Robert P. Schnall

Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude.

BACKGROUND Abnormalities in pulse wave amplitude (PWA) have been described in subjects with atherosclerosis and may be a marker of future cardiac events. We evaluated the relationship between changes in PWA of the finger and peripheral endothelial function. METHODS We performed measurements of PWA with a novel finger plethysmograph (peripheral arterial tonometry [PAT]) and compared the findings with a simultaneous noninvasive measurement of peripheral endothelial function with brachial artery ultrasound scanning (BAUS) in 89 subjects. The PAT hyperemia ratio was defined as the ratio of PWA during reactive hyperemia relative to the baseline. Flow-mediated dilation (FMD) was defined by BAUS as the ratio of the brachial artery diameter during reactive hyperemia relative to the baseline. Sixty-eight subjects underwent exercise myocardial perfusion imaging (ExMPI). RESULTS Fifty-four men and 35 women were examined. There was a linear relationship between the PAT hyperemia ratio and FMD during the same episode of reactive hyperemia (r = 0.55, P <.0001). Subjects in the lowest FMD quartile had the lowest PAT hyperemia ratio, whereas subjects in the highest FMD quartile had the highest PAT hyperemia ratio (P <.001 for trend). Similar to BAUS, the PAT hyperemia ratio was more impaired in subjects with cardiovascular risk factors and in subjects with ExMPI studies that were indicative of coronary artery disease. CONCLUSIONS Assessment of PWA with PAT demonstrates patterns of abnormality similar to that of BAUS assessment of FMD. PWA during reactive hyperemia is influenced by factors known to affect endothelial function, including cardiovascular risk factors and coronary artery disease. These findings support the concept that analysis of PWA with PAT during reactive hyperemia may be used to study peripheral vascular endothelial function.

Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease.

OBJECTIVES The goal of this study was to examine the effect of enhanced external counterpulsation (EECP) on endothelial function. BACKGROUND Enhanced external counterpulsation improves symptoms and exercise tolerance in patients with symptomatic coronary artery disease (CAD). However, the exact mechanisms by which this technique exerts its clinical benefit are unclear. METHODS Reactive hyperemia-peripheral arterial tonometry (RH-PAT), a noninvasive method to assess peripheral endothelial function by measuring reactive hyperemic response in the finger, was performed in 23 patients with refractory angina undergoing a 35-h course of EECP. In each patient RH-PAT measurements were performed before and after the first, at midcourse, and the last EECP session. In addition, RH-PAT response was assessed one month after completion of EECP therapy; RH-PAT index, a measure of reactive hyperemia, was calculated as the ratio of the digital pulse volume during reactive hyperemia divided by that at rest. RESULTS Enhanced external counterpulsation led to symptomatic improvement (>/=1 Canadian Cardiovascular Society class) in 17 (74%) patients; EECP was associated with a significant immediate increase in average RH-PAT index after each treatment (p < 0.05). In addition, average RH-PAT index at one-month follow-up was significantly higher than that before EECP therapy (p < 0.05). When patients were divided by their clinical response, RH-PAT index at one-month follow-up increased only in those patients who experienced clinical benefit. CONCLUSIONS Enhanced external counterpulsation enhances peripheral endothelial function with beneficial effects persisting at one-month follow-up in patients with a positive clinical response. This suggests that improvement in endothelial function may contribute to the clinical benefit of EECP in patients with symptomatic CAD.

Sublingual electrical stimulation of the tongue during wakefulness and sleep.

Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.

Peripheral vasoconstriction during REM sleep detected by a new plethysmographic method.

To the editor—Rapid-eye-movement (REM) sleep is associated with more sympathetic activation than is NONREM sleep. So far, there are no data regarding vascular tone during REM and NONREM sleep in humans. Using a new plethysmographic technique to measure peripheral arterial tone (PAT), we report here that REM sleep in humans is associated with considerable peripheral vasoconstriction. The apparatus is essentially a plethysmograph that, unlike models now available, is able to envelop the finger up to and beyond its tip with a uniform pressure field. The applied pressure field is sufficient to substantially unload arterial wall tension, thereby improving the dynamic range of the system, while preventing the potential occurrence of venous engorgement that promotes vasoconstriction. Pressure within the probe originates from a pressurized balloon located over its outside wall. Pulsatile volume signals were recorded as optical density changes from the finger’s palmar surface within the applied pressure field. The device was tolerated well for extended periods. We measured pulsatile finger blood flow throughout the night in 9 normal young adults (25–40 years of age) and 17 patients with light-to-moderate sleep apnea syndrome (35–60 years of age; mean respiratory disturbance index, less than 30). The PAT signals were analyzed by a dedicated computer program in terms of mean relative peak to peak amplitude in 1-minute ‘bins’ for the first and second REM periods, and for 20 minutes of NONREM periods before and after each REM period. PAT amplitudes were expressed as percentages of the mean amplitude during the initial 5 minutes of the NONREM period preceding each REM period. Minutes with body movements were omitted before analysis. In both groups, REM sleep was associated with considerable attenuation of the PAT signal (Fig. 1). The decrease in amplitude began during NONREM sleep and reached a nadir during REM sleep. As there were neither differences between groups nor differences between the first and second REM periods, we pooled data and analyzed these by repeated measures ANOVA . The percent change during REM sleep (–16.3 ± 19.7%) was significantly higher than that during NONREM sleep before (–3.39 ± 14%) or after (–2.39 ± 27.2%) REM sleep (P < 0.009). The curves describing the change in amplitudes during the transition from NONREM to REM and back to NONREM sleep could be fitted with a quadratic trend (P < 0.02) with a minimum occurring 8.5 minutes after the start of REM sleep. The intense sympathetic activation during REM sleep and the preponderance of REM in the early morning hours have led to the suggestion that REM sleep may be responsible for increased cardiac events seen at this time. Although we have no data to show that REM-related vasoconstriction also occurs in larger blood vessels or is specific to the periphery, the report that in a canine model, experimental occlusion of the coronary arteries during REM sleep results in a greater than expected decrease in coronary blood flow indicates that REM-related vasoconstriction may predispose patients with compromised coronary arteries to ischemic events during sleep.

Improved Upper Airway Patency Elicited by Electrical Stimulation of the Hypoglossus Nerves

The present study evaluated the mechanisms by which upper airway (UAW)-dilating muscle contraction, elicited by hypoglossus nerve (HGN) stimulation, improved UAW patency. Pressure-flow (P-V) relationships of the isolated UAW as well as the negative intraluminal pressures required to cause UAW collapse were assessed before and during electrical stimulation of the HGN in 8 anesthetized, ventilated dogs. Sectioning of the HGN shifted the P-V relationship to the left, while electrical stimulation resulted in a substantial shift of the curve to the right, indicating UAW dilatation. UAW resistance decreased from 9.0 +/- 1.5 to 0.3 +/- 0.1 cm H2O.1(-1).s during HGn stimulation (p < 0.01). The magnitude of negative intraluminal pressure at which UAW collapse occurred (the critical pressure) increased from -2.7 +/- 0.7 to -13.2 +/- 2.1 cm H2O (p < 0.002). The increase in UAW conductance and stability raised the maximal flow which could be sustained without collapse from 0.28 +/- 0.07 to 2.07 +/- 0.35 l/s during HGN stimulation (p < 0.001). These findings indicate that in the anesthetized dog, UAW muscle contraction improves UAW patency both by dilating the UAW and by stiffening its walls.

Effect of upper airway muscle contraction on supraglottic resistance and stability

The activation of upper airway (UAW) muscles is believed to increase UAW patency to air flow. To evaluate the mechanisms by which UAW muscles act to prevent UAW collapse, pressure-flow relationships of the isolated UAW as well as the negative pressure required to cause UAW collapse (Pcrit) were assessed before and during electrical stimulation of four UAW muscle pairs in anesthetized dogs. Stimulation of each of the muscles shifted the pressure-flow curve toward lower pressures for any given flow rate, indicating UAW dilatation. UAW resistance decreased from 7.9 +/- 0.6 to 0.4 +/- 0.1, 2.7 +/- 0.6, 2.3 +/- 0.8 and to 4.8 +/- 1.5 cmH2O.L-1.sec during genioglossus, geniohyoid, sternothyroid and sternohyoid stimulation respectively (P < 0.01 in all cases). However, only genioglossus stimulation significantly increased Pcrit (from -3.4 +/- 0.6 to -12.0 +/- 1.8 cmH2O, P < 0.001). Relaxation of the genioglossus thus appears to produce the main impediment to air flow through the UAW, and contraction of this muscle improves UAW patency both by dilating the supraglottic airway and by stiffening its walls.

Dependency of upper airway patency on head position: the effect of muscle contraction.

In the present study we examined the effect of flexion and extension of the head on upper airway (UAW) patency in anesthetized dogs, and compared the dilatory and stabilizing effects of electrically stimulated UAW muscles at the different head positions. Flexion of the head increased UAW resistance (Ruaw) and reduced maximal flow (Vmax), but had little effect on the negative pressure at which UAW collapse occurred (Pcrit). Extension of the head, on the other hand, resulted in more negative Pcrit values and increased Vmax without significantly affecting Ruaw. Electrically induced UAW muscle contraction affected the pressure-flow curve and Ruaw, as well as Pcrit. Changing head position had a substantial effect on the dilatory and stabilizing effect of the various UAW muscles. However, independent of head position, genioglossus stimulation was most effective in reducing Ruaw and increasing Pcrit. We conclude that in the anesthetized, supine dog, head position affects the mechanical properties of the UAW and the effects of UAW muscle contraction.

Assessment of peripheral artery tonometry in the detection of treadmill exercise-induced myocardial ischemia ☆

OBJECTIVES We sought to assess the added diagnostic value of peripheral artery tonometric (PAT) measurements, based on finger pulsatile arterial volume changes, to standard 12-lead stress electrocardiography (ECG), for detecting exercise-induced myocardial ischemia, using single-photon emission computed tomography (SPECT) as the standard of comparison in a double-blinded, multicenter protocol. METHODS An automated algorithm for identifying myocardial ischemia from PAT was derived from 345 training cases. The PAT outcome was combined with the ECG result (ischemic, nonischemic, or equivocal), giving a PAT-enhanced value. A threshold of normality was determined to optimize agreement with the SPECT results in the training sample. The PAT-enhanced analysis was then validated in 616 subjects, only two of whom had technically unacceptable PAT studies. RESULTS In the validation cohort, receiver operating characteristic curve analysis of the PAT-enhanced diagnosis yielded an area under the curve of 0.72, a sensitivity of 63.5%, compared with 44.7% for ECG alone (p < 0.0001), and a specificity of 67.8% common to both ECG and PAT-enhanced diagnoses. Similar results were found in the training sample. Although over 10% of validation subjects had equivocal ECG results, with the aid of PAT, it was possible to provide diagnostic information for all but one subject. CONCLUSIONS Peripheral artery tonometry may be useful for improving the diagnosis of exercise-induced myocardial ischemia by both enhancing the sensitivity without impairing the specificity and increasing the percentage of definitive test results.