Simvastatin Normalizes Autonomic Neural Control in Experimental Heart Failure

Pliquett, Rainer U.; Cornish, Kurtis G.; Peuler, Jacob D.; Zucker, Irving H.

doi:10.1161/01.cir.0000065606.63163.b9

Cited by 170 publications

(132 citation statements)

References 60 publications

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“…A modulating effect of statin therapy has been also reported on the sympatho-vagal balance in patients with ichaemic heart disease [25,26]. Accordingly, a modulatory effect on vagal tone should have been influencing the VO 2 gas kinetics by improving exercise chronotropic responsiveness.…”

Section: Discussionmentioning

confidence: 96%

Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients

Tumminello¹,

Reina²,

Vicenzi³

et al. 2007

Eur J Clin Investigation

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Background Statins represent a modern mainstay of the drug treatment of coronary artery disease and acute coronary syndromes. Reduced aerobic work performance and slowed VO 2 kinetics are established features of the clinical picture of post-myocardial infarction (MI) patients. We tested the hypothesis that statin therapy improves VO 2 exercise performance in normocholesterolaemic post-MI patients. Materials and methodsAccording to a double-blinded, randomized, crossover and placebocontrolled study design, in 18 patients with uncomplicated recent (3 days) MI we investigated the effects of atorvastatin (20 mg day − 1 ) on gas exchange kinetics by calculating VO 2 effective time constant (tau) during a 50-watt constant workload exercise, brachial artery flowmediated dilatation (FMD) as an index of endothelial function, left ventricular function (echocardiography) and C-reactive protein (CRP, as an index of inflammation). Atorvastatin or placebo was given for 3 months each.Results Atorvastatin therapy significantly improved exercise VO 2 tau and FMD, and reduced CRP levels. We did not observe changes in cardiac contractile function and relaxation properties during all study periods in either group. ConclusionsIn post-MI patients exercise performance is a potential additional target of benefits related to statin therapy. Endothelial function improvement is very likely implicated in this newly described therapeutic property.

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Section: Discussionmentioning

confidence: 96%

Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients

Tumminello¹,

Reina²,

Vicenzi³

et al. 2007

Eur J Clin Investigation

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“…We believe the large difference in survival for patients treated with statin therapy or not (97 vs. 84% at 1-year follow-up) may be due to the many actions of statins. Potential mechanisms include reduced inflammation, 10,11 reduced ischemia, 17,18 improved LV function, 14,15 and/or other pleiotropic effects, 19,20 all effects of statin therapy that reduce the likelihood of mortality in this high-risk population.…”

Section: Discussionmentioning

confidence: 99%

Effect of statins and white blood cell count on mortality in patients with ischemic left ventricular dysfunction undergoing percutaneous coronary intervention

Lipinski

Martin

Cowley

et al. 2006

Clinical Cardiology

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SummaryBackground: While morbidity and mortality were shown to be increased in the setting of an elevated white blood cell (WBC) count for patients with acute coronary syndrome, the impact of statin therapy on mortality for patients with an elevated WBC count is unknown in high-risk patients with coronary artery disease.Hypothesis: The goal of this study was to determine whether statin therapy improved survival in patients with elevated WBC count undergoing percutaneous coronary intervention (PCI) with preexisting left ventricular (LV) dysfunction, a population at high risk for adverse outcomes.Methods: We retrospectively evaluated consecutive patient procedures performed at our institution from 1996 through 1999. Patients had a technically adequate angiographic left ventriculogram with a calculated ejection fraction (EF) ≤ 50%. Patients with prior coronary artery bypass graft were excluded. Mortality data were retrieved using the U.S. Social Security Death Index. Follow-up ranged from 3.5 to 6.5 years. Means are provided with ± standard deviation, and p values < 0.05 were considered significant.

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“…109 As with ACEIs and aldosterone antagonists, statins also improve mortality in cardiomyopathy patients. Pliquette et al 110,111 showed that in rabbits with pacing induced heart failure, statin therapy with simvastatin normalizes sympathetic outflow and cardiovascular reflex regulation and showed a beneficial dose-dependent effect on baroreceptor sensitivity. The underlying mechanism for the beneficial effects of statin therapy in modulating the autonomic nervous system was further elucidated by recording renal sympathetic nerve activity and studying the effect of statins on angiotensin II type I gene expression and nicotinamide adenine dinucleotide phospate (NADPH) oxidase activity (a downstream protein activity by angiotensin II receptor activation) in the rostral ventrolateral medulla of rats.…”

Section: Medical Therapies Modulating Cardiac Autonomicsmentioning

confidence: 99%

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

336

233

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The cardiac autonomic nervous system consists of 2 branches-the sympathetic and the parasympathetic systems-that work in a delicately tuned, yet opposing fashion in the heart. This extrinsic control mechanism can dominate intrinsic regulatory mechanisms that modulate heart rate and cardiac output. These branches differ in their neurotransmitters (norepinephrine and acetylcholine) and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Stimulation of the sympathetic branch exerts facilitatory effects on function, increasing heart rate and myocardial contractility, whereas the stimulation of the parasympathetic branch exerts inhibitory effects that decrease heart rate and contractility. The interplay between these two branches is complex and susceptible to control at several levels, from centrally mediated baroreceptors and chemoreceptors to local interneuronal interactions.Alterations in autonomic function occur in several interrelated cardiac conditions including sudden cardiac death, congestive heart failure, diabetic neuropathy, and myocardial ischemia. Although the full extent of these changes has not been elucidated, multiple autonomic remodeling mechanisms have been observed at both the neuronal fiber and myocardial cellular level that contribute to an arrhythmogenic substrate. We describe the anatomy of both systems in this review. However, the review will premdominantly focus on the sympathetic system, whose role in the modulation of cardiac arrhythmias is slightly better delineated. Cardiac Autonomic Innervation: NeuroanatomyBoth branches of the autonomic nervous system are composed of both afferent and efferent as well interneuronal fibers (Fig 1). Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart and penetrate into the underlying myocardium similar to coronary vessels and end as sympathetic nerve terminals reaching the endocardium. Based on norepinephrine content studies, a gradient exists in sympathetic innervation from atria to the ventricles and from base to apex of the heart. Therefore, the atria are most densely innervated, but the ventricles are also supplied with a sympathetic network, most densely at the base. 1 Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. In contrast to sympathetic neurons, after parasympathetic fibers cross the atrioventricular (AV) groove along the surface of the heart,

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Simvastatin Normalizes Autonomic Neural Control in Experimental Heart Failure

Cited by 170 publications

References 60 publications

Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients

Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients

Effect of statins and white blood cell count on mortality in patients with ischemic left ventricular dysfunction undergoing percutaneous coronary intervention

The Role of the Autonomic Nervous System in Sudden Cardiac Death

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