Citations

We sought to determine the esophageal sensory function in patients with a C6 or C7 spinal cord injury. A balloon was repetitively distended 10 cm above the lower esophageal sphincter in five patients and nine normal control subjects. Sensation was reported on a scale from 0 to 2 with progressive distension to pain threshold (level 2). Cortical responses were recorded from midline scalp electrodes. Blinded determinations of quality and reproducibility of the potentials were performed. All subjects experienced sensation with esophageal balloon distension. Volumes to sensation showed a trend toward a higher sensory threshold in patients but were significant only for first sensation, not pain. In all subjects, a triphasic evoked potential response consisting of a negative-positive-negative complex was noted with distension but not with sham distension. Characteristics (amplitude, latency, reproducibility, and quality) of the evoked potentials were not different in patient and control groups. These data suggest sensory pathways from the distal esophagus are intact in patients with a C6 or C7 spinal cord injury.

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.

Airway function is largely preserved during exercise or isocapnic hyperventilation in humans and guinea pigs despite likely changes in airway milieu during hyperpnea. It is only on cessation of a hyperpneic challenge that airway function deteriorates significantly. We tested the hypothesis that nitric oxide, a known bronchodilator that is produced in the lungs and bronchi, might be responsible for the relative bronchodilation observed during hyperventilation (HV) in guinea pigs. Three groups of anesthetized guinea pigs were given saline and three groups given 50 mg/kg NG-monomethyl-l-arginine (l-NMMA), a potent nitric oxide synthase inhibitor. Three isocapnic ventilation groups included normal ventilation [40 breaths/min, 6 ml/kg tidal volume (Vt)], increased respiratory rate only (150 breaths/min, 6 ml/kg Vt), and increased respiratory rate and increased volume (100 breaths/min, 8 ml/kg Vt). l-NMMA reduced expired nitric oxide in all groups. Expired nitric oxide was slightly but significantly increased by HV in the saline groups. However, inhibition of nitric oxide production had no significant effect on rate of rise of respiratory system resistance (Rrs) during HV or on the larger rise in Rrs seen 6 min after HV. We conclude that nitric oxide synthase inhibition has no effect on changes in Rrs, either during or after HV in guinea pigs.

Airway function deteriorates significantly on cessation of exercise or isocapnic hyperventilation challenges but is largely preserved during the challenge in humans and guinea pigs. PGE2, an endogenous bronchodilator, might be responsible for the preservation of lung function during hyperventilation (HV). We hypothesized that PGE2might have a protective effect during HV, partially explaining the minimal changes in respiratory system resistance (Rrs) usually seen during HV in humans and guinea pigs. Therefore, changes in Rrs were measured during and after HV in anesthetized, mechanically ventilated guinea pigs treated with flurbiprofen (FBN) or placebo. With HV, there was an initial bronchodilation that was unaffected by FBN. Rrs then increased with time during HV, an effect that was blocked by FBN. After HV, Rrs increased further in all groups, but the increase in Rrs was less in the FBN-treated groups. FBN treatment reduced the PGE2concentration slightly in lung lavage fluid compared with placebo. We found no enhancement or refractoriness of the Rrs response to repeat bouts of HV and no effect of FBN treatment on the response of Rrs to repeat HV. These results suggest that a constrictor PG is released during and possibly after HV and that the post-HV increase in Rrs is the sum of effects of the PG released during HV and a second constrictor mechanism operating after HV. We found no evidence for bronchodilator PG during or after HV in the guinea pig.

Background The presence of valvular heart disease ( VHD ) may affect the risk of stroke and mortality in patients with atrial fibrillation ( AF ). Community‐based estimates of prevalence and outcomes of specific forms of VHD in patients with AF are lacking. Methods and Results We examined the prevalence of VHD , anticoagulation use, mortality, stroke/transient ischemic attack, and bleeding among a community cohort of patients with AF . Significant VHD was defined as follows: (1) moderate/severe mitral stenosis or mechanical valve; (2) bioprosthetic valve, surgical repair, or balloon valvuloplasty; and (3) moderate/severe aortic regurgitation or stenosis, mitral regurgitation, or tricuspid regurgitation. Proportional hazards models were performed to test the association between VHD groups and outcomes. Among 9748 patients with AF , 2705 (27.7%) had significant VHD . Anticoagulation use was highest among patients with mitral stenosis/mechanical valve (91.8%). Compared with individuals with no significant VHD , individuals with aortic regurgitation/aortic stenosis, mitral regurgitation, or tricuspid regurgitation (hazard ratio, 1.23; 95% confidence interval, 1.07–1.42) had the highest risk of death. There were no differences in stroke or transient ischemic attack and major bleeding among individuals with and without significant VHD . Patients with AF and aortic stenosis had the highest risk of death (hazard ratio, 1.32; 95% confidence interval, 1.08–1.62). Conclusions Significant VHD is common among patients with AF in community practice. In a community cohort of patients with AF and CHA 2 DS 2 ‐ VAS c score ≥2, most were anticoagulated. Individuals with AF and moderate‐to‐severe biological VHD have more comorbidities and a higher mortality risk; however, stroke and major bleeding are similar among those with and without significant VHD .

An open-circuit (OpCirc) acetylene uptake cardiac output (Q˙t) method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated uptake vs. end-tidal change in acetylene, and OpCirc2 was based on an iterative finite difference modeling method. Six subjects [28–44 yr, peak oxygen consumption (V˙o2) = 120% predicted] performed cycle ergometry exercise to compareQ˙t using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by a 10-min rest, and subsequently subjects exercised at 85–90% of their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%, OpCirc2, 12%, Fick, 10%) but were lower at moderate to high exercise intensities (OpCirc1, 3%, OpCirc2, 3%, Fick, 5%). OpCirc1 and OpCirc2 Q˙t correlated highly with Fick Q˙t( R2= 0.90 and 0.89, respectively). There were minimal differences between OpCirc1 and OpCirc2 compared with Fick up to moderate-intensity exercise (<70% peakV˙o2); however, both techniques tended to underestimate Fick at >70% peakV˙o2. These differences became significant for OpCirc1 only. Part of the differences between Fick and OpCirc methods at the higher exercise intensities are likely related to inhomogeneities in ventilation and perfusion matching ( R2= 0.36 for Fick − OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided reproducible, reliable measurements ofQ˙t during mild to moderate exercise. However, only OpCirc2 appeared to approximate FickQ˙t at the higher work intensities.

Studies were performed in anesthetized dogs to determine plasma endothelin (ET) concentrations in the presence and absence of experimental congestive heart failure (CHF) produced by rapid ventricular pacing for 8 days. These studies were also designed to determine the effect of exogenous low-dose ET upon integrated cardiorenal and endocrine function in the presence and absence of CHF. In these studies, plasma ET was significantly elevated in CHF (3.25 +/- 0.39 pg/ml) compared with normal (1.03 +/- 0.21 pg/ml) or sham-operated (1.08 +/- 0.27 pg/ml) groups. Compared with the control group, which was characterized by a significant cardiorenal vasoconstrictor response to low-dose ET, a significant attenuation of the vasoconstrictor and antinatriuretic actions of ET was observed in the CHF group. Despite these differential responses, exogenous ET suppressed plasma renin activity (PRA) and activated aldosterone in both control and CHF groups. Thus these studies demonstrate for the first time that experimental CHF is characterized by elevated plasma ET in association with an attenuated cardiorenal response to exogenous ET. In contrast, low-dose ET inhibited PRC and activated aldosterone in the presence and absence of experimental CHF.

Expired gas concentrations were measured during a multibreath washin of He in one female and seven male subjects at rest (seated) and during cycle exercise at work rates of 70–210 W. In a computational model, the ventilation distribution was represented as a log-normal distribution with standard deviation (ςV˙); values of ςV˙ were obtained by fitting the output of the model to the data. At rest, ςV˙ was 0.89 ± 0.18; during exercise, ςV˙ was 0.60 ± 0.13, independent of the level of exercise. These values for the width of the functional ventilation distribution at the scale of the acinus are approximately two times larger than those obtained from anatomic measurements in animals at a scale of 1 cm3. The values for ςV˙, together with data from the literature on the width of the functional ventilation-perfusion distribution, show that ventilation and perfusion are highly correlated at rest, in agreement with anatomic data. The structural sources of nonuniform ventilation and perfusion and of the correlation between them are unknown.

Proctor, David N., Kenneth C. Beck, Peter H. Shen, Tamara J. Eickhoff, John R. Halliwill, and Michael J. Joyner. Influence of age and gender on cardiac output-V˙o2relationships during submaximal cycle ergometry. J. Appl. Physiol. 84(2): 599–605, 1998.—It is presently unclear how gender, aging, and physical activity status interact to determine the magnitude of the rise in cardiac output (Q˙c) during dynamic exercise. To clarify this issue, the present study examined theQ˙c-O2uptake (V˙o2) relationship during graded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups ( n = 6–8/group): younger men (20–30 yr), older men (56–72 yr), younger women (24–31 yr), and older women (51–72 yr). Q˙c (acetylene rebreathing), stroke volume (Q˙c/heart rate), and whole bodyV˙o2were measured at rest and during submaximal exercise intensities (40, 70, and ∼90% of peakV˙o2). Baseline resting levels of Q˙c were 0.6–1.2 l/min less in the older groups. However, the slopes of theQ˙c-V˙o2relationship across submaximal levels of cycling were similar among all four groups (5.4–5.9 l/l). The absolute Q˙c associated with a given V˙o2(1.0–2.0 l/min) was also similar among groups. Resting and exercise stroke volumes (ml/beat) were lower in women than in men but did not differ among age groups. However, older men and women showed a reduced ability, relative to their younger counterparts, to maintain stroke volume at exercise intensities above 70% of peakV˙o2. This latter effect was most prominent in the oldest women. These findings suggest that neither age nor gender has a significant impact on theQ˙c-V˙o2relationships during submaximal cycle ergometry among chronically endurance-trained individuals.

To evaluate methods used to document changes in airway function during and after exercise, we studied nine subjects with exercise-induced asthma and five subjects without asthma. Airway function was assessed from measurements of pulmonary resistance (Rl) and forced expiratory vital capacity maneuvers. In the asthmatic subjects, forced expiratory volume in 1 s (FEV1) fell 24 ± 14% and Rl increased 176 ± 153% after exercise, whereas normal subjects experienced no change in airway function (Rl−3 ± 8% and FEV1−4 ± 5%). During exercise, there was a tendency for FEV1 to increase in the asthmatic subjects but not in the normal subjects. Rl, however, showed a slight increase during exercise in both groups. Changes in lung volumes encountered during exercise were small and had no consistent effect on Rl. The small increases in Rl during exercise could be explained by the nonlinearity of the pressure-flow relationship and the increased tidal breathing flows associated with exercise. In the asthmatic subjects, a deep inspiration (DI) caused a small, significant, transient decrease in Rl 15 min after exercise. There was no change in Rl in response to DI during exercise in either asthmatic or nonasthmatic subjects. When percent changes in Rl and FEV1 during and after exercise were compared, there was close agreement between the two measurements of change in airway function. In the groups of normal and mildly asthmatic subjects, we conclude that changes in lung volume and DIs had no influence on Rl during exercise. Increases in tidal breathing flows had only minor influence on measurements of Rl during exercise. Furthermore, changes in Rl and in FEV1 produce equivalent indexes of the variations in airway function during and after exercise.