clen & heart

[macrophage69alpha]

interesting (and somewhat conversely- though actually just a reversal situation) clenbuterol is used as a treatment for heart failure treatment with left ventricular assist device.

Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1468-76. Epub 2004 Nov 4. Related Articles, Links


Erratum in:
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2546.

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle.

Soppa GK, Smolenski RT, Latif N, Yuen AH, Malik A, Karbowska J, Kochan Z, Terracciano CM, Yacoub MH.

Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, Middlesex UB9 6JH, UK.

Clenbuterol (Clen), a beta(2)-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca(2+) handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg x kg(-1) x day(-1) Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca(2+) transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca(2+) content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-alpha. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca(2+) content, which results in increased amplitude of the Ca(2+) transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.

 

[krishna]

So even 20-40mcg a day is dangerous? I better reconsider ever using clen again.

 

[macrophage69alpha]

So even 20-40mcg a day is dangerous? I better reconsider ever using clen again.

its hard to say, the lack of human data is frustrating. Likely it has to be higher, though also likely within the normal usage limits

however there are measures that can be taken to reduce the risk, like ALCAR.

will try to take some time to put together a list of supps that should limit and perhaps even ameliorate the potential for damage

 

[Quiltie]

Thanks for the info mac69alpha, I'm terrorized enough to not use Clen at this point. Although I have read that many Olympians are prescribed Clen for asthma. The thought is that it is a legal way for them to enhance performance in endurance events. That may be just a rumor, though. Please keep us updated-

 

[6oxo User]

This could be why it is agreed Clen should be used for only 12 weeks with a 2 week on, 2 week off cycle.

If so, how long would one have to wait after the 12 week period before starting Clen again?

Bump because still in disbelief everyone has such strong opinions about this drug, but cannot answer this question.

 

[6oxo User]

interesting (and somewhat conversely- though actually just a reversal situation) clenbuterol is used as a treatment for heart failure treatment with left ventricular assist device.

Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1468-76. Epub 2004 Nov 4. Related Articles, Links


Erratum in:
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2546.

Effects of chronic administration of clenbuterol on function and metabolism of adult rat cardiac muscle.

Soppa GK, Smolenski RT, Latif N, Yuen AH, Malik A, Karbowska J, Kochan Z, Terracciano CM, Yacoub MH.

Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, Middlesex UB9 6JH, UK.

Clenbuterol (Clen), a beta(2)-agonist, is known to produce skeletal and myocardial hypertrophy. This compound has recently been used in combination with left ventricular assist devices for the treatment of end-stage heart failure to reverse or prevent the adverse effects of unloading-induced myocardial atrophy. However, the mechanisms of action of Clen on myocardial cells have not been fully elucidated. In an attempt to clarify this issue, we examined the effects of chronic administration of Clen on Ca(2+) handling and substrate preference in cardiac muscle. Rats were treated with either 2 mg x kg(-1) x day(-1) Clen or saline (Sal) for 4 wk with the use of osmotic minipumps. Ventricular myocytes were enzymatically dissociated. Cells were field stimulated at 0.5, 1, and 2 Hz, and cytoplasmic Ca(2+) transients were monitored with the use of the fluorescent indicator indo-1 acetoxymethyl ester. Two-dimensional surface area and action potentials in current clamp were also measured. We found that in the Clen group there was significant hypertrophy at the organ and cellular levels compared with Sal. In Clen myocytes, the amplitude of the indo-1 ratio transients was significantly increased. Sarcoplasmic reticulum Ca(2+) content, estimated by rapid application of 20 mM caffeine, was significantly increased in the Clen group. The action potential was prolonged in the Clen group compared with Sal. Carbohydrate contribution to the tricarboxylic cycle (Krebs cycle) flux was increased several times in the Clen group. This increase was associated with decreased expression of peroxisome proliferator-activated receptor-alpha. This study shows that chronic administration of Clen induces cellular hypertrophy and increases oxidative carbohydrate utilization together with an increase in sarcoplasmic reticulum Ca(2+) content, which results in increased amplitude of the Ca(2+) transients. These effects could be important when Clen is used in conjunction with left ventricular assist devices treatment.

Is this comparing apples to apples? Take this part of the clenbuterol article written by Peter Van Mol:

"In several animal studies1,2,3 Clenbuterol was also shown to act as an anabolic, believed to be able to impart muscle gains. This was never demonstrated in humans4 however, and there is more evidence that its effect on catabolic hormones invokes the opposite. In any case, the animal studies used much higher doses5 then one would safely recommend for humans. The late Dan Duchaine, by many held in high regard as a steroid guru and a former writer of the now defunct MM2K, believed it had something to do with the stimulation of a third beta receptor, which was different in humans as opposed to other mammals, and that this was the reason humans did not receive any anabolic benefits. As with most of what Dan said, this is very questionable, but one of many possible explanations in a debate that still rages on. Despite the many claims of other bodybuilders that still swear it has some form of anabolic action, I must say I've seen enough proof to the contrary to strongly advise against buying clenbuterol for promoting muscle mass. You may be more than sorely disappointed. Next time you see a 230 pound, 6 foot top-level cyclist, let me know and I may change my mind.

References

1 Ricart-Firinga C, Stevens L, Canu MH, Nemirovskaya TL, Mounier Y. Effects of beta(2)-agonist clenbuterol on biochemical and contractile properties of unloaded soleus fibers of rat. Am J Physiol Cell Physiol 2000 Mar; 278 (3) : C582-8

2 Hayes A, Williams DA. Long-term clenbuterol administration alters the isometric contractile properties of skeletal muscle from normal and dystrophin-deficient mdx mice. Clin Exp Pharmacol Physiol 1994 Oct; 21 (10) : 757-65

3 Maltin CA, Delday MI, Hay SM, Smith FG, Lobley GE, Reeds PJ. The effects of the anabolic agent, clenbuterol, on overloaded rat skeletal muscle. Biosci Rep 1987 feb; 7 (2) :143-9

4 Human fat cell beta-adrenergic receptors : beta-agonist dependent lipolytic reponses and characterization of beta-adrenergic bindingsiteson human fat cell membranes with highly selective beta-1 agonists. J lipid Res 1988 May; 29 (5) : 587-601

5 Prather ID, Brown DE, North P, Wilson JR. Clenbuterol : a substitute for anabolic steroids ? Med Sci Sports Exerc 1995 Aug; 27 (8) : 1118-21"

This is not the first time I have read the difference in beta receptors with rats versus humans and Clen. It's so funny how everyone is running for cover with Clen, and at the same time blasting themselves with AAS, which has been proven to cause much more negative long term effects. As morbid as it sounds, we need commentary from long term Clen users with effects on their bodies (if any) it caused.

 

[gjohnson5]

with respect to the "slowed heart rate", yes that is a potential effect of down regulated beta 2.


with respect to apoptic effects:

J Appl Physiol. 2005 Apr;98(4):1379-86. Epub 2004 Dec 10. Related Articles, Links


beta2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle.

Burniston JG, Tan LB, Goldspink DF.

Research Institute for Sports and Exercise Sciences, Liverpool John Moores Univ., Webster St., Liverpool, L3 2ET, United Kingdom. [email protected]

High doses of the beta2-adrenergic receptor (AR) agonist clenbuterol can induce necrotic myocyte death in the heart and slow-twitch skeletal muscle of the rat. However, it is not known whether this agent can also induce myocyte apoptosis and whether this would occur at a lower dose than previously reported for myocyte necrosis. Male Wistar rats were given single subcutaneous injections of clenbuterol. Immunohistochemistry was used to detect myocyte-specific apoptosis (detected on cryosections via a caspase 3 antibody and confirmed with annexin V, single-strand DNA labeling, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). Myocyte apoptosis was first detected at 2 h and peaked 4 h after clenbuterol administration. The lowest dose of clenbuterol to induce cardiomyocyte apoptosis was 1 microg/kg , with peak apoptosis (0.35 +/- 0.05%; P < 0.05) occurring in response to 5 mg/kg. In the soleus, peak apoptosis (5.8 +/- 2%; P < 0.05) was induced by the lower dose of 10 microg/kg. Cardiomyocyte apoptosis was detected throughout the ventricles, atria, and papillary muscles. However, this damage was most abundant in the left ventricular subendocardium at a point 1.6 mm, that is, approximately one-quarter of the way, from the apex toward the base. beta-AR antagonism (involving propranolol, bisoprolol, or ICI 118551) or reserpine was used to show that clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta1-AR, whereas in the soleus direct stimulation of the myocyte beta2-AR was involved. These data show that, when administered in vivo, beta2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through beta1- and beta2-AR, respectively.

macro , do you think this death of cardiac muscle cells applies to albuterol too?

 

[krishna]

its hard to say, the lack of human data is frustrating. Likely it has to be higher, though also likely within the normal usage limits

however there are measures that can be taken to reduce the risk, like ALCAR.

will try to take some time to put together a list of supps that should limit and perhaps even ameliorate the potential for damage

What doses do you recommend for ALCAR, potassium, and taurine while cycling clen?

 

[macrophage69alpha]

macro , do you think this death of cardiac muscle cells applies to albuterol too?

yes

 

[macrophage69alpha]

will not denigrate duchaine (he was an pioneer, of sorts, but being a pioneer means that he was WRONG.... A LOT).

He is almost singly responsible for the widespread nubain addiction problem (he himself died addicted to nubain, which likely was an aggravating factor death- due to congenital kidney issues)


with respect to clenbuterols actions, they are via beta 2 not via beta 3 which are more prevalent in animals (other than humans).

to put in no uncertain terms:

The implications of the study apply equally to humans.