Palpation of the radial pulses is an important technique in traditional Chinese medicine. Two double-blind randomized trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitized subjects) and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform were measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-min acupuncture period. In sensitized patients, arterial diameter significantly increased during real acupuncture, compared with the sham group (+7.5 ± 2.8 vs. −2.9 ± 2.7%, respectively; P < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time course of blood pressure, radial artery distensibility, and pressure waveform. Our results demonstrate that real acupuncture is associated with an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.
- randomized trial
acupuncture is the most frequent type of unconventional medicine in developed countries (10), despite its alleged irrational principles (27). It is doubtful whether any form of acupuncture has more than a placebo effect, despite some subjective benefits reported in controlled studies (8, 12, 21, 23). Traditional Chinese medical syndromes, treated by acupuncture, are diagnosed by recorded history and symptoms, together with examination of the tongue and the pulses at both radial arteries (24). Acupuncture therapy is adjusted according to the observed alterations of the radial pulses and monitored through changes in radial pulse patterns. Although palpation of the radial pulses is the most important technique in traditional Chinese medicine, to our knowledge no controlled study of the effects of acupuncture on the radial artery hemodynamic behavior has been reported. On the basis of the traditional descriptions of the changes in radial pulse patterns, and by inference from the works on acupuncture, exercise, and analgesia (3, 15), we hypothesized that acupuncture might be able to decrease smooth muscle tone at the site of the radial artery, thus inducing a vasodilatation and changing the pressure waveform.
We took advantage of the accuracy of a recently developed high-resolution echotracking system to quantify the changes in radial artery diameter during acupuncture therapy and used aplanation tonometry to monitor the changes in radial artery pressure waveform. Because previous exposure to acupuncture may modify its effects (3, 15), we studied two groups: patients previously treated with acupuncture on a regular base and healthy subjects not exposed to acupuncture. Each group was studied according to a double-blind, randomized, and controlled trial. In each trial, real acupuncture treatment was compared with sham acupuncture. The primary goal of the present studies was to assess whether traditional Chinese acupuncture therapy could objectively modify the hemodynamic properties of the radial artery, independently of its subjective efficacy for relieving the various symptoms alleged by the patients.
Patients and Studies Designs
Two studies were successively performed according to a double-blind, randomized, and controlled design. The first study included 19 consecutive patients (5 males and 14 females, 45 ± 4 yr), regularly exposed to acupuncture therapy, and subsequently considered as sensitized patients. All of the patients presented various functional symptoms (dorsalgia, headache, dyspepsia, and anxiety) unrelated to organic lesions, as assessed by physical examination and conventional diagnosis workup. The patients were randomly allocated to real or sham acupuncture therapies, according to a parallel group design. The second study included eight healthy subjects, devoid of any symptoms, who had not been exposed to acupuncture (naive subjects). To increase the power of detecting significant changes in radial artery hemodynamics, the naive subjects were included in a two-session crossover study.
Real acupuncture therapy was given by R. Corvisier, who was trained in both orthodox Western medicine and traditional Chinese medicine. We used 4-cm-long disposable stainless steel needles (Shen Long; Phytorient Biodev) with no additional electrical or laser stimulation. In patients and subjects, the diagnostic workup included recording of medical history and symptoms, together with examination of the tongue and the pulses at both radial arteries, according to the Chinese medicine principles. Acupuncture therapy was adjusted according to the observed alterations of the radial pulses and monitored through changes in radial pulse patterns. In the case of real treatment, acupuncture needles were inserted into “specific acupuncture points” corresponding to the established diagnosis. In the case of sham treatment, insertion points were chosen outside the specific acupuncture points. In both cases, needles were maintained in place for 20 min and removed thereafter. “Sham-treated” patients and subjects were assessed in the same ways, were given the same amount of attention, and received the same number of needles, which were left for the same length of time, as their pairs. The only difference was that needles were inserted into nonacupuncture “dead” points. Concerning the primary objective of the study, the trial was double-blind because patients or subjects and clinical investigators (P. Boutouyrie, D. Lemoine, B. Laloux, and S. Laurent) measuring radial artery parameters were not aware of the real or sham character of the acupuncture therapy. R. Corvisier assessed each patient or subject individually in a separate room before each treatment. He then opened a sealed envelope informing him whether real or sham acupuncture treatment should be given.
The study was reviewed by an ethics committee and patients and subjects gave informed written consent.
The measurements were performed in a quiet room with a stable ambient temperature of 24 ± 1°C. Blood pressure and radial artery hemodynamic parameters were studied with the subject in the supine position and after a rest of at least 20 min. Brachial blood pressure was monitored every 3 min with an oscillometer (Dinamap model 845; Critikon) during the whole investigation. Measurements of internal diameter and its systolic-diastolic variations were performed over 3 min, before the insertion of the needles, then during minutes 7-10, and minutes 17–20after insertion. For practical reasons, the right radial artery was selected for diameter measurements, and the left radial artery was selected for pulse waveform measurements, and the measurements were then performed simultaneously. One sensitized patient among 20 could not have reliable measurements of radial artery diameter during treatment (real acupuncture) and was therefore excluded from the final analysis. All naive subjects were included in the final analysis.
Measurements of radial artery internal diastolic diameter and stroke change in diameter were obtained with a 10-MHz ultrasound system analyzing the radio frequency signal (NIUS 02; SMH; Bienne, Switzerland), previously described, validated, and used in clinical studies (4, 5, 13). Cross-sectional compliance and distensibility were estimated through the variations in arterial lumen cross-sectional area and blood pressure during systole as previously described (4, 5, 13), assuming the lumen to be circular. Local radial artery pulse pressure was used in these calculations (5).
Radial artery pressure waveform was determined noninvasively with aplanation tonometry, by using a pencil-type probe incorporating a high-fidelity strain-gauge transducer (model SPT-301; Millar Instruments, Houston, TX), as previously described and validated in vitro and in vivo in humans (5). Because the tonometry principle gives only a relative pressure, the resulting pressure waveform was calibrated on mean arterial pressure. The pressure-wave morphology was assessed through its frequency content, determined after a 8,192-sample fast Fourier transformation (∼60 cycles) (25). The spectral power (area under the curve) was calculated for each peak of the spectrum, for the first two harmonics. We estimated the global morphology of the pressure wave from the ratio between the second harmonic (H2) and the first harmonic (H1), because most of the spectral power is contained in the first two harmonics, and this procedure minimizes the influence of nonspecific changes in signal spectrum amplitude (25).
The primary goal was to analyze the arterial changes after real or sham acupuncture treatments. All results are reported according to an efficacy sample analysis. Data are expressed as means ± SD. In the first study, the homogeneity of the randomized groups at baseline was determined with an unpaired Student's t-test and χ2-test. For comparison of serial changes in blood pressure and arterial parameters, repeated-measures ANOVA was performed to examine treatment differences and interactions (11). Statistical analysis was performed with the use of NCSS 2000 software. Statistical significance was assumed for P < 0.05.
Study of Sensitized Patients
We randomized 9 patients to real acupuncture and 10 patients were allocated to the sham procedure. Both groups were comparable in relation to age (42 ± 3 vs. 49 ± 3 yr, respectively) and body mass index (21.8 ± 2.9 vs. 22.7 ± 2.5 kg/m2, respectively). The sex ratio was four males to five females in the real group and one male to nine females in the sham group (with a trend for a significant difference; P = 0.09). Baseline values of blood pressure, heart rate, and arterial parameters did not differ significantly between groups.
Radial artery internal diameter increased significantly during real acupuncture, compared with sham acupuncture (significant “time × treatment” interaction; P < 0.01; Fig.1 and Table1). Indeed, during the 7- to 10-min period, the diameter changes from baseline were +169 ± 61 versus −68 ± 58 μm, respectively, i.e., +7.5 ± 2.8 versus −2.9 ± 2.7%. During the 17- to 20-min period, the diameter changes from baseline were +117 ± 62 versus −28 ± 59 μm, respectively, i.e., +5.4 ± 2.8 versus −1.2 ± 2.7%. No significant difference was observed between real and sham acupuncture, concerning the time course of systolic blood pressure, diastolic blood pressure, pulse pressure, radial artery stroke change in diameter, and the first two harmonics of the pressure wave (Table 1). There was a trend (P = 0.07) for an increase in the H2-to-H1 ratio of the tonometric pressure waveform in the real acupuncture treatment group, compared with the sham group. Heart rate decreased significantly in both groups, without any significant difference between groups.
Study of Naive Subjects
All of the eight subjects (26 ± 3 yr, 182 ± 7 cm, 80 ± 12 kg wt) completed the study. No significant difference was observed between real and sham acupuncture, concerning the time course of systolic, diastolic, and pulse pressures, radial artery diastolic diameter, stroke change in diameter, compliance, distensibility, the first two harmonics of the pressure wave and their ratio (Table2). Systolic blood pressure significantly increased, and pulse pressure tended to increase with time (P = 0.09). Compliance, distensibility, and the H2-to-H1 ratio decreased significantly with time.
The present trials were designed to test, in a double-blind randomized manner, whether traditional Chinese acupuncture could specifically modify the hemodynamic properties of the radial artery. Because previous exposure to acupuncture may modify its effects, we studied patients regularly treated with acupuncture and subjects not exposed to acupuncture. The two main findings are the following:1) in patients regularly exposed to acupuncture, the radial artery internal diameter increased during real acupuncture and did not change in the sham group, and 2) in naive subjects, radial artery internal diameter did not change during real acupuncture, by contrast to sensitized patients.
The radial artery was studied for two main reasons. First, radial artery pulse characterization is a major base of diagnosis and treatment adjustment in Chinese medicine. Second, we took advantage of the properties of the high-resolution echotracking device NIUS 02 to measure radial artery diameter and distensibility with high precision and repeatability (4, 5, 13).
Although many articles are centered on acupuncture (n = 7,266 Medline entries), randomized controlled studies are rare (n = 314). Double-blind studies are even more scarce (n = 56) and have not included radial artery behavior. We applied the practices of clinical trials to the present study. Both studies were randomized and blind for both the patients (or subjects) and the physicians who measured the radial artery parameters. The skill necessary for practicing acupuncture (either diagnosis or treatment) foreclosed the use of a blind investigator for applying acupuncture. Our aim was to measure the effects of needles inserted into specific acupuncture points in comparison with those induced by needles inserted into nonacupuncture dead points. R. Corvisier was advised to optimize acupuncture therapy in the real treatment group and to be as neutral as possible in the sham-treated group. An equal number of needles was given over an equal length of time thus giving similar levels of care and attention to real and sham groups. All of the patients and subjects were equally wrong when asked about their treatment allocation group (as assessed by standardized questionnaire), showing that they were truly blinded according to treatments.
Radial artery vasodilatation in sensitized patients.
In patients regularly exposed to acupuncture, radial artery internal diameter significantly increased during real acupuncture in all but two patients, whereas it did not change in the sham group. The amplitude of the radial artery vasodilatation observed during real acupuncture (+7.5 ± 2.8% vs. baseline during the 7- to 10-min period) was higher than physiological spontaneous oscillations (2.6%; 17) or flow-dependent vasodilatation (3.6%; 18), but lower than pharmacological vasodilatation observed with high doses of sodium nitroprusside (12.5%) or acetylcholine (15.5%) administered intra-arterially (19), in studies measuring radial artery diameter with the same echotracking system.
Despite the randomization procedure, the number of male patients selected in the real acupuncture group tended to be larger than in the sham group. Thus one may question whether this may have influenced the changes in radial artery vasomotor tone and artificially ascribed to real acupuncture a placebo vasodilation effect occurring mainly in male patients. Such a possibility is unlikely, because no such effect was observed in the healthy male volunteers. In addition, no difference in time-related changes in radial artery diameter occurred between the male group (5 patients) and the female group (14 patients), when both groups were analyzed independently of their allocation to real or sham acupuncture.
It is conceivable that blood pressure did not change in the real acupuncture group despite the vasodilatation of the radial artery, because distal muscular medium-sized arteries, like the radial artery, have mainly a conducting function and no resistive one (9,25). However, it is more difficult to conciliate the vasodilatation of the radial artery with the lack of modification in distensibility and compliance, because a decrease in large artery smooth muscle tone, leading to diameter enlargement, should theoretically be associated with an increase in distensibility and compliance, even when blood pressure does not drop (9). These changes have been observed at the site of the radial artery during some acute studies in healthy subjects (17) or in patients with congestive heart failure (14). However, there was a trend for the H2-to-H1 ratio of pressure wave to increase during real acupuncture and to decrease in the sham group, suggesting modifications of the radial artery pulse waveform during real acupuncture and associated increase in distensibility along the brachio-radial arterial axis.
Taken together, these findings suggest that the radial artery vasodilatation, observed during real acupuncture, was the consequence of the insertion of acupuncture needles in specific points and not anywhere else. By inference from the works on acupuncture, exercise, and analgesia (2, 3, 7, 15, 16, 20, 22, 26), one may suggest that acupuncture might be able to decrease smooth muscle tone at the site of a muscular artery. Inhibition of sympathetic vasoconstriction by acupuncture has been suggested (7, 16, 22,26) through various mechanisms, including a centrally mediated reflex response (15, 26) and a presynaptic inhibition of sympathetic nerves (15, 22, 26). Particularly, endogenous opioids, including β-endorphin, have been suggested to play a role in the regulation of sympathetic activity in response to acupuncture (2, 3, 15, 16), because naloxone was able to suppress the acupuncture-induced sympatho-inhibition (3, 7).
Hemodynamic changes in naive subjects.
In naive subjects, real acupuncture was not associated with an increase in radial artery diameter. This may be explained by a nonspecific increase in smooth muscle tone (because it occurred after both real and sham acupuncture), counteracting the relaxing effect of acupuncture (9). Indeed, the increase in systolic blood pressure was associated with a decrease in compliance, distensibility, and H2-to-H1 ratio. A sensitization phenomenon (1, 3, 15, 28) may represent another explanation, through the potentiation of smooth muscle relaxation in patients regularly exposed to acupuncture. Endogenous opioids may be involved. Indeed, a morphine-induced locomotor sensitization has been reported in mice (28). Naltrexone was shown to potentiate the analgesia induced by electroacupuncture in naive rats, but to antagonize it after two preexposures to electroacupuncture (3). In the present study, we observed a significant vasodilation effect of naloxone on the radial artery of naive subjects, independently of needles implantation (data not shown). Thus if the effects of acupuncture on the radial artery were to be mediated by endogenous opioids, the mechanisms would likely be very complex, involving other mediators.
There were significant differences in baseline hemodynamic parameters between sensitized patients and naive subjects. The main difference concerned radial artery diameter, which was significantly larger in naive subjects than in sensitized patients, most likely because of the larger body surface area (+22%) of the healthy young male volunteers. However, this difference did not affect the main result. Indeed, radial artery diameters were not significantly different between naive subjects and sensitized patients after adjustment to body surface area. Adjusted radial artery diameter increased significantly during real acupuncture in sensitized patients, compared with sham acupuncture, whereas no significant difference was observed between real and sham acupuncture in naive subjects (data not shown).
Distensibility was significantly lower in naive subjects than in sensitized patients. This may be explained by the psychological stress undergone by the volunteers who anticipated the needle implantation, leading to an increase in smooth muscle tone, by contrast to sensitized patients already accustomed to this procedure. This nonspecific effect of smooth muscle tone, counteracting the relaxing effect of acupuncture, has already been discussed above.
In traditional Chinese medicine, the practitioner “feels” what he believes is the shape of the pulse wave under his fingers and classifies it according to typical pulse wave shapes (29). In sensitized patients, vasodilatation of the radial artery or modification of the pulse waveform may have led to changes in the perception of the pulse by the practitioner. However, this was not the case in naive subjects, because no objective hemodynamic change was observed.
In conclusion, the present study shows a significant radial artery vasodilatation during real acupuncture in sensitized patients, contrasting with no change in naive subjects. In the context of an ongoing controversy about whether acupuncture has more than a placebo effect, the present study gives support to a measurable objective effect of acupuncture therapy in patients previously exposed to it.
The authors thank Philippe Labbe, Jacques Gautron, Gilles Chatellier, and Jean-Charles Schwartz for help in the realization of this study.
This study was supported in part by grants from Institut National de la Santé et de la Recherche Médicale and Institut Electricité Santé.
Address for reprint requests and other correspondence: S. Laurent, Service de Pharmacologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France (E-mail:).
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- Copyright © 2001 the American Physiological Society