Fujiya Kishi

Relation of Oxygen Delivery, Mixed Venous Oxygenation, and Pulmonary Hemodynamics to Prognosis in Chronic Obstructive Pulmonary Disease

We studied the relation of oxygen delivery, mixed venous oxygenation, and pulmonary hemodynamics to prognosis in 50 randomly selected patients with chronic obstructive pulmonary disease. Cardiac catheterization was performed when the patients were clinically stable. Four years later, 27 patients (54 per cent) had died of respiratory failure. At the time of catheterization, patients who subsequently lived were similar to those who died in age, physical characteristics, and hematocrit. Nonsurvivors had significantly lower arterial and mixed venous oxygen tension and significantly higher arterial and mixed venous carbon dioxide tension. The mean pulmonary arterial pressure, pulmonary arteriolar resistance, right ventricular work, coefficient of oxygen delivery, and cardiac index did not differ between the two groups. After inhalation of 100 per cent oxygen for one hour, the mixed venous oxygen tension of nonsurvivors rose to a level equivalent to that of survivors, and their mean pulmonary arterial pressure fell significantly. These results indicate that, with respect to oxygen supply to the tissues, mixed venous oxygenation is one of the important prognostic factors in chronic obstructive pulmonary disease. Pulmonary and right ventricular hemodynamics measured during periods of clinical stability do not differentiate nonsurvivors from survivors.

Ventilatory and heart rate responses to hypoxia and hypercapnia in patients with diabetes mellitus.

The ventilatory response to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia in 24 diabetic patients were compared with those of sex and age matched normal control subjects. The heart rate response to hypoxia was also measured in both groups. In diabetic patients the ventilatory and heart rate responses to hypoxia were significantly lower than those in the control group (0.10 v 0.24 l/min/% fall/m2 and 0.5 l v 1.27 beats/min/% fall respectively). The ventilatory response to hypercapnia was significantly higher (1.09 v 0.76 l/min/mm Hg/m2) in the diabetic patients. There was a significant correlation between the hypoxic ventilatory response and the heart rate response in diabetic patients (r = 0.56), but not in the control group (r = 0.28). In addition, both the ventilatory and the heart rate responses to hypoxia in diabetic patients had weak but significant correlations with the heart rate variation during deep breathing. It is concluded that the ventilatory and heart rate responses to hypoxia in diabetic patients are impaired, whereas the ventilatory response to hypercapnia is well preserved.

Serum selenium and vitamin E concentrations in families of lung cancer patients

Whether or not serum selenium and vitamin E (alpha‐tocopherol) concentrations were changed was examined among healthy families of lung cancer patients. Family members as a whole (115 sons and daughters of 55 patients with primary lung cancer) were found to have a trend to lower serum selenium levels (0.116 ± SD 0.024 μg/ml, 0.05 < P < 0.1). Particularly among families of adenocarcinoma patients, the mean level was significantly lower (0.111 ± 0.019 μg/ml, P < 0.05) than that (0.122 ± 0.014 μg/ml) in age‐ratio matched controls who did not have cancer patients among their second‐degree relatives. Serum vitamin E levels (11.85 ± 2.85 μg/ml) were significantly lower among family members of adenocarcinoma patients than the controls (14.1 ± 3.1 μg/ml, P < 0.01). Serum selenium and vitamin E levels were significantly lower in lung cancer patients (n = 37, mean age, 63.9 ± 11.2 yr) than in the controls (P < 0.001). These data suggest that there are familial factors in serum selenium and vitamin E levels among families of lung cancer patients.

Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.

BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.

Pharmacological Effects on Hemoglobin-Oxygen Affinity in Vitro and in Patients with Chronic Obstructive Pulmonary Disease

We examined the effects of pentoxifylline, coenzyme Q10 (CoQ10) and calcium hopantenate on hemoglobin-oxygen affinity in vivo and in vitro. In vitro study, pentoxifylline at 3 and 15 micrograms/ml significantly increased P50 from the placebo (27.0 +/- 0.3 Torr, mean +/- SE) to 28.2 +/- 1.7 and 28.1 +/- 1.3 Torr respectively (p less than 0.05) after 4 hours incubation. With 75 micrograms/ml pentoxifylline, P50 increased slightly to 27.8 +/- 1.4 Torr (0.05 less than p less than 0.1). 2,3-DPG was slightly higher (0.05 less than p less than 0.1) with pentoxifylline of 3 (11.15 +/- 4.12 mumol/gHb) and 75 micrograms/ml (10.62 +/- 2.32 mumol/gHb) than placebo. Other agents, 1-100 micrograms/ml of CoQ10 and 0.01-1 mg/ml of calcium hopantenate, neither P50 nor 2,3-DPG, Hb,ATP and glucose were changed compared to placebo. In vivo study, after administration of pentoxifylline 300 mg per day orally for 4 weeks to seven patients with COPD, P50 increased significantly from 29.0 +/- 0.6 to 30.4 +/- 0.6 Torr (p less than 0.05) and 2,3-DPG increased slightly from 11.67 +/- 0.56 to 14.33 +/- 1.12 mumol/gHb (p less than 0.1). These results suggest that pentoxifylline reduces hemoglobin-oxygen affinity by increasing 2,3-DPG and improves oxygen delivery to the tissues in patients with COPD.

Relationship between the Ability to Detect Added Resistance at Rest and Breathlessness during Bronchoconstriction in Asthmatics

The ability to detect added resistance at rest was compared to the magnitude of breathlessness (evaluated by a modified Borg scale) during bronchoconstriction in 27 stable asthmatics. Threshold for resistive load detection was analyzed in terms of the Weber fraction (delta R/R0) and mouth pressure (P) at the threshold. Bronchoconstriction was induced by inhalation of aerosolized acetylcholine. Both delta R/R0 and P correlated inversely with the Borg score during bronchoconstriction (r = -0.537 and r = -0.689, respectively; p less than 0.01). On the other hand, during bronchoconstriction the Borg score did not correlate with increased lung volume, acute changes in arterial blood gas composition and drive and timing component of ventilation during bronchoconstriction, although bronchoconstriction caused significant changes in these variables. These results indicate that central processing of afferent stimuli rather than peripheral sensor contribute both to the ability to detect added resistance at rest and to the magnitude of breathlessness during bronchoconstriction in asthmatics.

Criteria for Pulmonary and Respiratory Failure in COPD Patients – A Theoretical Study Based on Clinical Data

In 58 patients with chronic obstructive pulmonary disease, pulmonary gas exchange efficiency was assessed by the ratio: arterial to mixed venous PO2 difference (efficient part) versus alveolar to mixed venous PO2 difference (driving pressure for O2 transport). Patients with PaO2 below 75 mm Hg had a ratio lower than 50%. Patients with PaO2 below 60 mm Hg had lower values for arterial to mixed venous O2 content difference and higher blood lactic acid concentration than patients with PaO2 over 60 mm Hg. Arterial to mixed venous PO2 difference decreased linearly against PaO2 till PaO2 reached 60 mm Hg from which the difference began to attenuate. These figures in PaO2 are in close agreement with the criteria for pulmonary failure presented by the Ciba guest symposium (PaO2 below 75 mm Hg) and for respiratory failure by the National Heart, Lung and Blood Institute (PaO2 below 60 mm Hg).

Role of Chemosensitivity during Exercise in Normal Subjects and Patients with Pulmonary Emphysema

In 11 normal subjects (mean age = 22.8 years) and 8 patients with pulmonary emphysema (mean age = 70.4 years), the role of chemosensitivity in determining ventilation, cardiac output, lactic acid, and cyclic AMP and GMP was evaluated quantitatively during 150 or 30 W exercise and simulated exercise. Simulated exercise was done while the subjects took a rest by regulating arterial blood gases at exercise levels in patients and at PaO2 = 65 mm Hg and PaCO2 = 48 mm Hg in normal subjects. In normal subjects, the role of arterial blood gases in determining exercise ventilation, cardiac output, cyclic AMP and GMP are large, while those contributed much less to lactic acid. In patients, PaO2 contributed only half of the exercise ventilation. It accounted for a negligibly small portion of exercise cardiac output, lactic acid, and cyclic GMP. These results indicate, by deduction, that either augmentation of chemosensitivity, pH, or humoral factors is responsible for about half of the changes of exercise ventilation in patients with pulmonary emphysema. These factors seem to influence cardiac output, lactic acid, and cyclic AMP and GMP more strongly than PaO2 alone in exercising patients.

Changes in Potassium Content of Erythrocytes during Exercise in Man

Abstract. Factors affecting erythrocyte K+ content and plasma electrolytes during light exercise were examined in 8 normal subjects and 27 patients with chronic obstructive lung disease. The patients were classified into bronchitis, emphysema and intermediate groups. Arterial blood was obtained during rest, after 2, 5, and 7 min. of exercise on a bicycle ergometer (30 km/h without mechanical brake), and at 10 and 20 min. during recovery for analysis of PO2, PCO2, plasma H, Na+, K, and Cl‐, erythrocyte K+ content and whole blood lactate. Plasma H increased significantly in all subjects after 2 min. of exercise and PCO2 rose in normal, bronchitis, and emphysema groups during exercise, whereas PO2 did not change significantly. Plasma K rose promptly after the beginning of exercise and remained at high values during exercise. The rapid rise in PCO2 was associated with a significant decrease of calculated erythrocyte K in patients with chronic bronchitis. Although changes in plasma H were dependent on both PCO2 and lactate, erythrocyte K+ changes were significantly related only to changes in PCO2. These results indicate that the decrease in erythrocyte K+ is mainly controlled by changes in arterial PCO2 during light exercise in patients with chronic bronchitis.

Effects of Differences of Oxygen Affinity on Circulatory Response to Hypoxia

It is well known that tissue hypoxia is an important prognostic predictor in patients with chronic obstructive pulmonary disease (COPD). Compensatory responses to acute hypoxia occur in various organs and the magnitude of such response may also be an important factor in prognosis. P50, (oxygen tension at which the hemoglobin is 50% saturated with oxygen) is recognized as one of the factors affecting oxygen supply to the tissue. These studies were made to determine whether differences of P50 affect the circulatory response to acute hypoxia. Studies were made on nineteen male patients with COPD. They were divided into two groups according to low (less than 26.6 torr) or high (greater than 26.6 torr) P50. Isocapnic hypoxia was induced progressively with the patients being under right cardiac catheterization. The low P50 (25.8 +/- SD 0.6 torr) group included ten patients, and the high P50 (27.4 +/- 0.6 torr) group included nine patients. No differences could be detected in respect of pH, PaCO2, PaO2 or any hemodynamic parameters. Heart rate increased in both low and high P50 groups but the degree of the increase (delta HR/HR ROOM AIR x 100) in the high P50 group (20.7 +/- 9.2%) was significantly greater than in the low P50 group (9.4 +/- 10.9%). An increase in cardiac output was observed in the high P50 group (4.4 +/- 0.8 to 5.3 +/- 0.6 1/min), but not in the low P50 group (4.5 +/- 1.0 to 5.0 +/- 0.9 1/min). There was a significant positive relationship (r = 0.903) between hypoxic circulatory response and oxygen transport (TO2).(ABSTRACT TRUNCATED AT 250 WORDS)