PMID- 10868514
OWN - NLM
STAT- MEDLINE
DCOM- 20000714
LR  - 20220321
IS  - 0004-8291 (Print)
IS  - 0004-8291 (Linking)
VI  - 29
IP  - 3
DP  - 1999 Jun
TI  - Sympathetic activation and the role of beta-blockers in chronic heart failure.
PG  - 418-27
AB  - Chronic heart failure (CHF) is associated with activation of the sympathetic 
      nervous system. This activation provides short term haemodynamic support to the 
      failing myocardium, but may be deleterious over longer periods as chronic 
      catecholamine excess appears to contribute to disease progression and increased 
      mortality in this condition. Therefore, blockade of sympathetic activation 
      represents a logical, if somewhat counter-intuitive, approach to the management 
      of the patient with systolic CHF. Pharmacological approaches to blockade of this 
      system include inhibition of central sympathetic outflow (using central 
      sympatholytics, e.g. rilmenidine, moxonidine), blockade of the catecholamine 
      biosynthetic pathway (dopamine beta hydroxylase antagonists) and blockade of the 
      cardiac effects of sympathetic activation (beta-adrenoceptor blocking agents). 
      Beta-blockers have now been extensively studied in patients with symptomatic CHF 
      of the New York Heart Association (NYHA) Class II and III severity. Provided 
      beta-blocker therapy is carefully up-titrated from sub-therapeutic doses and 
      given for at least three to four months, these agents have been associated with 
      favourable long term haemodynamic, functional and mortality outcomes. 
      Furthermore, beta-blockers delay disease progression in CHF by reversing the 
      pathological myocardial remodelling process that accompanies the disease. 
      Non-selective beta-adrenoceptor blocking drugs appear to be of particular benefit 
      in CHF therapy. Myocardial beta2 receptors are down-regulated to a lesser extent 
      than beta1 receptors in CHF, therefore blockade of the beta2 receptor sub-type 
      may assume greater importance in inhibiting the deleterious effects of 
      sympathetic activation on the myocardium in this disease. Newer agents that 
      possess additional vasodilator properties (carvedilol, bucindolol, nebivolol) may 
      be useful in overcoming the initial negative inotropy of the beta-blocking 
      component of the drug, however, it is unlikely that vasodilation contributes 
      greatly to long term clinical benefits. Drugs such as carvedilol are also 
      anti-oxidant, anti-proliferative and have anti-endothelin actions; the clinical 
      significance of these properties is yet to be determined. Unanswered questions 
      remain regarding the use of beta-blockers in heart failure. Ongoing studies are 
      further examining mechanisms underlying the clinical benefits of these agents as 
      well as their therapeutic potential in NYHA Class IV patients, heart failure 
      post-myocardial infarction and patients with asymptomatic left ventricular 
      dysfunction.
FAU - Krum, H
AU  - Krum H
AD  - Clinical Pharmacology Unit, Monash University, Alfred Hospital, Melbourne, Vic.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Australia
TA  - Aust N Z J Med
JT  - Australian and New Zealand journal of medicine
JID - 1264322
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Carbazoles)
RN  - 0 (Propanolamines)
RN  - 0 (Vasodilator Agents)
RN  - 0K47UL67F2 (Carvedilol)
SB  - IM
MH  - Adrenergic beta-Antagonists/*therapeutic use
MH  - Carbazoles/therapeutic use
MH  - Carvedilol
MH  - Disease Progression
MH  - Heart Failure/*drug therapy/pathology/*physiopathology
MH  - Hemodynamics
MH  - Humans
MH  - Myocardium/pathology
MH  - Propanolamines/therapeutic use
MH  - Sympathetic Nervous System/*physiopathology
MH  - Vasodilator Agents/therapeutic use
RF  - 45
EDAT- 2000/06/27 11:00
MHDA- 2000/07/25 11:00
CRDT- 2000/06/27 11:00
PHST- 2000/06/27 11:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/06/27 11:00 [entrez]
AID - 10.1111/j.1445-5994.1999.tb00737.x [doi]
PST - ppublish
SO  - Aust N Z J Med. 1999 Jun;29(3):418-27. doi: 10.1111/j.1445-5994.1999.tb00737.x.