Impact of aging on conduit artery retrograde and oscillatory shear at rest and during exercise: role of nitric oxide

Aging has been recently associated with increased retrograde and oscillatory shear in peripheral conduit arteries, a hemodynamic environment that favors a proatherogenic endothelial cell phenotype. We evaluated whether nitric oxide (NO) bioavailability in resistance vessels contributes to age-related differences in shear rate patterns in upstream conduit arteries at rest and during rhythmic muscle contraction. Younger (n=11, age 26 ± 2 years) and older (n=11, age 61 ± 2 years) healthy subjects received intra-arterial saline (control) and the NO synthase inhibitor N(G)-Monomethyl-L-arginine. Brachial artery diameter and velocities were measured via Doppler ultrasound at rest and during a 5-minute bout of rhythmic forearm exercise. At rest, older subjects exhibited greater brachial artery retrograde and oscillatory shear (-13.2 ± 3.0 s(-1) and 0.11 ± .0.02 arbitrary units, respectively) compared with young subjects (-4.8 ± 2.3 s(-1) and 0.04 ± 0.02 arbitrary units, respectively; both P<0.05). NO synthase inhibition in the forearm circulation of young, but not of older, subjects increased retrograde and oscillatory shear (both P<0.05), such that differences between young and old at rest were abolished (both P>0.05). From rest to steady-state exercise, older subjects decreased retrograde and oscillatory shear (both P<0.05) to the extent that no exercise-related differences were found between groups (both P>0.05). Inhibition of NO synthase in the forearm circulation did not affect retrograde and oscillatory shear during exercise in either group (all P>0.05). These data demonstrate for the first time that reduced NO bioavailability in the resistance vessels contributes, in part, to age-related discrepancies in resting shear patterns, thus identifying a potential mechanism for increased risk of atherosclerotic disease in conduit arteries.     

Oxygen consumption at rest and during exercise in pregnancy.

The oxygen consumption (Vo2) of 12 normal women was measured at monthly intervals during pregnancy and 2, 6 and 12 weeks and 6 months postpartum. At each study session measurements were made sitting at rest, during standard steady-state exercise on a bicycle ergometer, and for 10 minutes of recovery. A significant increase in exercise Vo2 was observed in late pregnancy when compared to paired postpartum values. The oxygen debt incurred by standard exercise was also greater in late pregnancy than 12-14 weeks postpartum.     

Respiration in conscious dogs at rest and during exercise.

25 mongrel dogs (average b.w. 24.6 kg) were studied on several occasions at rest and during treadmill exercise of up to 10 mph (15% incline). Minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), tidal volume (VT) and respiratory frequency (f) were determined at rest and at each level of exercise. Individual variability in resting VO2 was considerable (71--695 ml/min). Most often the dogs panted, with VE's above 25 liters/min and f's above 100 min-1. The averate VE/VO2 was 109 at rest. VO2 was linearly related to VE (VO2 = 9.17 VE + 66.9; r = 0.80). Differences in resting VE were largely due to differences in f (f = 3.57 VE + 21.2; r = 0.82). Considerable individual variability in VO2 for a given work load was also observed during exercise. Some dogs showed significant differences in VO2 from experiment to experiment while running at a given treadmill speed. These differences were largely related to the levels of VE. VE/VO2 decreased to 50. We found a leveling off of VO2 (at about 60 ml/min/kg) at treadmill speeds of 5 mph, suggesting that the maximal VO2 in dogs is less than previously reported.     

Circulatory changes in acute glomerulonephritis at rest and during exercise.

In order to evaluate the effects of acute glomerulonephritis on the circulation, 6 patients were investigated at rest and during moderate exercise. With the patients in a state of rest the cardiac index and the stroke volume index were significantly higher in acute glomerulonephritis than normal, despite significantly raised right and left atrial pressures. Oxygen consumption was significantly increased (P less than 0.01) and the arteriovenous oxygen difference was narrowed significantly (P less than 0.001) in acute glomerulonephritis as compared to normal subjects. The calculated increase in cardiac output was due to both a rise in oxygen consumption and a narrowing of arteriovenous oxygen difference, the latter being more significant. The exercise-induced changes in cardiac output in the patients with glomerulonephritis were not different from those in normal subjects. These results showed that the circulatory changes in the oliguric stage of acute glomerulonephritis resemble those in the hyperkinetic states; the raised mean right atrial and pulmonary wedge pressures do not indicate the presence of heart failure when resting cardiac output is above normal level and response to exercise is normal.     

Circulatory changes in acute glomerulonephritis at rest and during exercise.

In order to evaluate the effects of acute glomerulonephritis on the circulation, 6 patients were investigated at rest and during moderate exercise. With the patients in a state of rest the cardiac index and the stroke volume index were significantly higher in acute glomerulonephritis than normal, despite significantly raised right and left atrial pressures. Oxygen consumption was significantly increased (P less than 0.01) and the arteriovenous oxygen difference was narrowed significantly (P less than 0.001) in acute glomerulonephritis as compared to normal subjects. The calculated increase in cardiac output was due to both a rise in oxygen consumption and a narrowing of arteriovenous oxygen difference, the latter being more significant. The exercise-induced changes in cardiac output in the patients with glomerulonephritis were not different from those in normal subjects. These results showed that the circulatory changes in the oliguric stage of acute glomerulonephritis resemble those in the hyperkinetic states; the raised mean right atrial and pulmonary wedge pressures do not indicate the presence of heart failure when resting cardiac output is above normal level and response to exercise is normal.     

Effect of breathing dry warm air on respiratory water loss at rest and during exercise

The changes in respiratory water loss with time, expressed as the mass of water vapour lost per liter BTPS of ventilation (MH2O), and expired temperature (TE), used to calculate the relative humidity (ERH), were investigated in ten normal subjects while breathing warm dry air by mouth (PIH2O = 0 kPa; TI = 30 degrees C): at rest for a period of 35 min; during 15 min light muscular exercise (50 W); at increasing work load from 50 to 100 W between the 5th and 10th min of the exercise. The data collected were compared to those obtained in room air conditions (PIH2O = 0.68-1.3 kPa) and under conditions with slightly heated inspired air (TI = 28-30 degrees C). At rest, when breathing dry warm air MH2O and ERH fell during the first 15 min, while they recovered their initial values during the last 20 min. In contrast no differences in MH2O or ERH were observed when breathing ambient warm air. At constant and moderate work load for 15 min, the respiratory water loss fell significantly (compared to the 5th min) at the 10th and the 15th min when breathing warm dry air. The added hyperpnea which was obtained by increasing work load from 50 to 100 W between the 5th and 10th min of exercise did not further reduce MH2O and ERH. The transient fall in MH2O and ERH, which lasted at least 15 min either at rest or during muscular exercise, suggested that the mechanism underlying humidification of expired gas is overwhelmed by thermal stress. Since the upper airways mucosa is unable to saturate expired gas, this also suggested that the mucosa is dehydrated and probably hyperosmotic. The progressive recovery in MH2O and ERH after 15 min of warm dry air breathing at rest, suggest operation of a slow adaptive mechanism.     

Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects of a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3,100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean +/- SD, -17 +/- 14%), increases in mean right atrial (31 +/- 21%), mean pulmonary artery (14 +/- 14%) and mean pulmonary capillary wedge (17 +/- 14%) pressures and an increase in cardiac index (18 +/- 10%) due to an increased heart rate without any significant change in stroke volume. During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease. It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients.     

Effects of nifedipine and diltiazem on hemodynamic responses at rest and during exercise in hypertensive patients

Twelve patients with uncomplicated systemic hypertension were treated with nifedipine (30 mg/day) and diltiazem (180 mg/day) for 1 month each, and performed two stage (50 watt and 100 watt) of bicycle ergometer exercise before and after each period of administration. Both drugs produced significant reduction in systolic and diastolic blood pressure at rest and during exercise, while the mean values of systolic blood pressure tended to be less with nifedipine than with diltiazem. Nifedipine caused a nonsignificant increase in heart rate at rest and during exercise, but diltiazem significantly decreased it at rest and during exercise. Cardiac output was significantly increased at rest and during mild exercise (50 watt), but not during more strenuous exercise (100 watt) with both drugs. Thus, different actions in arterial vasodilation and chronotropism between nifedipine and diltiazem in usual clinical doses were noted. However, nifedipine and diltiazem may be effective in hypertensive patients, probably with left ventricular dysfunction, because both drugs reduced systemic blood pressure even during exercise with simultaneous increase in cardiac output at rest and during mild exercise.     

Left ventricular function at rest and during exercise in acute hypothyroidism.

The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states. The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.     

Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD

INTRODUCTION: Inhaled anticholinergic drugs are often recommended for use as a first-line therapy for patients with COPD because they provide similar or more effective bronchodilating actions, as well as fewer side effects. It is not known, however, which class of bronchodilators is more advantageous for pulmonary hemodynamics, particularly during exercise. OBJECTIVES: To compare the effects of oxitropium and fenoterol on pulmonary hemodynamics in patients with COPD at rest and during exercise. PATIENTS: The study participants consisted of 20 consecutive male patients with stable COPD, a mean (+/- SD) age of 68+/-8 years old, and an FEV1/FVC ratio of 47.5+/-10.0%. METHODS: Eleven patients inhaled two puffs of oxitropium, and nine patients inhaled two puffs of fenoterol. Seven members of each group performed incremental exercise using a cycle ergometer. The hemodynamic measurements with right heart catheterization were performed by taking the average of three consecutive respiratory cycles before and after the administration of inhaled bronchodilators at rest and during exercise. RESULTS: At rest, despite a similar improvement of spirometric data with the two drugs, fenoterol, not oxitropium, caused significant increases in heart rate and cardiac output, a decrease in pulmonary vascular resistance, and a deteriorated Pao2. During exercise, however, both drugs similarly attenuated elevations in the mean pulmonary arterial pressure (40+/-12 to 38+/-10 mm Hg by oxitropium, and 41+/-9 to 36+/-9 mm Hg by fenoterol), the mean pulmonary capillary wedge pressure, and the mean right atrial pressure. CONCLUSION: Our findings indicate that both classes of bronchodilators are equally beneficial in the attenuation of right heart afterload during exercise in patients with COPD.     

Effects of nifedipine on arterial oxygenation at rest and during exercise in patients with stable angina

The effects of nifedipine on arterial oxygenation and hemodynamics were studied at rest and during bicycle exercise in 12 men (mean age 55 years, range 41 to 67) with stable exertional angina. The study was conducted double-blind on 2 days, 1 week apart, using a placebo-controlled crossover design. On each day, measurements at rest were made before and 20 minutes after 20 mg sublingual nifedipine or placebo and were followed by measurements made during exercise. Compared with placebo, nifedipine reduced mean arterial pressure, systemic vascular resistance and pulmonary vascular resistance, and increased heart rate and cardiac output at rest and during exercise. It did not alter mean pulmonary artery or pulmonary artery wedge pressures at rest, but decreased them during exercise. Nifedipine decreased arterial oxygen tension (PaO2) from 96 +/- 10 to 90 +/- 13 mm Hg (p less than 0.05) at rest and from 99 +/- 11 to 92 +/- 12 mm Hg (p less than 0.005) at submaximal exercise (33 +/- 21 W), but did not alter it (100 +/- 12 versus 100 +/- 16 mm Hg, p = NS) at maximal exercise (68 +/- 30 W). The reduction in PaO2 was not due to alveolar hypoventilation, because nifedipine did not alter arterial carbon dioxide tension, or to changes in mixed venous oxygen tension, which nifedipine increased at rest (39 +/- 2 versus 43 +/- 3 mm Hg, p less than 0.001) and during submaximal exercise (31 +/- 4 versus 33 +/- 4 mm Hg, p less than 0.03) and maximal exercise (27 +/- 3 versus 31 +/- 3 mm Hg, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nifedipine on systemic and regional oxygen transport and metabolism at rest and during exercise

In a placebo-controlled, randomized, cross-over, double-blind study of 12 patients with stable exertional angina, we measured at rest and during bicycle exercise the effects of 20 mg of nifedipine administered sublingually on hemodynamics and systemic and regional oxygen extraction and metabolism. Nifedipine decreased systemic vascular resistance by 38% at rest (p less than .001) and by 28% during exercise (p less than .001). Cardiac output increased from 4.6 +/- 0.6 to 6.0 +/- 0.9 liters/min (p less than .001) at rest after nifedipine and from 10.6 +/- 3.7 to 11.8 +/- 3.4 liters/min (p less than .005) during exercise. After nifedipine, the arterial-mixed venous O2 content difference decreased from 4.7 +/- 0.6 to 3.5 +/- 0.5 ml/100 ml (p less than .001) at rest and from 10.5 +/- 1.7 to 8.8 +/- 1.6 ml/100 ml (p less than .001) during exercise. After nifedipine the arterial-iliac venous O2 content difference also decreased at rest, from 5.9 +/- 1.5 to 4.8 +/- 1.7 ml/100 ml (p = .06) but increased during exercise from 13.1 +/- 1.5 to 14.0 +/- 1.8 ml/100 ml (p less than .05). Oxygen consumption was not significantly altered at rest or during exercise. Nifedipine decreased mixed venous carbon dioxide tension (PCO2) during exercise from 53 +/- 3.5 to 50 +/- 4.0 mm Hg (p less than .05) but increased iliac venous PCO2 slightly from 61 +/- 4.6 to 63 +/- 5.2 mm Hg (p less than .01). Exercise pH was not significantly altered, but arterial lactate increased more after nifedipine (2.65 +/- 1.95 mmol/liter placebo, 3.54 +/- 2.74 mmol/liter nifedipine; p less than .05). Thus nifedipine produces similar changes in O2 extraction in mixed venous and iliac venous blood at rest but directionally opposite changes during exercise. The data support the hypothesis that nifedipine does not alter the distribution of cardiac output to the legs at rest, but during dynamic leg exercise reduces the redistribution of cardiac output to the legs. This probably results from the shunting of blood flow away from exercising muscles by the generalized vasodilatation of nifedipine.     

Effect of betaxolol on heart rate at rest and during exercise

Betaxolol, a new beta-receptor blocking drug administered as a single dosage of 40 mg given orally, causes a maximal reduction of heart rate at rest of 30%, during a submaximal exercise of 28% and at rest after exercise of 33%. The reduction in heart rate is still highly significant 48 hours after administration at rest, during exercise as well after administration. A smaller but still significant reduction in heart rate was found after the oral administration of 20 mg of betaxolol. Betaxolol appears to be more effective than a single oral dose of 160 mg of long-acting propranolol. No significant differences were found between 9 submaximal exercise tests performed within a period of 50 hours in normal subjects.     

Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at rest and during exercise in COPD

STUDY OBJECTIVES: To investigate the effect of volitional pursed-lips breathing (PLB) on breathing pattern, respiratory mechanics, operational lung volumes, and dyspnea in patients with COPD. SUBJECTS: Eight COPD patients (6 male and 2 female) with a mean (+/-SD) age of 58 +/- 11 years and a mean FEV1 of 1.34 +/- 0.44 L (50 +/- 21% predicted). METHODS: Wearing a tight-fitting transparent facemask, patients breathed for 8 min each, with and without PLB at rest and during constant-work-rate bicycle exercise (60% of maximum). RESULTS: PLB promoted a slower and deeper breathing pattern both at rest and during exercise. Whereas patients had no dyspnea with or without PLB at rest, during exercise dyspnea was variably affected by PLB across patients. Changes in the individual dyspnea scores with PLB during exercise were significantly correlated with changes in the end-expiratory lung volume (EELV) values estimated from inspiratory capacity maneuvers (as a percentage of total lung capacity; r2 = 0.82, p = 0.002) and with changes in the mean inspiratory ratio of pleural pressure to the maximal static inspiratory pressure-generating capacity (PcapI) [r2 = 0.84; p = 0.001], measured using an esophageal balloon, where PcapI was determined over the range of inspiratory lung volumes and adjusted for flow. CONCLUSION: PLB can have a variable effect on dyspnea when performed volitionally during exercise by patients with COPD. The effect of PLB on dyspnea is related to the combined change that it promotes in the tidal volume and EELV and their impact on the available capacity of the respiratory muscles to meet the demands placed on them in terms of pressure generation.