Gaowa Saren

Chronic Intermittent Low-Level Transcutaneous Electrical Stimulation of Auricular Branch of Vagus Nerve Improves Left Ventricular Remodeling in Conscious Dogs With Healed Myocardial Infarction

Background—Vagus nerve stimulation attenuates left ventricular (LV) remodeling after myocardial infarction (MI). Our previous study found a noninvasive approach to deliver vagus nerve stimulation by transcutaneous electric stimulation of auricular branch of vagus nerve. So we hypothesize that chronic intermittent low-level tragus stimulation (LL-TS) could attenuate LV remodeling in conscious dogs with healed MI. Methods and Results—Thirty beagle dogs were randomly divided into 3 groups, MI group (left anterior descending artery and major diagonal branches ligation to introduce MI, n=10), LL-TS group (MI plus chronic intermittent LL-TS, n=10), and control group (sham surgery without stimulation, n=10). Tragus stimulation was delivered to bilateral tragus with ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold for setting LL-TS at 80% below that. LL-TS group was given 4 hours stimulation at 7–9 AM and 4–6 PM on conscious dogs. At the end of 90-day follow-up, LL-TS group significantly reduced LA and LV dilatation, improved LV contractile and diastolic function, reduced infarct size by ≈50% compared with MI group. LL-TS treatment alleviated cardiac fibrosis and significantly decreased protein expression level of collagen I, collagen III, transforming growth factor &bgr;1, and matrix metallopeptidase 9 in LV tissues. The plasma level of high-specific C-reactive protein, norepinephrine, N-terminal pro-B-type-natriuretic peptide in LL-TS group was significantly lower than those in MI group from the 7th day to the end of follow-up. Conclusions—Chronic intermittent low-level transcutaneous electric stimulation of auricular branch of vagus nerve can attenuate LV remodeling in conscious dogs with healed MI.

Spinal cord stimulation protects against ventricular arrhythmias by suppressing left stellate ganglion neural activity in an acute myocardial infarction canine model.

BACKGROUND Previous studies have shown that spinal cord stimulation (SCS) may reduce ventricular arrhythmias (VAs) induced by acute myocardial infarction (AMI). Furthermore, activation of left stellate ganglion (LSG) appears to facilitate VAs after AMI. OBJECTIVE The purpose of this study was to investigate whether pretreatment with SCS could protect against VAs by reducing LSG neural activity in an AMI canine model. METHODS Thirty dogs were anesthetized and randomly divided into SCS group (with SCS, n = 15) and sham group (sham operation without SCS, n = 15). SCS was performed for 1 hour before AMI. Heart rate variability (HRV), ventricular effective refractory period (ERP), serum norepinephrine level, LSG function measured by blood pressure increases in response to LSG stimulation, and LSG neural activity were measured for 1 minute at baseline and 1 hour after SCS. AMI was induced by left anterior descending coronary artery ligation, and then HRV, LSG neural activity, and VAs were measured. RESULTS Compared to baseline, SCS for 1 hour significantly prolonged ventricular ERP, increased HRV, and attenuated LSG function and LSG activity in the SCS group, whereas no significant change was shown in the sham group. AMI resulted in a significant decrease in HRV and increase in LSG neural activity in the sham group, which were attenuated in the SCS group (frequency: 99 ± 34 impulses/min vs 62 ± 22 impulses/min; amplitude: 0.41 ± 0.12 mV vs 0.18 ± 0.05 mV; both P <.05). The incidence of VAs was significantly lower in the SCS group than in the sham group. CONCLUSION SCS may prevent AMI-induced VAs, possibly by suppressing LSG activity.

Carotid baroreceptor stimulation prevents arrhythmias induced by acute myocardial infarction through autonomic modulation.

Abstract: Electrical carotid baroreceptor stimulation (CBS) has shown therapeutic potential for resistant hypertension and heart failure by resetting autonomic nervous system, but the impacts on arrhythmias remains unclear. This study evaluated the effects of CBS on ventricular electrophysiological properties in normal dog heart and arrhythmias after acute myocardial infarction (AMI). In the acute protocol, anesthetized open chest dogs were exposed to 1 hour left anterior descending coronary occlusion as AMI model. Dogs were received either sham treatment (Control group, n = 8) or CBS (CBS group, n = 8), started 1 hour before AMI. CBS resulted in pronounced prolongation of ventricular effective refractory period and reduction of the maximum action potential duration restitution slope (from 0.85 ± 0.15 in the baseline state to 0.67 ± 0.09 at the end of 1 hour, P < 0.05) before AMI. Number of premature ventricular contractions (277 ± 168 in the Control group vs. 103 ± 84 in the CBS group, P < 0.05) and episodes of ventricular tachycardia/ventricular fibrillation (7 ± 3 in the Control group vs. 3 ± 2 in the CBS group, P < 0.05) was decreased compared with the control group during AMI. CBS buffered low-frequency/high-frequency ratio raise during AMI. Ischemic size was not affected by CBS. CBS may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone.

Low-Level Carotid Baroreceptor Stimulation Suppresses Ventricular Arrhythmias during Acute Ischemia

Background The autonomic imbalance during acute ischemia is involved in the occurrence of life-threatening arrhythmias. Objective To investigate the effect of autonomic nervous system (ANS) modulation by low-level carotid baroreceptor stimulation (LL-CBS) on ventricular ischemia arrhythmias. Methods Anesthetized dogs were received either sham treatment (SHAM group, n = 10) or LL-CBS treatment (LL-CBS group, n = 10). The voltage lowering the blood pressure was used as the threshold for setting LL-CBS at 80% below the threshold. Treatment started 1 hour before left anterior descending coronary (LAD) occlusion, and continued until the end of experience. Ventricular effective refractory periods (ERP), monophasic action potential duration at 90% (APD90), ventricular arrhythmias, indices of heart rate variability, left stellate ganglion nerve activity (LSGNA) and infarct sizes were measured and analyzed. Results Ventricular ischemia resulted in an acute reduction of blood pressure, which was not significantly affected by LL-CBS. After 1 hour of LL-CBS, there was a progressive and significant increase in ERP, increase in APD90, and decrease in LSGNA vs the SHAM group (all P<0.05). LL-CBS apparently reduced premature ventricular contractions (PVC, 264±165 in the SHAM group vs 60±37 in the LL-CBS group; P<0.01) during LAD occlusion. Number of episodes of ventricular fibrillation (VF) was 8 in the Control group versus 3 in the LL-CBS group (80% versus 30%, P<0.05). LL-CBS obviously increased high frequency (HF) component (P<0.05) and decreased low frequency/high frequency ratio (P<0.05) compared with the SHAM group. Ischemic size was not affected by LL-CBS between the two groups. Conclusions LL-CBS reduced the occurrences of ventricular arrhythmias during acute ischemia without affecting blood pressure. The procedure was associated with changes of electrophysiological characteristics, nerve activity and heart rate variability. Therefore, LL-CBS may protect from ventricular arrhythmias during acute ischemic events by modulating ANS.

Low-level transcutaneous electrical stimulation of the auricular branch of vagus nerve ameliorates left ventricular remodeling and dysfunction by downregulation of matrix metalloproteinase 9 and transforming growth factor β1.

Abstract: Vagus nerve stimulation improves left ventricular (LV) remodeling by downregulation of matrix metalloproteinase 9 (MMP-9) and transforming growth factor &bgr;1 (TGF-&bgr;1). Our previous study found that low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve (LL-TS) could be substituted for vagus nerve stimulation to reverse cardiac remodeling. So, we hypothesize that LL-TS could ameliorate LV remodeling by regulation of MMP-9 and TGF-&bgr;1 after myocardial infarction (MI). Twenty-two beagle dogs were randomly divided into a control group (MI was induced by permanent ligation of the left coronary artery, n = 8), an LL-TS group (MI with long-term intermittent LL-TS, n = 8), and a normal group (sham ligation without stimulation, n = 6). At the end of 6 weeks follow-up, LL-TS significantly reduced LV end-systolic and end-diastolic dimensions, improved ejection fraction and ratio of early (E) to late (A) peak mitral inflow velocity. LL-TS attenuated interstitial fibrosis and collagen degradation in the noninfarcted myocardium compared with the control group. Elevated level of MMP-9 and TGF-&bgr;1 in LV tissue and peripheral plasma were diminished in the LL-TS treated dogs. LL-TS improves cardiac function and prevents cardiac remodeling in the late stages after MI by downregulation of MMP-9 and TGF-&bgr;1 expression.