Cardiac Function - Science topic

Did you get a satisfactory answer to this, or do you still need one?

The best explanation I ever found was by Peter Backx on youtube. He goes through both activation and inactivation on his channel. This is the link to his inactivation one. Let me know if you need anything else cleared up.

https://www.youtube.com/watch?v=5CH5iGdTOis&t=519s

Yes, you can estimate LV compliance from single P-V loop at steady state. The limitation Is it’s accuracy Issue.

Dear Emily,

If you mean that myths can affect people's lives, I have no problem with that. I also agree that is probably what has inflated the popularity of the polyvagal speculations. Wampold, in his work, makes a very convincing case that improvements in psychological wellbeing don't rely very much at all upon the method (or, perhaps, ritual would be a better word) chosen: improvement has more to do with having some ritual one believes in, a practitioner of it who seems competent to the client, a joint plan and goals, and maybe most importantly an atmosphere of trust and compassion.

However, my problem is that the ritual becomes conflated with science in this case, and the scientific aspect is used to sell the approach, when all the scientific evidence speaks against the speculations. There are, I hope you will agree, multiple myths that could be invoked to explain the various conditions to which you allude. Why not construct an explanation (myth) more consistent with what we know? That would provide, in my opinion, a much healthier approach for the therapy (i.e. ritual), as well as the societal acceptance of it, in the long run. Right now, what might happen to a client who has gone through a therapy with a polyvagal explanation (and who believes in "science" as the new religion) when they eventually read that in the New York Times that the polyvagal ideas have been thoroughly debunked? What happens to the credibility among scientists of a potentially helpful therapy (ritual) when the underlying scientific premises are thoroughly falsified, as seems to be happening. I don't think that is good for anyone. And I strongly believe one could adjust the vagal myth, employing autonomic explanations that have been around for at least a century before the polyvagal speculations were suggested. That is all I am trying to get at.

Sorry, this is probably too late now, but can I ask you what perfusion pressure you are using? If the heart is hypoxic, it may manifest more ectopy. If you turn off the stimulator after the recording, what is the spontaneous HR? If it's low (150-180), it might be an indication of underperfusion, perhaps?

Dear Stephanie,

this is what I use;http://eurheartj.oxfordjournals.org/content/ehj/26/9/865.full.pdf

Sometimes there is a disctepancy between the mannual calculation and thw calculator.

Dear Eliana inversion of the P wave not  could explaine MI of any localisation. Best regards.

Dear Ashish Rohila,

HRV does not allow the diagnosis of any disease. HRV has limited predictive capabilities. It is much better to think about the HRV, as a method for investigation of sinus node physiology.  When someone is interested in the mechanisms HRV, he will have to learn a lot of related issues, such as baroreflex, the extracellular matrix of the heart, synaptic transmission, etc. The researcher, who painstakingly examines the sinus node anatomy, its autonomic innervation and molecular machinery of cellular pacemaking, can much better understand nature of cardiac arrhythmias.  And not only the arrhythmias but also many other diseases. That's why I love HRV, for the breadth of physiological concepts!

You mean have it functional for 24h ? This is quite impossible. Unless you perfused it in a very controlled environment with reconstituted blood (I mean washed red cells resuspended in an adequate media and equilibrated for O2 and CO2 content and so on...) Look to my publications, the one by Stucker. You'll get the info.

I think this phenomenon has 3 reasons :

1. Rich blood supply (oxygen-rich tissue)

2. High numbers of mitochondria

3. Presence of myoglobin

I will go through them. Thanks.

Looks like you have diagrammed a classic "windkessel". The pressure in the balloon should increase if the balloon's outlet is closed ( analogous to isovolumic contraction). Open up the  balloon outlet's per Johns suggestion and pressure will rise when pump  volume delivery rate exceeds ejection rate (the strong ejection phase)- and balloon pressure will fall  when ejection rate exceeds  pump delivery rate (weak ejection)

Zahran,

Some differences in sensitivity of detection within your experiments (batch to batch variation) are not uncommon. But 10-100x difference is not something you should accept. I expect that you have already tested increasing number of washes etc (with detergent containing buffer) - helps reduce the non-specific binding, thereby increasing signal to noise ratio.

As for what someone else published, this is where it gets a little tricky. It could be because your conditions are not optimized well enough - this is one extreme.  The other extreme scenario is the published procedure represents the best results they ever got, and readers get the impression that they represent typical results.  ;)

If you must have higher sensitivity, there are many ways to achieve it. All of them will require fair bit of testing, as you test by changing one variable at a time, be it concentration of 1º, 2º antibody, number of washes etc. There are also possibilities on the detection end - for example, try a conjugate where you can use chemiluminescence or fluorescence.

Hi Davi,

In our lab we isolate cardiac fibroblasts from adult rats. The procedure we follow is:

1. Perfuse the heart in a Langendorf system for 5 min.

2. In a sterile hood wash the heart with sterile PBS.

3. Mince the heart as much as posible using a scarpel.

4.Incubate a 37ºC in digestion solution (Collagenase type II ( 1mg/ml) + protease type XIV (0.1mg/ml + 10µM CaCl2 ) for 25 to 40 min. The time depends on the heart; usually 30 to 35 min will be enough.

5. Stop digestion using 2% FBS diluted in calcium free tyrode. Same volume as digestion solution.

6 Centrifuge for 10 min to 400G

7 Discard surnatant, resuspend the cells in DMEM FBS 10% and plate the cells in 2 T25 Flasks.

8 Three hours later, wash the culture with PBS and add fresh culture media.

Dear Josè i'll report an article (with citations) i found in this book:

Clinical Approaches to Tachyarrhythmias; Mechanisms of Arrhythmias Pag.18-20.

[...] By infusing dogs with cesium, pleomorphic ventricular tachycardias resembling torsades de points have been induced⁶⁵. In such animals, oscillation resembling EADs have been seen in epicardial recording of monophasic action potentials^66,67. Similar observations have been made in the dog's ventricle subjected to sudden outflow obstruction⁶⁸, in cats during ischemia and reperfusion⁶⁹, in humans undergoing valvuloplasty for pulmonary stenosis⁷⁰, and in humans with prolonged repolarisation and the long QT syndrome⁷¹. [...] The arrhythmia most likely caused by EADs is torsade de pointes, a nonsustained ventricular tachycardia with a characteristic ECG pattern, where QRS complexes twist irregularly around the isoelectric line. It is frequently associated with a long QT interval and bradycardia and is often initiated by a premature beat following a long cycle^73,74. The characteristics of this arrhythmia and the fact that it may occur in patients taking antiarrhytmic drugs that prolong the action potential duration strongly support the notion that is caused by triggered activity based on EADs⁷⁴. Another argument in in favor of this mechanism is he fact that the most effective treatment in patients with an acquired long QT syndrome and torsade de points is pacing, which shortens the QT interval⁷⁴. In addition, magnesium sulfate is effective, and this may be related to suppression of EADs⁷⁵. Still, reentry based on dispersion of refractoriness⁷⁶ and multiple foci, either automatic or triggered⁷⁷, are possible as well.

In summary, Arrhythmias caused by EAD-induced triggered activity should appear as the heart rate slows and disappear as the heart rate increases. Predisposing factors are pauses, low extracellular potassium concentration, and situations where action potentials are prolonged (long QT syndrome and excess use of class III antiarrhythmic drugs). They should be suppressed by drugs that blocksodium and calcium currents, by magnesium, and by adrenergic blockade.

65. Brachmann J, Scherlag BJ, Rosenstraukh LV, Lazzara R. Bradycardia dependent trigger activity: relevance to drug-induced multiform ventricular tachycardia. Circulation 1983;68:846

66. Ben David J, Zipped DP. Differential response to right and left ansae sublaciae stimulation of early afterdepolarizations and ventricular tachycardia induced by cesium in dogs. Circulation 1988;78:1241

67. Levine JH, Spear JF, Guarnieri ML et al. Cesium cholride-induced long QTsyndrome: demonstration of afterdepolarizations and triggered activity in vivo. Circulation 1985;72:1092

68. Franz MR, Burghoff D, Yeu DT, Sagawa K. Mechanically induced action potential changes and arrhythmias in isolated and in situ canine hearts. Cardiovasc Res 1989;23:213

69. Priori SG, Mantica M, Napolitano C, Schwartz PJ. Early afterdepolarizations induced in vivo by reperfusion of ischaemic myocardium. A possible mechanism for reperfusion arrhythmias. Circulation 1990;81:1911

70. Levine Jh, Guarnieri T, Kadish AH, White RI, Calkins H, Kan JS. Changes in myocardial ripolarization in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis: evidence for contraction-excitation feedback in humans. Circulation 1988;77:70

71.Bonatti V, Rolli A, Botti G. Monophasic action potential studies in human subjects with prolonged ventricular repolarization and long QT syndrome. Eur Heart J 1985;6 suppl D:131

73. Dessertenne F. La tachycardie ventriculaire a deux foyers opposés variables. Arch Mal Coeur 1966;59:263

74. Leenardt A, Coumel P, Slama R. Torsades de Pointes. J Cardiovasc Electrophysiol 1992;3:281

75. Bailie DS, Inoue H, Kaseda S, et al. Magnesium suppression of early afterdepolarisations and ventricular tachyarrhythmias induced by cesim in dogs. Circulation 1988;77:1395

76.Surawicz B, Knoebel SB. Long QT: good, bad or indifferent? J Am Coll Cardiol 1984;4:398

77. Naumann d'Alnoncourt C, Zierhut W, Lüderitz B. "Torsade de pointes" tachycardia: Re-entry or focal activity? Br Heart J 1982;48:213.

I hope to be usefull.

Best regards

Giacomo Rozzi

The location and relative magnitude of the first and the second aortic pressure peak is a matter of interaction between forward and backward flow and pressure waves.

Although forward waves are less variable (at least when speaking of their shape in their first moments), the amplitude and timing of their reflections is very complicated. Taking into consideration a number of paper about wave trapping, re-reflection, etc., only reflections originated somehow close to the ascending aorta are able to impact in a considerable manner the ascending aortic waveform, thus determining the type of the shape. High reflection patterns create type A waveform, while low reflections result in a more type C aortic pressure wave. It is important to underline that type A and type C refer to aortic waveform, and have not meaning at radial artery, although surely aortic shape influences the radial one.

Considering these wave phenomena, it is unlikely that a lumped model can faithfully reproduce all these very characteristics details of a specific person. What you can obtain is a lumped representation of the heart load, which will derive from the choice of the parameters describing resistance, inertance and elastic properties. As you will not deal with any local properties which would results in a subject-specific reflection patter, I think that you will not be able to differentiate between type A and type C aortic waveforms.

I work with Kubios Software. If you transfer your data in a .txt file it would be working.

Not at all. As you indicate, Ang II is made by the sequential actions of angiotensinogen produced largely by the liver; renin, made by the kidney; and ACE, present in many cells and predominantly in lung endothelial cells. ACE levels in the heart might be important for local conversion of ang I to ang II, but will not reflect systemic Ang II. Also, AT1R mRNA in the heart might reflect local expression of the receptor's mRNA, but would not reveal systemic AT1R or the protein levels. A good journal would reject any notion that cardiac levels of these reflect Ang II "regulation".

PVCs are generally not an issue unless they are extremely frequent. Bradycardia is a concern as the sensitivity and positive predictive value of the test is greatly affected by the heart rate attained when the patient is on the treadmill. If the patient is unable to exercise a drug such as dobutamine may be used as it mimics the effects of heart rate  and BP produced by exercise. The arrhythmia that is of most concern is atrial fibrillation as the irregularity of the rhythm results in many beats not being counted or being double counted. Gating is helpful but does not totally solve the problem with atrial fibrillation.

Thanks all. I'm looking for an automated method to define the ROI (left ventricle) for tagged MR images.

To Aymeric Histace, I think the paper you recommended me is useful to me. I'm interested with the mean-std image method which I have personally tried to apply. But I ran into some problem. I've attached the image of the mean-std image below. The mean-std image i generated does not show a a significant contrast between the cavity and the left ventricle wall. I think I'm doing it wrong or missing some steps.

Here are the steps I have taken using Matlab to process the image.

1) compute local mean image using 'conv2' with kernel size N=11

2) compute local std image using 'stdfilt' with kernel size N=11

3) compute uendomap(i,j)=w_m.m_N(i,j) - w_o.O_N(i,j) with w_m=1/3 and w_o=2/3 where wm+wo=1 and wo/wo=2.

Any help is appreciated as I might adopt this method to localize my tagged MR images for my coming paper. Thanks.

See the relevant chapter in my wonderful new book. CARDIORENAL CLINICAL CHALLENGES.  Eds Goldsmith, Covic, Spaak. Published by Springer Jan 2015.

I am less and less inclined to believe that lowering heart rate with pharmacological interventions can lower cardiac risk. As you state in your question, higher heart rates are strongly associated with reduced cardiorespiratory fitness. Simply giving a drug can't and won't change that. Recent studies do not suggest beta blockers help much for patients with CAD or recent MI; however, there is still compelling evidence that they help for patients with systolic CHF so I can't write them off completely.

As stated by the previous interventions, it is only possible to evaluate the linear systolic PV relation with PV measurements under varying load. Load can be varied with caval occlusion but also with pharmacological interventions, provided that the latter does not affect contractility. 

There is also an evaluation of the systolic ventricular elastance on a single beat analysis, which was developed by Dave Kass' group. Chen et al. PMID: 11738311. We used this method non invasively in a population of 2524 subjects and it worked quite well (PMID: 17287452). 

I am really interested in this problem, especially in the context of muscle pain and chronic fatigue syndrome. The mechanisms controling blood flow in the microcirculation are perfectly described in physiology text-book by Traczyk (unfortunately in Polish).

Briefly, they involved release of metabolits, .e.g. ADP, that cause dilatation of precapillary arterioles, which in turn causes increase shear stress affecting bigger arteries, e.g. femoral artery, and their dilitation (via NO secretion). Together with these regional changes, there is an activation of the sympathetic nervous system, which additionally drives flow to regions of increased demand.

Hank you- that has been my concern- having the right preparation and equipment to be efficient and to not waste energy (literally!) as well as potentially create erroneous counterproductive lesions.

i think SCI is usuless for CRT planing,

From my experience slow flow phenomenon with normal coronary artery mostly duo to endothelial dysfunction and vasomotor change in coronary vessel, so I noted marked improve in symptomatic patient with calcium channel blocker like amlodepine, and dual anti platelet colopedogril and acetylsalicylic acid, without extra benefit gained from VIT K antagonist anticoagulant

The short answer is no one can be sure. There are valid concerns that removing the MR off-load mechanism will lead to increased LVEDP as the underlying cardiomyopathy is still present. Right now, we have to approach each case individually. In my limited experience, MitraClip can and does help patients with cardiomyopathy and functional MR, and some patients improve from NYHA Class III-IV to Class I. Of course these are only isolated cases. One could assess for presence of myocardial reserve before proceeding with MitraClip.

You can use Cardiocode for that. It’s possible to accurately evaluate the IVS and myocardium contraction and all the hemodynamics, data on acid-alkaline balance status of the heart (including blood glucose level) are also delivered. Please visit www.cardiocode.ru for more details. We’ll be glad to help and cooperate.

Dear Fahmi, thank you for sharing this unlucky case. Ill-fated cases are seldom reported in the literature. However, strokes in patients with prosthetic heart valves and/or atrial fibrillation despite adequate anticoagulation are not rare in my experience, so they are undoubtedly worth of discussion. I would add some personal thoughts to this discussion. 1) If this case would have been included in a clinical trial, I would probably adjudicate the death to heart valve thrombosis. Sudden death is not the usual clinical presentation of ischemic stroke superimposed bleeding. 2) A two weeks period of warfarin suspension is reasonable when facing a very large brain infarction, but this seems to me a too long time for a patient with a mechanical valve. 3) To my knowledge the only result one can expect from a prophylactic dose of LMWH is the prevention of deep vein thrombosis. 4) In my country, no LMWH is licensed for use in atrial fibrillation or in patients with mechanical heart valves, at any dosage. This is a very relevant legal pitfall. I would therefore have preferred standard heparin in continuos infusion, with close neurologic monitoring, resuming warfarin as soon as possible under clinical judgement. I agree with José, since unfractionated heparin is easily stopped if the neurological state deteriorates. 5) You've certainly done the right thing in daily monitoring with echocardiography. I agree also with aspirin.

Dear Dr. mishra

I fully agree with you regarding the pharmacokinetics, and I wish dearly if the physicians understand drug metabolism because a lot of drug interactions and reactions depends on that. I have suffered a lot with even graduate students to put things together and link pharmacology with biochemistry, kinetics and mechanism of action but they dont see the value. May be future physicians will learn. Good luck