Archive for the ‘cardiac embryology’ Category

William Heberden first introduced the term angina to the medical community in 1772. His descriptions became immortal. Still, no one would ever know what was the angina-related artery, Heberden was alluding to.

Now, some jobless cardiologist is asking this question after 200 years. How is angina from the LAD system differ from the RCA  system? or let me put it another way, How does angina of anterior circulation (LAD) differ from posterior circulation (RCA/LCX)? Though there is distinct hemodynamic profiling of RCAvs LAD ACS, surprisingly, cardiology literature does not answer the chest pain aspect of it. One rare study, done  4 decades ago throws some light

Here is a curious little study, with a simple & crisp conclusion.

chest pain and IRA localisation angina LAD angian RCA

It concludes, that LAD angina rarely radiates to JAW or epigastrium. While RCA angina relay radiates to the left shoulder.

So, why does this happen?

What I could guess is the ubiquitous vagal fibers that travel in the posterior aspect of the heart, and carries pain signal directly up to the jaw whenever these areas become ischemia. LAD is less likely to irritate the vagus. Of course, there can be a definite overlap.

OMG, give me some time to keep in touch with  basic science 

Now, fellows of cardiology, please take a  pause from your regular aggressive cardiac cath lab workouts and get a break at least once in a while. How does the ischemia of myocardial tissue generate pain? Why it is severe in some, trivial in others, and even dead silent in some, 

The chest pain genesis is initiated by sensory electrical neural action potential, that captures the epicardial neural plexus first, switching over from somatic to the visceral pathway and trespassing the para ganglionic plexus and traveling further to the spinal cord. Where it may collide with other incoming sensory signals ascends in specific myelinated and non-myelinated neural cables, reaching the brainstem, interacting with local nuclei, and finally reflecting on subcortical and cortical pain matching centers.  We haven’t yet located the exact center for anginal pain. (Perithalmic and amygdala could be closer to real centers) 

So, it is a really complex sensory world yet to be understood fully. Mind you, I haven’t touched upon the neurophysics of referred pain, linked or clandestine angina.

  • What is the effect of cardiac denervation, autonomic neuropathy, or on the perception of chest pain(Does a quadriplegic feel angina ? or post-transplant heart immune to angina ? (Gallego Page JC,Rev Esp Cardiol. 2001) 
  • Is it biochemical or neural, can substance P in blood cause pain hitting the amygdala? 
  • Will hypoglycemia and anemia cause angina due to lack of glucose and oxygen?
  • Finally, how is Infarct pain is different from ischemic pain (Ischemic)

Where do get the answer to these questions?

This paper from Dr. Robert Formean(Ref 2) university of Oklahoma is just the best source I think, to explore and understand the topic. (Reading time 60 minutes: Let me tell you, it is worth more than a time spent on an insignificant angioplasty of painless PDA lesions)

Final message 

So, what have you learned from this post? Does this question about angina matter at all? Surely not. in this space-age cardiac care where we are right inside the coronary even before we listen to the patient’s complaint properly. We are always at liberty to do what we want( or love) to do. But, the urge to understand the foundations of clinical science is the last remaining hope, that will keep the specialty of cardiology enchanting. 

A comprehensive reference for the genesis and signal processing  of chest pain 

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Though heart is known primarily as a pump, it is the four cardiac valves that ensures the critical , non-stop unidirectional flow that sustain the circulation . It is to be recalled these valves originate in the very early days of cardiac development when the primitive heart tube loops , even as the chambers expand from primitive ventricle. Mesenchymal differentiation controlled by various genes that cleaves the valve from myocardial tissue.

While heart by itself is the supreme vascular organ ,  its surprising  few structures inside the heart , like the valves are quiet avascular ( or is it really so ?)

The valves that beat average of 30 billion time in life time ,seem  to get its nourishment from Nowhere ?

Layers of heart valve 


Image source : Huk D., Lincoln J. (2017) Oxidative Stress in Cardiac Valve Development. In: Rodriguez-Porcel M., Chade A., Miller J. (eds) Studies on Atherosclerosis. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Boston, MA

It’s primarily made up of  complex stratified connective tissue covered by endothelial cells with intervening interstitial cells. The extracellular matrix (ECM) layers are rich in elastin proteoglycan (spongiosa) and collagen (fibrosa). It has been found myocytes and dormant fibroblasts are scattered in the valve leaflets. This forms the basis of focal origins of  Cuspal Ventricular tachycardia J Cardiovasc Electrophysiol. 2002 Jun;13(6):551-6.  from electricaly activated myocytes.

Is there a dynamic cell turnover within the valve tissue ? Where does it get the nourishment ? What is the effect of  aging and CAD on valve tissue ? 

There is growing evidence for valvular extra cellular  matrix are indeed dynamic. This explains valvular lesions in connective tissue disorders like Rheumatoid arthritis. Progressive degenerative changes of aging  involves  remodelling , tissue engineering . Calcification of cardiac valves in endocrine disorders like  hyperparathyroid states implies  cardiac valvular interstitium is in continuum of systemic metabolic pool. There has been very little published evidence  correlating  CAD and Ischemic degeneration of valve.

Evidence for vascularity of valves

It is surprising , this simple question of  vascular supply to cardiac valves has  confronted the scientists for too long.

1.Histopathological and  autopsy studies have revealed vascular channels.(Harper 1938 BMJ)

2.X-ray projection microscopy was used to image the valves after injecting radio opaque microparticles in the ascending aorta. This is probably the one of the few original studies done in UK in 1968 (Clarke et al ) it revealed significant  vascularity of the valve .It was found 16 % the tricuspid valve, in 10% of the mitral valve, and was maximum in Aortic valve (24%).

3.The fact that statins reach the Aortic valve tissue in lipomatous Aortic stenosis indicate significant vascular port of entry to valves.

Direct evidence : Why don’t we ask the surgeon ?

When I asked my surgical colleagues  Does the valve  bleed  as they cut it  ? Most of them were amused with my query , still Iam not sure I got the answer right. At least one of them said since the heart is on pump ,  it won’t bleed any way !


Conclusive evidence : From a 1968 study 

It is academically humiliating to note we have to go back 50 years in time to get a proof for vascularity in cardiac valve.(Or anything new I am missing ? readers may share !) I think , this is strongest proof  for valve cusps are supplied by end coronary arteries. However the penetrance is not deep into all layers of the valve and distally

Is hematogenous spread of Infective endocarditis(IE) occur ?

How does systemic infection reach the valves ? We still believe the IE is due to direct colonisation from circulating blood .Hematogenous spread of IE do occur but difficult to prove. It seems infection of valves primarily happen from outside initiated by  endothelial injury over the valves .

*There seems to be a contribution from  systemic bacteremia  reaching  from within through the pre-existing capillary twigs as well.(Evidence elusive !)


Final message

Is cardiac valves vascular ?  It is curious even in this era , we struggle to answer this query with certainity.

Yes, they are vascular structures , but at best it has partial vascular capillary network. It is also possible  the valves can live a durable life even without these vascular Innervation.(I haven’t heard of a condition called mitral valve infarct or necrosis in RCA/LCX STEMI which supply the base of the heart)

Still, this partial  vasculaity can become Important at times of pathology like infection or degeneration. Expecting more research in this unique area of valvular heart disease


THE VALVES OF THE HUMAN HEART BY   From the Department of Anatomy, University of Glasgow, Glasgow Brit. Heart J., 1965, 27, 420


3.Dow, D.R. and Harper, W.F. The vascularity of the valves of the human heart. J Anat193266610–617

4.Ritter, S.A., Gross, L., and Kugel, M.A. Blood vessels in the valves of normal human hearts: from a study of 700 human hearts. Am Heart J19283433–446

5. Saini N, Saikia UN, Sahni D, Singh RS.  Vascularity of human atrioventricular valves: a myth or fact? J Thorac Cardiovasc Surg. 2014 Jan;147(1):517-21. 

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