On The Pursuit Of Arterial Plaques

In patients of disorders of lipid metabolism as in metabolic syndrome, diabetes mellitus and hypercholesterolemia, cholesterol laden plaques develop in the lumen of arteries. These plaques hinder the flow of blood leading to peripheral arterial disease (PAD). The narrowing of blood vessel that occur gives rise to symptoms of intermittent claudication and rest pain. Intermittent claudication is characterized by pain of the lower extremities as the person walks a few steps. This may progress to rest pain which is continually present, irrespective of whether the person walks or not. These plaques may also restrict blood flow to the heart causing myocardial ischemia.

What happens when these plaques rupture or loosen and detach? Fatal myocardial infarction (MI) and stroke (Cerebrovascular accident) may result when the heart or the brain arteries are involved respectively. We know that dyslipidemia of diabetes predispose us greatly to atherogenous plaque formation. LDL (low density lipoprotein), particularly oxidized LDL is a grave offender in this regard. Now imaging modalities are at hand which will let us visualize these atherosclerotic events, in real time.

Inflammation by oxidized LDL and their ilks increase the production of TNF-alpha (Tumor Necrosis Factor) and IL-1 (InterLeukin-1). They in turn increase the expression of vascular cell adhesion molecule-1 (VCAM) and P selectin. These intracellular adhesion molecules kind of attract leukocytes, which bind loosely to the plaque. These are the ominous plaques seething to rupture and loosen.

Micro Particles of Iron Oxide (MPIO) targeted with anti-VCAM-1 monoclonal antibody (mAb) are now being used to probe and identify these lesions. While the monoclonal antibody will latch onto the antigen (VCAM) as a key fits onto a lock; the microparticles of iron will act as a marker when seen in NMR (Nuclear Magnetic Resonance) imaging. Also called MRI or magnetic resonance imaging, this technique detects the density and spins of protons (H+ or hydrogen nuclei). In areas where contrast is less, contrast agents are employed to get a clear picture. Now, a team from National Taiwan University has developed this technique which employs dextran-coated iron oxide nanoparticles tagged with anti-VCAM-1 to get a glimpse of whats going on inside arterial lumen. A combination of anti-VCAM-1 mAb and anti-P-selectin mAb (VCAM-MPIO-P-selectin) is also being developed.

Although we already have angiography, intravascular ultrasound, and optical coherence tomography to detect these plaques, the newer techniques will certainly throw more light on this insidious killer process within.

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The Circus of Arrhythmias

Everything goes well as long as the heart 'plays its own symphony' and 'orchestrates this opera with the elan of a master conductor'. Problems occur when there is a fault in the generation or conduction of this rhythm or both. Arrhythmias (aka dysrhythmia), an emergency, sometimes fatal, may occur.

Consider for example, that if the SA Node STOPS producing its impulse (sinus arrest), will we die then?
There are other parts in the heart which are capable of generating impulses. For example, in physiology, you can find two such in the His bundle itself; one proximally (near the SA Node) and the other distally (further away from the SA Node) in the His bundle. They produce impulses, under such circumstances. So, when the pacemaker of the heart ( SA Node) fails, we don't die as these centres take over. If you go down the hierarchy of impulse generating pacemakers from the SA Node, the pace of discharging frequency decreases. Proximal His bundle has a pace of about 45 beats per minute while distally in the His bundle the frequency is around 35. This really is a remarkable safety feature of the heart (another safety feature is that the heart muscle can not be tetanised).

Thus, in sinus arrest, the lower parts in the conduction system will start functioning (as the normal pacemaker fails), albeit at a reduced rate. When the SA node is producing impulses but these impulses are NOT being CONDUCTED to the atria (Sino-atrial exit block), a similar situation will result. The heart continues beating, but at a lower rate.

Broadly speaking, arrhythmias has been divided into two types: bradyarrhythmias and tachyarrhythmias. When the heart rate is less than 60 per minute, it is known as bradyarrhythmia (brady meaning slow) while in tachyarrhythmias (tachy=rapid), heart rate is above 100 per minute. Suppose on its conduction to the ventricles, the impulse faces a block, and no impulse is reaching the ventricles: a condition known as complete heart block or third degree heart block will result. The second-in- hierarchical command will take over then i.e. the centers in the His bundle will now assume function.

Since these centers have lower frequency of operation, they are dominated over by their high frequency cousins, 'the SA node'. Given their low discharge rates they are 'overdriven' by the SA node pacemakers. Thus when the SA node blacks out or there is a conduction disturbance, these lower centers don't resume spot on (because it takes time for them to 'recover' from the 'overdrive'). The ventricles beat at a low rate independent of the atria, a phenomenon called the Idioventricular rhythm, starts. It takes time for the ventricles to resume function. The brain passes out after about 5-7 seconds as it can not tolerate the hypoxia. the silence of the ventricles (No impulse means no contraction) and Stokes-Adams syndrome consisting of dizziness, vertigo (feeling of the head spinning) and syncope (fainting) may occur. The above are examples of bradyarrhythmias.

Tachyarrhythmias occur when there is enhanced automaticity ( exogenous or endogenous catecholamines, digitalis glycosides, hyperkalemia make the cardiac tissue more excitable), triggered activity (changed electrical property of the heart, triggered by factors such as early after depolarizations or EAD and delayed after depolarizations or DAD) and re-entry or circus movement. Normally, the impulse propagates unidirectionally. If a unidirectional block occurs along the conduction system, it may give rise to re-entrant arrhythmias. Also, in WPW syndrome (or Wolff Parkinson White syndrome) an abnormal bypass tract, called the bundle of Kent, connects the right ventricle with the atria. The speed of conduction through this aberrant bundle is more rapid than through the AV bundle. The impulse that goes forward (antegrade) through this bundle comes back to re-excite the atria (retrograde) through the normal AV bundle, establishing a re-entry circuit. The heart beats fast. In conditions such as atrial flutter (picture on the left), the impulse goes around and around, at rates as high as 200-350 per minute. In atrial fibrillation, multiple ectopic foci discharges, and that too in a haphazard manner. The rate of discharge is between 300-500 per minute. But not all these impulses will find their way through to the ventricles, since the AV node can not carry impulses more than 230 per minute. The diseased muscles of the ventricles, like their atrial counterparts, acquire the ability of self discharging giving rise to conditions as ventricular tachycardia and ventricular fibrillation, a very fatal outcome of myocardial infarction (MI), where the ventricles feel like 'bag of worms'.

Not all arrhythmias are pathological though. All sinus tachycardia, sinus bradycardia need not be considered a medical problem, since they may be found in cases of anxiety ( tachycardia) and in athletes (bradycardia) respectively. However, sick sinus syndrome, which presents with bradycardia is pathological.
Sinus arrhythmia refers to increase in heart rate with respiration. This is absolutely physiological. In fact, in diabetics sinus arrhythmia is absent. The human body is really puzzling!

You might be tempted to ask how does arrhythmia harm us anyway. Tachyarrhythmias make the heart beat so fast that it hardly has enough time to fill itself with enough blood for the system. The cardiac output fails. There may be clot formation (thrombosis) in the cardiac chambers, specially atria, and concomitant embolism. Bradyarrhythmias on the other hand, deprive the brain of its vital dose of oxygen. In either case, a sensation of an irregular beat or palpitation, may make the patient anxious and apprehensive.