What do self-driving cars, solar airplanes and renewable energy have in common with the human heart? At first thought, not a great deal, yet a recent scientific endeavour called the Living Heart Project has brought together experts in engineering, aeronautics and energy to produce a sophisticated new model of the human heart for use in medical research.
This 21st century approach to understanding heart disease is vitally important. Heart failure is a serious problem affecting 26 million people worldwide. It can occur at any age, but becomes more common as we get older. Plus, different forms of heart failure affect men and women differently and require different treatments.
Efforts like the Living Heart Project are long overdue, since medical research funding agencies continue to pour millions of scarce health care funds into laboratory experiments involving young, healthy, male rats, dogs and other non-human animals to investigate the mechanism(s) of heart disease. This is despite significant physiological differences between human and rat hearts and differences between how men and women experience heart disease and respond to treatment.
Rodent ‘models’ have been used for nearly half-a-century, with various strategies to induce heart failure in rats, including injecting toxins to directly damage heart tissue, or tying off the blood supply to the heart. Often these operations are carried out on very young animals so that the researchers can examine the progressive worsening of disease as the animal grows. At three to four weeks old, rat pups have the blood flow to their heart restricted so that by the time they reach eight weeks, they are panting, with swollen bellies and fluid on their lungs – all signs of overt heart failure. But are these ‘animal models’ really relevant to people?
The short answer is no. Despite a half-century of research funding and countless rodent experiments, ‘translation’ of animal data to people has been poor to non-existent. This has led to calls for ‘improved animal models’ for human heart disease, with dogs being the favoured species. This is because in comparison to rodents, dog cardiac physiology more closely resembles human.
Dogs, however, walk on four legs whilst humans stand upright, yet the canine ‘models’ of human disease never account for this major difference. In research laboratories, dogs do not live long enough to develop heart failure naturally and as the young, healthy dogs in research laboratories don’t have heart failure, it has to be experimentally induced. The experiments involve extensive surgery – one model requires introduction of catheters into the arteries followed by destruction of the nerves that control the heartbeat. In some cases, metal hooks are inserted into the heart valves to destroy rhythmic beating.
Experimental induction of heart failure is therefore severe and distressing.
In people, kidney disease is often associated with heart disease: reduced kidney function increases the heart rate as more blood is pumped to the kidneys, which increases blood pressure and impacts the heart. To investigate the effects of high blood pressure in the canine models of disease, dogs have their kidneys wrapped tightly to block blood flow and cause irreversible damage. In 2016, nine elderly dogs underwent this operation in a study to investigate tissue changes in the heart. This occurred despite earlier evidence of this so-called ’tissue remodelling’ in people with heart failure and the use of markers of tissue remodelling to diagnose heart failure in people. In 2015, the Living Heart Project showed that sophisticated computer models can predict the heart tissue changes that are seen in the clinic. This represents a major advance and further reduces justification for the animal experiments.
The change in research approach that the Living Heart Project heralds is much needed – survival rates for heart failure patients have not improved since the 1990s. Severely manipulated rodents and dogs undergoing extensive surgery are not providing the new, life-saving treatments that human heart patients so urgently need.
Other advances are also moving us away from reliance on animal models. Would it surprise you to know that it is possible to produce beating human hearts in the lab? In 2015, scientists from Massachusetts General Hospital and Harvard Medical School used human skin cells, grown under specially designed conditions, to produce a functioning heart, with the ultimate aim of creating a perfect match for people in need of a heart transplant. Thousands of people need a heart transplant, but there is a shortage of donors and the complication of organ rejection. Rejection reactions—where the transplanted organ is ‘attacked’ by your body—damages the donated organ, but adapting your own cells to make a new heart would prevent rejection. Further advances focus on developing new drugs – the European heart-on-a-chip initiative is using human stem-cell derived cardiac models to screen potential treatments for heart failure. The Living Heart Project recently signed a five-year collaborative research agreement with the U.S. Food and Drug Administration to use their computer models to develop new pacemakers and other supportive devices.
It seems that there is much to celebrate in human-relevant heart research, and no need to break any more animal hearts.