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Posts Tagged ‘cardiac interstitium’

LVH is supposed to produce tall R waves . But , we know  often LVH is misdiagnosed as   myocardial infarction especially  anterior MI.  (With deep q waves*  in v1 to v3 and sometimes q in inferior leads as well)

Infarct tissue  is a  cluster of dead cells  , while  LVH is a bundle of live cells . How can the ECG produce similar changes  in both ?

One need to realise ,  ECG does not function  as  a tissue identifying  machine.  It’s job is to simply  tell which direction the current  is traveling with reference to the  recording electrode .

If it comes towards  the electrode ,  R  wave is recorded and  if it goes away Q is recorded.

In infarction it is obvious the dead cells  form a distinct electrically inert  window so that the  muscle  mass located in the opposite pole  (If viable ) will record  q waves.

In LVH  how the  direction of  current get reversed ?

We know,  cardiac muscle  is made  up of not only myocytes , it is enriched with, fibroblasts, interstitial cells, collagen and other extracellular matrix .These non contractile cells have little electrical energy to show off.  In physiological LVH there is  not much proliferation of interstitium . It simply  reflects hypertrophy of  individual contractile units. It robustly produce good quality electricity and the ECG inscribes a tall r waves

Causes of  physiological LVH include

  • Athletic heart
  • Many of the hypertensive patients
  • Early stages of Aortic stenosis
  • Any LVH due to increased loading conditions( In the initial stages )

Pathological LVH

Here  LVH  is predominately  due to  proliferation of fibroblasts  and interstitial cells  .This interferes with the alignment of sarcomeres of myocytes. When the  architecture of contractile units  are  altered ,  it finds difficult to generate good quality action potentials  . Since the ECG is the summation of action potentials  ,  it gets distorted  with local delay,   notch ,slur etc . Ultimately it many  cases q waves are inscribed .

Th  q waves ,  gets amplified by the fibrotic process which is  technically dead cells for the ECG machine at least !.

Note: Pathological LVH grows well with excellent nourishment from ACE gene dependent growth factors. In fact , who will develop pathological LVH  (and who will not  )  is  predetermined by our ancestral genes.  (Other wise called fate or destiny  !)

Conditions  causing pathological q waves

  • About 10% of  LVH due HT can manifest q waves
  • HOCM
  • Late stages of Aortic stenosis
  • Some cases of Diabetic HT combination
  • HT with CKD

* There is one more cause for q in LVH .This is technical .   As  the  heart rotates counterclockwise ,  septal activity instead of  recording a r wave  ,  merges  with the s wave mimicking q waves. In fact this could be very common cause for labeling LVH as MI.

Final message

Q waves are not sacred to diagnose MI.It can be generated  even by live myocytes  when it behaves like an  electrically dead ones.

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Human body is made up of trillions of cells. Some of these cells are specialised and connected together to form various organs.The cells that connect each other  provides the   structural  support  and   maintain the organ   shape  and function.  Traditionally  these supporting cells were  thought  to have little functional role. Now it is well recognised these cells   could be as  important as  the myocytes or   hepatocyte . God  has  never created any of the human cells with  out any purpose . They may  have  important paracrine function.  Healthiness  of these interstitial cells are vital for the intercellular communication, cell nutrition  and it’s  proper function . These cells are called by  various names , the old  terminology could be the connective tissue -the tissue that connects  cells. Many times  fibroblasts is the common name given to all interstitial cells . Interstitium is not only filled with some bizarre mesenchymal cells it is also a  depot of  sticky molecules.  Now we have  deeper knowledge about these  , and identified various intercellular adhesion molecules, matrix metallo proteins   , vitronectins, etc.

cardiac interstitum intersitial fibrosis amyloidosis

It is  a great  medical paradox   the specialised the myocytes, hepatocytesaxonal cells are given  due respect,  while the role of  cells and molecules that bind them together is least  appreciated . In fact in any given organ the functional cells constitute  only one third  of it’s weight.In the heart myocytes form only 30% of it’s weight. It is a clear cut case of discriminating the majority !

Interstitial disorders and  diseases

In the lung Interstitium becomes very much important because the gas exchange has to  traverse the interstitium and enter the alveloar cells. So any abnormality  here  is immediate and profound.The diffusion capacity reduces  .Patients  develop  progressive COPD.

In the kidneysinterstitium has a functional component as the absorbed fluid and electrolytes  has to reach the blood circulation .Hence  acute and chronic interstitial  nephritis are distinct clinical  entities .

In the brain dysfunctional  inter neuronal cells can interfere  with various CNS  functions dementia the major  disorder  id thought mainly contributed by the interstitial fibrosis.

cardiac interstitum interstitial fibrosis myocardial

So when each of the vital organ has a potential  to suffer from  interstitial    pathology How can heart  alone escape ?

No, it does not . The  currently popular entity   , heart failure with normal ejection fraction   could be nothing but   chronic  interstitial  carditis. or chronic progressive interstitial  fibrosis.  Hypertensive heart disease is a major cause . CAD can also contribute .

The interstitial  fibrosis  is also a feature of  dilated and restrictive cardiomyopathies. (Classical amyloid heart disease ) .Initially  these fibrosis do not affect the  contractile  function of  myocyte .In later stages it encroach  upon the contractile  cells and impair the EF. This explains  the natural  history of many of the RCMs which   go for dilatation and contractile dysfucntion in terminal state.

What is the difference  between myocyte relaxtion and  cardiac  relaxation ?

  • It is now recognised , cardiac  interstitium has a big  role in relaxation .
  • Cardiac relaxation is not synonymous with myocardial or myocyte relaxation .
  • For  myocyte to  relax ,  it has to eject back the calcium from the actin myosin complex  into the  sarcoplasmic reticulum where the calcium uptake protein   phospholamban holds it till the next systole.
  • As the myocyte relaxes  it has the additional  burden of stretching &  relaxing the adjoining  non myocytic cells  , unfortunately this   weighs 70% more than it’s own weight .One can imagine how much the heart is stressed during  even diastole ! So as  the sheets of myocytes feel the diastolic interstial stress the whole LV struggles to relax and LVED raises and diastolic dysfunction begins to set in.
  • The interstitial l plasticity and elasticity is vital for cardiac chamber to  reach it’s pre contractile  state . It is now recognised the rate of LV relaxation  (Negative dp/dt )  is directly proportional  to the interstitial  agility and turgor .

How to overcome interstitial  fibrosis and stiffness ? Anti fibrotic drugs ? .

We are in search for such a universal anitifibrotic drug that can work in liver fibrosis ( Cirrhosis ) lung  and myocardial fibrois. D penicillamine has  showed some promise. How to make the interstitial interface more flexible ? Collagenolytic agents , elastase MMP inhibitors etc may become the   future targets.  A much established  way to regress myocardial fibrotic process is ,  with ACEI and aldosternoe antogonists. (EPESUS, RALES study) .Some of the   anti myocardial remodelling  action of  ACEI is attributable to it’s  anti  growth factor properties and can  the resultant regression of  interstitial fibrosis.

Apart from the look out for sophisticated drugs ,  applying common sense can do  a “great deal of good “for the myocardium in  diastolic cardiac failure  . A stiff  skeletal muscle need physiotherapy. A stiff cardiac muscle will also   need exactly this. For  cardiac muscle physiotherpy can not be administered by a therapist  ! , we have to do it  , regular  exercises   to make it contract  and   relax  fast . So ,  it is important to recognise  exercise   prescription and training  could be the  most  important modality  for preventing progression of diastolic heart failure.

Clinical situations  where   cardiac interstitial pathology is  relevant

  1. All forms of cardiac failure
  2. Some forms  of myocarditis
  3. Myocardial interstitial  edema ,Post MI/Reperusion
  4. Myocardial interstitial edema mediated no reflow following primary PCI
  5. Acute and cardiac transplant rejection
  6. Drug induced adrimycin carditis .
  7. Cardiac interstitium arrhythmias : Many of the cardiac arrhythmias are due to re entry circuits mediated by cardiac interstitial fibrotic substrates.
  • Atrial fibrillation
  • Post MI ventricular  tachycardias

Final messge

Deep dissections  of  pathological hearts   in pursuit of   culprit cells has surprisingly ,  lead us  not into myocytes and conducting  cells but into inter cellular spaces” . There is  big secret  world over there within the cardiac interstitum.Young scientists and students  argued to   explore and unravel the mysteries !

Reference

A landmark article in Circulation 1991

Pathological Hypertrophy and  Cardiac Interstitium  Fibrosis and Renin-Angiotensin-Aldosterone System
Karl T. Weber, MD, and Christian G. Brilla, MD, PhD

http://circ.ahajournals.org/cgi/reprint/83/6/1849.pdf

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