The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients.

The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 mol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6 percent; IDDM, 10.5 percent; NIDDM, 9.0 percent). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 æmol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50 percent hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected

Age-related reduction in 99Tcm-DTPA alveolar-capillary clearance in normal humans.

Age is known to reduce the efficacy of body organs and systems, even in the absence of disease. The alveolar-capillary clearance (ACC) rate is representative of the alveolar-capillary barrier's functional state. We studied 29 healthy non-smokers, who were selected after clinical and radiographic evaluation. The patients were divided into three groups based on age: Group I, < or = 30 years (n = 10); Group II, 31-55 years (n = 9); Group III, > or = 56 years (n = 10). Each patient inhaled 750 MBq 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) aerosol generated by a Venticis nebulizer (particles with a mean diameter of 1.1 microns) for 5 min. Forty frames of 30 s duration each were acquired and the ACC rates for the right and left lungs determined using a computer program. The mean ACC rates for the three groups were as follows: Group I, 1.31% min-1; Group II, 1.08% min-1; Group III, 0.76% min-1. The differences between Groups I and III (P < 0.001) and Groups II and III (P = 0.03) were shown to be significant. There was no significant difference between Groups I and II. Possible explanations for an age-related reduction in ACC rates include a reduction in the internal alveolar surface, the closure of the small airways, a reduction in the lung blood capillaries and a reduction in cardiac output. We conclude that there appears to be an age-related reduction in ACC rates in healthy non-smokers, even in the absence of clinically and radiographically detectable lung disease. However, larger studies are required.

Pulmonary function of individuals with congenital cleft palate.

Ventilatory pulmonary function was investigated in 160 children and adults with repaired or unrepaired congenital cleft palate in comparison with 130 normal children and adults. Pulmonary function tests included measurement of lung volumes, of maximal voluntary ventilation (MVV) and of forced spirometry parameters: forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio and mean forced expiratory flow during the middle half of FVC (FEF25-75). Patients with cleft palate demonstrated significant differences from normal individuals in some of the measurements made. Functional alterations were observed at higher frequency among adult patients with unrepaired clefts and mainly consisted of a reduction in expiratory flows and MVV. However, the deviations observed were usually discrete and probably of low physiopathologic significance. The results permit us to conclude that, in contrast to data reported by others, subjects with congenital cleft palate have little impairment of pulmonary ventilatory function.

Cholinergic bronchomotor tone and airway caliber in insulin-dependent diabetes mellitus.

It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the present study, we assessed the cholinergic bronchomotor tone in 34 insulin-dependent diabetic patients and in a control group of 32 healthy subjects (group C). As an index of the intensity of cholinergic tone to the airways, we measured the increase in specific airway conductance (Gaw/VL) induced by aerosol administration of atropine sulfate. In all of the patients and normal individuals the autonomic cardiovascular activity was also evaluated by the tilting test and by the magnitude of the respiratory sinus arrhythmia (RSA). In 19 patients without symptoms of autonomic neuropathy (AN) (group D-1), the autonomic cardiovascular activity was comparable to that of group C. The other 15 patients presented with at least one symptom of AN and a depressed heart rate (HR) control when submitted to the tests of autonomic activity (group D-2). Before atropine administration, Gaw/VL was significantly higher (p less than 0.05) in group D-2 (2.48 +/- 0.12 s-1.kPa-1 [mean +/- SE]) than in group D-1 (2.11 +/- 0.10 s-1.kPa-1). Aerosol atropine caused a significant increase (p less than 0.001) in airway caliber in all three groups; however, the increase in Gaw/VL was significantly lower in group D-2 (0.26 +/- 0.05 s-1.kPa-1) when compared with group D-1 (0.63 +/- 0.09 s-1.kPa-1; p less than 0.01) and group C (0.67 +/- 0.06 s-1.kPa-1; p less than 0.001). A weak but significant (p less than 0.02) correlation was observed between the increases in Gaw/VL provoked by atropine and the magnitude of RSA. Our findings suggest that the reduction in parasympathetic bronchomotor tone may cause an increase in basal airway caliber in diabetic patients with AN, compared to patients without AN.

Pneumomediastinum, pneumothorax and subcutaneous emphysema following the measurement of maximal expiratory pressure in a normal subject.

Mediastinal and subcutaneous emphysema have been reported as a consequence of deliberate manipulations of the breathing pattern producing a Valsalva-like maneuver in healthy subjects. We present a case of pneumomediastinum, pneumothorax and subcutaneous emphysema occurring in a normal volunteer after repeated measurements of the PEmax.

Evaluation of the autonomic nervous system of the heart in male patients with mitral valve prolapse syndrome using respiratory sinus arrhythmia and dynamic exercise.

The autonomic nervous system of the heart was evaluated in two male groups composed of 11 patients with mitral valve prolapse and of 10 normal subjects, using the heart rate response in two types of tests: respiratory sinus arrhythmia at rest and dynamic exercise. Sinus arrhythmia was of higher magnitude in patients with mitral valve prolapse when compared to the control group; however, the differences reached statistical significance only at a respiratory frequency of 7 cycles/min. With respect to dynamic exercise (25, 50, 100, 150 W during 4 min), the heart rate response, either in terms of the early, vagus-dependent fast tachycardia (first 10 s), or the late, sympathetic-dependent tachycardia (1-4 min) was normal in both groups studied, the same occurring with aerobic exercise capacity evaluated by measurement of the anaerobic threshold. Thus, our results show that in the group of male patients with mitral valve prolapse studied here, the parasympathetic abnormalities, if present, are of questionable physiological significance and do not affect the sympathetic and parasympathetic control of heart rate during dynamic exercise.

The use of isometric exercise as a means of evaluating the parasympathetic contribution to the tachycardia induced by dynamic exercise in normal man.

Fourteen normal subjects were submitted to isometric exercise (IE), dynamic exercise (DE) and a combination of the two (IE + DE). The main purpose of the present study was to use IE as a means of evaluating the mechanism of the heart rate (HR) increase induced by DE. To this end, the magnitude of the IE (handgrip) was standardized so as to cause an elevation of HR almost exclusively by vagal withdrawal: IE was performed using a dynamometer strain-gauge system with a linear response at 75% of maximum voluntary contraction (MVC) for 10 s, repeated at 1 min intervals. The change in HR evoked by IE under control conditions was compared with that evoked during DE, and during the corresponding recovery period. DE was performed by the legs, with the subject in the seated position for 4 min, at workloads of 55 and 105 watts, separated by a rest period. In the combined protocol, IE was performed at the beginning of DE, as well as at 1, 2 and 3 min during DE, and at 0, 1, 2, 3 and 5 min during recovery period. The following results were obtained: (1) IE associated with DE always induced smaller increase in heart rate than IE alone, and this effect was more marked at 105 than at 55 W; this finding suggested a workload-dependent vagal withdrawal at the very beginning of DE that was sustained until the end of effort.(ABSTRACT TRUNCATED AT 250 WORDS)

Limitations of facial immersion as a test of parasympathetic activity in man.

1. The heart rate response to immersion of the face in water, as an isolated manoeuvre or in combination with apnoea, was studied in eight normal volunteers to establish the conditions under which it could be used as a standardized, simple, non-invasive and reproducible test of parasympathetic activity. 2. The following procedures were evaluated: (a) 10 s apnoea in air at different lung volumes; (b) facial immersion in water for 2 min at various temperatures (5, 15 and 25 degrees C), with respiration maintained through a closed circuit; (c) combination of immersion and apnoea at different lung volumes. Three volunteers were re-evaluated after pharmacological blockade with atropine sulphate (0.04 mg/kg body weight). 3. The results showed that: (a) apnoea in air triggered lung volume-dependent heart rate responses; (b) facial immersion in water induced transient bradycardia which was maximum between 20 and 30 s of immersion; (c) there was no appreciable difference in the bradycardia evoked by immersion at different temperatures; (d) the combination of immersion and apnoea caused heterogeneous heart rate responses with no potentiation of bradycardia in relation to each manoeuvre as performed separately; (e) atropine did not reduce the magnitude of bradycardia induced by immersion in two of the subjects studied. 4. The variability of responses observed in the present study was probably due to the multiple receptors and afferent pathways that are simultaneously excited during these manoeuvres. As a consequence, the autonomic efferent response will depend on the unpredictable net effect of interaction of these mechanisms. This is a limiting factor for the standardization of this test as a simple and reproducible method for the assessment of parasympathetic activity. 5. Furthermore, the results obtained under pharmacological blockade indicate that the vagal efferent mechanism is not the only factor responsible for the bradycardia caused by facial immersion without apnoea.

Effects of intravenous atropine on static P-V curves of the lung in normal man.

In eight normal subjects we studied the effects of intravenous (i.v.) injection of 2 mg atropine sulfate on the static lung recoil pressure-volume (PV) curves, plethysmographic airway resistance (Raw), and maximum expiratory flow rates (Vmax). In addition, we determined the influence of atropine injection in esophageal elastance (Ees) by measuring the esophageal pressure with an esophageal balloon containing five different volumes (0.5 to 4 ml) of air and by calculating the change in esophageal pressure per unit change in balloon volume (delta Pes/delta Vb). This procedure allowed us to obtain static lung recoil pressure (Pst(1] at a balloon volume extrapolated to zero, thus avoiding the interference of changes in esophageal tone following atropine administration with the measurement of Pst(1). After vagal blockade with atropine, Pst(1) significantly decreased with a shift to the left of PV curves, Raw decreased, and Vmax increased mainly at lower lung volumes. Ees also decreased with parasympathetic blockade. We interpret these findings to indicate that inhibition of vagal tone results in dilatation of large and small airways, and also in the relaxation of smooth muscle in terminal lung units.

Multiple pulmonary thromboembolism diagnosed by two-dimensional echocardiography.

A 55-year-old man was admitted to our hospital because of progressive dyspnea, orthopnea and hemoptysis. Two-dimensional echocardiography multiple echo-dense images 1-4 mm in diameter were consistently seen crossing the tricuspid valve. A hypothesis of multiple pulmonary thromboembolism was raised. Clinical and postmortem evidence were later obtained to confirm this diagnosis.

Respiratory impedance in normal humans: effects of bronchodilatation and bronchoconstriction.

Total respiratory resistance and reactance from 3 to 30 Hz were determined by the method of forced random noise oscillation in 12 normal male subjects before and after bronchodilatation and bronchoconstriction induced by deep breaths of aerosols of isoproterenol and atropine and of methacholine and histamine. Isoproterenol and atropine induced small decreases in total respiratory resistance at most frequencies, and isoproterenol decreased resonant frequency slightly (P less than 0.01). After administration of both methacholine and histamine, resonance frequency increased (P less than 0.01) and total respiratory resistance became more frequency-dependent, increasing mainly in the lower frequency range. In six of the subjects, we attempted to produce central deposition of methacholine by rapid, shallow breathing and peripheral deposition of the drug by slow, deep breathing. Only two subjects had suggestive evidence of central bronchoconstriction. No difference was noted, however, in the impedance behavior with either type of breathing. In awake humans, impedance analysis does not seem to distinguish between central and peripheral airway constriction.

Parasympathetic contribution to bradycardia induced by endurance training in man.

Seven normal subjects of sedentary habits were submitted to a 10 week period of endurance physical training on a cycloergometer. The training programme produced a mean 15.6 +/- 1.4% (+/- SE) increase in VO2max (from 39.7 +/- 2.0 ml . kg-1 . min-1 to 45.9 +/- 2.4 ml . kg-1 . min-1) and a reduction in resting heart rate (HR) from 69 +/- 1.9 to 58 +/- 1.7 beats . min-1 in the supine position. After pharmacological blockade of the parasympathetic system with atropine sulphate, HR rose on average by 53 +/- 3.9 beats . min-1 before training and 47 +/- 3.6 beats . min-1 after training, the difference being statistically nonsignificant. The magnitude of respiratory sinus arrhythmia (RSA) was similar before and after the period of physical conditioning. The respiratory variation in HR ( Delta HR) at the 1 litre tidal volume was 20 +/- 2.4 beats . min-1 and 20 +/- 2.6 beats . min-1 before and after training, respectively. At the 2 litre tidal volume, these values were 25 +/- 3.2 and 27 +/- 4.5 beats . min-1. Similar results were obtained with the RSA test when a group of 13 sedentary individuals (VO2max = 39.4 +/- 1.3 ml . kg-1 . min-1) was compared with a group of 7 athletes who are medium distance runners (VO2max = 53.8 +/- 1.3 ml . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of pharmacological blockade of the cardiac parasympathetic system with atropine in normal men.

The effect of parasympathetic blockade with intravenously administered atropine (0.04 mg/kg body weight) on the heart rate (HR) of 11 normal males was evaluated using a standardized isometric exercise (handgrip). This type of exercise, when maintained for 10 s at the maximum intensity tolerated by the volunteer, causes tachycardia mediated almost exclusively by parasympathetic withdrawal. The test was performed under baseline conditions and at 20 +/- 3, 33 +/- 3, 42 +/- 3, 52 +/- 3 and 61 +/- 3 min after atropine infusion. The heart rate of the subjects at rest in the supine position (mean +/- SEM) was 70 +/- 2 bpm, reaching values of 119 +/- 3 bpm after atropine. Under control conditions (sitting position), the increase in HR induced by isometric exercise was 22 +/- 1.8 bpm. After blockade, the increase was 4 +/- 0.8, 4 +/- 0.7, 5 +/- 0.6, 4 +/- 1.0 and 4 +/- 0.8 bpm, respectively, at each repetition of the test. These results suggest that the blockade induced by this dose of atropine is effective for at least 1 h. They also indicate the need for a more rigorous definition of the functional half-life of atropine in the heart, when considering physiological tests that either stimulate or withdraw parasympathetic activity upon the heart.

Subtle cardiac autonomic impairment in Chagas' disease detected by baroreflex sensitivity testing.

The sensitivity of baroreflex bradycardia and tachycardia was determined in fourteen patients with Chagas' disease who seemed to be normal with respect to cardiac autonomic control evaluated in terms of heart rate responses to the conventional atropinization and Valsalva maneuver tests. Eleven normal subjects were studied for comparison. Baroreflex sensitivity was determined by relating the beat-to-beat pulse intervals to systolic pressure values during transient phenylephrine- and amyl nitrite-induced changes in arterial pressure. Chagasic patients showed mean bradycardia sensitivity (10.1 +/- 1.3 ms/mmHg) which was significantly lower than that obtained for the control group (16.7 +/- 2.1 ms/mmHg). When only the subgroup of ten patients with overt disease (cardiac and/or digestive form) was considered, the value fell to 8.6 +/- 1.4 ms/mmHg. The lowest individual values were exhibited by the majority of patients with exclusive cardiac or associated cardiac and digestive disease. Patients with only digestive disease or without overt disease (indeterminate form) had values within the normal range. Tachycardia sensitivity (6.3 +/- 0.8 ms/mmHg) was similar to that obtained for the control group (6.6 +/- 1.0 ms/mmHg). Only one patient with associated disease presented a reduced value. These data show that the estimation of baroreflex sensitivity can be used to identify impaired cardiac autonomic control in chronic Chagas' disease not detectable by conventional tests. The reduced baroreflex sensitivity appears to be due to the subtle impairment of the parasympathetic influence on the heart. Furthermore, there is a relationship between the degree of baroreflex sensitivity and the clinical form of organic involvement in Chagas' disease.

Comprometimento das vias aereas na forma cronica da doenca de Chagas. / Airways involvement in chronic Chagas' disease

Sao relativamente poucos os estudos relacionados com o comprometimento primario dos pulmoes na forma cronica da doenca de Chagas. Exames anatomo-patologicos realizados anteriormente mostraram dilatacao das vias aereas e degeneracao dos ganglios parassimpaticos bronquicos em pacientes chagasicos cronicos. Dilatacoes anormais das vias aereas foram tabem observadas atraves de estudos broncograficos de pacientes com doenca de Chagas.Resultados de investigacoes anteriores sugeriram aumento da reatividade bronquica a drogas colinergicas neste grupo de pacientes. Entretanto em estudo recentemente realizado em nosso laboratorio, nao se observou diferenca significante de reatividade bronquica a metacolina entre individuos normais e pacientes chagasicos. A avaliacao cuidadosa de pacientes com a fase cronica da doenca de Chagas em laboratorio de funcao pulmonar levou a conclusao de que na ausencia de insuficiencia cardiacas os resultados dos diferentes testes estao nos limites normais. Em estudos anteriores foram referidos pequenos decrescimos dos fluxos expiratorios maximos ou do volume expiratorio forcado em um segundo em alguns grupos de pacientes chagasicos

Impairment of baroreflex control of the sinoatrial node after cardiac operations with extracorporeal circulation in man.

The sensitivity of the baroreceptor reflex to transient hypertension was determined in 13 patients before (control) and after (72 hours) open cardiac operations with extracorporeal circulation (ECC). In all patients early postoperative values were appreciably decreased (p less than 0.01) as compared to the preoperative values. This decrease suggested severe impairment of baroreflex control of the sinoatrial node. These changes were not correlated with concurrent alterations in heart rate or systemic arterial, left atrial, or right atrial pressures. In addition, respiratory sinus node arrhythmia was absent in all subjects. In four patients, subsequent studies 4, 8, 10, and 12 months, respectively, after the operation revealed good recovery of baroreflex sensitivity and respiratory influences on beat-to-beat variation. No similar effects were observed in two patients studied before and after cardiac operations without ECC. It is possible that direct trauma to the nervous supply of the sinoatrial node is a major factor in that reversible dysfunction; in fact, in three patients evidence was obtained that while sinoatrial node responses were impaired, the reflex control of the atrioventricular region remained unaltered. These findings point to further impairment of the fine control of heart rate imposed by the conditions of cardiac operations with ECC in patients with previously curtailed cardiac reserve.

Intraoperative measurement of the orifice area in patients with mitral valve stenosis.

This study was carried out in ten patients in order to compare results of mitral valve area evaluated by a new intraoperative technique and those provided by conventional hemodynamic methods. The results obtained correlated very well (r = 0.95) with values calculated by the Gorlin formula. Paired data checking were closer than 0.3 cm2 in all but one of patients with moderately severe mitral stenosis. It is concluded that the method for intraoperative measurement of the mitral valve area is simple, safe and reliable.

Chagas' heart disease as an experimental model for studies of cardiac autonomic function in man.

Patients presented here include apparently healthy persons who had diagnostic evidence of chronic cardiac Chagas' disease in the form of a positive complement-fixation test and an abnormal electrocardiogram. They had never been in heart failure. All were examined for autonomic cardiac function. Normal persons served as controls. Patients with Chagas' disease with sole involvement of hollow viscera were also included. In patients with cardiac Chagas' disease, failure of the heart rate to increase after administration of atropine and greatly reduced reflex changes in cardiac rate are believed to be a functional disorder related to degeneration of the neuronal supply to the sinoatrial region of the heart. It is concluded that Chagas' disease is a model of spontaneous denervation of the heart which may be used for the assessment of autonomic control of cardiac function in man.