Atherosclerosis - Science topic

Hello Dr Ali Banagozar Mohammadi

There is other literature to agree with your point:

Wójcik-Cichy K, Koślińska-Berkan E, Piekarska A. The influence of NAFLD on the risk of atherosclerosis and cardiovascular diseases. Clin Exp Hepatol. 2018 Mar;4(1):1-6. doi: 10.5114/ceh.2018.73155

Baratta F, D'Erasmo L, Bini S, Pastori D, Angelico F, Del Ben M, Arca M, Di Costanzo A. Heterogeneity of non-alcoholic fatty liver disease (NAFLD): Implication for cardiovascular risk stratification. Atherosclerosis. 2022 Sep;357:51-59. doi: 10.1016/j.atherosclerosis.2022.08.011.

It seems the answer is yes and this is because of shared risk factors.

As you set up your ATD prediction database, and you should do so for your own research purposes since your regional laboratory and my reference lab may differ in the results. About 40 years ago the New York City health department collected a large volume of blood and had the CDC determine the level of total cholesterol (CT) in the sample. The health department then divided the reference sample into 50 samples and then each sample into two sub-samples. The health department then sent out one of the sub-samples for CT measurement one week and the second sub-sample the next week--again for CT measurement. The samples were sent to 50 local laboratories. The CT results varied widely, though were consistent for each individual laboratory. Remember that CT is the most accurately measured lipid fraction and that HDL-c is the least accurately measured lipid fraction, so one can imagine that there may be a lot of variability between labs. My regional lab standardizes against CDC standards on a weekly basis. Perhaps your cab could do the same thing.

When you set up your spreadsheet and calculate the CRF, you will note that perhaps as much as 1% of CRF values may be negative. This is virtually always seen in people with low LDL-c and normal HDL-c, mostly children. Only two of my adult patients with negative CRF values developed ATD: the 60 year old was a cigarette smoker with a sky high blood pressure and the other was a 89 year old patient who had never smoked cigarettes. The former patient died from a cardiac arrest and the latter patient died in her 90's. So I don't think that this need be of concern.

One last comment for this session: Don't get lost in dogma. There are those who think that LDL-c is the be all and end all for the lipid portion of ATD prediction. This is not true. Remember that in (true) science, appeal to authority is not acceptable. When a hypothesis is presented, along with the supporting data, the hypothesis is tested to see if it is valid--it is not rejected out of hand just because it differs form your deeply held beliefs. The hypothesis is only rejected when it can not be replicated by independent researchers. This must be remembered in the case of the CRF and the change in HDL-c measurement in 1999. All of my data and the published angiographic regression studies I cited are based on the precipitation method of HDL-c measurement. Use of the enzymatic method of HDL-c measurement must be corrected for this change--or you could set up your own database using the enzymatic method, using the principles I have discussed.

First contact the Editorial office of the Journal. then write a letter, signed by all authors, explaining the situation surrounding the manuscript, and the reason for its withdrawal.

Great, All the best

Yes EMohamed Elsharawy , I am not sure about atheroma does not invade adventitia but more atheroma , more chance of stroke

There is no direct link of typhoid and atherosclerosis. But Non typhoid salmonelosis has association with endovascular infection , more study needed to prove the definitive evidence of association of typhoid with atherosclerosis. Mechanism play role , might be endothelial injury make prone to attach with plaque , composition of cholesterol and lipoprotein

WLNC 2023

CVB 2023

The key lipid risk factor is the balance between LDL-c and HDL-c, but especially the ratio between these two--a ratio such as the Cholesterol Retention Fraction (CRF, defined as [LDL-HDL]/LDL). (The LDL-c:HDL-c ratio is slightly less sensitive and suffers from poor reproducibility.) There is no doubt that HDL-c--or more specifically, apo A-1--is protective against atherothrombotic disease, so the amount of LDL-c accumulating within the artery wall depends upon its associated HDL-c level. Non-HDL-c is simply LDL-c with TG-c, but whn TG-c is high HDL-c is virtually always low. IDL-c is not a player in most people. CT should be relegated to the dylsipidemia historical files

I was staining lipids in atherosclerotic plaques.

Dear Dr Mehmet Rami Helvaci . See the following very useful RG link:

As we know that Fat , cholesterol and other substances like Calcium , are the building block for the formation of plaque inside the lumen of coronary arteries , partially or totally block the blood flow to heart , leads to Ishaemia or infarction. There is no specific novel biomarkers to assess the progression of atherosclerosis. Besides the usual novel biomarkers like BNP , NT-Pro BNP , tropinin HDL-c , HDL function ,now researcher are eager to find out the novel biomarkers( produced by cardiac tissues) like miRNA , protein , fat by use of new technologies like Mass spectroscopy ,pcR bases array and MS based lipidomics

If you need a positive control, just treat them with H2O2. Otherwise nicotine or high calcium (3.6 or 5.4 mM) worked in my hands, in primary human vascular smooth muscle cells.

The problem might be in the MOVAS cells themselves? Maybe the fact that it's a cell line makes them insensitive to stimuli.

Yes, dear Fa Ro they can present in lymph node.

Thank you sir@ Daniel P. Moriarity

It is difficult to find out the LDL oxidation process at 234 nm. You will get nice conformation by Thiobarbituric Acid-Reactive Substances (TBARS) assay.

First I would recommend being crystal clear in language.

You may have cardiovascular disease (CVD) and cardiovascular events, maybe say CVE. Events are occurrences that happen more or less at once, while a disease is a continuous condition.

Endpoints are usually events. Maybe you can use clear-cut conditions that are correleted with immediate risks, not with long-term risks, to define a substitute endpoint.

It appears that the aspect risk should also be carefully considered. Risks are not endpoints!

Having said this and not being an expert in that field I could imagine that hospitalisation or certain intensive care measures related to renal conditions could be defined as endpoint(s), rather as substitute endpoint(s).

The lab condition you mentioned above I would rather consider as marker of risk.

Coronary angiography is a luminogram and that explains low sensitivity for diffuse disease

Smooth muscle cells (generally primary isolated cells, but there are also cell lines). I have worked with rat media and intima smooth muscle cells, endothelial cells, monocyte/macrophages typ M1, and more, depending on the interest!

There are now provider offering "atherosclerosis on the chip"!

Dear Ermin Rachmawati, I'm sending you 3 articles' references which can help to clarify your question.

1. Fan, J., Kitajima, S., Watanabe, T., Xu, J., Zhang, J., Liu, E., & Chen, Y. E. (2014). Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Pharmacology & therapeutics, 146, 104-19.

2. Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies A Scientific Statement From the American Heart Association. Alan Daugherty; Alan R. Tall; Mat J.A.P. Daemen; Erling Falk; Edward A. Fisher; Guillermo García-Cardeña; Aldons J. Lusis; A. Phillip Owens III; Michael E. Rosenfeld; Renu Virmani. Arterioscler Thromb Vasc Biol. 2017;37:e131–e157. DOI: 10.116

3. Arq Bras Cardiol. 2010 Aug;95(2):272-8.

Experimental atherosclerosis in rabbits.

[Article in English, Portuguese]

Dornas WC1, Oliveira TT, Augusto LE, Nagem TJ.1/ATV.0000000000000062.)

Atherosclerosis is a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls, by definition you can't induce atherosclerosis in the cell lines but you can induce the marker or components of atherosclerosis in the cell line, in addition there may be some 3D model of atherosclerosis available that you can use to study the lesions.

Check this for example;

2. The major interest of the article you refer to is that they found opposite results as compared to what the authors were expecting.

In fact, there are multiple studies that point in the opposite direction, that is: IL-1 and IL-2 show pro-atherosclerotic effects. Very recently, the large RCT CANTOS showed that inhibition of IL-1 beta prevents cardiovascular events in patients with previous Myocardial Infarction.

These intriguing results just raise the point that things are a bit more complex than previous hypotheses.

On this basis I don't believe it justify the development of a therapeutic approach.

The point is not just raising HDL, but the efficacy of the oxLDL uptake at the site of atheroma and removal by the liver. That blocking CETP didn't work was logical from this point of view Just putting more garbage collecting trucks on the road while not improving the uptake at home nor delivery at the destruction site just creates traffic jams.

This was most clearly addressed in the apo-I Milano study where a population was found with extremely low HDL levels and still no atherosclerosis. So, better understanding of the reverse LDL transport system is of uttermost importance.

Interesting

I have found some that work for Western but not for IMF.

I spent some time in eastern Africa as an environmental officer, my home was in Nairobi. On an assignment to Uganda, I ran across an old Brit MD and we discussed heart and vascular disease. He commented that the local diet was high in fat but that the prevalence of heart disease was low but had increased following the establishment of sugar plantations and refineries.

The fat may impact the ability of the endothelial cell to generate NO and the sugar generate ROS, thus pro inflammatory transcription factors, hence upregulation of ICAM-1

See, for example: Mitochondrial Reactive Oxygen Species Mediate Lysophosphadylcholine-induced Endothelial Cell Activation, by Xinyuan Li, et al.

Dr Edo McGowan

Yes according to a recent work done by my collaborator. Nonpublished yet.

I am a PhD student in my first year working in a lab that searching for naturaceutical as a therapy for atherosclerosis. For example my project is on Pinolenic acid (PNLA) as PUFA have anti-atherogenic action on LDL, monocyte migrations etc... in vitro. Following this going to work on mouse model to see the effect of PNLA on atherosclerosis

. Regards Sphingolipids I have no idea really. Thanks Joseph for providing an answer. As soon as I finish my mini viva and getting more results I ll plot any update . Thanks all and best wishes.

i agree to Dr.qassim answer

In addition to what our colleagues wrote, I mention chronic Inflammatory conditions like Psoriasis, autoimmune diseases causing arteriitis, and also linked to metabolic syndrome, as well as Hypercoagulation syndromes. In addition risk factors like Lp(a), Fibrinogen, pHcy.

Decalcification is necessary to get a fine paraffin section. Otherwise, the section will tear. If you want to skip decalcification, you could try plastic/ resin sectioning approaches.

Assuming you want paraffin, just trim and fix tissue as you normally would, then transfer to decalcification solution for 24-48 hours. These are sold commercially (we use 'Cal-Ex' from Fisher Scientific) or you can make buffered solutions of HCl and/or EDTA, which is what these solutions usually contain.

Note that the solution only takes out the calcium ions, not the cells or other cell products. Your atherosclerotic plaque region will still be present, but no longer crystalline.

Dear colleagues

Thanks for the informations

I agree with you and we have to use statins in high doses to improve microvascular function and reduce systolic dysfunctio.

Hello everyone could someone give some help or some interesting articles related to: <<The application of inorganic nanoparticles in drug delivery.>>?

Thank you in advance!

Yes, it will eventully end in bone for the most part.

Thank you so much! I will definitely look into this.

Hi Jonathan i have send u a message on your watts app, let me know mate thanks 

Thank you, it is really interesting high quality article. Good day. With respect, Sergii.

There is a mistake on this question. I am not an author of this article. Sorry about that.

Statins have pleotropic properties encompassing anti inflammatory effects, countering of smooth muscle proliferation and prothrombosis. It has been reported to also cause some blood pressure reduction. These ameliorate atherosclerosis even if hypolidaemic effect is not great

Thanks all

I think these articles can help you

You can use the fluorometric methods using BODIPY-cholesterol or NBD-cholesterol.

See these papres:

A sensitive assay for ABCA1-mediated cholesterol efflux using BODIPY-cholesterol.

The implication of cigarette smoking and cessation on macrophage cholesterol effl ux in coronary artery disease patients.

I don't see what would the mechanism for such a proatherogenic cause consist of?

Is there any experminetal/observational evidence for the correlation of Vit. K antagonists intake and atherosclerosis build-up? Since there are a lot of patients taking warfarin, there must've been something noticed, if that's what happens?

ROS is directly associated with arthrosclerosis. If your compound is able to attenuate ROS, I believe you can target and portray ROS pathways. You can approach via anti-oxidant mechanisms for example: Renin induced hypertension and testing your compound. Screening of mitochondrial damage by ROS induction and testing your compound would also be an excellent approach.

In that case put them on diet for 6-8 weeks depending on the age of your mice, because ApoE-ko can develop lesions on normal Chow diet as well.

Obviously, there is no good model for a complex process such as atherosclerosis in a cell culture system.  However, you could test your compounds in isolated cells in culture or co-culture if you have a predicted mechanism of action.  For instance, if you expected an effect on monocyte targeting, you could examine monocyte adhesion to the endothelium (preferably under flow) in response to an atherogenic stimulus such as oxLDL treatment.  However, the model will be limited to the specific process you are trying to reproduce in culture.

J Pharmacol Exp Ther. 2005 Oct;315(1):320-8. Epub 2005 Jul 14.

Calcium channel blocker inhibits Western-type diet-evoked atherosclerosis development in ApoE-deficient mice.

Kyselovic J1,

Please find below a paper dealing with a new generation probiotic isolated from gut :

Regards

Dear Hugues Beaufrere,

I am really sorry that i have not your expected data ...i do not get a sound scope for working on this field .

Dear researchers,

Endothelial cells are polar cells with apical and basolateral domains which has to do with their attachments to the substratum, usually a basal lamina consisting of various types of collagen, fibronectin, laminin etc. Thus it is essential to grow them on a coated surface because glass surface is not known to these cells in their natural environment. I believe this will help us to deal with cells that are sane in our experiments.

If you are interested in knowing about a gene (not necessarily the protein) and its relationship with a disease, try DisGeNET. (http://www.disgenet.org/web/DisGeNET/menu;jsessionid=15gl6du1cmyrv77xqzmqt2b1a)

It links articles which may have suggested association or functional aspects of a given gene with the disease. 

Dear Dr. Yakala,  You can try to contact the 

You can try to contact the  following groups

1 and 2 for human human ES cells and 3rd is for murine ones

All the best,

Tushar

Dear Cassi, we´re doing ORO staining from aortic root cryosections following this protocol: 60´air dry, 3x wash H2O, circumvent section using pap pen, dehydration 5-10´in 100 % propyleneglycol, 60´filtered ORO at RT, 2x3 min dips in 85 % propyleneglycol, 3x wash H2O and counterstaining. Make sure your ORO is filtered properly, in case you dont see red stained droplets, increase time and or temperature. Good luck!

thank you for answering my question.

have you ever heard about IHC for defining the lesion. I want to use CD68 for checking the foam cell, VCAM-1 antibody and also thickness of tunika intima,Is it possible to do that in umbilical artery??

I know that the Harefield Hospital trust near Uxbridge has a centre for LDL apheresis of familial hypercholesterolemia patients - not sure if you can recover the LDL after the procedure or if this would be suitable for your experiments...

Gregory and Ali, 

Thank you for your comments! It seems that there are some quite complex differences between atherosclerosis risks in mice and humans, but a lot of research papers still translate results obtained on mice to humans. Gender differences are particularly interesting. I have seen several explanations and I feel this is important area of research that may not in the beginning yield results that can directly be translated to human practice, but definitely give us knowledge about shared pathophysiological pathways. How would you comment on the fact that female mice are more susceptible to atherosclerosis than male mice. 

Best regards,

Jan 

Atheroma site specificity correlates strongly with regions of disturbed shear stress, I.e. on the outer wall at a flow divider, e.g. bifurcation - where shear is low, or at regions of vessel curvature, e.g the aortic arch. Also, contrary to popular believe, shear is not uniform across the circulation. In fact, it is considerably higher in small arteries and especially arterioles. Also, between species there is an inverse relation between shear and body mass, e.g. shear is around 15 times higher in the abdominal aorta of a rat than the same region in a human. Coincidence that rats don't spontaneously develop atheroma?? Notably, shear is a powerful inducer and suppressor of the genes pertaining to vasodilation and vascular disease. 

Hope that helps,

Dave

Si estoy de acuerdo que la obesidad es un proceso generalizado de inflamación generalizada, que origina enfermedades diversas en toda la economida del organismo y que se debe realizar un tratamiento intensivo para mejorar el IMC

I confirm that HT1080 with TPA is a good way to recover MMP-9 in conditioned medium.

In general I would expect that freshly secreted HDL particles are not modified, within the ER and the Golgi system no oxidation should occur. As soon as the particle enters the blood (or the cell culture medium if you are working with isolated cells) its open for modifications and the time scale depend on several parameters (O2 saturation of the blood, antioxidant conc., free radicals, enzymatic activities in the blood and on the HDL particle itself ...).

the question has many answers, all -more or less- plausible. First, there are many different vegetarian diets, which act differently in different races and in different individuals. The reaction is, usually, detached. Second, there is no "vegetarian diet" but the product of an eating habit (and its variability during the life) for a certain time, at a certain stage of life, in interaction with numerous genetic, epigenetic and environmental factors. Third, we must not forget that atherosclerosis is a systemic disease, proliferative and degenerative, slowly progressive, but reversible, which extends along the life, and that ATS is one of the rate-limiting step in the life span of individuals and in growth of populations. Fourth, the experimental methods available currently are not correct and do not provide answers to multidimensional problems with hundreds of variables. Fifth, there is no need to assume that the study of "average trends" (as in controlled clinical research) can help to predict individual responses. Fifth, predictive medicine and medicine of complexity models (i.e. so called System Medicine) have not yet suitable to solve the problems, nor sufficient computing power. (we hope for the future)

So, from the empirical point of view, how would the Doctors of Salerno School of Medicine, many centuries ago, we can say that we have enough evidence to say that certain dietary habits may be healthy. We also know well enough evil: that some diet errors can cause illness. But we should not expect too much from a science that is still in its infancy. From a practical standpoint, we have to go to a few elements essential and I shared when we give instructions to our patients, limiting the essential advice to those trying to customize them also on the basis of elements of clinical and physiopathological  reasoning  NOT encoded by the guidelines or the EBM ( cave canem,  without giving too much weight to a myriad of studies and experiments, each one seemingly plausible but all together completely impossible. For example: if you do the sum of all the proven benefits in GCP published (on dietetic products and nutraceuticals) you will always result in eternal life and perfect health in all men, and yet.........

Prasad, The original description of the sIgM -/- mice is described here. The apoE -/- and LDLR -/- background should not directly affect the immune system. You may be observing differences in the mechanism of atherosclerosis development. Have you considered the comparing atherosclerosis in the 2 different apo E -/- mice on a chow diet where the development of atherosclerosis will be slower?    http://www.jimmunol.org/content/160/10/4776.full.pdf+html

In my view first of all see its interaction with the ligand already attached with the complex at pdb database or you can visualize it on chimera or some other visualiztion software.

In order to assess its activity docking can be done on different ligands or biomolecule that enhance the or decrease AMPK activity. Docking score will give us an idea or extent at which this molecule is expressed in different condition

The  topic  is  worth  investigating.

With  echocardiography  the  epicardial  fat  thickness  can  be  easily  quantified  in  a  reproducible  manner.

Establishing  a  cut  off  value  for  predicting  metabolic  syndrome  and  coronary  arterial  disease  may  need  a  triad  study  involving  epicardial, visceral  and  subcutaneous  adipose  tissue  and  then  correlating  them  individually  with  certain  biomarkers,  in  a  longitudinal  study.

This  triad  study  will  involve  2D  or  3D ultrasound  for  visceral  and  subcutaneous  adiposity  and  echocardiography  for  epicardial  adiposity. It  would  be  reasonable  to  do  it  that  way  to  be  sure  of  the  best  predictor   for  metabolic  syndrome  and  coronary  artery  disease.

We  did  a   little  work  on  visceral  adipose  tissue  quantification  with  ultrasound  which  will  still  be  developed  in  future. 

The  link  below  may  be  helpful.

Thank  you.

Foamy macrophages (gitter cells) do migrate out of the MS plaque into the perivascular space and then into the blood stream.

hi Li, could the attached review help you?   

Dr. Kar thanks for the answer. We will be waiting for the manuscript to better understand the mechanisms involved.

I believe in it. Do you think it is possible to develop strategies to measure the diferents sizes of HDL and establish its impacts in the development of atherosclerosis?

Thank you Dr. Mishra for yours considerations, with which I agree. Let's wait for the new studies to establish the behavior improvements .

Stop researching risk factors and get into prevention. If you want to research risk factors, find a disease we haven't already studied to death. 

Data from population studies dating back from the Framingham study/substudies among others demonstrated quite clearly that a sedate lifestyle and a diet high in calories were risk factors for the development of atherosclerosis. I am not aware of any studies looking specifically at "screen time" which I assume you mean computer screen time but any such activity, whether watching TV, playing video games or what have you that limit physical activity will have the same effect of classically measured low activity lifestyles. I am not aware of a US study on the effects of weather but the Scandinavians may have conducted a few.

Dear Peter,

an expert in your field of interest would be Dr. Wolfgang Miesbach, head of the hemophilia clinic at the university clinics of the Goethe University in Frankfurt/Main, Germany.

If you can send an email directly to m.mueller@blutspende.de, I will send you his mail address.

Best,

Markus

Each organissation develops their own clinical guidelines. Depending on your research you should target each country and the national organisation in charge of developing the guidelines. For Spain you can find the information on this website: :http://portal.guiasalud.es/web/guest/guias-practica-clinica. they collect all the different clinical guidelines developed by the different regional governments (17 in Spain), so usually if they exist you can find them on this website, if not I;m afraid that you should contact each autonomous community  one by one.

You could contact Guia Salud (through the website)and ask if they keep track of old guidelines.

For European Countries having different regional health governments (Germany, Italy) you will probably face the same problems of non-centralised information.

For UK, they use the guidelines of NECP , ATP III, as mentioned ,through the NIH you can find them easily on their website, the one I found is from 2002 and I also  found an 2004 update in an interesting  article: http://www.nhlbi.nih.gov/files/docs/guidelines/atp3upd04.pdf    ,page 237

Triton WR-1339 reliably induces hyperlipidemia in rodents treated with it without fatalities unlike triton X-100 which kills animals as a result of its attendant hemolysis for which it is notoriously reputable. 

From the perspective of mechanistic systems biology and kinetic modeling, we always want to know what separation technique was used to define lipoprotein fractions. Michael's answer is right on target for ultracentrifugation because protein composition will change in the ultracentrifuge. 

A related question that we worry about is: Shouldn't we expect a continuous distribution of lipoprotein size at least for the apoB100-containing lipoproteins? Since LPL and LCAT and PLA2 and CETP and other intravascular processes are constantly modifying lipoprotein composition, we build our models with each lipoprotein species (defined by density or size or apoprotein composition) permitted to have variable lipid composition. The question then becomes: Can we account for the measured compositional and kinetic data given what we know about the intravascular processes AND the characteristics of each subfraction as defined by the separation technology?

I am not unbiased, as you can imagine. The answer also depends on your objectives. I am skeptical about the distinction about aging and age-related diseases and also try to avoid going to semantics. There are many biomarkers of aging but all they are "weak", in a sense. Using the frailty index approach we can find a summary measure that is much superior to any single biomarker.  Aging is a systemic property of the organism therefore any assessment should also be systemic, i.e. to combine available information.  Such information can be based on clinical assessment  or even self-reports but also can be more "objective". Take a look at the recent paper Howlett et al. BMC Medicine, 2014 where the lab tests were combined together in a FI-Lab. To go in this direction you should not hate math, although math is very basic.

Arnold

Many of these originate in the stump of the ductus and are grossly mobile. They usually are discovered because of embolic presentation. Many can be very large. We resect these by open operation.

The ones that are just layered along the more distal aortic wall we watch with serial CT scans. We do not really know a cause for these.

The original question was what do we have to monitor with high statin therapy. If we use other therapies may other metabolic Parameters would also have to be considered. In statin therapy I would monitor lipids, glucose and HbA1c, ALAT, may be  CK (at least at the beginning) and eventually hsCRP.

In addition to the previously mentioned answers, I would like to add the following information;

Through PPARγ binding elements in the promoter region of their genes, PPARγ has been reported to upregulate the expression of Catalase and superoxide dismutase.

This may be helpful.

Ref:

Okuno Y, Matsuda M, Kobayashi H, Morita K, Suzuki E, Fukuhara A, Komuro R, Shimabukuro M, Shimomura I. Adipose expression of catalase is regulated via a novel remote PPARgamma-responsive region. Biochem Biophys Res Commun 2008; 366:698-704.

Girnun GD, Domann FE, Moore SA, Robbins ME. Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter. Mol Endocrinol 2002; 16:2793-2801.

Gong P, Xu H, Zhang J, Wang Z. PPAR expression and its association with SOD and NF-κB in rats with obstructive jaundice. Biomed Res- India 2012; 23 (4): 551-560.

TNF-alpha,  IL-1 beta

It is true that a lot of factors play a role and also that the morphology of coronary dominance will probably not influence directly the pump rate. But i can imagine that one or another morphology can influence the blood flow of some smaller parts of the myocardium (for example in the interventricular septum) and in that way some parts can get their oxygen in a more efficient way than other parts. Which could have its repercussions on sustained efforts. These are just assumptions, but I thought to myself that it might be interesting to look at coronary dominance in this context. Gr Tim