transbronquica c eventualmente. outros exames. O aumemo da percentagem dos eosinoflos no LBA foi encontrado em detcnninadas doencs especificas como: Pneumonia Eosinofila e Bronquiolite Obliterante com Pneumoniu. Por outro lado os autores, constataram que outras doencas como a Tuberculose Miliar, a Pneumonia de Hipersensibilidadc e a Pneumonia a Pneumocystis carinii tem uma percentagern muito elevada de linfocitos no LBA. COMENTARIO A identificoo das causas da Insuficiencia Respiratoria Aguda (IRA) acompanhada por Infiltrados Pulmonares Difusos (IPD) e a maior parte das vezes difficil. O LBA tem sido utilizado como meio de diagnostico nas mais variadus situacooes clinicas. Os autores neste estudo so chegaram a djagnostico definitivo quando isolaram no LBA o Mycobacterium tuberculosis , a Legionella pneumofila eo Pneumocyslis carinii , sendo os outros diagnosticos de suspeicao. Os autores constataram Eosinofilia e Linfocitose no LBA em 2% e 30% dos casas respectivamente. Relacionando estes dados com diagnosticos referidos, verificaram que 50% das eosinofilias constatadas no LBA estavam relacionadas com a Pneumonia eosinofila e como BOOP,que 76% dos casas com linfocitose no LBA estavam relacionados com a Tuberculose Miliar, a Pneumonia de Hipersensibilidade e a Pneumonia a Pneumocystis carinii .

Erythropoietin and base excess levels in patients with chronic pulmonary diseases

Factors which could influence serum erythropoietin (s-EPO) levels in patients with chronic pulmonary diseases were investigated, paying special attention to the role of changes in acid-base balance (PaCO2, HCO3- and base excess levels) in EPO production. Data from 30 patients with chronic pulmonary diseases (chronic pulmonary emphysema, chronic bronchitis and post-tuberculosis status) were obtained in the morning and were analyzed with a stepwise forward multiple regression analysis, evaluating the statistical significance of seven factors which may potentially influence s-EPO levels: arterial pH, PaCO2, PaO2, HCO3-, base excess (BE), SaO2 and hemoglobin (Hb). Significant simple correlations (P < 0.01) of log(s-EPO) were obtained with PaO2 (r = -0.66), PaCO2 (r = 0.59), HCO3- (r = 0.67), BE (r = 0.71) and SaO2 (r = -0.77). The stepwise forward multiple regression analysis revealed that significant correlate variables for the outcome variable of log(s-EPO) were SaO2 and BE, with r = 0.823 (P < 0.0001). In patients with chronic pulmonary diseases it was shown that SaO2 was a negative correlate and BE was a positive correlate of s-EPO levels. It was speculated that s-EPO levels in the morning reflected daytime hypoxemia (SaO2) and nocturnal desaturation evoked by hypopnea during sleep (indicated as BE) in these patients.

Abdominal Muscle Function with Change in Posture or CO2 Rebreathing in Humans.

The relative respiratory function of the individual abdominal muscles in humans is not well defined. Abdominal muscles have been reported to act as a single unit during breathing1, yet others have reported differential activation of specific abdominal muscles during respiration2.