Acupuncture is effective for the prevention of acute myocardial ischemia (AMI), a condition causing damage to the heart from reduced cardiac blood flow and oxygen deprivation. Anhui University of Traditional Chinese Medicine researchers conclude that acupuncture applied to acupoints Shenmen (HT7) and Tongli (HT5) protects myocardial cells from ischemic injuries. In a laboratory experiment, the university researchers have proven that acupuncture prevents myocardial ischemia by regulating pro-inflammatory factors and hippocampal neurotransmitters. [1] The researchers note, “Electroacupuncture can protect myocardial cells in AMI rats, which may be associated to its effect in inhibiting the expression of serum creatine kinase (CK), hippocampal norepinephrine (NE), interleukin 6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor- alpha (TNF-α).”
Biomarkers and Pathogenesis
AMI is an inflammatory process wherein IL-6, IL-1β, and TNF-α are the main biomarkers. IL-6 is a multifunctional cytokine that plays a major role in inflammatory responses. [2] IL-1β is produced by mononuclear phagocytes and can induce apoptosis with TNF-α. TNF-α is one of the cytokines that make up the acute inflammatory response system. [3] These proinflammatory cytokines activate the hypothalamic-pituitary-adrenal glandular (HPA) axis and stimulate sympathetic nerve activity in the autonomic nervous system, thereby aggravating myocardial injuries. [4]
Creatine kinase (CK) is an enzyme in heart, brain, skeletal muscle, and other tissues. Clinically, CK is used as a marker of damage in CK-rich tissue affected by myocardial ischemia. [5] The neurotransmitter norepinephrine (NE) is secreted in response to increased expression of proinflammatory cytokines. Excessive NE acts on the corticotropin-releasing hormone α1 (CRH-α1) receptors. Excess NE activates CRH neurons, overexcites sympathetic nerves, and causes heart dysfunction such as increased heart rates and high blood pressure. [6]
Research Gaps
The researchers conducting the investigation note, “Previous studies investigated that acupuncture can inhibit inflammatory responses in rats with myocardial ischemia by down-regulating the expression of proinflammatory cytokines such as IL-6, IL-1β and TNF-α. Some studies also found that acupuncture can regulate the activity of the nervous system and neurotransmitters in the hypothalamus and other related nerve nuclei, thereby improving acute myocardial ischemia.” They add, “However, whether the proinflammatory cytokines and hippocampal neurotransmitters interact together in the process of acupuncture against myocardial ischemia has not been reported before.” This study demonstrates that the IL-6, IL-1β, and TNF-α were positively correlated with the NE levels, and that acupuncture influences both proinflammatory cytokines and hippocampal neurotransmitters in AMI rats. This opens up directions for future research to build on this foundation of knowledge.
Acupuncture Treatment
The laboratory rats in this investigation were randomly divided into three groups, with 6 rats in each group. The first group received surgery to create an AMI model, in which the anterior descending branch (ADB) of the left coronary artery was occluded. The second group received sham AMI surgery, in which a surgical suture was simply threaded beneath the ADB without ligation. The third group was an AMI surgery model that received electroacupuncture (EA) on the bilateral heart meridian segment between the following two points:
- Shenmen (HT7)
- Tongli (HT5)
Upon selection of the aforementioned acupoints based on Chinese acupuncture principles, three 0.30 mm × 25 mm needles were evenly inserted into the Shenmen (HT7), Tongli (HT5), and the middle point between HT7 and HT5, with an interval of 2 mm. Next, the acupuncture needles were connected to an electroacupuncture device with an alternating frequency setting (1 mA, 2 Hz/15 Hz). The needles were retained for 30 minutes after initiating electroacupuncture. One 30-minute electroacupuncture session was conducted daily, for a total of 3 consecutive days.
Results
Before and after the surgery and acupuncture treatment, evaluations were performed. First, the electrocardiogram (ECG) readings of the neck-thoracic lead were recorded. Second, the contents of serum CK, hippocampal IL-6, IL-1β, and TNF-α were assayed. Third, the concentration of NE in the hippocampal CA1 area was detected.
Compared with the sham group, the ECG-ST height, serum CK, hippocampal NE, IL-6, IL-1β, and TNF-α contents of the CA1 region were significantly increased in the model group. After electroacupuncture intervention, the serum CK, hippocampal NE, IL-6, IL-1β, and TNF-α contents were significantly downregulated. The IL-6, IL-1β, TNF-α contents were positively correlated with the NE level.
Summary
The results of the investigation demonstrate that acupuncture is a laboratory proven treatment modality for the treatment of AMI. Researchers demonstrate that the IL-6, IL-1β, and TNF-α contents are positively correlated with NE levels in AMI rats, and that acupuncture alleviates AMI while simultaneously downregulating proinflammatory cytokines and neurotransmitters responsible for causing ischemic injury in AMI. Notably, these results are not isolated. Other researchers have demonstrated similar clinical outcomes in prior laboratory investigations.
University of California
Researchers from the University of California Los Angeles (UCLA) find acupuncture effective for protecting the heart. Electroacupuncture at PC6 (Neiguan) and P5 (Jianshi) in anesthetized rabbits with coronary artery occlusion resulted in a significant decrease in ventricular arrhythmias. Also, electroacupuncture decreased heart infarct size. [7] Essentially, acupuncture treatment protected heart tissue from cell death due to obstruction of normal blood and oxygen supply. The researchers proved that electroacupuncture causes a decrease in left ventricle dysfunction. A decrease in harmful ST segment elevation was recorded in response to needling PC6 and PC5. This is important because an ECG measuring a raised ST segment may indicate a myocardial infarction.
The results were published in the American Journal of Physiology Heart and Circulatory Physiology. Five groups were compared: non-treatment, electroacupuncture, sham (non-acupuncture point stimulation), and two additional experimental electroacupuncture groups. The experimental groups combined acupuncture with chemical blocking agents designed to block the regulation of the cardiac nervous system, opioid receptors, and PKC (Protein Kinase C) pathways.
PKC is a kinase enzyme that modifies proteins. PKC is active in signal transduction of extracellular stimuli, including hormones and growth factors. The researchers learned something very important by using PKC and other cardiac nervous system blocking agents. They discovered an important pathway involved in the therapeutic actions of electroacupuncture because electroacupuncture did not produce cardioprotective effects when the blocking agents were used.
Based on the evidence, the researchers conclude that electroacupuncture protects the heart by regulating the cardiac nervous system, opioid receptors, and PKC pathways. The group provided with electroacupuncture, without interference from blocking agents, demonstrated significant cardiac improvements. Every other group in the study did not show significant improvements. This evidence demonstrates clinically effective biochemical pathways active in electroacupuncture treatments.
References:
[1] Wang K. Wu SB, Cui S, Xiang SY, Wu X, Zhou MQ. Effect of Electroacupuncture on Hippocampal IL-6, IL-1β, TNF-α, Norepinephrine Levels in Acute Myocardial Ischemia Rats [J]. Acupuncture Research, 2018(6).
[2] Gwechenberger M, Mendozalh, Youkeray, et al. Cardiacmyocytes Produce Interleukin-6 In Culture and Inviable Border Zone of Re-Perfused Infarctions[J]. Circulation, 1999, 99(4): 546-551
[3] Chen BY, Li XQ, Chen XL. Clinical study on the relationship between tumor necrosis factor-α, IL-1β, IL-6 levels and congestive heart failure [J]. Journal of Clinical Internal Medicine, 2006, 23 (3): 184 – 185.
[4] Kangy M, Zhangzh, Xueb, et al. Inhibition of brain Proinflammatory cytokine synthesis reduces hypothalamic excitation in rats with ischemia-induced heart failure [J]. Am J Physiol Heart Circ Physiol, 2008, 295(1): 227-236.
[5] labtestsonline.org/tests/creatine-kinase-ck
[6] Zhao B, Ma L, Zhan LY et al. Role of inflammatory factor in SAFE pathway on brain injury in rats induced by myocardial ischemia reperfusion [J]. Hainan Med J, 2017, 28 (20): 3269-3271.
[7] Am J Physiol Heart Circ Physiol. 2012 May;302(9):H1818-25. Epub 2012 Feb 24.
Cardioprotection of electroacupuncture against myocardial ischemia-reperfusion injury by modulation of cardiac norepinephrine release. Zhou W, Ko Y, Benharash P, Yamakawa K, Patel S, Ajijola OA, Mahajan A. Department of Anesthesiology, UCLA - University of California, Los Angeles.