Extreme stretching for extreme gains

[strester]

should be a sticky

[browndustin]

Wow, I think I’ll have to break open the dictionary or dig through my moms medical books…

All that I know is that stretching really does work. I’ve obviously improved flexibility, recover quicker and have seen some noticeable physics gains. I’ve got the stretch marks to prove it

Thanks for the excellent posts, boys.

[pu12en12g]

Very interested stuff Dr Dave

[Dr.Dave1]

J Physiol. 2003 Jul 15;550(Pt 2):347-56. Epub 2003 May 23. Links
Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice.Nguyen HX, Tidball JG.

Nitric oxide (NO) can function as either a pro-inflammatory or anti-inflammatory molecule, depending upon its concentration and the microenvironment in which it is produced. We tested whether muscle-derived NO affects muscle inflammation and membrane lysis that occur in modified muscle use. Transgenic mice with muscle-specific over-expression of neuronal NO synthase (nNOS) were generated in which transgene expression was driven by the human skeletal muscle actin promoter. Transgenic mice and non-transgenic littermates were subjected to hindlimb muscle unloading followed by reloading, which causes muscle inflammation and membrane lysis. NOS expression decreased in transgenic and non-transgenic mice during muscle unloading. Muscle inflammation was assessed by immunohistochemistry after 24 h of muscle reloading following 10 days of unloading. Soleus muscles of non-transgenic mice showed significant increases in the concentrations of neutrophils (4.8-fold) and macrophages (11.3-fold) during reloading, compared to mice that experienced unloading only. Muscles of transgenic mice showed 51 % fewer neutrophils in reloaded muscles than those of non-transgenic mice, but macrophage concentrations did not differ from non-transgenic mice. Muscle membrane damage was determined by measuring influx of an extracellular marker dye. Significantly more membrane damage occurred in muscles of non-transgenic mice experiencing reloading than in ambulatory controls. However, membrane damage in the reloaded muscles of transgenic mice did not differ from that in ambulatory mice. In vitro cytotoxicity assays confirmed that mouse neutrophils lyse muscle cell membranes, and showed that inhibition of NOS in muscle and neutrophil co-cultures significantly increased neutrophil-mediated lysis of muscle cells. Together, these data show that muscle-derived NO can function as an anti-inflammatory molecule in muscle that experiences modified loading, and that NO can prevent neutrophil-mediated damage of muscle cell membranes in vivo and in vitro.

[Dr.Dave1]

1: Am J Physiol Regul Integr Comp Physiol. 2005 Feb;288(2):R345-53.
Inflammatory processes in muscle injury and repair.Tidball JG.

Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.

[Dr.Dave1]

interesting article

J Anat. 2006 Apr;208(4):459-70. Related Articles, Links
The role of neutrophils in injury and repair following muscle stretch.
Toumi H, F'guyer S, Best TM.

Stretch injury to the myotendinous junction is a common problem in competitive athletes and those involved in regular physical activity. The major risk factor for recurrent injury appears to be the primary injury itself. Physicians, physical therapists, athletic trainers and athletes alike continue to search for optimal treatment and prevention strategies. Acute inflammation is regarded as the body's generalized protective response to tissue injury. An especially important and unexplored aspect of inflammation following injury is the role of inflammatory cells in extending injury and possibly directing muscle repair. It has been suggested that the inflammatory reaction, although it typically represents a reaction to damage and necrosis, may even bring about some local damage of its own and therefore increase the possibility for scarring and fibrosis. Limiting certain aspects of inflammation may theoretically reduce muscle damage as well as signals for muscle scarring. Here we focus on the role of neutrophils in injury and repair of stretch-injured skeletal muscle. A minimally invasive model that generates a reproducible injury to rabbit skeletal muscle is presented. We present a plausible theory that neutrophil-derived oxidants resulting from the initial stretch injury are responsible for extending the damage. An anti-CD11b antibody that blocks the neutrophil's respiratory burst is employed to reduce myofibre damage. An intriguing area that is currently being explored in our laboratory and others is the potential role for neutrophils to contribute to muscle growth and repair. It may be possible that neutrophils facilitate muscle repair through removal of tissue debris as well as by activation of satellite cells. Recent and ongoing investigations point to interleukin-6 as a possible key cytokine in muscle inflammation and repair. Studies to elucidate a clearer understanding of this possibility will be reviewed.

[Dr.Dave1]

Exp Cell Res. 2005 Nov 1;310(2):417-25. Epub 2005 Sep 15. Related Articles, Links
Stretch-induced myoblast proliferation is dependent on the COX2 pathway.
Otis JS, Burkholder TJ, Pavlath GK.

Skeletal muscle increases in size due to weight bearing loads or passive stretch. This growth response is dependent in part upon myoblast proliferation. Although skeletal muscles are responsive to mechanical forces, the effect on myoblast proliferation remains unknown. To investigate the effects of mechanical stretch on myoblast proliferation, primary myoblasts isolated from Balb/c mice were subjected to 25% cyclical uniaxial stretch for 5 h at 0.5 Hz. Stretch stimulated myoblast proliferation by 32% and increased cell number by 41% 24 and 48 h after stretch, respectively. COX2 mRNA increased 3.5-fold immediately poststretch. Prostaglandin E2 and F2alpha increased 2.4- and 1.6-fold 6 h after stretch, respectively. Because COX2 has been implicated in regulating muscle growth and regeneration, we hypothesized that stretched myoblasts may proliferate via a COX2-dependent mechanism. We employed two different models to disrupt COX2 activity: (1) treatment with a COX2-selective drug, and (2) transgenic mice null for COX2. Treating myoblasts with a COX2-specific inhibitor blocked stretch-induced proliferation. Likewise, stretched COX2-/- myoblasts failed to proliferate compared to controls. However, supplementing stretched, COX2-/- myoblasts with prostaglandin E2 or fluprostenol increased proliferation. These data suggest that the COX2 pathway is critical for myoblast proliferation in response to stretch.

looks like stretching can trigger hyperplasia in vitro via PGs but their results showed a larger inc in PGE2 than PGF2 . . .

[pu12en12g]

Taking this into account, the above "tourniquet" method (vascular occlusion http://forum.bodybuilding.com/showth...2#post10662032 )would induce hypoxia leading to an increased release of PGs, which would then lead to increases in protein synthesis.

Just to make it clear I am not suggesting everyone goes around with tourniquets on their arms. I do not want to see a post on here that someone's arm fell off b/c they read lifitng with a tourniquet would increase their gains. This is more informational at the moment

Agreed... I think there are some better ways to reach the same (or similar / safer) end result and it's no "kinkydink" that they are fatty acid related:

GlycerGROW
X Factor
Sesamin

It's ALSO no "kinkydink" that all of the above have fatloss effects (even though 2 out of 3 were never marketed for fatloss).

[Dr.Dave1]

FYI

^^good info^^ That reminds me of an article I had seen recently and helps draw it all in together . . . .

Small study but interesting results. I'm going to assume that we are all familiar with the role PGs play in promoting protein synthesis (aka theory behind X-factor and such). Here is a tie in to that with the tourniquet study I mentioned above.

J Appl Physiol. 2005 Jul;99(1):45-52. Epub 2005 Mar 3.
Contribution of prostaglandins to the dilation that follows isometric forearm contraction in human subjects: effects of aspirin and hyperoxia.
Win TS, Marshall JM.

In 11 healthy volunteers, we evaluated, in a double-blind crossover study, whether the vasodilation that follows isometric contraction is mediated by prostaglandins (PGs) and/or is O2 dependent. Subjects performed isometric handgrip for 2 min at 60% maximal voluntary contraction (MVC), after pretreatment with placebo or aspirin (600 mg orally), when breathing air or 40% O2. Forearm blood flow was measured in the dominant forearm by venous occlusion plethysmography. Arterial blood pressure was also recorded, allowing calculation of forearm vascular conductance (FVC; forearm blood flow/arterial blood pressure). During air breathing, aspirin significantly reduced the increase in FVC that followed contraction at 60% MVC: from a baseline of 0.09 +/- 0.011 [mean +/- SE, conductance units (CU)], the peak value was reduced from 0.24 +/- 0.03 to 0.14 +/- 0.01 CU. Breathing 40% O2 similarly reduced the increase in FVC relative to that evoked when breathing air; the peak value was 0.24 +/- 0.03 vs. 0.15 +/- 0.02 CU. However, after aspirin, breathing 40% O2 had no further effect on the contraction-evoked increase in FVC (the peak value was 0.15 +/- 0.02 vs. 0.16 +/- 0.02 CU). Thus the present study indicates that prostaglandins make a substantial contribution to the peak of the vasodilation that follows isometric contraction of forearm muscles at 60% MVC. Given that hyperoxia similarly reduced the vasodilation and attenuated the effect of aspirin, we propose that the stimulus for prostaglandin synthesis and release is hypoxia of the endothelium

Taking this into account, the above "tourniquet" method (vascular occlusion http://forum.bodybuilding.com/showth...2#post10662032 )would induce hypoxia leading to an increased release of PGs, which would then lead to increases in protein synthesis.
Just to make it clear I am not suggesting everyone goes around with tourniquets on their arms. I do not want to see a post on here that someone's arm fell off b/c they read lifitng with a tourniquet would increase their gains. This is more informational at the moment

[pu12en12g]

The Role of PGF2a in Muscle Growth

After that brief introduction into prostaglandins, we can now begin to discuss more specifically the role of prostaglandins in muscle growth. In a nutshell, mechanical stimulation (i.e. intermittent stretch) results in the production and efflux of two prostaglandins, PGE2 and PGF2a. PGE2 increases protein degradation where as PGF2a increases protein synthesis. Muscle hypertrophy is usually achieved by an increase in protein synthesis as well as a proportionately smaller increase in degradation. The simultaneous release of both PGE2 and PGF2a creates this condition.

It is well known that mechanical stretch, without any electrical activity, is sufficient to induce muscle hypertrophy. Recent studies have shown that the mechanism by which mechanical stretch leads to prostaglandin production and ultimately muscle growth, involves G proteins embedded in the cell membrane. These G proteins increase the amount of cyclo-oxygenase, the enzyme responsible for making prostaglandins from arachidonic acid. Skeletal muscle cyclooxygenase generates PGE2 and PGF2 alpha at a ratio approximately equal to one.

The exact mechanism by which PGF2a increases protein synthesis is not entirely clear. That’s just a spineless way of saying, "I don’t know the exact answer to that!" We are free to speculate though. It may involve short phase protein synthesis and/or long phase protein synthesis.
2 phases of protein synthesis Modulation

Modulation of protein synthesis rates occurs at two levels, the short phase and the long phase. The short phase alteration in protein synthesis rates occurs by altering the activity of existing ribosomes and/or eukaryotic initiation factors (eIFs). This happens within minutes of the appropriate physiological trigger. The long phase modulation of protein synthesis happens by way of increasing the number of myonuclei. This mechanism involves hormones and growth factors such as HGH and IGF-1 bringing about the activation of myogenic stem cells. This can take several days to effect protein synthesis rates. This is a simplified view but for our purposes it is sufficient.

The role of PGF2a in short phase protein synthesis in muscle tissue is speculative at best. In non-muscle tissue, prostaglandins effect calcium fluxes, plasma membrane ionic channel activities, and cyclic nucleotide levels. All of which are important regulators of protein synthesis rates in muscle. PGF2a has been shown to interact with the S6 small ribosomal subunit, increasing its potential to form the ribosomal initiation complex with the large subunits. It is also plausible that PGF2a may effect the activity of eIFs.

Initiation of translation (the binding of mRNA to the ribosomal pre-initiation complex) requires group 4 eukaryotic initiation factors (eIFs). These initiation factors interact with the mRNA in such a way that makes translation (the construction of new proteins from the mRNA strand) possible. Two eIFs, called eIF4A and eIF4B, act in concert to unwind the mRNA strand. Another one called eIF4E binds to what is called the "cap region" and is important for controlling which mRNA strands are translated and also for stabilization of the mRNA strand. Finally, eIF4G is a large polypeptide that acts as a scaffold or framework around which all of these initiation factors and the mRNA and ribosome can be kept in place and proper orientation for translation. There is yet no direct evidence to confirm that PGF2a works through this mechanism however.

Long term modulation of protein synthesis involves the activation of myogenic stem cells or satellite cells. If you recall, when a muscle is stretched it not only produces PGF2a, but also PGE2. PGE2 is a potent inducer of satellite cell proliferation and fusion. This is how existing muscle cells increase the number of nuclei they contain. This is important because in order for a muscle to grow rapidly, it must produce more mRNA. This is done in the nucleus of the muscle cell. The more nuclei you have, the more mRNA you can produce. Within the cell, prostaglandins may also be involved in regulating the number of ribosomes. This could have long term implications on growth and development as well as stretch induced hypertrophy.

FYI

[pu12en12g]

Extreme stretching, Prostaglandins, and X-Factor:

Prostaglandins are largely locally acting hormones. I would suspect you can have a signifcant increase in local levels in trained muscle without dramatically increasing totaly body output.. The main focus here is loading high levels in skeletal muscle, so these tissues are more reponsive in terms of prostaglandin output when stretched during exercise.

[jaymdubbs]

i mean this in the most sincerest way, but if you guys have trouble eating so much, wouldnt it be easier to drop a few pounds to lower the daily cal intake to maintain? i know its "heresy" to talk about losing muscle, but id rather be happy and STILL jacked then unhappy/depressed/nauseated and REALLY JACKED


i realize im only 187 pounds, but i know if i was in that situation i would take a hit in size so i could function without worrying about it.
i still have trouble meeting my calorie requirements because im NOT as hungry as i should be, so i definetely know where you guys are coming from. thats why im a little hesitant to really put some serious mass on- i dont think i could eat enough to maintain it.



but like browndustin said, you do have a whole community behind you, which def. is a plus

[browndustin]

Shitty dude. I can empathize with the depression. Sometimes it can get crippling and words can't explain it. I hope you find something to pull yourself out of it. You've got a whole community here on your back.

Thanks for posting that stretching article. I was searching for some good stretches because I started after seeing those posted at bb.com. I noticed big differences in soreness, doms, growth, strength and recovery. I don't always stretch as much as I want to, but I stretch my chest good, lower back and legs the best. If you have some good stretches, I'd like to here them. I've yet to check out those sites, so don't worry, I'll be doin my homework.

I want to stretch the middle back and arms a little better... I can see that there's definitely something going on when you stretch, and I figure that I should get serious about it eh. Thanks again for the links, if I find anything else I'll be sure to come back and post it here.

[Dr.Dave1]

Appetite is my weakness right now... I wake up... start force feeding and all day long I just want to puke. I've had the doctors test everything they can think of... and all they come back to is depression (well that and severe neck / shoulder pain)... so I have plenty of Celexa and Wellbutrin on hand (last resort )

I hear you there, eating a lot is tough enough on its own but when you throw depression on top of that it makes it even worse. I know if I feel down I do not want to eat much at all. Then if you add the nausea and anorexia that can be side effects of those meds ya get a double whammy if they are not working effectively on the depression.
I did a quick search to see if there was much literature on appetite stimulants. It seems that most of the research in that area is for HIV and cancer patients so the interventions are pretty extreme (relatively) and probably not sometihng your docs would try (but I could be wrong). For example I doubt they would prescribe megasterol acetate (a progestin) or ghrelin.
If they can get the depression controlled your appetite might return
Kind of unrelated but since you mentioned it . . . did they determine the cause of the back/shoulder pain? Chronic pain can lead to depression as I am sure they have mentioned.

[pu12en12g]

hmmm . . . I may have to give that a try; I could definitely use some bulk

Appetite is my weakness right now... I wake up... start force feeding and all day long I just want to puke. I've had the doctors test everything they can think of... and all they come back to is depression (well that and severe neck / shoulder pain)... so I have plenty of Celexa and Wellbutrin on hand (last resort )