A Comparison of the Efficacy of Surgical Renal Denervation and Pharmacologic Therapies in Post-Myocardial Infarction Heart Failure

Hu, Jialu; Li, Yinliang; Cheng, Weiguo; Yang, Zhen; Wang, Fang; Lv, Ping; Niu, Conway; Hou, Yuemei; Yan, Yan; Ge, Junbo

doi:10.1371/journal.pone.0096996

Cited by 32 publications

(30 citation statements)

References 13 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

“…Recent animal studies in which heart failure was induced by coronary ligation in rats (47) or rapid ventricular pacing in dogs and rabbits (126,136) showed that renal denervation performed prior to the induction of heart failure improved cardiac function. Further, a pilot study in chronic heart failure patients showed improved exercise capacity following bilateral renal denervation (21).…”

Section: Pathophysiologymentioning

confidence: 99%

Role of renal sensory nerves in physiological and pathophysiological conditions

Kopp

2015

American Journal of Physiology-Regulatory, Integrative and Comp

135

140

View full text Add to dashboard Cite

Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation.

show abstract

“…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

A Comparison of the Efficacy of Surgical Renal Denervation and Pharmacologic Therapies in Post-Myocardial Infarction Heart Failure

Cited by 32 publications

References 13 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

Role of renal sensory nerves in physiological and pathophysiological conditions

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

Contact Info

Product

Resources

About