Biomedical subjects

T W Chick

Publications and source records attributed to T W Chick.

At least 19 recordsLinked to original sources

PubMed1996

Pre-exercise glycerol hydration improves cycling endurance time.

The effects of glycerol ingestion (GEH) on hydration and subsequent cycle ergometer submaximal load exercise were examined in well conditioned subjects. We hypothesized that GEH would reduce physiologic strain and increase endurance. The purpose of Study I (n = 11) was to determine if pre-exercise GEH (1.2 gm/kg glycerol in 26 ml/kg solution) compared to pre-exercise placebo hydration (PH) (26 ml/kg of aspartame flavored water) lowered heart rate (HR), lowered rectal temperature (Tc), and prolonged endurance time (ET) during submaximal load cycle ergometry. The purpose of Study II (n = 7) was to determine if the same pre-exercise regimen followed by carbohydrate oral replacement solution (ORS) during exercise also lowered HR, Tc, and prolonged ET. Both studies were double-blind, randomized, crossover trials, performed at an ambient temperature of 23.5-24.5 degrees C, and humidity of 25-27%. Mean HR was lower by 2.8 +/- 0.4 beats/min (p = 0.05) after GEH in Study I and by 4.4 +/- 1.1 beats/min (p = 0.01) in Study II. Endurance time was prolonged after GEH in Study I (93.8 +/- 14 min vs. 77.4 +/- 9 min, p = 0.049) and in Study II (123.4 +/- 17 min vs. 99.0 +/- 11 min, p = 0.03). Rectal temperature did not differ between hydration regimens in both Study I and Study II. Thus, pre-exercise glycerol-enhanced hyperhydration lowers HR and prolongs ET even when combined with ORS during exercise. The regimens tested in this study could potentially be adapted for endurance activities.

Adult↗

PubMed1994

Hemodynamic effects of nasal and face mask continuous positive airway pressure.

Studies of the hemodynamic effects of nasal continuous positive airway pressure (n-CPAP) in normal subjects have had conflicting results. The largest study (n = 19) found no effect of up to 15 cm H2O on heart rate (HR), cardiac stroke volume (SV), or cardiac index. We hypothesized that n-CPAP, by increasing intrathoracic pressure, should decrease SV and cardiac output (CO) in a dose-dependent fashion in normal subjects. We also hypothesized that mouth position, i.e., open or closed, could affect intrathoracic pressure and thus SV and CO. Six normal subjects were tested with four levels of CPAP (5, 10, 15, and 20 cm H2O) under three mask conditions-face mask and nasal mask with the mouth open (mo) or with the mouth closed (mc). Noninvasive pulsed Doppler measurements of SV and HR were made under each condition. N-CPAP (mc) and face mask CPAP (f-CPAP) resulted in significant dose-dependent decreases of SV-24 +/- 5 ml (21%) and 33 +/- 5 ml (28%), respectively--from baseline to 20 cm H2O (p < 0.05). HR were unchanged and CO significantly decreased with n-CPAP(mc) and with f-CPAP, 1.6 +/- 0.38 L/min (23%) and 2.29 +/- 0.54 L/min (31%), respectively, from baseline to 20 cm H2O (p < 0.05). Esophageal pressure measurements verified increasing intrathoracic pressure with increasing levels of f-CPAP and n-CPAP (mc) but not with n-CPAP (mo). In conclusion, n-CPAP (mc) and f-CPAP resulted in significant and similar dose-dependent decreases in SV and CO.

Adult↗

PubMed1993

A comparison of the effects of nifedipine and verapamil on exercise performance in patients with mild to moderate hypertension.

Twenty-four patients completed a double-blind, randomized clinical trial comparing the effects of nifedipine GITS (N) and verapamil SR (V) on blood pressure (BP) control and exercise performance. After a 2-week placebo phase, all subjects had measurements of VO2max, maximal workload, and endurance time. They were then randomized to either N (30 to 90 mg/day) or V (240 to 480 mg/day) and retested when BPs had stabilized. At rest, N lowered systolic (S) BP by 12 mm Hg (P = .02 compared to baseline) and diastolic (D) BP by 11 mm Hg (P = .001). V lowered SBP by 8 mm Hg (P = .013) and DBP by 11 mm Hg (P = .002). Neither drug affected resting heart rate. V significantly decreased resting epinephrine (P = .05) and there was a tendency for V to reduce norepinephrine (P = .07) and dopamine (P = .08). N tended to increase plasma renin activity (P = .07). During graded cycle ergometry N, compared with placebo, significantly lowered DBP at all exercise levels (P = .011), but had no significant effect on heart rate (HR), SBP, or heart rate pressure product (HRPP). Pulse pressure (PP) was significantly increased (P = .045), which was most noticeable at high exercise levels. Compared with placebo, V caused a marked reduction of exercise HR (P < .001), which was more pronounced at high levels, SBP (P = .004), DBP (P = .004), mean arterial pressure (MAP) (P = .001), and HRPP (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗

PubMed1993

Sources of variability in posterior rhinomanometry.

Sources of variability in nasal airway resistance measured by posterior rhinomanometry were studied in 5 subjects tested on 5 different days and 56 subjects tested on 2 different days. On each day, a questionnaire on upper airway health and nasal symptoms was completed. The mean individual difference in nasal airway resistance between the 2 test days in the group of 56 subjects was 5.3% (SD 52.7%). Between-subject variability accounted for 74.9% and 72.5% of the total variability in the group of 5 and the group of 56 subjects, respectively. For the 5 subjects, by accounting for a change in upper airway symptoms or upper respiratory tract infection that occurred over the 5 test days, there was a significant decrease in the between-subject variability. The difference in sources of variation due to a change in upper airway symptoms was not seen in the group of 56 subjects. We conclude that the largest source of variability in nasal airway resistance is due to between-subject differences.

Adult↗

PubMed1993

Efficacy and safety of clarithromycin compared to cefixime as outpatient treatment of lower respiratory tract infections.

BACKGROUND: Clarithromycin is a new acid-stable, 14-membered macrolide active against many of the organisms responsible for lower respiratory tract infections. It has been administered to over 5,000 patients worldwide and has been shown to be a safe and effective treatment for acute bacterial exacerbations of chronic bronchitis and bacterial pneumonia when given twice daily (250 to 500 mg). Cefixime is an amino-thiazolyl cephalosporin with an extended spectrum of antibacterial activity inhibiting beta-lactamase-producing respiratory pathogens. It has a long half-life, allowing once-daily administration. METHODS: This randomized, double-blind multicenter study compared clarithromycin and cefixime as treatment for patients with community-acquired lower respiratory tract infections (n = 213). Patients had bacterial pneumonia (clarithromycin, 19 percent; cefixime, 21 percent) or acute bacterial exacerbation of chronic bronchitis or asthmatic bronchitis (clarithromycin, 81 percent; cefixime, 79 percent). Patients received 500 mg of clarithromycin twice daily (n = 103) or 400 mg of cefixime once daily (n = 110) for 7 to 14 days. RESULTS: Clinical cure or improvement occurred in 86 percent of the clarithromycin-treated patients and 88 percent of the cefixime-treated patients. When only patients with identified infections with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae were considered, clinical success rates were 97 percent for clarithromycin and 96 percent for cefixime; the rate of bacteriologic eradication was 91 percent for clarithromycin and 90 percent for cefixime. Adverse events occurred in 29 percent of the clarithromycin-treated patients and 23 percent of the cefixime-treated patients. CONCLUSIONS: This study demonstrates that clarithromycin and cefixime are effective treatments for pneumonia and acute bacterial exacerbations of bronchitis of mild to moderate severity caused by the most common infecting organisms.

Adult↗

PubMed1993

Hyperoxic training increases work capacity after maximal training at moderate altitude.

High-intensity training may be difficult to sustain due to limitations in systemic oxygen transport, particularly at high altitudes. The purpose of this study was to examine the effects of a high-intensity training protocol using hyperoxic gas breathing in athletes "maximally trained" at an altitude of 1,600 m. Five subjects underwent progressive cycle training until they reached a plateau of aerobic capacity, maximal workload, and endurance time at 85 percent maximal workload. Significant decreases (2 to 6 percent) in arterial oxygen saturation were found after the 85 percent maximal workload tests. Training intensity was then increased to 95 percent maximal workload while the subjects breathed a gas mixture containing at least 70 percent oxygen. After 6 weeks of hyperoxic training, exercise parameters were compared with the plateau values obtained during the baseline training period. Total time during maximal cycle testing increased from 19.1 to 19.6 min (p = 0.015), heart rate at 85 percent maximal workload decreased from 168 to 163 bpm (p = 0.047), and endurance time at 85 percent maximal workload increased from 6.2 to 8.2 min (p = 0.012). There was a trend toward improvement of maximal workload. We conclude that hyperoxic training increases work capacity after attainment of "maximal training" at moderate altitude.

Adult↗

PubMed1993

Assessment of heart rate as a predictor of ventilation.

The rate of ventilation and route of breathing (i.e., nasal versus oronasal) are potential determinants of pollutant doses to target sites in the lung. However, the lack of accurate methods for ambulatory measurement of ventilation has hindered estimation of exposure and dose in freely ranging individuals, complicating the interpretation of the relationships among exposure, dose, and response in epidemiological studies. The goal of this project was to develop and validate a method of monitoring ventilation for large-scale epidemiologic investigations. We estimated ventilation for individual subjects from ambulatory heart rate monitoring, using the relationship between ventilation and heart rate that had been obtained during exercise testing. Fifty-eight subjects participated in the study, which included healthy adults and children, and subjects with lung and heart disease. Subjects performed cycle exercise and tasks involving lifting and vacuuming. Work loads of progressive and variable order were used in the testing. Conventional methods were used to measure heart rate and total ventilation, and a sampling mask was developed to measure the partitioning of breathing between oral and nasal routes. The minute ventilation-heart rate relation was evaluated under steady-state and varying work loads. In a second phase, subjects wore wristwatch monitors that recorded their heart rates, minute by minute, throughout the day. Subjects recorded activities, locations, and levels of exertion. Two 16-hour monitoring periods were obtained from each subject. The laboratory findings documented considerable intersubject variability in the minute ventilation-heart rate relation with a two- to five-fold range in the coefficients describing the change in ventilation relative to heart rate. This variation implies that individual testing is required to derive accurate predictive equations. Minute ventilation-heart rate regressions for the maximal progressive exercise test and for the test with a nonprogressive submaximal work load sequence were comparable, indicating that varying the sequence of work loads does not substantially affect the minute ventilation-to-heart rate ratio. During upper body work (e.g., lifting), the minute ventilation-to-heart rate ratio was one-third greater than during lower body exercise. Diverse patterns of partitioning breathing between oral and nasal routes were observed with increasing oral ventilation in most subjects as work load increased. In the field, heart rate and activity patterns were monitored successfully in adults and children with low rates of instrument failure and noncompliance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1992

Neutrophil responses to intravascular pneumococcal sonicate.

Leukopenia and pulmonary leukostasis are prominent features in patients succumbing to pneumococcal (PNC) infections. We examined mechanisms involved in recruitment of polymorphonuclear neutrophils (PMNs) into pulmonary capillaries and alveolae after PNC sonicate injection. We showed that by 15 min postinjection, PMN chemotactic activity was found in bronchoalveolar lavage (BAL) fluids and increased with time until the end point of the study at 90 min. Accompanying the increased chemotactic activity in BAL fluids was a decrease in circulating PMNs more pronounced in the femoral artery (FA) than the pulmonary artery (PA). Superoxide anion (O2-) production by peripheral PMNs was depressed following PNC sonicate injection, and comparison of FA and PA showed that FA PMNs produced less O2- than PA PMNs. PA PMNs also showed enhanced random migration when compared to the depressed random migration of FA PMNs. This study demonstrated that an intravascular challenge of PNC sonicate was associated with increased chemotactic activity for PMNs in BAL fluid. Fewer PMNs and altered PMN function resulted from passage through the pulmonary microvasculature after PNC sonicate injection.

Animals↗

PubMed1992

Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange.

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.

2,4-Dinitrophenol↗

PubMed1992

A multivariate model for the prediction of relapse after outpatient treatment of decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop and validate a multivariate model for predicting relapses after treatment of decompensated chronic obstructive pulmonary disease in an emergency department. METHODS: A 5-year survey was conducted, including training and validation periods. Stepwise logistic regression was used to develop a multivariate predictive model using clinical data obtained at the time of each visit. A relapse was defined as an unscheduled return to the emergency department within 48 hours. SITE: The study was conducted in the emergency department of the Albuquerque (New Mexico) Veterans Affairs Medical Center. SUBJECTS: The subjects were 289 patients with documented chronic obstructive pulmonary disease. MEASUREMENTS AND MAIN RESULTS: During the first 3 years, there were 705 visits in which the patient was treated and released from the emergency department. Relapse occurred 82 times (11.6%). Logistic regression showed that the following variables had an effect on the risk of relapse: the relapse rate for previous visits, a previous visit within 7 days, long-term home oxygen therapy, the number of doses of nebulized bronchodilators, the administration of aminophylline, and the use of antibiotics and prednisone at the time of discharge from the emergency department. During the next 2 years, the 48-hour relapse rate was 9.9% (47 of 476 discharges). When the model was fitted to these data, all of the original variables contributed to the prediction of relapse except antibiotic use and long-term home oxygen therapy. The logistic model was used to categorize each visit during the validation phase. The relapse rate for "high-risk" visits was significantly higher than that for "low-risk" visits (18.4% vs 6.1%). The method identified 57.4% of visits that ended in relapse at 48 hours. CONCLUSIONS: A multivariate model can be used to identify patients with a poor prognosis after the outpatient treatment of decompensated chronic obstructive pulmonary disease.

Ambulatory Care↗

PubMed1992

A multivariate model for predicting hospital admissions for patients with decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop a method for predicting hospital admissions for patients with decompensated chronic obstructive pulmonary disease treated in an emergency department. METHODS: A 4-year survey including training and validation periods was conducted. Stepwise logistic regression was used to develop a multivariate model using information from the patient's previous visits and results of baseline pulmonary function tests. MEASUREMENTS AND MAIN RESULTS: During the first 2 years, there were 693 visits to the emergency department for decompensated chronic obstructive pulmonary disease. The patient was admitted to the hospital on 210 occasions (30.3%). Logistic regression showed that the probability of admission was related to the following: the admission and relapse rates for previous visits, the proportion of previous discharges from the emergency department in which "conservative therapy" was given, the highest baseline post-bronchodilator forced expiratory volume in 1 second within 3 years of entry, and the highest baseline pre-bronchodilator forced expiratory volume in 1 second-vital capacity ratio. A relapse was defined as an unscheduled return to the emergency department within 48 hours. "Conservative therapy" was any treatment regimen that did not include parenteral medications. During the next 2 years, the model was validated with patients not previously treated at this medical center. Seventy-six (28.3%) of 269 episodes resulted in hospital admission. The logistic model was used to categorize each visit during the validation phase. "High-risk" visits had calculated probabilities of admission greater than .208, while "low-risk" visits had values that were less. The admission rate for 98 low-risk visits (8.2%) was much lower than the rate for 171 high-risk visits (39.8%). CONCLUSIONS: A multivariate model can be used to identify patients with decompensated chronic obstructive pulmonary disease who are unlikely to need hospitalization. This model could be used to select episodes of decompensated chronic obstructive pulmonary disease for treatment at home.

Aged↗

PubMed1991

Treatment of decompensated chronic obstructive pulmonary disease in the emergency department--correlation between clinical features and prognosis.

STUDY OBJECTIVE: Patients with decompensated chronic obstructive pulmonary disease (COPD) are at high risk of relapse after treatment in an emergency department. The purpose of this study was to determine if the risk of relapse correlates with the clinical features of the disease. PATIENTS: Three hundred fifty-two patients with documented COPD who were treated for dyspnea in the ED of the Albuquerque Veterans Administration Medical Center over a three-year period. METHODS: We reviewed the clinical features and pulmonary function tests of the patients, who were considered to have COPD if the baseline prebronchodilator one-second forced expiratory volume (FEV1) was less than 80% predicted, and less than 80% of the forced vital capacity and inhaled bronchodilators failed to increase the FEV1 to levels of more than 80% predicted. Visits for pneumonia, pneumothorax, pleural effusion, or pulmonary emboli were excluded. A relapse was defined as an unscheduled revisit to the ED within 14 days of initial treatment. Data were entered into a microcomputer data base and analyzed by a commercial statistical package. RESULTS: Of 877 visits in which the patient was treated and released from the ED, 281 (32.0%) resulted in relapse and were considered unsuccessful Compared with successful visits, unsuccessful visits were characterized by a shorter duration of dyspnea (P = .002), a lower entry FEV1 (P = .027), a lower discharge FEV1 (P = .040), a greater number of treatments with nebulized bronchodilators (P = .009), more frequent use of parenteral adrenergic drugs (P = .006), and less frequent use of oral prednisone on discharge (P = .016). Patients with one or more relapse visits during the study period (relapsers) differed from nonrelapsers in several respects. Relapsers had a greater bronchodilator response on baseline FEV1 than nonrelapsers (P = .047). Nevertheless, relapsers required more bronchodilator treatments in the ED (P less than .001); were treated more frequently with parenteral adrenergic drugs (P less than .001), IV glucocorticoids (P less than .001), and oral prednisone (P less than .001); and recovered less of their baseline FEV1 (P less than .014). CONCLUSION: Bronchodilator response on baseline pulmonary function testing appears to identify patients with COPD who have a poor prognosis after emergency treatment. Their poor response to intensive bronchodilator treatment suggests that loss of bronchodilator response may be involved in the pathogenesis of respiratory decompensation.

Aged↗

PubMed1991

The effect of aging on submaximal exercise performance and recovery.

The upward drift of gas exchange variables during 70% maximal exercise and recovery half-times in aged and young subjects of equivalent age-predicted aerobic capacity was measured. In the aged subjects, upward drift of VE, VO2, and HR was reduced compared with the young group. The recovery of VE, VCO2, and VO2 was slowed in the aged. However, at 10 minutes post-exercise, VCO2, VO2, and HR had returned to similar relative values for both groups; in the young subjects VE remained elevated at the end of recovery. The reduced upward drift of gas exchange variables and HR during exercise in aged subjects is consistent with an attenuated response of glycogenolysis and lactate production to adrenergic stimulation and/or to selective loss of type II skeletal muscle fibers. The slowed recovery of VE, VCO2, and VO2 in elderly persons is consistent with age-related reduced CO2 chemosensitivity, delaying elimination of the exercise-induced CO2 load.

Adult↗

PubMed1991

Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs.

The separate and combined acute effects of hypoxia (HY-11% O2), head-down tilt (HD-30 degrees) and fluid loading (FL-1.0 L saline) on hemodynamics and pulmonary gas exchange were determined in 17 anesthetized, mechanically ventilated dogs. Both during HY and normoxia (NO), the total respiratory compliance was decreased by HD, attributable to pulmonary vascular congestion. The reductions in compliance were twice as great with FL, indicating pulmonary interstitial edema, which was supported by histological observation of lung tissue. Pressure-flow relationships in the pulmonary circulation indicated that superimposing HD on HY doubled the increase in vascular resistance due to HY alone, while in the systemic circulation the resistance was returned to below NO by HD. A significant positive correlation between the changes in blood volume and pulmonary artery pressure for experimental transitions suggests that a shift in blood volume from systemic to pulmonary circulations and changes in total blood volume probably contributed substantially to these apparent changes in resistance. Pulmonary gas exchange efficiency, whether expressed in terms of shunt or ventilation/perfusion distribution from arterial-end-tidal PCO2 and PO2 differences, showed a significant inverse relationship with pulmonary driving pressure for the experimental conditions imposed. No clear synergistic effects of HY on HD were evident in contributing to pulmonary edema when superimposed prior to FL, but after FL this risk must be considered.

Acute Disease↗

PubMed1990

Rate-adaptive cardiac pacing in children using a minute ventilation biosensor.

Chronotropic integrity is required for a normal cardiac output response to exercise. We evaluated a rate-adaptive ventricular demand pacemaker (Telectronics, META-MV) which uses minute ventilation as the sensed physiological variable for adjusting pacing rate, in seven young patients with a mean age of 11.4 years. All patients had clinically significant bradycardia related to complete heart block (n = 4) or sinus node dysfunction (n = 3). For the entire group, paced heart rates increased from 70 +/- 10 beats/min to 151 +/- 19 beats/min with exercise testing. The onset of rate adaptation took less than 30 seconds. Changes in paced rate were linearly related to workload, VO2 (5.9 to 20.7 mL/min/kg) and minute ventilation (8-65 L/min). The decline in pacing rate after exercise was related directly to the gradual decrease in minute ventilation and VO2. Our data show that minute ventilation closely and accurately reflects the metabolic demands of varying workloads in children and can be used to achieve physiological, rate-adaptive pacing.

Adult↗

PubMed1990

Training-induced skeletal muscle adaptations are independent of systemic adaptations.

To isolate the peripheral adaptations to training, five normal subjects exercised the nondominant (ND) wrist flexors for 41 +/- 11 days, maintaining an exercise intensity below the threshold required for cardiovascular adaptations. Before and after training, intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) were measured by 31P magnetic resonance spectroscopy. Also maximal O2 consumption (VO2 max), muscle mass, and forearm blood flow were determined by graded systemic exercise, magnetic resonance imaging, and venous occlusion plethysmography, respectively. Blood flow, Pi/PCr, and pH were measured in both forearms at rest and during submaximal wrist flexion at 5, 23, and 46 J/min. Training did not affect VO2 max, exercise blood flow, or muscle mass. Resting pH, Pi/PCr, and blood flow were also unchanged. After training, the ND forearm demonstrated significantly lower Pi/PCr at 23 and 46 J/min. Endurance, measured as the number of contractions to exhaustion, also was increased significantly (63%) after training in the ND forearm. We conclude that 1) forearm training results in a lower Pi/PCr at identical submaximal work loads; 2) this improvement is independent of changes in VO2 max, muscle mass, or limb blood flow; and 3) these differences are associated with improved endurance and may reflect improved oxidative capacity of skeletal muscle.

Adaptation, Physiological↗

PubMed1990

Pentoxifylline relaxes isolated pulmonary arteries after preconstriction with norepinephrine.

Pentoxifylline (PTX) is a methylxanthine derivative which improves systemic microvascular flow and tissue oxygen delivery, presumably through actions on platelet aggregation and erythrocyte deformability. Although PTX also improves pulmonary vascular flow, recent evidence suggests that part of this improvement may be due to pulmonary vasodilation. To evaluate these effects we studied isolated rabbit lobar pulmonary artery (PA) ring segments to determine if PTX had direct effects on PA tissues and whether these effects could be modulated pharmacologically or by endothelial disruption. PTX had no effect on PA at resting tension. However, if the PA tension was actively increased by norepinephrine (5 microM), subsequent PTX application caused concentration-dependent PA relaxation. Relaxation occurred promptly and was maximal within 45-60 s. The threshold PTX concentration necessary for relaxation was 1 microM. PTX-induced relaxation was not affected by pretreatment with the cyclo-oxygenase inhibitor indomethacin (1 microM). Endothelial disruption by gentle rubbing of the intimal PA surface abolished relaxation of preconstricted PA by acetylcholine, but had no effect on relaxation by PTX. Although PA at resting tension displayed no response to PTX, PA constriction by norepinephrine in the presence of PTX concentrations greater than 10 microM was significantly decreased. These data indicate that PTX has direct actions on isolated rabbit PA which are not blocked by indomethacin nor require the presence of intact endothelium. Furthermore, PTX can suppress norepinephrine-induced constriction of isolated PA.

Animals↗

PubMed1990

Skeletal muscle response to exercise training in congestive heart failure.

To examine the ability of the skeletal muscle of congestive heart failure (CHF) patients to adapt to chronic exercise, five patients performed localized nondominant wrist flexor training for 28 d. Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training. Simultaneous measurements of limb blood flow were made by plethysmography at 12, 24, and 36 J.min-1. Forearm muscle mass and endurance were measured by magnetic resonance imaging and wrist flexion exercise before and after training. The Pi/PCr ratio and pH were calculated from the measured Pi and PCr. Exercise cardiac output, heart rate, plasma norepinephrine, and lactate measured during training were not elevated above resting values, confirming that training was localized to the forearm flexor muscles. After training, muscle bioenergetics, as assessed by the slope of the regression line relating Pi/PCr to submaximal workloads, were improved in the trained forearm of each patient, although muscle mass, limb blood flow, and pH were unchanged. Forearm endurance increased by greater than 260% after training. In the dominant untrained forearm, none of the measured indices were affected. We conclude that localized forearm exercise training in CHF patients improves muscle energetics at submaximal workloads in the trained muscle, an effect which is independent of muscle mass, limb blood flow, or a central cardiovascular response during training. These findings indicate that peripheral muscle metabolic and functional abnormalities in CHF can be improved without altering cardiac performance.

Aged↗