Analysis of the Effects of Electroacupuncture at the Pericardium 6 Acupoint on Heart Function in Patients with Angina Using Equilibrium Radionuclide Angiocardiography Quantity Analysis Technique

Abstract

Objective:

To analyze changes in cardiac function indices after electroacupuncture (EA) at the pericardium 6 (PC-6) acupoint using the equilibrium radionuclide angiocardiography (ERNA) quantity analysis technique.

Design:

Analysis of clinical outcomes after EA at PC-6 measured by ERNA.

Setting:

The study was conducted in a hospital.

Participants:

31 participants (17 patients with angina and 14 healthy volunteers).

Intervention:

The study used ERNA to study outcomes of EA at PC-6 on heart function.

Outcome measure:

ERNA images were taken before the treatment (T0), at the end of the treatment (T1), and 20 minutes after the treatment (T2) and then processed.

Results:

Regional left ventricular ejection fraction (REF) increased after EA in the angina and control groups. REF at T2 was significantly higher than at T1 in the angina group (p<.01). In the control group, REF was higher at T1 than at T0 (p<.01) but did not differ between T1 and T2 (p=.08). The REF deviation among ventricular regions in the angina group was significantly greater than that in the control group at T0 (p<.01) but was reduced to the level of that in control group after EA (p=.52). Peak filling rate was lower in the angina group than in controls at all three time points (all p<.01). After EA, peak filling rate increased markedly in the angina group but not in the control group. The cardiac cycle was shorter in the angina group than in the control group at T0 (p<.01) and increased after EA. The cardiac cycle of the control group did not change.

Conclusion:

Effects of EA at PC-6 on heart function can be detected and quantified by ENRA.

Introduction

Several studies have demonstrated that acupuncture at the pericardium 6 acupoint (PC-6) is effective for improving cardiac functions.^1

–4 PC-6, known as neiguan on the Xin-Bao meridian in Traditional Chinese Medicine, is located 2 cm above the transverse crease of the wrist, between the m. palmaris longus and m. flexor radialis tendons.⁵ The mechanism by which PC-6 acupuncture affects myocardial ischemia may be related to neural regulation,⁶ vasoactive substances regulation,⁷ gene expression,⁸ or an antiarrhythmic effect.⁹

An imaging method called equilibrium radionuclide angiocardiography (ERNA) is performed routinely to assess the extent of regional and global left ventricular dysfunction.¹⁰ It displays the shape, size, and wall movement of cardiac cavities and calculates local and global ventricular systolic and diastolic functional measures. This technology is not affected by ventricular geometry and is noninvasive, repeatable, and reliable.^11,12 Heart function can be directly studied by ERNA measures. Therefore, this study used ERNA to examine the direct effect of PC-6 electroacupuncture (EA) on heart function.

Although prior studies have reported beneficial effects of PC-6 acupuncture on heart functions, the research methods used previously were invasive, and most studies were conducted in animals. A direct physiologic effect has yet to be described by noninvasive methods. The current study used ERNA to noninvasively examine the effects of EA at PC-6 on heart function in healthy people and patients with angina. Specifically, we compared regional left ventricular ejection fraction (REF), REF deviation (REFd), and peak filling rate (PFR) between patients with angina and a control group before EA (T0), immediately after EA (T1), and 20 minutes after EA (T2). Additionally, because previous studies have demonstrated that the cardiac cycle is affected by acupuncture,⁹ we also compared cardiac cycle between the groups at the same three time points.

Methods

Participants

A total of 17 patients with angina and 14 healthy volunteers were recruited for the study from March 2011 to December 2012. All the participants signed informed consent forms. The study was approved by the Harbin Medical University Ethics Committee.

Exclusion criteria for the healthy volunteers were hypertension, high cholesterol, diabetes, chronic respiratory diseases, history of genetic disorders, and evidence of any organic disease or myocardial infarction on cardiac ultrasonography. The angina group participants were required to meet the chronic stable angina criteria set forth in the Chronic Stable Angina Diagnosis and Treatment Guidelines (Chinese Medical Society of Cardiology, 2007) and to have experienced at least one angina attack within the month before the study that was induced by activity that increased cardiac oxygen consumption and that was relieved by nitroglycerin. All myocardial ischemia preventive drugs were stopped for the 3 days immediately preceding the experiment.

Gated ERNA

First, a pyrophosphate saline mixture (5 mg/1 mL) purchased from Jiangsu Gangwon Pharmaceutical Factory (Wuxi, China) was injected into the cubital vein of each participant. Sodium pertechnetate solution (740 MBq) obtained from HTA Co., Ltd. (Beijing, China) was injected into the contralateral cubital vein 20 minutes later. Then, 30 minutes after the second injection, the participants lay in the supine position, with their hands resting up around their heads. Electrocardiogram electrodes were attached at three points: in the intercostal space between the first and second ribs at the cross-point of the midclavicular line on both sides, at the cross-point of the midclavicular line, and at the arch of the rib on the left side. The electrocardiographic equipment was connected with a single- photon emission computed tomography (SPECT) machine. The SPECT detector was positioned at a 30°–45° left anterior oblique angle to distinguish the left and right ventricles. The detector angle was maintained before and after acupuncture. Electrocardiograms were recorded by using the R wave as the trigger point, and data from 400–500 consecutive cardiac cycles were collected, with per cardiac cycle divided into 32 frames. Images in a 64×64 matrix (zoom, 1.85) were collected at T0, T1, and T2.

EA

Participants were kept in the supine position, with their hands resting at their sides. Acupuncture needles (length, 40 mm; diameter, 0.3 mm; Hwato, China) were inserted perpendicularly at the PC-6 sites on both arms to a depth of 1.0 cm and connected to a program-controlled EA device (DC, bidirectional sharp wave with wavelength of 1 ms). A stimulus voltage of 9 V (current, 1.0 mA) was applied through the needles for 20 minutes. The acupuncture treatments were implemented by an experienced acupuncturist (L.H.).

Image processing

Extended Brilliance Workspace Release v4.5.3.4013 software (Eindhoven of Holland) was used to sketch the left ventricular region of interest after scanning (when unsatisfactory, the outline was modified manually). A time-radioactivity curve, left ventricular function data, cardiac function data, and various image measures were obtained on the basis of ventricle radioactive counts. The software divided the left ventricle into eight regions and calculated their REF values, including the mean REF (REFx) and REFd, at T0, T1, and T2 (Fig. 1). Group means of the eight REF values were compared at T0, T1, and T2. PFR, which was measured as the end-diastolic volume per second, and cardiac cycle, which was measured in milliseconds, were also compared between the groups at each time point.

FIG. 1.

Regional left ventricular ejection fraction (REF) of healthy controls (A) and patients with angina (B) at different time points. (A1) T0. (A2) T1. (A3) T2. In the control group, mean REF (REFx) increased significantly from T0 to T1, immediately after EA, but remained stable from T1 to T2. (B1) T0. (B2) T1. (B3) T2. In the angina group, no significant difference in REFx was observed between T0 and T1, but the deviation of REF among all sections was reduced at T1; REFx increased significantly from T2 to T0 and T1. EA, electroacupuncture.

Statistics

The data were analyzed by using SPSS software, version 17.0 (IBM, Chicago, IL) and are reported as means±SDs. Multigroup comparisons were conducted with repeated-measures analyses of variance (ANOVAs). The detailed differences underlying group×time point interactions were analyzed with the Dunnett post hoc test. P values<0.05 were considered to indicate statistically significant differences.

Results

Participants

The pretreatment characteristics of the 14 healthy volunteers and 17 patients with angina are shown in Table 1.

Table 1.

Summary of Participant Characteristics by Group

Characteristic	Control group (n=14)	Angina group (n=17)
Men/women (n/n)	6/8	6/11
Mean age±SD (y)	55.69±6.26	61.33±9.57
Hypertension (n)	–	2
Diabetes (n)	–	1
Genetic disease (n)	–	–
Abnormal findings on electrocardiography, n (%)	–	9 (52.9)
Abnormal findings on echocardiography, n (%)	–	5 (29.4)

ERNA measures

All mean ERNA parameter values and associated statistical values are reported in Table 2. ANOVA revealed significant effects of time point and of group on REFx, as well as a significant time point×group interaction. The Dunnett post hoc test showed that the angina group had a lower REFx than the control group at all three time points. REFx at T0 was lower in the angina group than in the control group. In the control group, REFx increased significantly from T0 to T1, immediately after EA, but remained stable from T1 to T2. Conversely, in the angina group, REFx did not significantly differ between T0 and T1; however, REFx at T2 differed from REFx at T0 and T1 (Table 2).

Table 2.

Summary of Mean ERNA Measures (±SD) for Each Group and Time Point with Analysis of Variance and Post Hoc Statistical Values

	Control group			Angina group			ANOVA, F_df and p-value
Variable	T0	T1	T2	T0	T1	T2	Group	Time	Group×time
REFx (%)	66.90±6.17	70.00±6.25	71.35±5.90	60.28±3.76	62.36±4.02	67.27±3.66	12.82_df <.01	68.86_df <.01	6.92 _df <.01
Intra-G p vs. T0	–	<.01	<.01	–	.08	<.01
Intra-G p vs. T1	<.01	–	.08	.08	–	<.01
Intra-T vs. controls				<.01	<.01	.03
REFd (%)	9.57±2.26	9.41±1.64	9.42±1.53	17.50±2.14	9.83±1.85	9.41±2.98	21.84_df <.01	57.75_df <.01	53.31_df <.01
Intra-G p vs. T0	–	> .99	> .99	–	<.01	<.01
Intra-G p vs. T1	> .99	–	> .99	<.01	–	> .99
Intra-T vs. controls				<.01	.52	.99
PFR, end-diastolic volume per second	3.33±0.71	3.58±0.69	3.69±0.59	2.25±0.41	2.53±0.46	2.99±0.56	57.57_df <.01	20.59_df <.05	3.11 _df > .05
Intra-G p vs. T0	–	.06	.17	–	.02	<.01
Intra-G p vs. T1	.06	–	> .99	.02	–	<.01
Intra-T vs. controls				<.01	<.01	<.01
CC (ms)	903.50±85.98	926.79±91.20	958.86±89.58	805.94±99.14	858.12±101.39	907.18±117.28	4.64_df <.05	30.32_df <.05	2.66 _df > .05
Intra-G p vs. T0	–	.33	.08	–	< .01	< .01
Intra-G p vs. T1	.33	–	.20	<.01	–	<.01
Intra-T vs. controls				<.01	.06	.19

Significant statistical values are shown in bold. Analysis of variance p-values are reported with their respective F statistics and degrees of freedom (df ).

ERNA, equilibrium radionuclide angiocardiography; REFx, mean of regional ventricular ejection fraction; G, group; T, time; REFd, REF deviation; PFR, peak filling rate; CC, cardiac cycle.

Additionally, ANOVA indicated significant effects of time point and of group on REFd, as well as a significant time point×group interaction (Table 2). According to the Dunnett post hoc test at T0, the mean REFd was markedly greater in the angina group than in the control group. REFd remained stable across the three time points in the control group but decreased from T0 to T1 in the angina group and then remained stable from T1 to T2. Hence, at T1 and T2, mean REFd values in the angina group were similar to control values (Table 2).

PFR is a sensitive and reliable indicator of left ventricular diastolic function. The results of ANOVA revealed significant effects of time point and group on PFR, but not a significant interaction (Table 2). PFR in the control group was higher than that in angina group at all three time points. In the control group, PFR remained stable across the three time points. However, in the angina group, PFR increased after EA (from T0 to T1) and increased further over the subsequent 20 minutes (from T1 to T2).

Finally, ANOVA revealed significant effects of time point and of group on cardiac cycle, but no significant interaction (Table 2). At T0, cardiac cycle was shorter in the angina group than in the control group. In the angina group, cardiac cycle gradually lengthened after acupuncture, such that cardiac cycle at T1 was greater than at T0, and cardiac cycle at T2 was greater than at T1 (Table 2). Although a similar upward trend was observed over time after EA in the control group, the values at the time points did not differ from one another.

Discussion

The present results showed that EA at PC-6 had immediate beneficial effects on cardiac function in patients with angina, as evidenced by changes in REF, PFR, and cardiac cycle. After EA at PC-6, the patients with angina exhibited an increased REF, decreased REFd, increased PFR, and lengthened cardiac cycle, bringing all of these values toward those observed in controls. These findings also show that ERNA is a valuable tool with which to directly examine cardiac effects of acupuncture.

Historically, acupuncture at PC-6 has been used to relieve palpitations, vertigo, choking sensation in the chest, and pericardial pain, all of which are symptoms of cardiovascular diseases.¹³ However, the details and mechanisms of the effects of PC-6 acupuncture on the cardiovascular system have not previously been studied in detail in humans because of technical limitations. ERNA is used to assess risk in patients with coronary heart disease and for other therapeutic interventions.¹⁴ It provides cardiac structural imaging that allows good assessment of cardiac morphology and function,¹⁵ especially with respect to left ventricular function at rest versus during exercise.¹⁶ ERNA measurements of the left ventricular ejection fraction are used as an index of global left ventricular systolic function. ERNA data are more repeatable and show good consistency with radiographic angiography data.¹⁷ Motion synchronization of the atrioventricular node, ventricle, and ventricular systolic and diastolic myocardial segments could help achieve normal cardiac output,¹⁸ particularly in patients with coronary heart disease, who often have left ventricular de-synchronization.^19,20

Cardiac contraction coordination is often associated with myocardial perfusion.²¹ The current observation of a progressively increasing REFx after EA is consistent with the notion that acupuncture at PC-6 can robustly improve coordination of cardiac function. As shown in Table 2, a time point×group interaction was observed (p<.01), showing that the two groups had different trends after EA. In the control group, REF in all sections was increased at T1 (Fig. 1A). Meanwhile, in the angina group, the deviation of REF among all sections was reduced at T1 and REFx did not increase enormously; REFx at T2 reached pre-EA control levels (Fig. 1B). Moreover, the fact that REFx changes were apparent after EA further suggests that acupuncture at PC-6 may improve myocardial contractility. The REFd value is an index of contraction coordination between different ventricular regions; coordination of left ventricular systolic segments correlates inversely with REFd.^18,19 The observation that REFd in the angina group, which was initially greater than that in the control group, was reduced after PC-6 EA is direct evidence that the treatment improved contraction coordination in patients with angina. A significant time point×group interaction (p<.01) indicated that the two groups had different regulation trends after EA. Of note, REFd was not changed by PC-6 EA in the control group, suggesting that the treatment had a normalizing influence on the contraction coordination.

Myocardial relaxation is not a passive process.²² In the early stage of myocardial ischemia, systolic function can be normal with diastolic function abnormalities, while abnormalities in relaxation may already be present.²³ The current finding that PFR in the angina group went from below normal at T0 to closer to normal at T1 and T2 suggests that EA at PC-6 may improve diastolic function, especially relaxation, within a short period. An insignificant time point×group interaction analysis result (p>.05) indicated that the two groups showed similar trends, but the change in the control group was not significant. Similar to the current REFd data, the control group data for PFR did not differ significantly between time points, further suggesting that PC-6 EA has a normalizing effect.

A longer cardiac cycle not only reduces the myocardial burden by way of affording a longer diastolic time but also improves the cardiac blood and oxygen supply, which can protect against subsequent myocardial ischemia and reperfusion injury.²⁴ In the current study, the cardiac cycle in patients with angina went from shorter than in controls before PC-6 EA to approaching the that in the control group after PC-6 EA. The cardiac cycle in the angina group did not plateau after T1 but rather progressively lengthened from T0 to T2; this finding suggests a long effect of the treatment. Meanwhile, consistent with Lin Hong's report,²⁵ the current study found that PC-6 EA did not significantly alter cardiac cycle in the control group.

Conclusion

In conclusion, these results demonstrate that the effects of EA at PC-6 on angina can be identified by quantitative ENRA analysis. EA at PC-6 improved heart function, as evidenced by an increased PFR and cardiac cycle. The REF data also provide direct evidence of improved heart motion coordination and compliance following EA treatment in patients with angina.

Footnotes

Acknowledgments

This study was supported by the Heilongjiang Provincial Education Department (no. 11541222) and the Heilongjiang Provincial Science and Technology Foundation (no. D201189).

Disclosure Statement

No competing financial interests exist.

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