These used and reconditioned devices have the potential to increase access to pacemaker therapy in low- and middle-income countries, where many patients cannot afford the treatment.

Researchers from the U-M Health Frankel Cardiovascular Center reported the findings as a late-breaking abstract at the 2024 American Heart Association Scientific Sessions.

The international clinical trial involved nearly 300 people across seven countries in Africa, North and South America.

It compared the function and safety of reconditioned pacemakers to new devices, with patients randomly assigned one or the other.

Investigators found no significant differences in pacemaker function up to 90 days after the procedure.

Just five patients developed localized pocket infections at the site where the pacemaker was implanted, three of whom had initially received new devices.

Three deaths occurred in the group with reconditioned pacemakers, but none were related to the implantation procedure, device infection or malfunction.

“These positive early results bring us closer to the reality of a large-scale pacemaker donation and reconditioning that could save lives across the globe,” said principal investigator Thomas C. Crawford, M.D., a cardiac electrophysiologist at the Frankel Cardiovascular Center.

“Unlike in the United States, pacemaker therapy is often not available or affordable for people in low- and middle-income countries. Our program is determined to change that.”

It has been estimated that hundreds of thousands of individuals from around the world die from lack of a pacemaker, typically in countries with limited resources.

While implanting a recycled pacemaker is not legal in the U.S., the Food and Drug Administration does allow refurbished devices to be exported.

The “My Heart Your Heart” program began sending reconditioned pacemakers abroad in 2010 for cases of compassionate use, in which there is no alternative to treat a life threatening cardiac condition.

The refurbished devices either come from deceased individuals or those who need a pacemaker upgrade to a device with more advanced functions. 

The U-M team sorts and interrogates recycled pacemakers, only reconditioning those that have more than four years of battery life.

The devices are reprocessed in a joint laboratory with World Medical Relief in Southfield, Mich., and Northeast Scientific, Inc., re-sterilizes them free of charge in Connecticut.

Many of the pacemakers come from Implant Recycling, LLC, a Michigan environmental and recycling company that services the crematory and cemetery industries.

The program has received donations from funeral homes in all 50 states.

This idea is more than a decade in the making, with each step carefully studied, said co-author Kim A. Eagle, M.D., founder of the program and a director of the Frankel Cardiovascular Center.

“We started with the beliefs and attitudes of patients, families, physicians and funeral home directors. The process of proper extraction, analysis of function, sterilization, packaging and ultimate implantation and follow-up has been rigorously sought. We have created a published roadmap, if you will, of how other centers and partners in the world can join is this most worthy cause.”

The Michigan-led team plans to continue follow-up with participants to determine the long-term safety and efficacy of recycled pacemakers.

The longevity of new pacemakers varies depending on how much the patient is using it but usually exceeds 10 years.

“It is imperative that we move forward with this research and determine the optimal way to reduce the gap in access to lifesaving pacemaker therapy,” Crawford said.

“The three-month outcomes are encouraging, but the six- and 12-month outcomes will be vital in understanding whether, with the exception of battery life, the reprocessed pacemakers can function like new ones.”

The research has been supported by the Frankel Cardiovascular Center, grateful patients and donors and a number of foundations. Inquire about pacemaker donations.

Additional authors: Eric Puroll, Eva Kline-Rogers, N.P., Patricia Bruenger, Chih-Wen Pai, Ph.D., MSPH, Constantina Alexandris-Souphis, R.N., B.S.N., AJ Hale, M.B.A., Ed Goldman, J.D., Hakan Oral, M.D., all of University of Michigan. Outside authors: Azorena Aponte, Vicente Finizola, M.D., Maria Milagro Arends, M.D., Eusevio Arends, M.D., Hector Monasterios, M.D., Emmanuel Edafe, M.D., Adrian Ebner, M.D., Ceci Martinez, M.D., Oluwaseye Oladimeji, M.D., Mahmoud Sani, M.D., Constantine Akwanalo, M.D., Jorge Bahena, M.D., Edgar Carrizales, M.D., Albertino Damasceno, M.D., James Russell, M.D., Joel Dunning, M.D., George Samson, Ph.D., Noah Klugman, Ph.D., Lane Powel, J.D., Sheldon Davis, M.S., Marion Davis, Craig Allmendinger and Brad Wasserman.

In his previous role as Chief Scientist at the RPS he took a particular interest in the unwelcome resurgence in the misuse of dinitrophenol (DNP) for weight loss.  Despite being described in the 1930s as “extremely dangerous and not fit for human consumption”, it has reappeared in Internet sales. Professor Martini argues that it should now be banned.

He has also campaigned against the recreational use of nitrous oxide. It is often believed to be harmless but prolonged or intense exposure leads to inactivation of vitamin B₁₂ and potentially serious neurological damage.

The recent appearance of large (empty) canisters of nitrous oxide on the streets suggests an escalation in its use. The gas has legitimate uses in the food industry and this makes its misuse difficult to combat. Proper checks at the time of purchase, combined with measures to raise awareness of the problems could reduce the quantities available on the streets, he suggests.

The Precision Health Technologies Accelerator (PHTA), at the University of Birmingham, will bring together innovators and entrepreneurs in life sciences and connect them with clinical and academic experts in the West Midlands region. As the Chief Executive of the PHTA, part of Professor Martini’s role is to bring in new businesses and encourage start-ups from universities and hospitals in the region.  Pharmaceutical expertise is important in translational medicine and is needed more than ever now that increasing numbers of biological agents are being developed, he argues.

Experiences during the coronavirus pandemic have shown the real value of community pharmacy and Professor Martini believes that community pharmacists could take on more diagnostic and prescribing functions. Moreover, the pharmacy degree can be seen as a ‘passport qualification’ that provides opportunities for pharmacists in numerous areas. “Don’t be constrained by your thinking…. Utilise the qualification for what it is – a kitemark of value, a kitemark of your ability to do things differently”, he says.

Visit www.phta.co.uk for more information on the Precision Health Technologies Accelerator (PHTA).

Read and watch the full series on our website or on YouTube.

“As a volunteer, I vaccinated 5000 people – I was one of the first people to do that”, he says.  “I also went back into practice in the community because, you know, the local pharmacist was just inundated with prescriptions – but, actually, we were open, you see, and patients came in to speak to the pharmacist”, he adds.  It used to be the norm for people to consult the pharmacist first for health problems and one of the results of the pandemic is that “patients [have] rediscovered the value of the pharmacist”. Professor Martini believes that community pharmacists could undertake diagnostic tests such as C-reactive protein tests for patients with suspected bacterial infections who might need antibiotic treatment. “Why can’t the pharmacist then give the antibiotic to that patient there and then – I don’t see why he can’t; I think you can…. I see the role to be really growing, ……more and more”, he says.

As Chief Scientist at the Royal Pharmaceutical Society, a large part of his role during the pandemic was to translate much of the scientific and policy information into practical guidance.  When a question arose over the use of ibuprofen for covid infections, he correctly advised that it could safely be used. He also provided correct advice on vaccines and on the matter of cold chain supply.  “It was a very, very interesting time – it really put science forward……. We shouldn’t lose that – we should try and make sure we’ve got our hands on that ball and keep hold of it”, he says.

Taking a wider perspective, Professor Martini sees a bright future for young pharmacists. People who study medicine are taught that they are highly-educated, highly-skilled and able to turn their hands to anything. He believes that pharmacists are in a similar position and effectively have a “passport qualification” that will allow them to go anywhere and work anywhere around the world. In this respect, chemical engineering, pharmacy and medicine are similar, he says. In some ways he is a living example – he started his career in community pharmacy, has subsequently worked in the pharmaceutical industry, in academia and for a professional body and now he is running a science park. “It’s just a mindset – understanding that actually what the degree gives you is an opportunity to do something different and to adapt to your environment…. Don’t be constrained by your thinking…. Utilise the qualification for what it is – a kitemark of value, a kitemark of your ability to do things differently and to use your clinical judgment ……  and also, to understand science, which I think pharmacy brings to you. So, to me it’s all about versatility and adaptability and I think pharmacy gives you that training”, he says.

Visit www.phta.co.uk for more information on the Precision Health Technologies Accelerator (PHTA).

Read and watch the full series on our website or on YouTube.

The University of Birmingham is developing a huge life sciences campus just a five-minute walk away from the University and a similar distance from the Queen Elizabeth Hospital. The 700,000 square-foot campus is currently under construction and will open in 18 months’ time. Professor Martini’s task is to attract innovators and entrepreneurs to the site and foster collaboration with each other and with local academics and clinicians.

Professor Martini says, “We forget that over the last 25-30 years, [of] all the innovative medicines that were launched in Europe, most of them were actually developed or overseen by somebody based in the UK because either the MHRA was     involved or our experts were involved”.  Birmingham has a wealth of expertise in its clinicians, academics and hospitals, he notes. “I also want to make sure the right patients get the right medicine. There’s been a big debate… about what precision healthcare means. It used to mean ‘the right drug at the right dose at the right time, the right cost but actually – it’s the right patient”, he adds.

Birmingham has a stable population of some six million with 30% [minority] ethnicity – something that is ideal for investigating new medicines and innovative treatments. “Proper clinical trials done in the proper representative patient populations will be absolutely crucial in developing the latest breakthrough treatments and medicines”, explains Professor Martini.  “Anybody who has worked in the industry like I have understands that clinical trials is the lifeblood – and if you’re not actually testing in     the appropriate population then actually …. patient benefit will be will be hampered”, he says.

Professor Martini says, “My role as the Chief Executive is to bring in new businesses and encourage more start-ups from the universities in the region and from hospitals but, more importantly, [to] connect those individuals who need access to our key opinion leaders – [that is] the guys working at the university and the guys working in the Birmingham Health Partners, which is a big conglomerate of hospital trusts in and around the West Midlands.”

Pharmaceutical expertise is important in translational medicine not least because pharmacists understand how dosage forms are developed and are able to combine understanding of the clinical development of a drug with understanding of drug delivery. “The whole definition of translation is ‘from molecule to bed-side’. Well think about what pharmacists do – we’re right in that sweet spot…” says Professor Martini.

During his career he has seen the role of pharmacists in industry grow and develop.  In the past there were many positions that were not open to pharmacists but now this has changed and pharmacists are taking on a variety of role including leading clinical trials. “It has really changed quite dramatically in our favour”, he says. Moreover, biological agents require more care and attention than small inorganic molecules. “All these biologicals are very susceptible to sheer and shaking ……and our skills are needed now more than any other time”, he concludes.

Visit www.phta.co.uk for more information on the Precision Health Technologies Accelerator (PHTA).

Read and watch the full series on our website or on YouTube.

The campaign against the misuse of nitrous oxide has included an article in the British Medical Journal and various news items.  “It was a little bit ironic that one of one of the changing points, what …. triggered more debate was the environmental issue because councils were getting really fed up of seeing all these canisters      everywhere and so that kind of drove it”, recalls Professor Martini. A number of MPs were also concerned about the significant costs involved in cleaning up the litter left by nitrous oxide abusers, he adds.

“I have just found large canisters of nitrous oxide…..  lying on the streets in London and in Manchester.  What’s happened is – it’s now jumped a level in terms of abuse”, says Professor Martini. At one point there were reports of nitrous oxide cylinders being stolen from hospitals. However, the appearance of large canisters of nitrous oxide on the streets suggests an escalation is its use. “My mission was to advise parents of young kids, [that] when you see these little silver ampoules on the street – we’ve all seen them – that’s being misused”, he says.

Small doses of nitrous oxide, for example for pain relief during labour, are not toxic but prolonged or intensive use is associated with toxicity. “It’s not exactly clear how much you do need but [there was a report] of a Chinese man in China doing about a     thousand ampoules a day ….. The problem is – the buzz you get is very quick and they like it and so they do it again and then do it again and do it again and that’s where it starts becoming a little bit of a problem. It’s very hard to quantify but if you’re doing hundreds a week, you’re in serious trouble, if you carry on”, says Professor Martini.

Nitrous oxide is available for anyone to purchase and suppliers are supposed to check that the intended use is legitimate, for example use in food preparation.  Professor Martini says that more rigorous checks – including photo identification and proof of a legitimate use – should be introduced.

Visit www.phta.co.uk for more information on the Precision Health Technologies Accelerator (PHTA).

Read and watch the full series on our website or on YouTube.

Nitrous oxide is often believed to be harmless but prolonged exposure leads to inactivation of vitamin B_12.  ^“ Vitamin B₁₂ is what you need for healthy myelin, which is the material around your spinal nerves, your spinal cord”, explain Professor Martini. The end result is degeneration of the spinal cord that can manifest as numbness in the fingers, problems with walking and, in some cases, paralysis. If diagnosed early enough then the condition is reversible. This issue has been a cause of concern for both senior pharmacists and medical officers.

Shortly after nitrous oxide was first synthesised during the 1800s ‘laughing gas’ parties became popular but they stopped when the association between prolonged use of nitrous oxide and “people keeling over” was realised.

Professor Martini explains: “It’s not a chemical that you want to play around with. The issue we have – and what’s causing confusion – it is used in the food industry.” Whipped cream canisters use nitrous oxide to produce the foam. This is a legitimate use for nitrous oxide and is safe because the gas it is not inhaled. He first became aware of the scale of the problem when as a governor of a local school he saw two or three hundred [empty] nitrous oxide ampoules next to a primary school. “I picked them up and I showed them to parents and not one parent knew that this was a nitrous oxide canister and actually this was being abused – put into balloons and inhaled – and could cause harm”, he says.

Ever since then he has campaigned to raise awareness of the nitrous oxide misuse and the harm that it can cause.  Parents may have seen their children purchasing nitrous oxide online and not realised that it could be harmful, he adds.

Visit www.phta.co.uk for more information on the Precision Health Technologies Accelerator (PHTA).

Read and watch the full series on our website or on YouTube.

The PHTA has been conceived to spur innovation in the West Midlands as part of the Birmingham Health Innovation campus – a new science park designed to concentrate life sciences in the region. In his previous role as Chief Scientist at the RPS he took a particular interest in the unwelcome resurgence in the misuse of dinitrophenol (DNP) for weight loss. “I always took the view that every life was important; I never subscribed to the view that because [only] 36 people died as a result of exposure to DNP or to nitrous oxide, for example, that it wasn’t important. Well, you try to have that conversation with the parents who just lost their daughter or their son…..”, he says.

He believes that pharmacists should play a role in stopping misuse of harmful chemicals. “Dinitrophenol is a disgusting chemical”, he says. In the 1930s it was banned by the Food and Drug Administration in the USA and described as “extremely dangerous and not fit for human consumption”.¹

Professor Martini says: “Effectively what DNP does – it actually stimulates the mitochondria in your cells to work faster and therefore they generate more heat,   and unfortunately young people who’ve been taking it suddenly overheat and die of heat exposure. It’s a horrible way to die.”  The recent resurgence in use of DNP prompted Professor Martini and his predecessors, Professor Jayne Lawrence and Professor Tony Moffat to campaign for its removal. Recent Presidents of the RPS, Ashok Soni and Sandra Gidley have also been involved and have spoken to the parents of victims, he notes.

It has been argued that dinitrophenol cannot be banned because it is required for some industrial processes. However, Professor Martini says, “My preference is for it to be banned and ….. I believe the current position from the Royal Pharmaceutical Society is for it to be banned…….  I can’t see any use for it in fertilizers. I just think it’s completely outdated for use in the 2020s.”

“I’ve had those conversations with the with the parents of a number of young people who’ve passed away because this dreadful chemical – and it is a dreadful chemical”, he emphasises.

Another option might be to ban the compounding of DNP into capsules or sachets. Professor Martini says: “People were shipping this chemical in bulk – and so if you banned the compounding of it – you actually stop it from being put into capsules or sachets, because that’s how it was being given to young people. So, it’s almost like another step that says, “Hold on, you know you can’t say you didn’t know what was going to happen because you’ve taken the step to compound it, i.e. put it into a capsule. Therefore, that’s illegal so you can’t do it.”  Anything that adds another obstacle in people trying to distribute this particular chemical I think is a good thing – but let’s get back to basics, let’s get it banned outright or certainly under control of a pharmacist. …..   Let’s just get this thing out of circulation. “

Finally, some people have called for DNP to be made a Class C drug under the Misuse of Drugs Act. “Well, you see, we shouldn’t be calling it a drug. I’ve been very careful ….  I’ve used the word ‘chemical’. During the 1930s we were told that there was no medical use for it – it’s a chemical. ….. Any rescheduling is just a waste of time because it has no therapeutic use at all. So, treat it as a chemical, treat it as a nasty chemical and then and just get it banned – or so restricted that nobody can get their hands on it”, he concludes.

Reference

1. 2,4 Dinitrophenol(DNP): A weight loss agent with significant acute toxicity and risk of death. Grundlingh J et al. J Med Toxicol. 2011 Sep; 7(3): 205–212. doi: 1007/s13181-011-0162-6

Visit www.phta.co.uk for more information on the Precision Health Technologies Accelerator (PHTA).

Read and watch the full series on our website or on YouTube.