Characteristics of nasal airflow and the effect of a nasal dilator in normal human subjects.

Nasal resistance contributes to negative airway pressure during breathing. We sought to define normal patterns of nasal flow and the effects of mechanical dilatation and splinting of the nares on flow during forced inspiration and expiration. Maximal inspiratory and expiratory flow volume loops (FVL) were determined in 17 normal subjects. Oral FVL were obtained with nares clamped and nasal FVL through a mask with and without dilatation of nares using a plastic splint (Nozovent). Oral FVL were normal in all. Two patterns of nasal FVL were observed: one indicating 'variable' extrathoracic obstruction, the other indicating 'fixed' extrathoracic obstruction. Maximal inspiratory flow at 50% of vital capacity (FiF50) was improved by the Nozovent only in those with a 'variable' pattern (FIF50 (L/sec): 1.54 +/- 0.3 to 2.86 +/- 0.5; P < 0.05, versus 1.92 +/- 0.3 to 2.21 +/- 0.3: P = 0.5). In subjects with a fixed pattern, failure of dilatation of the nares to increase flow suggests that the site of inspiratory flow limitation is within the bony nostril.

Impact of habitual cocaine smoking on the physiologic response to maximum exercise.

BACKGROUND: Habitual smoking of alkaloidal cocaine (crack) has been reported to be associated with a number of cardiopulmonary complications that may not be clinically obvious but could potentially interfere with normal physiologic responses to exercise and thus impair maximum exercise performance. STUDY OBJECTIVE: To evaluate the impact of regular use of cocaine on maximum exercise. DESIGN: Observational study in crack users and age- and gender-matched control subjects. SUBJECTS: Thirty-five habitual cocaine smokers (21 male and 14 female) and 29 age-matched sedentary control nonsmokers of cocaine (15 male and 14 female), all of whom were in good general health. METHODS: In these subjects, we compared physiologic responses to symptom-limited, incremental maximal exercise performed on a cycle ergometer using a ramp protocol. Comparisons were made for men and women separately. RESULTS: For both men and women, long-term cocaine smokers had a reduced aerobic capacity (maximum oxygen consumption) compared with control nonsmokers but did not show evidence of ventilatory limitation, reduced gas exchange threshold, increased physiologic dead space, or gas exchange abnormality at maximum exercise compared with the healthy control subjects. Although cocaine smokers had reduced maximum heart rates compared with control subjects, the relationship between submaximal heart rate and oxygen uptake was normal, indicating a normal cardiovascular response pattern. However, effort perception was similar between the two groups despite the difference in heart rate at maximum exercise, suggesting the possibility of perceptual dysfunction for effort. Differences in aerobic capacity between the crack users and nonusers could not be explained by differences in physical fitness or altered perception of dyspnea. CONCLUSION: In the subjects we studied, long-term cocaine smoking was associated with reduced maximum exercise performance, probably due to poor motivation or altered effort perception. No other identifiable physiologic abnormality appeared to limit exercise in the habitual crack users.

Acute effects of inhaled and i.v. cocaine on airway dynamics.

BACKGROUND: Wheezing has been reported by 32% of habitual smokers of crack cocaine, and several cases of crack-related acute exacerbations of asthma have been reported. STUDY OBJECTIVE: To compare the acute effects of physiologically active doses of smoked cocaine base and, i.v. cocaine hydrochloride (HCl), a subphysiologic dose of cocaine base (smoked "placebo"), and i.v. saline solution placebo on bronchomotor tone, subjective level of intoxication, and cardiovascular responses in healthy habitual crack users. DESIGN: A single-blind crossover study in which the order of route of administration (inhaled vs i.v.) was random but placebo always preceded the active drug. SUBJECTS: Fourteen healthy, nonasthmatic current crack-smoking subjects, 34 to 48 years of age, with a history of previous i.v. cocaine use (1 to 12 times per lifetime). METHODS: Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and measurements of airway resistance (Raw) and specific airway conductance (SGaw) were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min after administration of smoked cocaine base (38.5 +/- 2.3 [SEM] mg), smoked placebo (2.3 +/- 0.9 mg cocaine base), i.v. cocaine HCl (30.0 +/- 2.0 mg), and i.v placebo (saline solution). RESULTS: Both smoked active cocaine and i.v. cocaine HCl caused comparable, significant (p < 0.05) peak levels of acute intoxication (6.7 +/- 0.7 and 7.3 +/- 0.8, respectively) and increases in heart rate from baseline (29.6 +/- 2.9% and 21.4 +/- 3.7%, respectively, at 5 min). However, only smoked active cocaine caused significant decreases from baseline in SGaw (25.4 +/- 6.3% at 5 min), in contrast to nonsignificant changes after i.v. cocaine HCl (5.6 +/- 7.0% increase) and smoked placebo (10.2 +/- 6.0% decrease). CONCLUSIONS: Smoked cocaine base, but not systemically administered cocaine HCl, causes acute bronchoconstriction that is probably mediated by local airway irritation and could account for reports of crack-induced wheezing and asthma attacks in nonasthmatic and asthmatic individuals, respectively.

Bromocriptine and Triac therapy for hyperthyroidism due to pituitary resistance to thyroid hormone.

Although a number of patients with generalized resistance to thyroid hormone have been treated with bromocriptine (Brc), only one previously reported patient with nontumoral TSH-mediated hyperthyroidism, presumably due to pituitary resistance to thyroid hormone (PRTH), has been successfully treated with bromocriptine (Brc). In addition, several studies suggested that the T3 analog 3,5,3'-triiodothyroacetic acid (Triac) may control hyperthyroidism in patients with PRTH. In the current study a patient with PRTH diagnosed at age 15 yr underwent separate therapeutic trials with Brc and Triac, during which time physical parameters, thyroid function tests, systolic time intervals (STI), and oxygen consumption (VO2) were measured. On Brc therapy (12.5 mg/day), heart rate decreased (108 to 72/min), TSH decreased (5.7 to 1.2 mU/L), T3 decreased (9.9 to 1.7 nmol/L), free T4 decreased (205 to 21 pmol/L), STI lengthened (left ventricular ejection time, 0.389 to 0.405 s), and VO2 did not change (164 to 162 mL/min). We found no significant clinical improvement with a maximal dose of Triac (2.1 mg/day), only minimal reduction in goiter size; mild decreases in T3 (9.9 to 6.7 nmol/L), free T4 (205 to 113 pmol/L), and TSH (5.7 to 5.4 mU/L); no change in STI (left ventricular ejection time, 0.389 to 0.401 sec); and an increase in O2 consumption (VO2, 164 to 209 mL/min). Thus, the results favor Brc as effective therapy for this patient with PRTH.

Exercise-induced hypertension in normotensive patients with NIDDM.

The aim of this study was to determine whether blood pressure during mild to moderate exercise is abnormal in patients with non-insulin-dependent diabetes mellitus (NIDDM). The study group consisted of 11 patients with NIDDM and 11 nondiabetic subjects of comparable age and body mass index. All subjects were sedentary and basally normotensive. Bicycle ergometry was used to assess the effect of exercise on blood pressure at a steady state of 70-75 W, with a target duration of 20 min. Blood pressure was measured basally and every 5 min. Greater exercise-induced systolic blood pressure (mean max 208.0 +/- 6.0 vs. 177.0 +/- 3.0 mmHg) occurred in the NIDDM group (P less than 0.001). Neither pulse rate nor diastolic blood pressure differed between the groups before or during exercise. Return to basal pulse and blood pressure was similar. Mild to moderate exercise induces greater systolic blood pressure in sedentary patients with NIDDM. Because exercise is recommended as one therapeutic modality, intraexercise blood pressure should be considered in assessing the safety of this form of treatment.

Does exercise alter anaerobic threshold in coronary artery disease during beta blockade?

The effect of propranolol on cardiac patients undergoing exercise training is reported to increase exercise tolerance and maximum oxygen uptake (VO2 max) but its effect on anaerobic threshold (AT) is unknown. It was the purpose of this study to determine the role of exercise training with propranolol on AT in patients with coronary artery disease (CAD). Eight men and one woman with significant (CAD) were selected for this study. Each patient completed a maximum treadmill stress test (MTST) following the Bruce protocol on propranolol 40-160 mg/day as a control study. Cardiorespiratory variables were measured at rest and at each stage of the treadmill test. These patients underwent an exercise training programme for 12-16 weeks on the same dose of propranolol. Training sessions were for a minimum of 30-40 minutes, 3 times a week, with training heart rate of 75%-85% of the pretraining peak heart rate. Training heart rate ranged from 98 to 128 beats/min. They were retested with a MTST after the training programme, on the same dose of propranolol. AT was calculated noninvasively by measuring respiratory variables every 30 seconds in relation to work increment. AT was identified by measuring the time course of VE, VCO2, VE/VO2, etc. in relation to incremental work. The mean values of VO2, O2P and % VO2 max at AT before and after training on propanolol were as follows: VO2 = 1.43 L/min +/- .25 and 1.86 L/min +/- .44, O2P = 14.35 +/- 2.40 and 18.73 +/- 4.00 ml/beat, % of VO2 max = 68.20 +/- 6.31 and 73.59 +/- 5.84. The mean changes of VO2 O2P, and % of VO2 max were + 0.43 L/min +/- 0.20 (P < .003), + 4.38 +/- 2.55 (P < .003) and +/- 5.07% +/- 4.84 (P < .001). After exercise training on propanolol, the mean peak exercise tolerance time and absolute VO2 max increased by 2.8 min (from 9.0 to 11.8 min) (P < .001) and 22.7% (P < .007), respectively. We conclude that the increase in anaerobic threshold in patients with coronary artery disease may be due to improvement in VO2 max, increased stroke volume, and peripheral O2 extraction.

R--pulse wave timing: a technique for continuous cardiovascular monitoring in obstetrics--preliminary report.

A simple, noninvasive technique for continuous cardiovascular monitoring in obstetrics using R--pulse wave timing is described. This preliminary study suggests that different maternal heart rate/R pulse patterns are found in different clinical circumstances. A significant decrease in the R pulse interval occurred in the third trimester in both normal and diabetic women in the left lateral position when compared to the supine position. The R pulse intervals were all prolonged in the standing position in both gravid and nongravid women. During labor R pulse interval usually shortened during uterine contraction. Prolongation of R pulse interval was observed during thiopental injection, hypotension, and excessive bleeding at cesarean section. Exercise testing in healthy male subjects suggested that the change in R pulse interval becomes constant when the oxygen consumption rate reaches a plateau at 100% maximal work load. Further extensive clinical study appears worthwhile since it may add another dimension to cardiovascular monitoring and give an early indication of cardiovascular reserve.

Ventilatory and gas exchange responses to cycling with sinusoidally varying pedal rate.

To investigate factors controlling ventilation under conditions where the applied work load remains constant, but where hypothesized proprioceptive influences would be expected to vary, five subjects exercised at a constant work rate of 50 W on a cycle ergometer at pedaling rates which varied sinusoidally between 40 and 80 rpm. Each subject exercised continuously for 30 min at each of five sinusoidal periods. Minute ventilation (VE), carbon dioxide output (VCO2), oxygen uptake (VO2), and heart rate were computed breath-by-breath and amplitude and phase relations were extracted. We observed small fluctuations in VCO2 and VO2 engendered by varying metabolic requirements of moving the legs at varying rates. VE fluctuations were closely in phase with VCO2 and the amplitudes of the fluctuations were highly significantly correlated (r = 0.83, P less than 0.001); consequently end-tidal carbon dioxide tension fluctuations were small. Variation of pedaling rate, therefore, did not produce a ventilatory response independent of the effect of VCO2. The ventilatory responses to these forcings are inconsistent with an appreciable role for neurally mediated influences from the exercising limbs and provide further evidence that the exercise hyperpnea is linked to CO2 flow to the central circulation.

Some respiratory and metabolic effects of exercise in moderately obese men.

The effects of varying levels of exercise on oxygen uptake, CO2 production, blood pressure, arterial blood gasses, and arterial concentrations of glucose, insulin, and growth hormone were examined in ten normal weight and ten moderately overweight young men. At comparable external work loads with a bicycle ergometer, the lean men required less oxygen than the obese men. When oxygen uptakes were matched during exercise on a treadmill, the lean men were walking on a steeper grade or at a higher rate than the obese men. The efficiency of exercise as assessed by the relation between oxygen uptake and work did not differ between the two groups. Blood pressure rose more in the obese during exercise than in the lean. The fall in lactate and rise in bicarbonate was of greater magnitude during cycle ergometry than during treadmill exercise. Obese and lean men, however, showed similar changes. With each level of exercise, there was a fall in arterial insulin levels, but the concentrations in the blood of overweight men always remained significantly above that of the normal men. Growth hormones tended to be higher in the normal weight men, but the differences were usually not significant, and there was no significant rise with exercise in either group until the highest levels of work were achieved. Glucose concentrations tended to be higher in the obese men, but fell to constant levels in both groups during exercise. Blood pressure rose to a greater extent in the overweight men during exercise.

Ventilatory and gas exchange dynamics in response to sinusoidal work.

The dynamic relationships between ventilation and gas exchange variables during exercise were determined utilizing frequency analysis techniques. Five subjects exercised on a cycle ergometer for 30 min at work rates which fluctuated sinusoidally between 25 W and 80% of the anaerobic threshold at sinusoidal periods of 0.7, 1,2,4,6, and 10 min. VE, VCO2, VO2, and HR were computed and displayed breath-by-breath. From these and steady-state response data, digital computer routines extracted amplitude and phase relations between each variable and the perturbing work load. These response characteristics were well described by first-order linear dynamics with time constants for VE, VCO2, VO2, and HR averaging 1.4, 1.2, 0.8, and 0.8 min, respectively. The time constants of VE and VCO2 were strongly correlated among subjects (r = 0.97). Further, there was no evidence that neural afferents from the exercising limbs induced fast components in the ventilatory response to these forcings. These results are consistent with the hypothesis that exercise hyperpnea is linked to metabolism via carbon dioxide production.

Role of the carotid bodies in the heart rate response to breath holding in man.

To investigate the role of the carotid bodies in regulating the bradycardia of breath holding in man, we studied heart rate (HR) responses to prolonged breath holding (BH) in five asymptomatic asthmatic patients whose carotid bodies had been resected (CBR). Seven normal subjects served as controls. BH experiments were randomly initiated with single breaths of 100%, 21%, or 12% 92. During BH with 21% O2, normal subjects displayed the typical bradycardia; this response, however, was attenuated with the other O2 concentrations. In contrast, the CBR subjects manifested BH tachycardia which was inversely proportional to the O2 tension. HR increased in be CBR group by 5%, 31%, and 45% during BH with 100%, 21%, and 12% O2, respectively. These results demonstrate that the bradycardia of BH in normal man is under the influence of the carotid bodies. During BH and in the absence of carotid bodies, an O2 tension-dependent tachycardia is unveiled.

Ventilatory responses to the metabolic acidosis of treadmill and cycle ergometry.

Ventilation and acid-base responses were studied at comparable levels of O2 uptake during cycle ergometer and treadmill exercise, to determine the extent to which the type of exercise affects these responses. Twenty male subjects performed 50-, 100-, and 150-W cycle ergometer exercise and three work rates of similar O2 uptake on a treadmill. At comparable oxygen uptakes, arterial lactate and VE were higher and arterial pH and bicarbonate were lower for cycle ergometer than treadmill exercise. These differences could be accounted for by the greater degree of metabolic acidosis during cycle ergometer work. The increment in VE over that predicted (from an extrapolation of the linear relationship of the VE-VO2 relationship for low work rates) was linearly related to the decrease in arterial bicarbonate; VE was increased by approximately 4 1/min for each meq/1 of bicarbonate decrease for both treadmill and cycle ergometry.

Effect of carotid body resection on ventilatory and acid-base control during exercise.

To investigate the role of the carotid bodies in exercise hyperpnea and acid-base control, normal and carotid body-resected subjects (CBR) were studied during constant-load and incremental exercise. There was no significant difference in the first-breath ventilatory responses to exercise between the groups; some subjects in each reproducibly exhibited abrupt responses. The subsequent change in Ve toward steady state was slower in the CBR group. The steady-state ventilatory responses were the same in both groups at work rates below the anaerobic threshold (AT). However, above the AT, the hyperpnea was less marked in the CBR group. Ve and acid-base measurements revealed that the CBR group failed to hyperventilate in response to the metabolic acidosis of either constant-load or incremental exercise. We conclude that the carotid bodies 1) are not responsible for the initial exercise hyperpnea, 2) do affect the time course of Ve to its steady state, and 3) are responsible for the respiratory compensation for the metabolic acidosis of exercise.