Effects of Renal Sympathetic Denervation on Post-Myocardial Infarction Cardiac Remodeling in Rats

Hu, Jialu; Ji, Meng; Niu, Conway; Aini, Asiyeguli; Zhou, Qina; Zhang, Ling; Jiang, Tao; Yan, Yan; Hou, Yuemei

doi:10.1371/journal.pone.0045986

Cited by 32 publications

(30 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the plasma levels of BNP, which is mainly released from the ventricles and is associated with a higher mortality in heart failure [17], were significantly decreased in MI rats with RDN compared with the MI group. These observations were similar to the findings of Hu et al [18,19].…”

Section: Discussionsupporting

confidence: 93%

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

Zhang

Chu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. Methods: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague-Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson's trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal propeptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. Results: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-β1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). Conclusions: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.

show abstract

Section: Discussionsupporting

confidence: 93%

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

Zhang

Chu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…The present study is unique that RDN was initiated 4 wk after the onset of HF (chronic), making it relevant to patients who may be administered RDN as a therapeutic modality after diagnosis of the chronic HF condition. Prior experimental animal studies initiated RDN protocols either before or at the onset of myocardial infarct and measured only one of the above parameters in a rudimentary way (14).…”

Section: Discussionmentioning

confidence: 99%

“…Recent clinical trials have demonstrated that renal denervation (RDN) is effective in drug-resistant hypertension to reduce the neurohumoral drive and blood pressure (13,19,39). There have been a couple of studies that have examined the effect of RDN before, or just after, myocardial infarct on cardiac function and Na ϩ excretion (14,15). Drug-resistant hypertensive patients with left ventricular hypertrophy and diastolic dysfunction show that RDN significantly reduces cardiac mass and improves diastolic function (2).…”

mentioning

confidence: 99%

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Zheng

Liu

Sharma

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Zheng H, Liu X, Sharma NM, Patel KP. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of ␤-adrenoceptors. Am J Physiol Heart Circ Physiol 311: H337-H346, 2016. First published June 10, 2016; doi:10.1152/ajpheart.00999.2015.-Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area Ͼ30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) Ͼ20 mmHg. ␤ 1-and ␤2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of ␤ 1-adrenoceptor (by 47%) and ␤2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 g/kg)-induced increase in ϩdP/dt (by 71%) and ϪdP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts ␤-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. renal nerve; sympathetic nerve activity; cardiac function; heart failure NEW & NOTEWORTHYThis study shows in a comprehensive way that renal denervation initiated after a period of chronic heart failure enhances cardiac contractility and the responsiveness of hearts to isoproterenol stimulation, and these effects are due in part to renal denervation-induced increase in ␤-adrenoceptor protein and function.WORLDWIDE, MORE THAN 100 MILLION people are afflicted with chronic heart failure (HF), imposing a significant burden on the health care systems throughout the world. Chronic overactivation of the sympathetic nervous system is one of the major pathophysiological soliloquy abnormalities leading to the progression of chronic HF (28,29,48). Activation of sympathetic outflow is initially a hemodynamic adaptation to compensate for decreased cardiac function and output. This adaptation also includes an increase in Na ϩ and fluid retention and activation of the renin-angiotensin-aldosterone system (11, 34). Additional adverse effects of elevated sympathetic drive directed toward the heart have been shown to result in the desensitization or downreg...

show abstract

“…Because increased sympathoexcitation characterizes both hypertension and CHF, the efficacy of this procedure in the setting of CHF has begun to be evaluated more extensively. Recent studies have shown benefit for using bilateral renal DNx in both animal and patient models of CHF (7,19). The REACH pilot study provides evidence that in patients with chronic systolic heart failure, bilateral renal DNx increases exercise tolerance and provides patients with symptomatic improvement.…”

Section: Discussionmentioning

confidence: 99%

Unilateral renal denervation improves autonomic balance in conscious rabbits with chronic heart failure

Schiller

Haack

Pellegrino

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Schiller AM, Haack KK, Pellegrino PR, Curry PL, Zucker IH. Unilateral renal denervation improves autonomic balance in conscious rabbits with chronic heart failure. Am J Physiol Regul Integr Comp Physiol 305: R886 -R892, 2013. First published September 4, 2013 doi:10.1152/ajpregu.00269.2013.-A hallmark of chronic heart failure (CHF) is an increased sympathetic tone resulting in autonomic imbalance. Renal denervation (DNx) in CHF patients has resulted in symptomatic improvement, but the protective mechanisms remain unclear. We hypothesized in CHF, unilateral renal DNx would improve cardiac autonomic balance. The present study used conscious, chronically instrumented New Zealand White rabbits undergoing renal DNx prior to pacing-induced CHF. Four treatment groups were used: nonpace, non-DNx [Sham-Innervated (Sham-INV)], nonpace DNx (sham-DNx), pace non-DNx (CHF-INV) or pace DNx (CHFDNx). We examined several markers indicative of autonomic balance. Baroreflex sensitivity and time domain heart rate variability (HRV) were both decreased in the CHF-INV group compared with sham-INV and were restored to sham levels by renal DNx. Power spectral analysis indicated an increase in low-frequency/high-frequency (LF/ HF) ratio in the CHF-INV compared with the sham-INV, which was normalized to sham levels by DNx. To assess whether this was due to a withdrawal of sympathetic tone or an increase in parasympathetic tone, the heart rate response was measured after an intravenous bolus of metoprolol or atropine. Bradycardia induced by intravenous metoprolol (indicative of cardiac sympathetic tone) was exacerbated in CHF-INV rabbits compared with sham-INV but was normalized in CHF-DNx. Conversely, the tachycardia in response to intravenous atropine (indicative of cardiac vagal tone) was not improved in CHF-DNx vs. CHF-INV animals. Renal DNx also prevented the increase in circulating plasma NE seen in CHF-INV rabbits. These results suggest renal DNx improves cardiac autonomic balance in CHF by a reduction of sympathetic tone. sympathetic nerves; baroreflex; cardiac function; kidney BILATERAL RENAL DENERVATION (DNx) has recently entered clinical practice as a successful therapy for drug-resistant hypertension (35). This treatment, using a radiofrequency catheter to ablate the renal nerves, chronically lowers arterial pressure while producing virtually no short-term side effects (2,14). It is well established that most forms of hypertension are correlated with an overactive sympathetic nervous system, as indicated by elevated plasma norepinephrine (NE) or increases in muscle sympathetic nerve activity and increases in whole body NE spillover (27). There is anecdotal and recent evidence to suggest that renal DNx can reduce excessive sympathetic tone in hypertension (34, 17) in some cases. However, recent studies by Brinkmann et al. (4) and Hart et al.

show abstract

Effects of Renal Sympathetic Denervation on Post-Myocardial Infarction Cardiac Remodeling in Rats

Cited by 32 publications

References 26 publications

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Unilateral renal denervation improves autonomic balance in conscious rabbits with chronic heart failure

Contact Info

Product

Resources

About