The Heart

It’s at this point we should turn our attention to the thing that enables perfusion and fundamentally keeps us alive minute-to-minute. 

Pre-birth

The circulatory system we currently possess is very different to what we had as a developing fetus (notwithstanding congenital cardiac conditions). In utero, oxygen is derived from the placenta (as our lungs are fluid filled at this point), returning to the fetus via the umbilical vein, which branches into the ductus venosus and hepatic vein, to converge into the IVC. Unlike adult physiology, the right ventricle acts as the primary pump to the systemic circulation. Blood flow to the foetal heart takes one of three directions from the right atrium:

1. Directly to the lungs via the right ventricle; with oxygen derived from the placenta, the lungs aren’t much use. The vascular resistance here is high, and only a small amount of blood circulates through the lungs.
2. To the systemic circulation;
   • via the ductus arteriosus, blood travels from the pulmonary trunk to the aorta, before continuing to the systemic circulation
   • via the foramen ovale, blood shunts from the right heart into the left side.

After birth, that first gasp of air works to inflate the lungs, uncollapsing the lung tissue from the surrounding pulmonary blood vessels, and rapidly dropping the pulmonary vascular resistance. This reduced resistance shifts the pressure gradient and redirects blood flow into the lungs, whilst the rising pressure in the left atrium, as a result of return from the pulmonary veins, closes off the foramen ovale.

Over days and weeks, the left ventricle hypertrophies as it handles the systemic circulation, whilst the right ventricle atrophies as a result of low pressure requirements in the pulmonary circulation. By 3 weeks of age, the pulmonary pressures have normally fallen below systemic pressure. By adulthood, the RV is normally incapable of generating more than 40-60 mmHg acutely.

Outside the womb

From that first breath after we are born, the fetal circulation is altered, causing a number of clinically important differences between the right and left sides of the heart that persist through our lives.

Blood enters the right atrium under low resistance and low pressure, from the venous system via the SVC and IVC. The right ventricle (RV) is smaller and thinner than the left (RV free wall thickness around 1-3mm, with >5mm considered hypertrophic). Its free wall is crescent shaped, sharing the interventricular septum with the LV, and contraction of the RV occurs in a peristaltic manner from tricuspid annulus to pulmonary valve.

The right ventricle (RV) only needs low pressures to circulate blood to the lungs, around 15-25 mmHg SBP / 0-10 mmHg DBP (vs 100-140 / 3-12 mmHg of the LV). The pulmonary circulation owes its low pulmonary vascular resistance (PVR) to its huge capillary surface area, high vessel compliance, and short vessel lengths.

The RV was traditionally considered as purely providing capacitance to the pulmonary circulation, with experiments showing that ablation of the RV had no effect on cardiac output. But the contractile ability of the RV remains critical; RV infarcts demonstrate significant risk of systemic hypotension in the face of GTN administration, increased PVR, or any other pertubation that can affect preload or afterload of the RV (because its compensatory contractile function is diminished/obliterated).

The left ventricle (LV) is bullet shaped, larger and thicker walled than the RV, and contracts in a circumferential manner to generate higher pressures in order to eject blood against the much greater systemic vascular resistance (SVR), to supply the entire rest of the body. 

The heart also performs a limited endocrine function; increased volume and/or stretch of receptors within the atria raise circulating levels of BNP and ANP. These help regulate blood pressure over the longer term by stimulating natriuresis (excretion of sodium) in order to reduce the circulating volume within the body.

Electrophysiology

There are two distinct types of action potential within the heart; myocyte and pacemaker.

More than just medical school minutiae, it’s useful to know how these function as the physiological basis for different antiarrhythmic drugs. The Na/K ATPase pump ensures that for every 3 sodium ions exported, 2 potassium ions are imported into the cell. This sets up and maintains an ion gradient that can be triggered for depolarisation. 

The myocyte action potential, which triggers muscular contraction of heart tissue, has 5 phases:

• Phase 0 – rapid Na+ influx, leads to ventricular depolarisation
• Phase 1 – K+ efflux begins, to repolarise the cell
• Phase 2 – L type (slow) Ca2+ channels open, delaying repolarisation. This is the absolute refractory period
• Phase 3 – L type Ca2+ channels close, K+ continues to leave the cell, repolarisation continues
• Phase 4 – Na/K ATPase returns the myocyte to a resting baseline potential

The pacemaker action potential, which determines the rate and rhythm of the heart, is slightly different, with only 3 of the 5 phases:

• Phase 4 – slow Na+ influx (’funny’ current) with additional slow Ca2+ influx via T-type channels, leads to slow spontaneous depolarisation. L-type channels begin to allow more Ca2+ into the cell. 
• Phase 0 – There is then a rapid influx of Ca2+ through L-type channels, leading to rapid depolarisation
• Phase 3 – L-type (slow) Ca2+channels close, K+ channels open to allow K+ efflux, and the cell begins to repolarise, and then hyper-polarises to begin stage 4 once again. 

Higher sympathetic drive will increase the slope of phase 0, leading to a faster heart rate.

An understanding of the action potentials allow a better appreciation of the mechanisms of action of the major anti-arrhythmic drug classes.

Anti-arrhythmic drug classes

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Coronary circulation and perfusion

The oxygen demand of the heart can change by alterations in the heart rate, contractility, and cardiac wall stress.

The heart is very sensitive to ischaemia, with a high myocardial O2 extraction rate of around 60-70% at rest, which is near the maximal extraction rate the body is capable of. The volume of blood to the heart at rest is around 250ml/min (5% total CO), which can increase to 4-5x this during activity via coronary vasodilation.

Blood flow to the LV is intermittent, occurring only during diastole when the LV is not compressing the coronaries during contraction. The RV, however, is perfused throughout the cardiac cycle in systole and diastole, due to the lower RV pressures not compressing the arteries. 

The aortic root has 3 anatomic dilatations referred to as sinuses of valsalva, where the right and left main coronary arteries originate from to perfuse the entire heart. Eddy currents within the sinuses keep the aortic valve cusps away from the aortic walls, to ensure the coronary arteries remain patent. 

Aortic diastolic pressure (ADP) pushes blood through the coronary arteries via these aortic sinuses, whereas left ventricular end diastolic pressure (LVEDP) pushes back against that flow. Coronary perfusion pressure (CPP) describes the gradient between these two pressures; a normal CPP is around 60-85 mmHg.

CPP = ADP – LVEDP 

Adequate diastolic pressures are required for coronary blood flow and cardiac perfusion. Low diastolic pressures, such as in sepsis or other shock states, may result in myocardial hypoperfusion and subsequent type 2 myocardial infarction. 

This also explains why adequate chest was recoil is vital in chest compressions during cardiac arrest management. Around 15 mmHg CPP is required for return of spontaneous circulation (ROSC), so it’s vital to ensure chest compressions have good recoil. The downward action simulates systole, whilst the recoil will aim to perfuse the heart itself. 

Factors that influence coronary perfusion:

As the coronary oxygen extraction ratio is already near maximal at rest, increased oxygen demand is met primarily by coronary artery dilatation and an adequate MAP (remember, perfusion needs the requisite driving pressure – MAP – and ability to deliver the perfusion – coronary artery dilatation). Over the longer term, the heart is also capable of developing collateral coronary vessels.

• Autoregulation; arterioles will constrict and dilate in order to maintain coronary blood flow (CBF). Autoregulated target coronary perfusion pressures (CPP) range between approximately 60-140 mmHg. Below 60 mmHg, coronaries are maximally dilated to increase CBF, and will constrict as CPP increases.  
• Heart rate; tachycardia will decrease time in diastole and, thus, CBF. This is why it’s common to see rate-related ischaemic changes on and ECG in tachyarrhythmias. Interestingly, right coronary blood flow will remain largely unaffected; rate related ischaemia is therefore often most prevalent around the anterolateral leads (over the LV).
• Autonomic control; there is a weak influence on coronary dilation from parasympathetic (vagal) innervation, whereas increased sympathetic innervation may increase CBF from inotropy or higher heart rates. 

Drugs can significantly alter coronary blood flow:

• GTN causes coronary and systemic vasodilation, leading to reduced preload and afterload, which in turn lowers oxygen demand of the heart. 
• Beta-blockers reduce the heart rate, prolonging diastole and time for coronary artery perfusion. It also reduces beta adrenergic effects of increased contractility, reducing cardiac oxygen demand.
• Calcium channel blockers increase coronary and peripheral vasodilation, with the added reduction of heart rate and inotropy from non-dihydropyridines such as verapamil and diltiazem. 

Anatomy of the coronary circulation:

The right and left main coronary arteries branch off from around the aortic root.

• Left main coronary artery (LMCA) is around 5-10mm long and sits within the left atrioventricular groove. It bifurcates to the left anterior descending (LAD) and left circumflex (LCx)
• Left anterior descending (LAD); sits within the left anterior interventricular groove and supplies the anterolateral myocardium, apex, and anterior portion of the interventricular septum. Branches from the LAD include diagonal vessels (labeled D1, D2 and so on) which supply the anterior myocardium, and septal perforators.
• Left circumflex (LCX) runs along the left atrioventricular groove, supplying the postero/infero-lateral aspect of the LV. It gives off obtuse marginal branches (OM1, OM2, so on) which follow the left side of the heart. 
• Right coronary artery (RCA) travels vertically down the right atrioventricular groove, supplying the RA, and RV via the right marginal artery (the right sided equivalent of the LAD). In 60% of people the RCA supplies the SA nodal artery; the other 40% are supplied by the LCx.
• Posterior descending artery descends in the posterior interventricular groove, and is supplied by either the RCA or the LCx. Around 80% of people are right dominant (supplied by the RCA). The PDA supplies the posterior aspect of the interventricular septum.

The venous vessels generally follow the same path as the arteries, draining into the coronary sinus at the back of the heart, which drains back into the RA.