Effects of high-frequency transcutaneous electrical nerve stimulation on limb blood flow in healthy humans.

[Indergand HJ, Morgan BJ Effects of high-frequency transcutaneous electrical nerve stimulation on limb blood flow in healthy humans. Phys Ther. 1994;74:361-367.]

Key Words: Regional blood flow, Transcutaneous electric nerve stimulation.

Transcutaneous electrical nerve stimulation (TENS) has been used for pain management for more than 20 years. The effects of TENS on circulation, however, are incompletely understood. In patients with chronic pain and in healthy subjects, application of high-frequency TENS over peripheral nerves at intensities below the threshold for motor unit activation has been shown to increase regional blood flow.[1,2] In contrast, in healthy subjects, application of high-frequency TENS at intensities above the motor threshold appears to decrease regional blood flow.[3] The two studies in which blood flow increased advanced the concept that vasodilation may contribute to the pain-relieving properties of TENS, whereas the finding of decreased blood flow raises the concern that TENS may have potentially harmful effects in patients with vascular insufficiency. The postulated mechanism for the Tens-related blood flow alterations in these reports is either an inhibitory[1,2] or a stimulatory[3] influence on sympathetic vasoconstrictor fibers traveling in peripheral nerves,

All of the reports relating to blood flow and TENS are based on measurements of skin temperature. Although skin temperature measurements provide indirect estimates of skin blood flow, they do not provide information about blood flow to underlying muscle, a tissue that contributes importantly to total-limb blood flow. The goal of our study was to determine the effects of transcutaneous electrical stimulation of peripheral nerves on limb blood flow in healthy subjects. Accordingly, we measured calf blood flow using venous occlusion plethysmography during high-frequency TENS applications over the common peroneal and tibial nerves at intensities both above and below the threshold for motor unit activation.

Method

Subjects

Eleven asymptomatic subjects (4 men, 7 women), ranging in age from 20 to 44 years ([bar]X=30, SD=9), were recruited to participate in this study. None of the subjects reported a history of cardiovascular, neurologic, or musculoskeletal disease, and none were taking medication at the time of study. Informed consent was obtained from all subjects prior to participation,

General Procedures

Subjects were studied in the supine position. Subjects refrained from ingestion of food and caffeine-containing beverages for at least 2 hours prior to the study. Room temperature was maintained at 24[degrees] [+ or -] 1[degrees]C. All subjects were allowed to rest quietly in the laboratory for at least 20 minutes before the start of the stimulation protocols. Arterial pressure was measured by automated sphygmomanometer(*) at 1-minute intervals. In addition, continuous beat-by-beat determinations of arterial pressure were made by photoelectric plethysmography.([dagger]) Measurements obtained with both devices correlate well with intra-arterial measurements.[4,5] Skin temperature was measured using a thermistor probe([double dagger]) placed on the dorsum of each subject's left foot. The temperature monitor was calibrated with a mercury thermometer before and after each data-collection period and was found to be accurate to within [+ or -] 0.2[degrees]C. Because respiratory maneuvers are known to affect peripheral blood flow,[6] subjects were instructed to maintain a stable breathing pattern throughout the data-collection period. A stable breathing pattern was defined as the absence of sustained changes in the rate or depth of breathing. Respiration was monitored using a strain gauge pneumograph to ensure compliance with this instruction. The plethysmograph, arterial pressure, electrocardiograph, and respiration tracings were recorded continuously on papers[sections] and on videotape.([parallel]),(#) Skin temperature values were recorded manually at 1-minute intervals.

Measurement of Limb Blood Flow

Blood flow in the left calf was measured by venous occlusion plethysmography. This technique assesses blood flow noninvasively by measuring changes in limb circumference during periodic stoppages of venous outflow. The rate of change of limb circumference during venous occlusion is assumed to be proportional to the rate of arterial inflow. Details concerning the rationale for and assumptions underlying venous occlusion plethysmography have been published previously.[7,8]

The limb was elevated above the level of the right atrium to ensure adequate venous drainage of the leg between blood flow measurements. A Whitney strain gauge holder(**) fitted with a mercury-in-Silastic strain gauge([double dagger]) encircled the calf at the point of greatest circumference. A strain gauge was selected for each subject so that it was stretched by approximately 15% when mounted on the calf. A collecting cuff (standard thigh blood pressure cuff) was positioned above the knee. The strain gauge was calibrated after placement on the limb by turning a calibration screw mounted on the gauge holder. The amount of deflection recorded for a standardized amount of stretch of the gauge (one turn of the calibration screw) was noted. This calibration procedure was repeated after the period of data collection. The coefficient of variation for calibration-recalibration was [+ or -] 9%.

To obtain flow measurements, the collecting cuff was inflated rapidly to 40 mm Hg for four to five cardiac cycles every 20 seconds. A typical plethysmograph tracing is shown in Figure 1. To calculate blood flow values, a tangent was visually fit to the portion of the calf circumference tracing immediately following the inflation artifact. A protractor was used to measure the inflation-induced deviations from horizontal. Calf blood flow was calculated by the following formula:

Blood flow (mL/100 mL/min) =

[200 x Tangent x Paperspeed

x 0.635 / Calibration factor(mm)]/

Calf Circumference (mm) where tangent = tangent of the angle from horizontal, paper speed = chart paper speed (in millimeters per minute), calibration factor = chart paper deflection for one turn of the calibration screw, 0.635 = strain gauge stretch (in millimeters) for one turn of the calibration screw, and 200 = constant required for conversion of changes in circumference (in millimeters) to percentage of change in volume,

The coefficient of variation for steady-state flow measurements obtained in this manner was [+ or -] 8% Sixty-second averages of blood flow were used in computation of results. Vascular resistance in units was calculated as mean arterial pressure (one third pulse pressure plus diastolic pressure) divided by blood flow (in milliliters per 100 mL of tissue per minute).

Transcutaneous Electrical Nerve Stimulation

A two-channel portable stimulator([double dagger]) with four 16-[cm.sup.2] electrodes was used in the TENS protocols, Constant current output with a balanced, asymmetrical, biphasic waveform was verified by oscilloscope. A stimulation frequency of 110 pulses per second and a pulse duration of 150 microseconds were used in both protocols. One pair of electrodes was placed over the left common peroneal nerve, with one electrode immediately proximal and one electrode immediately distal to the fibular head. The other pair of electrodes was placed over the left tibial nerve in the popliteal fossa, with one electrode above and one electrode below the knee joint line. Electrode placement over the common peroneal and tibial nerves was verified by observing contraction of the appropriate muscle groups when stimulation was applied at suprathreshold intensities. Because the common peroneal and tibial nerves supply virtually all of the sympathetic innervation to blood vessels in the leg and foot, we reasoned that this electrode placement would maximize potential TENS-related changes in blood flow. For sensory-level TENS, the stimulation intensity was increased until the subject experienced a strong tingling sensation in the absence of palpable muscle contraction. For motor-level TENS, the intensity was increased until a visible, sustained muscle contraction was elicited in the calf and pretibial muscles.

Experimental Protocols

Protocol 1: TENS applications. Calf blood flow, arterial pressure, and dorsal foot skin temperature were measured until at least 5 minutes of stable baseline recordings were obtained. Measurements were continued during a 20-minute application of either sensory- or motor-level TENS randomized order) and a 5-minute recovery period. On a different day, five of the subjects returned to the laboratory for time-control experiments. At that time, measurements of calf blood flow, arterial pressure, and skin temperature were made during 30 minutes of supine rest.

Protocol 2: cold pressor test To assess each subject's ability to respond to vasoconstrictor stimuli, we measured the peak blood flow change produced by immersion of the hand in ice water. After at least 5 minutes of stable baseline measurements had been obtained, the subject's hand was placed in an ice water bath for 90 seconds. Measurements of calf blood flow, arterial pressure, and dorsal foot skin temperature were obtained during and for 5 minutes after immersion.

Protocol 3: reactive hyperemia test To assess vasodilator capacity, we measured the peak blood flow change following the termination of 5 minutes of vascular occlusion. After at least 5 minutes of stable baseline measurements had been obtained, a blood pressure cuff placed around the subject's left thigh was inflated to 160 mm Hg (a suprasystolic level in all subjects) for 5 minutes. After the release of vascular occlusion, 5 minutes of recovery measurements of blood flow, arterial pressure, and skin temperature were made.

Data Analysis

A one-way analysis of variance for repeated measures was used to compare group mean values for the variables of interest in the baseline period, the 10th minute of TENS, the 20th minute of TENS, and the 5th minute of the recovery period. Dunnett post hoc tests were used to identify the statistically significant changes. For the cold pressor and reactive hyperemia tests, paired t tests were used to compare the baseline values with the minimal (cold pressor) and maximal (reactive hyperemia) values observed during the intervention. Measurements were considered statistically significant at P<.05. All data in this report are expressed as means [+ or -] standard deviation).

Results

Protocol 1: TENS Applications

Neither sensory- or motor-level TENS influenced calf blood flow (Table, Figs. 2 and 3). Likewise, mean arterial pressure and calf vascular resistance were unaltered by either form of TENS (Table). Calf blood flow, calf vascular resistance, and arterial pressure were unaltered during time-control experiments (30 minutes of supine rest) (Table). Dorsal foot skin temperature decreased during both sensory-and motor-level TENS (P<.05) (Table).

[TABULAR DATA OMITTED]

Protocols 2 and 3: Cold Pressor and Reactive Hyperemia Tests

Immersion of the hand in ice water for 90 seconds produced an increase in arterial pressure (89 [+ or -] 14-106 [+ or -] 20 mm Hg, P<.05) and a decrease in calf blood flow (2.6 [+ or -] 0.7-1.5 [+ or -] 0.7 mL/100 mL/min, P<.05). Following the release of 5 minutes of vascular occlusion, calf blood flow increased markedly 2.7 [+ or -] 1.0-17.0 [+ or -] 9.0 mL/100 mL/ min, P<.05). The changes in calf vascular resistance caused by these interventions are shown in Figure 4.

Discussion

Direct electrical stimulation of sympathetic trunks in experimental animals activates preganglionic and postganglionic neurons and causes vasoconstriction.[9,10] Previous studies of transcutaneous electrical stimulation of peripheral nerves in humans have provided conflicting views of whether such stimulation influences regional blood flow.[1,3] The findings of our study, based on actual measurements of blood flow, indicate that TENS applied over peripheral nerves at clinically relevant pulse durations and frequencies does not affect limb blood flow.

We observed consistent, time-dependent, statistically insignificant decreases in calf blood flow during both motor- and sensory-level TENS applications. These blood flow decreases, however, were not caused by electrical stimulation of peripheral nerves, because comparable decreases were observed in time-control experiments in which no TENS was applied. These small decreases in blood flow can possibly be attributed to cutaneous vasoconstriction produced by exposure to a nonthermoneutral environment, This concept is supported by the observation of parallel declines in skin temperature. Similar decreases in skin temperature have been observed previously and were attributed to the influence of ambient temperature.[11]

A frequently recommended electrode placement for the clinical use of TENS is directly over the peripheral nerve that subserves the painful area.[12] Previous investigators,[4,13] who have observed decreased skin temperature during sensory-level and mild motor-level TENS applied over peripheral nerves, have raised the concern that TENS may decrease blood flow to the painful extremity by direct stimulation of sympathetic vasoconstrictor fibers. The results of our study argue strongly against this possibility. Although we did not measure sympathetic outflow, we calculated vascular resistance, a variable that provides a more direct estimate of vasoconstrictor drive than does skin temperature. Calf vascular resistance was not altered by either sensory- or motor-level TENS. Although dorsal foot skin temperature decreased in our subjects, it is unlikely that this change was caused by electrical stimulation of sympathetic vasoconstrictor fibers for two reasons. First, the decreases in skin temperature were not apparent until 10 minutes after the onset of TENS application, and they persisted in the recovery period. The time constant for vasoconstriction following direct stimulation of sympathetic nerves is known to be less than 10 seconds.[10] Thus, TENS-induced cutaneous vasoconstriction, if present, would be expected to have a rapid onset and offset relative to the period of stimulation. Second, and more importantly, comparable decreases in skin temperature were observed during time-control experiments.

Sustained isometric muscle contraction limits blood flow to the active muscle through a contraction-induced increase in tissue pressure.[14-16] At force outputs greater than 15% of the maximally achievable contraction, the blood supply is inadequate to meet the metabolic demands of the working muscle and reflex increases in arterial pressure and sympathetic vasomotor outflow occur.[17-19] Although the motor-level TENS used in our study produced sustained contractions of the pretibial and calf muscles, neither blood flow nor arterial pressure was altered. The most likely explanations for this finding are that the intensities of TENS-induced muscle contractions in our study were less than 15% maximal and that redistribution of blood flow within the vascular compartments of the calf (ie, from skin to muscle) allowed adequate perfusion relative to the metabolic needs of the contracting muscle.

Transcutaneous electrical stimulation that is of sufficient intensity to elicit a strong, rhythmic (nonsustained) muscle contraction increases regional blood flow both in healthy subjects and in patients with peripheral vascular disease.[11,20,21] Much of the increase in blood flow produced by rhythmic exercise is triggered locally by metabolic by-products of muscle contraction.[22] Although it is known that these metabolites can interfere with excitation-contraction coupling at the level of the vascular smooth muscle,[23] some investigators[1,21] have speculated that TENS has an independent inhibitory effect on sympathetic outflow to the peripheral vasculature. Our findings do not provide support for this concept because TENS applied over peripheral nerves at intensities below the threshold for strong muscle contraction did not alter blood flow.

The results of our study are at variance with those of a previous investigation[1] in which TENS applied over the ulnar nerve produced an increase in hand skin temperature. Although similar stimulation characteristics were used, the temperature-sensing technique used in the previous study (infrared thermography) was shown to be more sensitive than that used in our study ([+ or -]0.1[degrees]C versus [+ or -] 0.2[degrees]C). This discrepancy in measurement sensitivity could have led to differing estimates of the magnitude of TENS-induced changes in skin temperature. We believe, however, that this discrepancy cannot account for the contrasting results seen with TENS application in the two studies. Instead, ambient temperature differences (24[degrees]-27[degrees]C versus 24[degrees]C) and dissimilar recording sites (hand versus foot)24 are the probable causes of baseline differences in skin temperature in the two studies (33.8[degrees] [+ or -] 1.1[degreess]C versus 29.4[degrees] [+ or -] 1.7[degrees]C). These inconsistencies may also be responsible for the disparate responses to TENS, We emphasize that skin temperature provides only an indirect estimate of limb blood flow. Even though foot skin temperature decreased in our experiments, we observed no change in blood flow to the calf

We considered the possibility that a Type II error led to our acceptance of the null hypothesis. Venous occlusion plethysmography is a well-established method for measurement of limb blood flow.[7,8] This noninvasive technique has been validated previously using both direct and electromagnetic flow determinations.[25,26] In our experience, the technique is very reproducible (coefficient of variation, [+ or -] 8%). The statistical power associated with our analyses of Tens-induced blood flow changes was 77%. Therefore, we estimate the likelihood of a Type II error to be small.

It is possible that a nonspecific inability to respond to vasoconstrictor or vasodilator stimuli was responsible for the failure of TENS to affect blood flow in our subjects. This explanation is unlikely because our subjects responded as expected to immersion of the hand in ice water (which causes neurally mediated vasoconstriction) and to vascular occlusion (which causes metabolically mediated vasodilation). The baseline levels of calf vascular resistance in our subjects are similar to previously reported values.[27,28]

Conclusions

The present findings indicate that neither sensory-level nor low-intensity motor-level TENS delivered at high frequencies alters limb blood flow in asymptomatic individuals with normal vascular resistance. Caution must be exercised when applying these findings to other groups of individuals (eg, patients with augmented or diminished peripheral vascular resistance) because the magnitude of hemodynamic response to many interventions is known to be critically dependent on the baseline value.[29] In addition, these findings may not be applicable to forms of TENS that utilize different stimulation characteristics.

Acknowledgments

We thank Dr William Reddan of the Department of Preventive Medicine, University of Wisconsin-Madison, for the use of the telethermometer and for his critical review of the manuscript. We also appreciate the secretarial assistance of Ms Pat Mecum. (*) Dinamap model 1846SX/P blood pressure monitor, Critikon, PO Box 31800, Tampa, FL 33631. ([dagger)] Finapres model 2300 blood pressure monitor, Ohmeda, 3030 Ohmeda Dr, Madison, WI 53707. ([double dagger] Model 46TUC temperature monitor, YSI Inc, 1725 Brannum Ln, Yellow Springs, OH 45387 ([sections]) Model TA4000 physiologic recorder, Gould Inc, 3631 Perkins Ave, Cleveland, OH 44114. ([parallel]) Model 3000A PCM recording adaptor, AR Vetter Co, Box 143, Rebersburg, PA 16872, (#) Model HR-D86OU videocassette recorder, JVC Company of America, 41 Slater Dr, Elmwood Park, Nj 07407. (**) University of Iowa Medical Instruments Department, 8 Medical Laboratories, lowa City, IA 52242. ([double dagger]) Parks Medical Electronics Inc, Box 5669, Aloha, OR 97006. ([double dagger]) Dynex II model 2005 portable stimulator, La Jolla Technology Inc, 11558 Sorrento V Diego, CA 92121.

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HJ Indergand is a student in the Physical Therapy Program, University of Wisconsin-Madison, Madiso WI 53706.

BJ Morgan, PhD, PT, is Assistant Professor, Physical Therapy Program, Department of Kinesiology, University of Wisconsin-Madison. Address correspondence to Dr Morgan at 5175 Medical Sciences Center, 1300 University Ave, Madison, WI 53706-1532 (USA).

The study protocol was approved by the University of Wisconsin-Madison Clinical Science Center Human Subjects Committee.

This research was supported by a Wisconsin/Hilldale Undergraduate/Faculty Research Fellowship.

This article was submitted April 28, 1993, and was accepted December 7, 1993.