More ISAMS: Dr. S.C. Tjen-A-Looi Cardiovascular Acupuncture Mechanisms

I will leave you with the conclusions. The more specific aspects of the talk were deep into the physiology of the brain and spinal cord. These are the points that you can share with your patients if they ask "How does acupuncture work?"

Clinical Relevance of Point Specificity and Prolonged Action with Acupuncture Treatment
Stephanie C. Tjen-A-Looi, M.S., Ph.D.
School of Medicine
Susan Samueli Center for
Integrative Medicine
University of California, Irvine
Collaborators: Peng Li, John C. Longhurst, Liang-Wu Fu, Zhi-Ling Guo, Min Li
Goal To determine the biological effects of point specificity.
Conclusion
• Acupoint specificity does exist.
• Stimulation at acupoints over deep somatic nerves exert greatest inhibitory cardiovascular electroacupuncture influences.
• Stimulation of acupoints located on meridians activates underlying nerves to induce acupuncture inhibition.

Conclusion Long lasting effect of acupuncture
•Long-loop pathway
•Neural circuitry
•Neurotransmitter specific
•mRNA expressions

For more info on my practice click here.

Dr. Peng Li's Presentation Summarizing 50 years of Acupuncture Research

Dr. Li covered quite a bit of ground as you can imagine during his talk at ISAMS. I'll just feature a few highlights over the next few blog posts.
This slide is taken from Goldman's work entitled "Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture."
Dr. Li then goes on to describe the different protocols for choosing acupuncture points
1. Ashi point- local acupoints for Pain treatment
local release of chemicals, e.g. adenosine (A1 receptor).
convergent input to nearby spinal segment.
2.Acupoints related to Spinal segments
convergent inputs from internal organs and somatic n.
Gate control theory
3. Distant acupoints- supra-spinal integration
Selection of Acupoints

Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture.

Central Neural Actions of Acupuncture, Insights from Brain Imaging

This is the abstract from Richard Harris' talk at the ISAMS conference. Unfortunately, I had to leave before he gave his talk and it is a bit complicated. I have the slides from the talk and once I make my way through them, I will try to make some sort of comment. The abstract follows and after that is the final slide of the presentation.

Central Neural Actions of Acupuncture, Insights from Brain Imaging
Richard Harris PhD, Assistant Professor, Chronic Pain and Fatigue Research Center Department of Anesthesiology, University of Michigan
Functional neuroimaging has been used to study the mechanistic effects of acupuncture for the past 12 years. Over this time researchers have found specific effects of acupuncture on the central nervous system, both in healthy controls as well as in diseased populations. These effects appear to be largely divergent from the “placebo effect”. An investigation of the temporal dynamics of acupuncture yields a complex
array of actions on the central nervous system. During needle insertion and manipulation, acupuncture activates sensory cortical regions while deactivating the limbic system. The degrees of these effects are distinct from the sensation of pain and are related to the “De Qi” sensation. These effects are also more prevalent during electrical stimulation as compared to manual needle manipulation. Following needle removal, modulation of brain connectivity is observed wherein cortical and brain stem regions alter connection strengths between the pain network as well as the Default Mode Network. These effects may be related to analgesia. Over the course of long-term therapy, with multiple treatment sessions, there is a build-up of effects that involve synaptic plasticity and/or changes in synaptic strengths, involving dynamic regulation of neurotransmitter receptors. Finally, immediate actions of acupuncture on the nervous system are modulated over the course of therapy such that the effects of one acupuncture session may be different from a subsequent session. Acupuncture effects are clearly complex and multifactorial, having impact on the central nervous system as assessed by multiple neuroimaging methods.

(This is the final slide from the presentation.)
What if Mechanisms of Acupuncture and Sham are Different?
Implications for clinical trials: specific effects of needling are not additive with placebo effects. Would a pathway analysis make more sense?
Synergistic effects of acupuncture with other interventions.
Exogenous opiates administered following a course of acupuncture may be more effective. (Reduction in post surgical opiate use. Kotani et al. Anesthesiology2001.)
Acupuncture is not a sham.

(For more information about my practice, please click here.)

Treating Hypertension (High Blood Pressure) in the Acupuncture Clinic

This is the abstract from a study on hypertensive patients from Professor John Longhurst's lab. It is a sort of summary of his findings discussed here and here.
A few comments... He uses electroacupuncture because he says it's easier to make it standard across patients. This was something I noticed repeatedly at the conference: most researchers are using electroacupuncture. I had a few different discussions with Dr. Longhurst, and he thinks that if you don't do electroacupuncture, you're really not stimulating because the stimulus goes away during the session. I don't agree with that. I think that the needles provoke a "micro-injury" just by being there and work just fine, even if you don't repeatedly stimulate them. Manual acupuncture, without electro, is my standard operating procedure. I use electro acupuncture if I'm following a specific protocol, for example for infertility or PCOS, or in musculoskeletal cases where the patient has reached a "plateau." I hardly ever start with electrical stimulation because of the tendency for it to aggravate the condition and the patient. I would never have the heart to do electrical stimulation at P6, as they do in this study. It's such a sensitive spot, I will try their other choice of LI11 and LI10 which is equally effective according to their work.
1

Acupuncture Treatment of Hypertension
John C. Longhurst, MD, PhD and Peng Li, MD, Department of Medicine, University of California, Irvine
Heart disease in both men and women has become the major cause of death and disability in both developed and developing countries. Coronary atherosclerosis, the leading cause of heart disease, has a number of risk factors that increase its incidence. These include hypertension, hypercholesterolemia, diabetes mellitus, family history, obesity, physical inactivity and chronic stress. Hypertension, in particular, is reversible if patients are treated early and blood pressure is lowered to normal levels. Although a number of drug therapies have been shown to be valuable in lowering this risk factor, many patients do not take medications faithfully because of their common side effects and need for daily dosing. As such, there is a strong rationale developing alternative regimens to control blood pressure. One such therapy is acupuncture. Acupuncture is a form of integrative medicine that has substantial evidence demonstrating its mechanisms of action to lower sympathetic outflow, one of the major causes of elevated blood pressure. For example, studies in our laboratory show that, through an opioid mechanism in the brain stem, acupuncture can lower reflex elevations in blood pressure. Furthermore, we have shown that low frequency, low intensity electroacupuncture at some acupoints, such as P5-P6 and S36-S37, is most effective in lowering elevated blood pressure for prolonged periods of time. In the last decade several studies have been conducted showing that acupuncture is capable of lowering blood pressure to a small extent for the period of time during which it is applied. Although these studies indicate a possible role for acupuncture in treating hypertension, they have been confounded by use of a variety of different acupoints, some of which may not have strong cardiovascular actions, use of manual acupuncture, which unlike electroacupuncture cannot be standardized between patients, the use of very frequent acupuncture, which because of patient incompliance could limit success for long-term treatment, and the absence of regular follow-up, which does not provide an understanding of the duration of acupuncture’s action. To overcome these obstacles, we have embarked on a program of treatment of patients with mild to moderate hypertension using 30 min of low intensity (2 mA), low frequency (2 Hz) electroacupuncture at P5-P6 and S36-S37, a modality and site of action that we have shown has the greatest action on sympathetic outflow and elevated blood pressure in our experimental studies. Furthermore, all patients were off antihypertensive medications for the duration of the study and agreed to acupuncture treatment once weekly for an eight week period with a further follow-up for an additional eight weeks to determine acupuncture’s duration of action. Ambulatory automated blood pressure monitoring demonstrated that both average and 24 hour peak systolic and mean arterial blood pressures were lowered by electroacupuncture after 4-6 weeks of therapy by as much as 11-18 mmHg and that the duration of action of lasted for up to 4 weeks after termination of acupuncture in 73% of individuals treated. Conversely, 69% of a group of control hypertensive subjects treated at LI6-LI7 and GB37-GB39 (cardiovascular inactive acupoints demonstrated in our experimental studies), , did not demonstrate any change in blood pressure. These studies, guided by our results in experimental studies, suggest that low intensity and low frequency electroacupuncture applied once weekly at 2 acupoints demonstrated to have a strong influence on sympathetic activity after 4-6 weeks demonstrate a profound and prolonged antihypertensive response in many patients with mild or moderate hypertension. Additional work is needed to determine the optimal frequencies of repetitive stimulation during the initial period of intervention as well as during follow-up therapy for reinforcement of the blood pressure lowering action of acupuncture. Supported by grants from the NIH, HL063313 and HL072125-10, the Dana and Adolph Coors Foundations.

For more information about my practice, please click here.

Acupuncture's Effect in Induced Arthritis in Mice

This was my favorite presentation at the conference. It was convincing in that it showed decreases in different measures of inflammation and immune function after acupuncture. But what was sort of mind blowing for me was that they only used an acupoint on the back, Ming Men. None of the standard points at or around the limb in question. I never had the chance to ask the author how they picked this protocol. Might have been easier to do with unrestrained rats, but fascinating, nonetheless. Perhaps I should incorporate this is the clinic? A single point for arthritis??

Mechanisms of acupuncture's action in arthritis and immune modulation
Tadashi Hisamitsu, MD, PhD
Showa University, Tokyo, Japan
To evaluate the effects and possible mechanism of acupuncture on the arthritic disease, the influence of electro-acupuncture (EA) and Mox on collagen-induced arthritis (CIA) animal was examined. DBA/1J mice were immunized with bovine type II collagen (CII). The main incidence of arthritis started about on day 30 and lasted to day 60 after the first immunization. EA stimulation or Mox, begun on day 21 simultaneously with the second immunization, was applied three times a week for 3 weeks at the acu-point equivalent to GV4 (governor vessel 4, Ming Men, Meimon). The results showed that EA and Mox delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, these stimulation significantly increased serum IL-6 concentration and regulatory T cell (CD4+ CD25+ Foxp3+ T cell) number, and decreased splenic endogenous IL-1 β and serum prostaglandin E2 (PGE2) concentration. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1β and PGE2 and activation of regulatory T cell. In the Oriental Medicine, reduction of the blood fluidity is one of the important pathological symptom. In the pain and stress model animal, the blood fluidity is markedly lowered like “a stagnant blood”. Increase of platelet adhesion and/or reduction of erythrocyte deformability results from sympathetic activation, increase of blood ATP level and increase of oxidative stress may have important role on this changes. EA applied several acu-points significantly improved these changes.

Huang Study from ISAMS: Heart Rate Variability in the Acupuncture Clini

This was a study published by a group from China. Their results are not in agreement with most other studies on Heart Rate Variability and acupuncture as measured by FFT. They found that there was no change in the LF/HF ratio. They did find an increase in the Sample Entropy with acupuncture, which concurs with my findings posted in previous posts. She was not able to answer me how they filtered and checked for artifact in their heart rate tracings, so they might not have done that. That is a key part of the analysis for LF/HFR which may account for their different findings.
Abstract
Acupuncture has been shown to alter the functional status of the autonomic nervous system. The purpose of the present study was to study the effect of acupuncture on heart rate variability, using linear and non-linear methods of analysis. We consecutively recruited 40 patients, including cases of insomnia, stomachache,
diarrhea, dizziness, cervical syndrome, low back pain, gonarthritis, peripheral facial paralysis, post-traumatic organic brain syndrome and urinary retention. Different acupoint prescriptions were used, according to the textbook for Five-years-education of Traditional Chinese Medicine Specialty in Chinese Universities.
Heart rate variability was recorded before, during, and after acupuncture. Acupuncture substantially reduced variability, causing a 41 % reduction in the standard deviation. Using Fourier analysis, variance both in the low (LF) and the high frequency (HF) range were markedly reduced, whereas the LF/HF ratio (an indication of sympatho-vagal balance) was not altered. The heart rate was unchanged. Sample entropy, which is a measure of the complexity of time series, significantly increased (+ 35 %). Thus, acupuncture produced a pattern of changes different from that seen in pathological conditions, where increased variability and reduced complexity is expected.
Key words : acupuncture - fourier analysis - heart rate variability - sample entropy

Discussion:Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes

n
The goal of having a non-invasive monitoring system that can detect subtle shifts with acupuncture physiologically is the thrust of the author’s research. Exploring HRV with acupuncture over the last several years revealed, somewhat counterintuitively, that there is an intra-treatment increase in HRV. This phenomenon has been corroborated in other studies[i][ii]. The Bäcker study saw only decreases in LFR, other studies have only seen changes in HF.[iii]. With more trustworthy HRV data collection and analysis, comparing of acupoints, various types of acupuncture stimulation, duration of treatment, and spacing of visits would be of interest also.

nThis study is far from scientific, but rather a case study in monitoring HRV in the actual acupuncture clinic, and the author felt compelled to share and tabulate the results of these recent efforts. Clinical outcomes are not graded per se in this study, but are the result of careful interviews on subsequent patient visits.

nHRV measurement and analysis is an exacting undertaking, but with the addition of nonlinear measurements, which are less affected by artifact, the results are more trustworthy. In this study there are noted outliers where there were strong responders who had significant and profound relief from symptoms, but their HRV did not reflect that (PeAl,GuPa,RuSu). The correlation is not perfect.

nComparing patients and treatment sessions instead of control groups, can still give interesting and provocative findings. In controlled studies not available to the clinical practitioner, these trends could hopefully be verified.

nAnd finally, there is an ever increasing focus on the adverse physiological effects of stress. Recent Nobel Prize winning research[iv] shows the effects on a cellular level of stress on aging. Traditionally, in Chinese Medicine, prevention and anti-aging are pillars of practice. If acupuncture can be shown to be an effective treatment option for physiological stress, not only will the ancient practitioners be vindicated, but we will be offering real preventative treatment.

[i] Acupuncture in migraine: investigation of autonomic effects Bäcker M, Clin J Pain. 2008 Feb;24(2):106-15

[ii] Effect of acupuncture on heart rate variability in primary dysmenorrheic women.
Kim E, Cho JH, Jung WS, Lee S, Pak SC.Am J Chin Med. 2011;39(2):243-9.

[iii] Auton Neurosci. 2011 Apr 26;161(1-2):116-20. Epub 2011 Jan 7.

Acupuncture to Danzhong but not to Zhongting increases the cardiac vagal component of heart rate variability.

Kurono Y, Minagawa M, Ishigami T, Yamada A, Kakamu T, Hayano J

[iv] Accelerated telomere shortening in response to life stress. PNAS 2004 Dec 7;101(49):17312-5 Blackburn E
(For more information about my practice please click here.) For more of my research, please click here.

Results: Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes

Results

nIt is feasible to evaluate HRV in the acupuncture clinic both by nonlinear and linear measurements. The total calculation time is 7 minutes.

n

nPatients who responded to their acupuncture treatment tended to exhibit a decrease in their LFR/HFR ratio from segment “a” to segment “b”, an increase in their SD1/SD2, and an increase in their Samp En: all of these trends indicating a decrease in their stress response

n

nNon-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR from minute and a decrease in their SD1/SD2 from the first to second time window, and an increase in their Sample Entropy

n

nThere were notable exceptions, i.e. patients who were strong responders, who did not exhibit the consistent pattern above. In these patients, Sample Entropy was the strongest predictor of successful treatment.

n

nBecause of the prevalence of artifact in heart rate monitoring, the addition of nonlinear measures gives added confidence to the measurements obtained.

nChanging the needle placement prescription and type of stimulation changed outcomes corresponding to HRV results in some cases.
For more info on my practice please click here.
For more of my research please click here.e.

(

Materials and Methods Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes

Materials and Methods

Design, Setting, and Patients: Case study of 20 patients representing 80 treatment sessions. The presenting diagnoses were varied including hypertension(3), low back pain/sciatica (3), headache/migraine(5), depression/anxiety(4), peripheral neuropathy (2), allergy (1), IBS(1), PCOS (1). When patients were in a prone or lateral position, the data was collected but not used in the study.

Controls: This study did not use controls, rather compared like kind data between acupuncture sessions and between patients.

Intervention: All patients received body acupuncture according Traditional Chinese Medicine principles. Electro-acupuncture was used if following a protocol (PCOS), or if manual acupuncture was not proving effective. Heart rate data was collected after needle placement for 20 minutes, and analyzed after treatment. The heart rate tracing was analyzed by pasting into the Kubios system, read out in 5 minute windows starting at 1 minute. The use of 5 minute intervals has precedent in the literature, and is seen as an appropriate time window for analysis. The specific 5 minute intervals (minute 1 to 6, and then 6 to 11) are used because of previous studies showed them to be the most indicative. These were then saved as an Excel Spreadsheet for tabulating. The heart rate tracings had to be scanned for artifact by filtering. Tracings with too many artifacts were excluded from study.

Main Outcome Measure: Patients were assessed by symptom resolution. Some conditions were easier to quantify than others. Headaches, panic attacks, insomnia, knee pain easier to quantify than IBS and PCOS for example. Their HRV data were compared for the time frames “a” (60 to 360 sec) and “b” (360 to 660 sec) using Kubios shareware for:

1. Time series: pnn50 % (not included in current results because of poor correlation)

2. Frequency Domain: FFT (LFR/HFR) ratios and HFR ms

3. Nonlinear results: Poincaré Plots (SD1/SD2) and Sample entropy
For more information on my practice please click here.
For more research, please click here.

References for Heart Rate Variability in the Acupuncture Clinic

Here are the references for the previous post.

[i] Ernst M, Lee M. Sympathetic effects of manual and electrical acupuncture of the Tsusanli knee point: comparison with the Hoku hand point sympathetic effects. Exp Neurol. 1986;94: 1–10.

[ii] Anderson S, Lundeberg T. Med Hypothesis. 1995;45:273–28

[iii] Napadow- Monitoring acupuncture effects on human brain by FMRI.Hui KK, Napadow V, Liu J, Li M, Marina O, Nixon EE, Claunch JD, LaCount L, Sporko T, Kwong KK. J Vis Exp. 2010 Apr 8;(38). pii: 1190. doi: 10.3791/1190.

[iv] Autonomic Neuroscience 2007 May 30;133(2) 158-69Specific acupuncture sensation correlates with EEGs and autonomic changes in human subjects Shigekazu Sakai, Etsuro Hori, Katsurni Umeno, Nobuhide Kitabayashi, Taketoshi Ono, Hisao Nishijo *

[v] Acupuncture in migraine: investigation of autonomic effects Bäcker M, Grossman P, Schneider J, Michalsen A, Knoblauch N, Tan L, Niggemeyer C, Linde K, Melchart D, Dobos GJ Clin J Pain. 2008 Feb;24(2):106-15.

[vi] Medical Acupuncture Volume 19, Number 1, 2007Analysis of Heart Rate Variability in Acupuncture Practice: Can It Improve Outcomes? K. Sparrow, MD

[vii] Chambers AS, Allen JJ. Vagal tone as an indicator of treatment repsonse in major depression. Psychophysiology. 2002;39:861–864.

[viii] Poincaré Plots:A MiniReview ReyLab, Beth Israel Deaconess Medical Center Harvard Medical SchoolDept. Psychiatry, Taipei Veterans General Hospital, Taiwan Albert C.C.Yang, MD

[1] Tulppo et al. Circulation2005; 112:314-319

[1] Medicina (Kaunas) 2010;46(6):,393-400Linear and nonlinear heart rate dynamics in elderly inpatients.Relations with comorbidity and depression Cristina Blasco-Lafarga1, 2, Ignacio Martínez-Navarro1, María Elisa
(For more practice info please click here.)

HRV Analysis in the Acupuncture Clinic: Feasibility and Effectiveness

I had to rework my abstract for the upcoming (click on the logo for a link)
So I'll go ahead and post it here.  I've been working on my poster presentation and I will probably try to illustrate how I use the HRV to help guide my treatments rather than try to convince anyone of the scientific validity of the approach.  Once I get it all together, I'll post it here.  The committee wanted my abstract not to be so, er, abstract.  So I included the conditions treated and type of acupuncture used.  But since it had to be under 2,300 characters, I ended up changing it a fair amount. (For info on my practice, please click here.)

Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes

Kristen Sparrow, MD

Private Practice

San Francisco, California

Background:  Heart Rate Variability (HRV) analysis is a non-invasive method of assessing autonomic tone and has been studied in conjunction with acupuncture in a number of contexts. Acupuncture can lower sympathetic tone and enhance vagal activity, i.e decrease the stress reponse.

 In contrast to the research setting, there are time and efficiency constraints in the private acupuncture practice. In addition there can be monitoring artifacts which make frequency and time domain HRV analysis unreliable.  The author hypothesizes that analysis using nonlinear HRV analysis in addition to the aforementioned analysis methods will give a more sensitive and dependable evaluation of the patients’ autonomic state and show a more consistent correlation with clinical outcomes. The ultimate goal is to use HRV as an additional feedback in the clinic to achieve better results and hence, better outcomes.

Objective:

To correlate patient’s responses to acupuncture treatment with their intra- treatment HRV measurements across time, frequency and nonlinear domains.

Design, Setting, and Patients:  Case study of 20 patients representing 80 treatment sessions. The presenting diagnoses were varied including hypertension(3), low back pain/sciatica (3), headache/migraine(5), depression/anxiety(4), peripheral neuropathy (2), allergy (1), IBS(1), PCOS (1).

Intervention: All patients received body acupuncture according Traditional Chinese Medicine principles. Electro-acupuncture was used if following a protocol (PCOS), or if manual acupuncture was not proving effective.  HRV data was collected after needle placement for 20 minutes, and analyzed after treatment. 

Main Outcome Measure: Patients were assessed by symptom resolution. Their HRV data were compared for the time frames “a” (60 to 360 sec) and “b” (360 to 660 sec) using Kubios shareware for:

1. Time series: pnn50 %

2. Frequency Domain: FFT (LFR/HFR) ratios and HFR%

3. Nonlinear results:  Poincaré Plots (SD1/SD2) and Sample entropy

Results:

Patients who responded to their acupuncture treatment tended to exhibit a decrease in LFR/HFR in the segment “a,” compared to “b” by at least 30% and/or an increase from “a” to “b” in the nonlinear measurement SD1/SD2 by at least 20%.

 Non-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR from “a” to “b”   and a decrease in their SD1/SD2 from “a” to “b.”

Conclusions: In this study the correlation between increased HRV during acupuncture treatment and positive response to acupuncture was supported. Use of nonlinear analysis in addition to frequency domain measures added to the sensitivity of HRV outcome measures.