Wednesday, September 28, 2011

Some news.....

David M Diamond* made in public the following declaration in the THINCS Forum on June 22, 2011: “Carlos, your thesis on stress, acidic environment and CHD is brilliant. Particularly impressive is how you relate reduced pH to increased oxidation of LDL, which increases its atherogenicity”
* Ph.D, Professor, Depts of Psychology and Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD. Director, University of South Florida, Neuroscience Collaborative)

Friday, September 23, 2011

Sympathetic Predominance: The link between erectile dysfunction, atherosclerosis and cardiovascular disease?

Erectile dysfunction affects 40% of men above 40 year old, in some degree, and two thirds of men over 70 have significant symptoms of ED.
The association between erectile dysfunction and coronary artery disease (CAD) was suggested years ago, by observational studies. More recently it was found that erectile dysfunction is an early marker of CAD, as the canary in the coal mine*.
Indeed some studies have demonstrated that coronary atherosclerosis is more severe in patients with vascular ED, with the authors considering that ED may be an additional, early warning sign of coronary atherosclerosis (1).
A recent meta-analysis of prospective cohort studies, involving 36,744 participants, have suggested that ED significantly increases the risk of cardiovascular disease, coronary heart disease, stroke, and all cause mortality, and the increase is probably independent of conventional risk factors (2)
Erection is initiated through the parasympathetic nervous system, activation of which overrides the sympathetic tone that maintains the penis in a nonerectile (flaccid) state. This state is maintained mainly through the release of norepinephrine from penile adrenergic nerves. Norepinephrine contracts the vasculature and cavernosal smooth muscle. Arousal/erection is associated with a decrease of norepinephrine release in the penis, with a release of nitric oxide, and with a reduction in penile smooth muscle tone. Thus, nitric oxide is a mediator of the parasympathetic vasodilation in erectile function (3). So, when the parasympathetic system is continuously disabled there is a reduced production of NO.
Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. ED is associated with smoking, excessive alcohol intake, abdominal obesity, diabetes, hypertension and decreased antioxidant defenses, all of which reduce NO production (4,). Recent studies have discussed about the benefits of lifestyle interventions like healthier eating habits, getting exercise and avoiding smoke for improving erectile dysfunction (5) and also targeting CAD risk factors reduction (4, 6).
It is interesting to note that ED and atherosclerosis have many risk factors in common like ageing, physical inactivity, improper diet, psychological stress, cigarette smoking, high blood pressure and diabetes. In relation to this point there are diverse studies showing that: a) increased sympathetic activity and mental stress may affect erectile function with studies suggesting that an elevated central sympathetic tone may be one of the causes of psychogenic impotence (7, 8, 9); b) a study suggested that drugs acting within the central nervous system that reduce the sympathetic antierectile flow and enhance the parasympathetic proerectile flow to the penis may restore penile erection in cases of erectile dysfunction of both psychogenic and organic origin (10); c) other study have demonstrated that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep (11); d) A study has shown that men with idiopathic ED have evidence of endothelial dysfunction in forearm resistance vessels, increased pulse pressure and impaired heart rate variability. According the authors this support the concept that erectile dysfunction is a predictor of cardiovascular dysfunction and a precursor of clinical cardiovascular disease (13). e) and, finally, a very recent study have shown that patients with ED exhibited different heart rate variability compared with normal controls. This suggested to the authors that the patients with ED may have some kind of imbalance in the autonomic nervous system (ANS) and it may be possible that general imbalance of the ANS is one of the causes of ED (12).
Taking in view the above studies and our postulation that sympathetic predominance is the primary factor in the cascade of events leading to the atherogenic spiraling (14, 15), we have to assume that it really is the link between ED and cardiovascular disease.
14. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
15. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html

Carlos Monteiro

*As long as the canary still singing, it is all ok. However, a dead canary is a warning of a larger problem.

References:
1. Chiurlia E et al. Subclinical coronary artery atherosclerosis in patients with erectile dysfunction. J Am Coll Cardiol, 2005; 46:1503-6
2. Dong JY et al. Erectile dysfunction and risk of cardiovascular disease. Meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2011; 58:1378-1385
3. Andersson K, Stief C. Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms. Am J Cardiol. 2000 Jul 20;86(2A):23F-26F
4. Meldrum DR et al. The link between erectile and cardiovascular health: the canary in the coal mine. Am J Cardiol. 2011 Aug 15; 108(4): 599-606
5. Horasanli K et al. Do lifestyle changes work for improving erectile dysfunction? Asian J Androl, 2008; 10(1):28-35
6. Gupta PB et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: A systematic review and meta-analysis. Arch Intern Med, 2011. Published online September 12.
7. Junemann KP et al. Neurophysiological aspects of penile erection: the role of the sympathetic nervous system. Br J Urol, 1989 Jul;64(1):84-92
8. Pagani M. Hypertension, stress and erectile dysfunction: potential insights from the analysis of heart rate variability. Curr Med Res Opin, 2000; 16 Suppl1:s3-8
9. Diederichs W et al. The sympathetic role as an antagonist of erection. Urol Res. 1991;19(2):123-6
10. Allard J, Giuliano F. Central nervous system agents in the treatment of erectile dysfunction: how do they work? Curr Urol Rep 2001 Dec;2(6):488-94
11. Lavie P et al. Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction. J Sleep Res. 1999 Jun;8(2):135-42
12. Lee JY et al. Heart rate variability in men with erectile dysfunction. Int Neurourol J 2011;15:87-91. Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138849/pdf/inj-15-87.pdf
13. Stuckey BG, Walsh JP ET al. Erectile dysfunction predicts generalised cardiovascular disease. Evidence from a case control study. Atherosclerosis 2007, 194(2):458-6414.

Monday, September 5, 2011

The positive impact of humor and negative of stress over the vascular function

Chronic stress is correlated with increases in stress hormones cortisol and cathecolamines. There is strong scientific evidence linking negative emotional states like depression, anxiety, or anger with increased risk for cardiovascular disease. However, much less is known about the association between positive emotional states, the so called eustress, like laughter and happiness. The nicest of all laughter types is associated with humor and it is specified as mirthful laughter.
In this respect there are some studies made by Berk and colleagues, from the Loma Linda University, demonstrating that in comparison with chronic stress mirthful laughter reduced the levels of Cortisol by 39%; adrenaline by 70% and dopac by 38%. The conclusion in one of their papers was that humor appears to attenuate catecholamines and MI recurrence and thus could be an effective adjunct in post-MI care (1, 2, 3).
On the other hand Michael Miller, from the University of Maryland, presented a study at the European Society of Cardiology in the 2011 Congress (4) highlighting the link between endothelial function and laughter. His study showed that when people laughed their major blood vessels dilated allowing for easier blood flow, that indicates a reduced risk of cardiac events.
Dr. Miller’s idea to study positive emotions such as laughter came after studies that had shown that mental stress caused blood vessels to constrict. His first study about sense of humor and coronary artery disease was published in 2001 (5). In other paper, published in 2009 (6), he told about the tests made to confirm the hypothesis that mirthful laughter also favorably affect endothelial dependent flow-mediated vasodilation (FMD). In this way volunteers were randomized for two different phases in a randomized-crossover design. One phase included watching a movie or segment of popular comedies (ex: Saturday Night Live) whereas a second phase was to view a movie known to promote mental stress (ex: The opening segment of “Saving Private Ryan”). The assessment of endothelial dependent vasoreactivity was performed using high resolution ultrasound of the brachial artery, also referred as brachial artery reactivity test (BART). A total of 160 BART measurements were performed and demonstrated a divergent effect after watching a movie provoking mental stress as compared to mirthful laughter. Specifically, a 35% reduction in FMD compared to baseline followed mental stress whereas a 22% increase in FMD occurred in response to laughter (7). In 2008, Dr. Miller and colleagues, in an oral presentation entitled “Positive emotions and the endothelium: Does joyful music improve vascular health?”, made at the American Association Scientific Sessions, on 11/11/2008, conclude that the cardiovascular benefits of music are similar to those found in their previous study of mirthful laughter (8)
Dr. Sugawara and colleagues in 2010 have confirmed the findings from Dr. Miller saying that their results suggest mirthful laughter elicited by comic movies induces beneficial impact on vascular function (9).
Again, in the presentation made by Dr. Miller at the ESC, 2011, volunteers watched segments of a funny movie, such as the farce “There's Something About Mary” on one day and on another day watched the opening segment of the stressful movie “Saving Private Ryan”. When study volunteers watched the stressful movie, their blood lining developed a potentially unhealthy response called vasoconstriction, reducing blood flow. Overall, in this time, more than 300 measurements were made with a 30-50% difference in blood vessel diameter between the laughter and mental stress phases (4).
We think the above studies give additional evidence to our acidity theory of atherosclerosis (10), that has the following sequence of events:
I. Sympathetic dominance by continuous stress plus
II. Deficiency in production of endogenous digitalis-like compounds (DLCs) with alterations of Na(+), K(+)-ATPase activity results in:
III. Lowered pH (acidity) that increases perfusion pressure and provokes effects on contractility of coronary arteries leading to changes in hemodynamic shear stress and atherosclerosis as consequence.
Sympathetic activation, metabolic acidosis and vascular reactivity The studies by Berk and Miller confirm previous studies suggesting that the sympathetic activation with elevation of circulating catecholamine (adrenaline, etc..), cause coronary vasoconstriction and consequent reduction in blood flow.
On the other hand it is interesting to notice that increased lactate (or decreased blood pH) may evoke vascular smooth muscle relaxation and increase of blood flow (11).
These opposite forces working in sequence - with the sympathetic overdrive leading to metabolic acidosis -, in our view, may be reconciled to partially explain the occurrence of the resulting abnormal stretching/relaxing of coronary arteries, in different directions, simultaneously, producing atherosclerosis (10).
Carlos Monteiro

1. Berk LS, Tan SA and Berk B. Cortisol and cathecolamine stress hormone drecrease is associated with the behavior of perceptual anticipation of mirthful laughter. The FASEB Journal. 2008; 22;946.11
2. Tans SA, Berk LS et al. Humor as an adjunct therapy in cardiac rehabilitation, attenuates cathecolamines and myocardial infarction recurrence. Adv Mind Body Med 2007; 22(3-4): 8-12
3. Berk LS et al. The neuroendocrine and stress hormone changes during mirthful laughter. Am J Med Sci 1989;6:390-396
4. Miller M. Laughter and vascular function, ESC 2011.
5. Clark A, Seidler A, Miller M. Inverse association between sense of humor and coronary heart disease. Int J Cardiol. 2001 Aug; 80(1):87-8
6. Miller M, Fry WF. The effect of mirthful laughter on the human cardiovascular system. Med. Hypothesis 2009; 73(5):636 . Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814549/pdf/nihms-154943.pdf
7. Miller M, Mangano C, Park Y, et al. Impact of cinematic viewing on endothelial function. Heart 2006; 92:261-262
8. Miller M, Beach V, Mangano C, Vogel RA. Positive emotions and the endothelium: Does joyful music improve vascular health? American Association Scientific Sessions, on 11/11/2008
9. Sugawara et al. Effect of mirthful laughter on vascular function. Am J Cardiol 106:856-9 (2010).
10. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
11. Celotto AC, Capellini VK et al. Effects of acid-base imbalance on vascular reactivity. Brazilian Journal of Medical and Biological Research (2008) 41:439-445 Full free text at http://www.scielo.br/pdf/bjmbr/v41n6/7099.pdf