Feb 262018

The main function of the heart is the unidirectional flow of blood throughout the body. This is the same organ that beats upto 3 billion times. The blood is estimated to travel at 1.35±0.35 m/s. This is 3 miles per hour. Each time, the blood pumps from anywhere between 3-5L of blood in every cycle. Human body is truly remarkable. In one of our classes, we are looking at a fatigue analysis of a lug stud of a car wheel and we consider an infinite life with 1 million cycles in the context of material analysis. A heart goes through an even greater number of cycles, and therefore, more theoretical and practical knowledge of mechanical properties of heart valves and tissues is required in order to comprehend and treat the numerous heart related diseases.

To provide a little bit of motivation for towards the field of tissue engineered heart valves, numerous diseases are related to a not comprehensive understanding of our heart or a shortage of available products in the market for tissue transplant. Every year, 290,000 patients go through valve replacement surgeries worldwide, and this number is projected to increase to 850,000 by 2050. The reason these have to be replaced is because a large number of valves cannot be repaired. Since heart is a delicate organ, extracting and valve, treating it and then placing it back is a time consuming process and this risk, doctors are not willing to take. This is why there is a huge role for the field of Biomechanics to play in this heart valve tissue knowledge gap. About 110,000 people die every year due to valvular heart diseases in the United States and this is an urgent field of study that needs to be addressed.

There are three observable knowledge gaps. One is that there is a gap between the understanding of the mechanical properties of these valves that have not been very extensively researched yet. For example, the flexural properties, viscoelastic properties, fatigue properties, etc. There may be more outside of the context of the papers being discussed. The second gap is that the numerous deaths and replacements happen to children or youngsters. For them, the heart for the youngsters grow. Even if the first knowledge gap is fulfilled, the valve will be applicable only to the older people or for youngsters, the valve will need to be replaced frequently. In order to fit an external object into the body, anticoagulants are also needed, which has other side effects. Therefore, a development of a somatic growth and remodelling after the implantation is required. The valves must grow over time and gradually acquire the structural and mechanical characteristics of the native tissues via remodelling, repair and growth post implantation.

This is not mentioned in the paper, but I believe that computer science has some role to play in this second knowledge gap through artificial intelligence. This is related to machine learning. The artificial tissue when transplanted needs to learn about its atmosphere and adapt to the new environment. However, the designer also has a very important role to play to start with. For certain issues, the transplant needs to work immediately. Important measures need to be taken to implant the closest valve that fits accordingly in the environment. This process is crucial to the survival of the patient.

The third gap is the general gap between the availability of human specimens to test in comparison to that of animals. Most of the human specimens are gained from deceased humans, who choose to donate their organs. As reported in one of the paper, out of 5 specimen, 1 female died through poisoning while the other 4 men deaths were due to traffic accidents. The paper suggests that the transvalvular pressure in pigs is significantly higher to that of humans. In such situations, an understanding of the bovine heart structure may or may not be completely applicable to that of humans.

Humans are very diverse creatures, therefore the variance we find in the different mechanical properties is generally huge. Genetics, ancestry, age, creed gender, etc. play a crucial role in defining the true value of the properties and this is why a dynamic valve/tissue is required, which is capable of continuous remodelling to adapt to its surrounding.

The blood enters the heart through tricuspid and mistral valve and these valves help in regulating the amount of blood inflow. On the other hand, pulmonary and aortic valve regulate the outflow of the blood from the heart. When the heart beats, a muscle contraction creates a pressure difference between the inside and outside and the blood flows outwards. The left side of the heart faces about 5-8 times more transvalvular pressure in comparison to the right side. Yet, it is only 2 times thicker. The thickness and other dimensions have to be considered before transplantations.

Pulmonary and aortic valves have three sublayers called fibrosa, spongiosa and ventricularis, where fibrosa is the thickest one and is comprised of highly dense corrugated collagen type-I fibres. These are arranged more in the longitudinal directions than in radial directions. Fibrosa also consists of elastic, which is a very elastic protein that allows for the extreme stretching during contractions. Spongiosa is sandwiched in the middle, which consists of highly hydrated glycosaminoglycans (GAGs) and proteoglycans. This enables shearing between the two layers and transfers the load to the aortic wall. Ventricularis is the thinnest of the three layers and is the outside layer. It helps in reducing the large radial strains during the high blood flow when they are fully open. This tri-layered structure of the valves ensures the high tensile strength for resisting the high transvalvular pressures.

There are only two kinds of cells present in the heart: interstitial cells and endothelial cells. The interstitial cells are like the cardiac muscle cells that are responsible for the production of GAGs released in spongiosa. The endothelial cells form the blood vessels. This is the barrier between the blood and body tissues. Some nerve cells are also present.

There are two types of pressures developed in the heart – diastolic and systolic pressures. The minimum diastolic pressure occurs towards the beginning of the cardiac cycle when the ventricles are full with blood and the peak systolic pressure occurs towards the end of the cardiac cycle when the ventricles are contracting. The majority of the stresses and strains occur in the valves during the diastolic pressures. The total stresses in diastolic and systolic are 50kPa and 500kPa.

It has been set up that a more comprehensive understanding of the mechanical properties of these valves are required. In a stress-strain diagram, the valves tend to be very non-linear in nature, unlike the normal stress strain diagrams taught in solid mechanics in college. It is linear for very small strains, which is associated with the straightening of the crimped fibers of collagen and the elongation of the elastin fibers. The second stage suggests the transfer of force from the elastic to the collagen. Post elastic region, both collagen and elastin elongate and finally a non-linear rupture/fracture phase is observed. It is worthy of noticing that the properties of the valves rapidly change as we view the circumference in comparison to the radial directions. The paper also proceeds to discuss the biaxial tensile strength. These results are not very useful as the heart valves are extremely anisotropic. This is why tests need to be done for flexure deformations.

Numerous scenarios have been set up for flexure deformations. Depending on the side of the applied load, either the fibrosa stretches or compresses. As the valves are not made of the same uniform material, it is hard to monitor them throughout. As fibrosa is the thickest and more elastic, it contributes the most to circumferential bending properties. Through the cantilever bending, it was also found that the valve was 50% stiffer when bent against the physiological direction.

An area not explored at all is towards the viscoelastic properties of heart valves leaflets. It is found that all valve leaflets are stiffer in the circumferential directions in comparison to the radial direction. As these leaflets are made of viscoelastic materials, their stress-strain characteristics are strain rate dependent. Some mathematical models have been developed however, many viscoelastic properties have remained largely un-addressed. More understanding in this area will help in more durable heart valves constructs.

As mentioned earlier, the heart pumps a total of 3 billion times in 70 years of lifetime. For such a large and complex cycles, a fatigue analysis is crucial to the understanding of the fatigue and failure of these valves. The maximum test has only been done for 200 million cycles, only a fraction of the actual number. To gather results for such large sample size, computational models are used to predict the scenarios. Again, a better understanding of the fatigue of the valves would help in designing more durable heart valves constructs.

Before delving into this topic, I thought the articles would be completely about the whole heart (I did not read the title very well) but it soon changed when I realized that the whole focus is just on the valves. This truly reminds me that research starts from something very broad but very soon you have to start to focus on a very small aspect. My learnings through the readings have been about the structure of the heart and the valves, which I have listed above already. In each section, I have also included my reflections.

Pranav Mohan

Change and progress are two words that define my character and my ultimate goals. I have a vision to bring a global change by targeting the psychology, because that is the easiest to change. My aim is to incur a self-progressive routine for myself and then help the people around me to progress themselves. In my perspective, walking towards a defined target should be everyone’s goal while keeping in mind that things don’t go as planned but still the target should remain unchanged.

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