Saturday 25 October 2014

"Dead Heart" Transplant - World First in Cardiac Surgery

In Australia this month, surgeons have managed to resuscitate a heart from circulatory death and use it for transplant in patients with 'end-stage heart failure'. Prior to this, hearts used for transplant were only sourced from brain-dead patients but whose hearts were still beating. Some have heralded this as a 'paradigm shift' in organ transplantation. The heart was able to be revived using what has been  dubbed as the 'heart-in-a-box' machine (the OCS - Organ Care System). Now the machine is commercially available to hospitals in Europe and Australia for clinical use. Usually, a beating heart is kept iced for a long period of time, however this machine is claimed to be a 'portable, warm perfusion, monitoring machine'. As of now, St. Vincent's Hospital Heart Lung Transplant Unit in Australia has transplanted two patients using this technique. However it is important to note that the OCS has already been used and approved for other types of transplantation such as the liver, kidneys and lungs. Up until now, it has proved difficult to repeat the same technique on 'dead' hearts.

The benefits of this new technique prove essential - the maximum possible number of donor hearts available will inevitably increase. In fact, it is estimated that 30% more lives could be saved with the introduction of this technique. Professor Peter MacDonald, Medical Director of the St Vincent's Heart Transplant Unit has said "this is a timely breakthrough. In all our years, our biggest hinderance has been the limited availability of donor organs". With regards to the OCS machine, portability is useful if it is needed in various departments in a hospital. It would also mean ease of transportation nationwide, or even worldwide.

 

Top: OCS "Heart-in-a-box" machine (TransMedics)
Above: OCS machine maintaining liver for transplant (BBC)


Interestingly however, this isn't the first time that this idea of using a dead heart donor has been experimented. Professor Kumud Dhital perfumed both of the operations in Austrailia says that "It is interesting to note that DCD hearts were utilised for the first wave of human heart transplants in the 1960's with the donor and recipient in adjacent operating theatres. This co-location of donor and recipient is extremely rare in the current era leading us to rely solely on brain dead donors -- until now".

The recovery of patients is even more astounding. Michelle Gribilas, 57, was the first patient to be treated with the surgery. Before the operation she was suffering from congenital [end-stage] heart failure. Two months after the procedure, she told the BBC: "Now I'm a different person altogether. I feel like I'm 40 years old - I'm very lucky". Senior cardiac nurse at the British Heart Foundation, Maureen Talbot, added "without this development, [patients] may still be waiting for a donor heart".


Credit to the BBC for their article 'Surgeons transplant heart that had stopped beating', published 24th October 2014. More on the subject can be found here.

Credit to St Vincent's Health Australia, whose story was published in ScienceDaily on October 24th 2014. The original article can be found here.

Thursday 16 October 2014

BBC Documentary: Pain, Pus and Poison - Part 1

Over the last 150 years or so, the story of the advancements of drugs, treatment, and techniques in medicine has developed at a great pace. Dr Michael Mosley recently presented a trilogy of documentaries for the BBC, telling tales of the beginnings of anaesthesia and the birth of the antibiotic era. In part one of the series, he focused on man's pursuit to free pain. It begins where you may not expect - the poppy. From this rather innocent-looking plant, a resin was extracted and given the name opium. Dissolved in alcohol, the medicine was called laudanum. Morphine, the drug we are familiar today with unprecedented properties in alleviating excruciating pain, was formerly discovered by 19th century pharmacist Friedrich Sertürner. Morphine works by blocking nerve endings associated with pain at the site of pain and in the brain. The direct blockage of these signals proves morphine very effective. Eventually isolating the active ingredients in raw opium, he had managed to obtain a substance that could now be quantified and measured for ease of administration. This fact is often underestimated about drugs - simply by being able to measure out a quantity of a substance offers a huge element of control and indeed safety. It was considered back then that medicines which originated from plant sources were alkaloids, containing the suffix -ine in their name. Hence we are familiar with morphine, whose former name was morphium. According to Dr Moseley, these alkaloids were considered 'our first real medicines'. Dr Walter Sneader, Former Head of Pharmacy at the University of Strathcylde says that the discovery of morphine was 'the single most important event that has ever occurred in drug discovery - far more important than the introduction of penicillin, in terms of advancing the science'. Sertürner then went on to isolate many more alkaloid chemicals, some of which include caffeine, nicotine and quinine. Another well known alkaloid that was discovered was cocaine. Ironically enough, at the point of introduction in industry this compound dissolved in alcohol was approved by the Pope himself. The famous neurologist Sigmund Freud went on to investigate more into the properties of cocaine.



Although these alkaloids were a start, these weren't considered potent enough to be effective in the operating theatre. Sir Humphrey Davy saw nitrous oxide as a potential drug for use in surgery, however surgeons still went on to attempt operations on people who were unfortunately, fully awake. It was only until William Morton and the introduction of ether as a gaseous anaesthetic agent, that anaesthesia started to advance rapidly. To read more on the subject of William Morton's discovery, visit my post, 'The History of Anaesthesia'.

After this remarkable discovery, chemists from all around the world began to experiment with various substances, coal tar notably being one of the 'more unlikely places'. Chemist and presenter Andrea Sella, mentions that using coal tar was able to open 'a whole new library of starting materials'. Some of the most iconic drugs in today's world were a product of this seemingly unpromising raw material, aspirin and heroin just to name a couple. In the 20th century, many more drugs with anaesthetic properties were developed. However it wasn't just anaesthetics; the world's first sleeping pill was discovered, chloral hydrate which became very popular. The barbiturates were another group of drugs that had the ability to put people to sleep. Sodium thiopental was one of the more notable ones, the 'truth drug' so given the name for it's use in interrogation, is featured in the documentary.

Now in the 21st century, we have made great strides in the development of even more effective and safer drugs for use in surgery, prescription, and treatment of diseases. It has come to a point where we can, with suitable starting materials such as simple molecules, develop any molecule we want to. This means we can develop any drug we want to. A surge in technological advances in the last few decades has supplemented our understanding of anaesthesia and how pain is managed.


Credit to the BBC for their medical documentary trilogy, 'Pain, Pus and Poison', broadcasted in September 2014.

Thursday 2 October 2014

Repairing Damaged Heart Tissue With Embryonic Stem Cells

Heart disease is now considered the most common cause of death in the UK, according to the BBC. This pressing issue has initiated research projects to find the best treatments, long-lasting treatments that involve the regeneration of heart tissue. Experiments back in 2005 involved deliberately inducing heart attacks in 18 sheep in order to test the potential of embryonic stem cells from mice. Research prior to this revealed that attempting to use stem cells from the patient would prove futile as adult stem cells do not have the capacity to differentiate into heart (cardiac) tissue. If this was possible, this would undoubtedly be a desirable solution as the patient's own cells are being used, reducing the risk of rejection.

Therefore embryonic stem cells have been labelled the next hope in the regeneration of damaged heart tissue. The experiment back in 2005 involved separating the sheep into two groups, one the control, the other being given 'multiple injections' of the embryonic stem cells [from mice] after a rest period of two weeks. These cells had been given growth factors to trigger them into developing into cardiac cells. Five sheep from this group were also given immunosuppressants in case there is an issue of rejection. Tagging the stem cells with 'fluorescent proteins' helped scientists to track their progress of colonisation, which was successful after one month. As anticipated, the cells were effective in regenerating the heart tissue in the non-control group, replacing the scarred tissue. In fact, the scientists were able to measure the heart's effectiveness to pump blood from the left ventricle. In the control group, blood ejection rate decreased by an average of 6.6%, whilst it was raised by 10% in the group given stem cell treatment.

By this data, the treatment seems very effective, however only 18 sheep were used in this set of experiments and embryonic stem cells of mice were used. Nevertheless the fact that this technique works in principle gives hope of new treatments involving stem cells. What was more encouraging for the scientists, is that there was no evidence of an attempt of rejection by the immune systems of sheep that were administered immunosuppressant drugs. However geneticist Robin Lovell-Badge, researcher at the National Institute for Medical Research, London, says that there is a "need to be cautious. Other tissues might reject the stem cells". He also pointed out that the sheep were only monitored for one month after the investigation. Side effects to the treatment or rejection could well occur further down the line - this is another implication for human trials.

Since these experiments, another study at the University of Washington Institute for Stem Cell and Regenerative Medicine also found success in the use of embryonic stem cells to regenerate tissue, this time in monkeys. The study summary stated that the stem cells "assembled muscle fibres and began to beat in synchrony with macaque (monkey) heart cells". What was interesting is that this time, human embryonic stem cells were used. The findings were published 30th April 2014 in Nature. 



Above: Green areas depict newly transplanted stem cells forming a graft with the primates original cardiac muscle cells (red). Full credit to the University of Washington


Credit is given to Anna Gosline, writer for New Scientist. Article can be found here. Original study findings can be found in The Lancet (Volume 336, pg 1005). 

University of Washington findings report can be found at ScieneDaily here.