Ventilated Capsule Technique Research Articles

Pretreatment of microneedles enhances passive transdermal administration of pilocarpine and pilocarpine-induced sweat production in humans

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to ∼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands.

Agreement between the ventilated capsule and the KuduSmart® device for measuring sweating responses to passive heat stress and exercise.

The present study assessed agreement between a wireless sweat rate monitor (KuduSmart® device) and the ventilated capsule (VC) technique for measuring: (i) minute-averaged local sweat rate (LSR), (ii) sweating onset, (iii) sudomotor thermosensitivity, and (iv) steady-state LSR, during passive heat stress and exercise. It was hypothesized that acceptable agreement with no bias would be observed between techniques for all assessed sweating characteristics. On two separate occasions for each intervention, participants were either passively heated by recirculating hot water (49 °C) through a tube-lined garment until rectal temperature increased 1 °C over baseline (n=8), or a 60 min treadmill march at a fixed rate of heat production (∼500W, n=9). LSR of the forearm was concurrently measured with a VC and the KuduSmart® device secured within ∼2cm. Using a ratio scale Bland-Altman analysis with the VC as the reference, the KuduSmart® device demonstrated systematic bias and not acceptable agreement for minute-averaged LSR (1.17 [1.09, 1.27], CV=44.5%), systematic bias and acceptable agreement for steady-state LSR (1.16 [1.09,1.23], CV=19.5%), no bias and acceptable agreement for thermosensitivity (1.07 [0.99, 1.16], CV=23.2%), and no bias and good agreement for sweating onset (1.00 [1.00, 1.00], CV=11.1%). In total, ≥73% of all minute-averaged LSR observations with the KuduSmart® device (n=2743) were within an absolute error of<0.2mg/cm2/min to the VC, the reference minimum detectable change in measurement error of a VC on the forearm. Collectively, the KuduSmart® device may be a satisfactory solution for assessing the sweating response to heat stress where a VC is impractical.

Serum, interstitialand sweat ATP in humans exposed to heat stress: Insights into roles of ATP in the heat loss responses.

Hyperthermia increases intravascular adenosine triphosphate (ATP) and is associated with greater hyperthermia-induced cutaneous vasodilation. Hyperthermia may also increase skin interstitial fluid ATP thereby activating cutaneous vascular smooth muscle cells and sweat glands. We evaluated the hypothesis that whole-body heating would increase skin interstitial fluid ATP, and this response would be associated with an increase in cutaneous vasodilation and sweating. Nineteen (8 females) young adults underwent whole-body heating using a water-perfusion suit to increase core temperature by ~1°C during which time cutaneous vascular conductance (CVC, ratio of laser-Doppler blood flow to mean arterial pressure) and sweat rate (ventilated capsule technique) were measured at four forearm skin sites to minimize between-site variations. Dialysate from the skin sites were collected via intradermal microdialysis. Heating increased serum ATP, CVC, and sweat rate (all p ≤ 0.031). However, heating did not modulate dialysate ATP (median, baseline vs. end-heating: 2.38 vs. 2.70 nmol/ml) (p = 0.068), though the effect size was moderate (Cohen's d = 0.566). While the heating-induced increase in CVC was not correlated with changes in serum ATP (r = 0.439, p = 0.060), we observed a negative correlation (rs = -0.555, p = 0.017) between dialysate ATP and CVC. We did not observe a significant correlation between the heating-induced sweating and serum, dialysate, or sweat ATP (rs = 0.091 to -0.322, all p ≥ 0.222). Altogether, we showed that passive heating increases ATP in blood and possibly skin interstitial fluid, with the latter potentially blunting cutaneous vasodilation. However, ATP does not appear to modulate sweating.

Regional variation in the reliability of sweat rate measured via the ventilated capsule technique during passive heating.

The ventilated capsule technique is widely used to measure time-dependent changes in sweating in humans. However, evaluations of its reliability (consistency) have been restricted to the forearm, despite extensive regional heterogeneity in the sweating response. Given the importance of such information for experimental design, statistical analysis and interpretation, we determined the reliability of local sweat rate at nine sites during whole-body passive (resting) heating. On three separate occasions, a water-perfused suit was used to increase and clamp oesophageal temperature 0.6, 1.2 and 1.8°C above baseline in 14 young men [24(SD5)years of age], while sweat rate was measured at the forehead, chest, abdomen, biceps, forearm, hand, quadriceps, calf and foot using ventilated capsules (3.8cm2 ). Absolute and relative reliability were determined via the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. At low heat strain (0.6°C), almost all sites had acceptable relative reliability (ICC ≥0.70) and moderate absolute reliability (CV<25%).At moderate heat strain (1.2°C), only the abdomen, hand, quadriceps and foot had acceptable relative reliability, whereas the forehead, abdomen, forearm, hand and quadriceps had moderate absolute reliability. At high heat strain (1.8°C), relative reliability was acceptable at the abdomen, quadriceps, calf and foot, whereas the chest, abdomen, forearm, hand, quadriceps, calf and foot had moderate absolute reliability. Our findings indicate that the measurement site and level of heat strain impact the consistency of local sweat rate measured via the ventilated capsule technique, and we demonstrate the possible implications for research design and data interpretation.

Regional Variations in the Reliability of Local Sweat Rate Measured via the Ventilated Capsule Technique during Whole‐body Passive Heating

The ventilated capsule technique uses hygrometry to measure time‐dependent changes in sweating over small areas (~1–5 cm2) on the body surface. Despite the widespread use of this technique, evaluations of its reliability (i.e., consistency) are sparse and have been restricted to a single region (forearm) during exercise‐heat stress. This presents a critical knowledge gap, as the reliability of this technique may be region‐specific due to inter‐regional variation in sweat rate. Further, understanding regional variations in the reliability of this technique has important practical utility for experimental design, statistical analysis, and sample size estimates. We therefore assessed the reliability of local sweating across various body regions during exposure to increasing levels of whole‐body heat stress. Sweat rate was measured using ventilated capsules (3.5 cm2) at 9 locations (i.e., forehead, chest, abdomen, bicep, forearm, hand, quadriceps, calf, and foot) in twelve young men (age: 25 [SD 5] years). On three occasions, a whole‐body water perfused suit was used to raise and clamp esophageal temperature at three levels of hyperthermia: 1) +0.7 ± 0.1°C above baseline (low‐heat stress; LHS); 2) +1.3 ± 0.1°C (moderate‐heat stress; MHS); and 3) +1.8 ± 0.1°C (high‐heat stress; HHS). An average of the data collected in the final 5‐min of each heating stage (stable sweating) was used for analysis. Reliability was assessed using the interclass correlation coefficient (ICC; an index of measurement consistency), with values ≥0.7 considered suitable for research purposes. At LHS, average sweat rate across the 9 regions was 1.01 mg·min−1·cm−2, ranging from 0.85 to 1.28 mg·min−1·cm−2 (foot and chest, respectively). The average ICC across regions was 0.66, ranging from 0.35 to 0.94 (forehead and chest, respectively). Of the 9 regions, abdomen (0.94), calf (0.81), forearm (0.79), quadriceps (0.78) and chest (0.74) exceeded the 0.7 ICC threshold. In the MHS condition, average sweat rate across all sites was 1.21 mg·min−1·cm−2, ranging from 0.91 to 1.53 mg·min−1·cm−2 (bicep and chest, respectively). The average ICC across regions was 0.60, ranging from 0.15 to 0.88 (hand and abdomen, respectively). Of the 9 regions, abdomen (0.88), quadriceps (0.79) and forearm (0.77) exceeded the 0.7 ICC threshold. In the HHS condition, average sweat rate across all sites was 1.28 mg·min−1·cm−2, ranging from 1.02 to 1.62 mg·min−1·cm−2 (quadriceps and chest, respectively). The average ICC across regions was 0.59, ranging from 0.21 to 0.86 (hand and abdomen, respectively). Of the 9 regions, abdomen (0.86), quadriceps (0.77) and calf (0.73) exceeded the 0.7 ICC threshold. Our findings indicate that the region and level of hyperthermia will impact the consistency of local sweat rates measured with the ventilated capsule technique and therefore the likelihood of detecting an effect of an intervention/comparison if one exists.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada.

Wearing graduated compression stockings augments cutaneous vasodilation but not sweating during exercise in the heat.

The activation of cutaneous vasodilation and sweating are essential to the regulation of core temperature during exercise in the heat. We assessed the effect of graduated compression induced by wearing stockings on cutaneous vasodilation and sweating during exercise in the heat (30°C). On two separate occasions, nine young males exercised for 45 min or until core temperature reached ~1.5°C above baseline resting while wearing either (1) stockings causing graduated compression (graduate compression stockings, GCS), or (2) loose‐fitting stockings without compression (Control). Forearm vascular conductance was evaluated by forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure to estimate cutaneous vasodilation. Sweat rate was estimated using the ventilated capsule technique. Core and skin temperatures were measured continuously. Exercise duration was similar between conditions (Control: 42.2 ± 3.6 min vs. GCS: 42.2 ± 3.6 min, P = 1.00). Relative to Control, GCS increased forearm vascular conductance during the late stages (≥30 min) of exercise (e.g., at 40 min, 15.6 ± 5.6 vs. 18.0 ± 6.0 units, P = 0.01). This was paralleled by a greater sensitivity (23.1 ± 9.1 vs. 32.1 ± 15.0 units°C−1, P = 0.043) and peak level (14.1 ± 5.1 vs. 16.3 ± 5.7 units, P = 0.048) of cutaneous vasodilation as evaluated from the relationship between forearm vascular conductance with core temperature. However, the core temperature threshold at which an increase in forearm vascular conductance occurred did not differ between conditions (Control: 36.9 ± 0.2 vs. GCS: 37.0 ± 0.3°C, P = 0.13). In contrast, no effect of GCS on sweating was measured (all P > 0.05). We show that the use of GCS during exercise in the heat enhances cutaneous vasodilation and not sweating.

Individual variations in nitric oxide synthase-dependent sweating in young and older males during exercise in the heat: role of aerobic power.

We evaluated the association between aerobic power (defined by peak oxygen consumption; VO 2peak) and the contribution of nitric oxide synthase (NOS) to the sweating response in young and older individuals during exercise in the heat. Data from 44 young (24 ± 1 years) and 48 older (61 ± 2 years) males with mean VO 2peak of 47.8 ± 2.4 (range, 28.0–62.3) and 39.1 ± 2.3 (range, 26.4–55.7) mLO 2 kg−1 min−1, respectively, were compiled from our prior studies. Participants performed two 15‐ to 30‐min bouts of exercise at a fixed rate of metabolic heat production of 400 or 500 W, each separated by 15–20 min recovery in the heat (35°C, relative humidity of 20%). Forearm sweat rate (ventilated capsule technique) was measured at two skin sites that were continuously and simultaneously administered with lactated Ringers solution (Control) or 10 mmol/L NG‐nitro‐L‐arginine methyl ester (L‐NAME, nonselective NOS inhibitor) via intradermal microdialysis. Sweat rate during the final 5 min of each exercise bout was lower with L‐NAME compared to the Control in both groups (all P < 0.05). The magnitude of the attenuation in sweat rate induced by L‐NAME compared to the Control was not correlated with VO 2peak (all P ≥ 0.46) while this attenuation was negatively correlated with the sweat rate at the Control in both groups and in both exercise bouts (all P < 0.01, R ≤ −0.43). These results suggest that NOS‐dependent sweating is not associated with aerobic power per se, while it becomes evident in individuals who produce larger sweat rates during exercise irrespective of age.

An objective assessment of the sudomotor response after thoracoscopic sympathectomy

Thoracoscopic sympathectomy has become an accepted therapeutic option for palmar hyperhidrosis. Objective assessment of sweat output after sympathectomy, however, has not been reported to date. We report for the first time sweat output measurements after sympathectomy during a 3-year postoperative period. Thoracoscopic sympathectomy was performed by division of T2 and T3 sympathetic ganglia in 17 healthy adult patients with no comorbidities. Preoperative and postoperative sweat measurements were done at 29 degrees C (below sweat threshold, at baseline, after conversation, and after a mental arithmetic challenge) and at 40 degrees C (baseline and after exercise) with the ventilated capsule technique in left palm, sole, and chest wall. Serial postoperative measurements were conducted at 1 and 6 months and 1, 2, and 3 years. Sweat output fell significantly after sympathectomy relative to preoperative levels under all experimental conditions (P < .001, analysis of variance) in the left palm. Differences in sweat outputs in the left palm were statistically significant between groups at baseline and postoperatively after mental arithmetic challenge and exercise at 40 degrees C (P < .05, analysis of variance). Compensatory increases in the sweat outputs from the left sole and chest were observed after sympathectomy. No patients had recurrence of preoperative sweat output values at follow-up. According to objective sweat output measurements, thoracoscopic sympathectomy results in long-term control of palmar hyperhidrosis. This evaluation method is valuable in investigating recurrence of symptoms or compensatory hyperhidrosis after sympathectomy, providing a robust and objective criterion for planning intervention.

Thermoregulation during exercise in women who are taking oral contraceptives.

Thermoregulation during exercise was studied in seven women who were taking oral contraceptive pills for 3 weeks of each month. The subjects were studied once in the 3rd week of taking the pill (P) and once during the following week when they took no pil (N). Rectal temperature (Tre), heart rate (fc) and evaporative water loss (EWL, ventilated capsule technique) were measured while they walked on a treadmill for 60 min at 4.8 km.h-1 at a 10% gradient. Ambient temperature was 22 degrees C. A venous blood sample was drawn 30 min before each experiment for measurement of hematocrit (packed cell volume, PCV), plasma osmolality (Osmpl), and plasma levels of the endogenous pyrogens interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). Resting Tre was 0.31 degree C higher in P than in N (P < 0.01) and Tre remained higher in P throughout the entire exercise period (P < 0.01). Threshold Tre for the onset of EWL was 0.32 degree C higher in P than in N (P < 0.01). Exercise fc was 6.5 beats.min-1 higher in P than in N (P < 0.01). There was no significant difference in PCV, Osmpl, IL-1 beta or IL-6 between P and N. It was concluded that the administration of synthetic progestins in oral contraceptives causes an upward shift in the threshold for heat loss responses, resulting in higher body core temperatures both at rest and during exercise. There was no evidence that these alterations in thermoregulation were mediated by changes in body fluid balance or in plasma levels of IL-1 beta or IL-6.

Modified ventilated capsule for the measurement of sweating rate in the exercising horse.

Modification of a ventilated capsule technique for the measurement of sweating rate (SR) is described for application in an exercising horse. The plastic capsule was sealed against the coat of the horse. Dry air was blown through the capsule over the skin and the change in absolute humidity (g/m3) between air entering and leaving the capsule was used to calculate SR. The effect of flow rate on the response characteristics of the system was investigated and measured over a range of sweating rates in a group of horses completing a short exercise test. Repeatability of SR measurements made at 2 sites, one 10 cm distal to the tuber sacrale (SRS) and the other approximately overlying C4 in the neck (SRN), were compared. To encourage the rapid and complete evaporation of moisture from the area of coat enclosed by the SR capsule, it was demonstrated that the degree of saturation of the air leaving the capsule should be maintained below 15% relative humidity (RH). This was best achieved at flow rates exceeding 35 l/min. No significant difference was found between the 2 repeated tests separated by 3 days, with respect to right atrial temperature (TRA) and SR. The modified system for the measurement of SR in the exercising horse used in this study was shown to be fast responding and capable of measuring a wide range of sweating rates. A good seal was maintained throughout and the capsule was removed without causing damage to the coat.

Ventilated Capsule Measurements of Cutaneous Evaporation in Mourning Doves

To determine the contribution of cutaneous water loss to evaporative cooling in Mourning Doves (Zenaida macroura), we used a ventilated capsule technique to measure evaporation from the breast, back, and axilla of captive doves at 25 and 350C. Water loss from these surfaces averaged 4.1 ? 0.4 mg m-2 sec-' (SE) at 250C and was highest from the dorsum. At 350C, cutaneous evaporation increased to 8.3 ? 0.9 mg m-2 sec-'. Mean skin water-vapor diffusion resistance of the breast, back, and axilla together was 111.5 ? 9.5 sec/cm at 250C and decreased significantly to 69 ? 8.0 sec/cm at 350C. The large increases in cutaneous evaporation we observed between 25 and 350C result mainly from temperaturedependent reductions in the skin resistance to water loss. Our results suggest that augmented cutaneous evaporation is utilized as a means of heat defense by Mourning Doves.

A comparison of cutaneous evaporation rates in cattle exposed to heat in a climate laboratory and in the field

1. The cutaneous evaporation rates of three animals of different genotype have been determined under artificial heating in a climate laboratory and during exposure to field conditions. Cutaneous evaporation rates were measured from the backthoracic region using a ventilated capsule technique.2. In both climate-laboratory studies and field observations cutaneous evaporation showed little relationship with either rectal temperature, respiratory rate or skin temperature.3. Basal cutaneous evaporation rates in the unheated chamber at 10 a.m. were found to be 40% lower in animals which were housed overnight than in those which entered the chamber following exposure to the early morning sunlight.