Despite the use of acupuncture to treat a number of heart diseases, little is known about the mechanisms that underlie its actions. Therefore, we examined the influence of acupuncture on sympathoexcitatory cardiovascular responses to gastric distension in anesthetized Sprague-Dawley rats. Thirty minutes of low-current, low-frequency, (0.3-0.5 mA, 2 Hz) electroacupuncture (EA), at P 5-6, S 36-37, and H 6-7 overlying the median, deep peroneal, and ulnar nerves significantly decreased reflex pressor responses by 40, 39, and 44%, respectively. In contrast, sham acupuncture involving needle insertion without stimulation at P 5-6 or 30 min of EA at LI 6-7 acupoints overlying the superficial radial nerve did not attenuate the reflex. Similarly, EA at P 5-6 using 40- or 100-Hz stimulation frequencies did not inhibit the reflex. Compared with EA at P 5-6, EA at two sets of acupoints, including P 5-6 and S 36-37, did not lead to larger inhibition of the reflex. Two minutes of manual acupuncture (MA; 2 Hz) at P 5-6 every 10 min for 30 min inhibited the reflex cardiovascular pressor response by 33%, a value not significantly different from 2-Hz EA at P 5-6. Single-unit afferent activity was not different between electrical stimulation (ES) and manual stimulation. However, 2-Hz ES activated more somatic afferents than 10- or 20-Hz ES. These data suggest that, although the location of acupoint stimulation and the frequency of stimulation determine the extent of influence of EA, there is little difference between low-frequency EA and MA at P 5-6. Furthermore, simultaneous stimulation using two acupoints that independently exert strong effects did not lead to an additive or a facilitative interaction. The similarity of the responses to EA and MA and the lack of cardiovascular response to high-frequency EA appear to be largely a function of somatic afferent responses.

Li P, Tjen-A-Looi SC, Guo Z, Fu L, Longhurst JC. Long-loop pathways in cardiovascular electroacupuncture responses. J Appl Physiol 106: 620 -630, 2009. First published December 12, 2008 doi:10.1152/japplphysiol.91277.2008.-We have shown that electroacupuncture (EA) at P 5-6 (overlying median nerves) activates arcuate (ARC) neurons, which excite the ventrolateral periaqueductal gray (vlPAG) and inhibit cardiovascular sympathoexcitatory neurons in the rostral ventrolateral medulla (rVLM). To investigate whether the ARC inhibits rVLM activity directly or indirectly, we stimulated the splanchnic nerve to activate rVLM neurons. Micropipettes were inserted in the rVLM, vlPAG, and ARC for neural recording or injection. Microinjection of kainic acid (KA; 1 mM, 50 nl) in the ARC blocked EA inhibition of the splanchnic nerve stimulation-induced reflex increases in rVLM neuronal activity. Microinjection of D,Lhomocysteic acid (4 nM, 50 nl) in the ARC, like EA, inhibited reflex increases in the rVLM neuronal discharge. The vlPAG neurons receive convergent input from the ARC, splanchnic nerve, P 5-6, and other acupoints. Microinjection of KA bilaterally into the rostral vlPAG partially reversed rVLM neuronal responses and cardiovascular inhibition during D,L-homocysteic acid stimulation of the ARC. On the other hand, injection of KA into the caudal vlPAG completely reversed these responses. We also observed that ARC neurons could be antidromically activated by stimulating the rVLM, and that ARC perikarya was labeled with retrograde tracer that had been microinjected into the rVLM. These neurons frequently contained ␤-endorphin and c-Fos, activated by EA stimulation. Therefore, the vlPAG, particularly, the caudal vlPAG, is required for ARC inhibition of rVLM neuronal activation and subsequent EA-related cardiovascular activation. Direct projections from the ARC to the rVLM, which serve as an important source of ␤-endorphin, appear also to exist. arcuate nucleus; ventrolateral periaqueductal gray; rostral ventrolateral medulla; D,L-homocysteic acid; kainic acid CARDIOVASCULAR DISEASE IS the greatest cause of death in middle-aged and elderly North Americans and Europeans. Although western science has developed a number of effective treatment strategies for this disease, treatment is not perfect and often is associated with side effects. As such, there has been increasing interest from the western countries in exploring alternative medicinal treatments and considering new therapies, such as acupuncture, for cardiovascular disease. According to the World Health Organization, acupuncture is effective in more than 40 medical conditions, including cardiac pain and hypertension (24). Experimental studies have shown that lowcurrent, low-frequency electroacupuncture (EA) employed over deep nerves, like P 5-6 (pericardial meridian) overlying the median nerve, effectively inhibits cardiovascular sympathoexcitatory reflexes and the rostral ventrolateral medulla (rVLM) presympathetic neuronal responses. Conversely, electrical stimulation ...

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal‐afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.

The heart at the time of Sir William Harvey originally was thought to be an insensate organ. Today, however, we know that this organ is innervated by sensory nerves that course centrally though mixed nerve pathways that also contain parasympathetic or sympathetic motor nerves. Angina or cardiac pain is now well recognized as a pressure-like pain that occurs during myocardial ischemia when coronary artery blood flow is interrupted. Sympathetic (or spinal) afferent fibers that are either finely myelinated or unmyelinated are responsible for the transmission of information to the brain that ultimately allows the perception of angina as well as activation of the sympathetic nervous system, resulting in tachycardia, hypertension, and sometimes arrhythmias. Although early studies defined the importance of the vagal and sympathetic cardiac afferent systems in reflex autonomic control, until recently there has been little appreciation of the mechanisms of activation of the sensory endings. This review examines the role of a number of chemical mediators and their sources that are activated by the ischemic process. In this regard, patients with ischemic syndromes, particularly myocardial infarction and unstable angina, are known to have platelet activation, which leads to release of a number of chemical mediators, including serotonin, histamine, and thromboxane A(2), all of which stimulate ischemically sensitive cardiac spinal afferent endings in the ventricles through specific receptor-mediated processes. Furthermore, protons from lactic acid, bradykinin, and reactive oxygen species, especially hydroxyl radicals, individually and frequently in combination, stimulate these endings during ischemia. Cyclooxygenase products appear to sensitize the endings to the action of bradykinin and histamine. These studies of the chemical mechanisms of activation of cardiac sympathetic afferent endings during ischemia have the potential to provide targeted therapies that can modify the angina and the deleterious reflex responses that have the potential to exacerbate ischemia and myocardial cell death.