Scientists have found that ordinary voluntary muscle can be transformed into the specialised muscle tissue found in the heart. They are using this discovery to produce a natural pump with no risk of tissue rejection for people awaiting heart transplants.
The surgical approach, called dynamic cardiomyoplasty, is already under trial in Italy, Germany and the US. Its great advantage is that the patient's own tissues are used to build the "assist pump", so there is no need for powerful drugs to stop rejection.
"It is still very experimental," explained Dr Kay Ohlendieck of University College Dublin's Department of Pharmacology in the Conway Institute of Biomolecular and Biomedical Research. A UCD team under Dr Ohlendieck is analysing the muscle transformation process to find the best possible method for making this change in the tissue.
"What we have found is that muscle is very plastic," he explained. "Muscle is very unique tissue in that external stimulants dictate its internal biochemistry."
Heart muscle is "slow" muscle, involuntary and fatigue-resistant, he said. Skeletal muscle is "fast", in that it responds quickly, is voluntary but can rapidly be overcome by fatigue. The researchers, however, can "change the biological pulse pattern" - the electrical signals which stimulate the tissue - and in so doing can transform one muscle type into another.
The work in Dublin has prompted two research papers, one on the complex biochemistry inside muscle cells, published last month in the International Journal of Molecular Medicine. The other will be published next January in the Journal of Applied Physiology. So impressed was its US publisher, the American Physiological Society, that it decided to issue a commendation on the quality of the science.
The UCD research group includes Dr Gabi Froemming, Ms Shona Harmon, Mr Niall Lennon and Ms Clare O'Reilly. It also involves German collaborators from the University of Konstanz, led by Prof Dirk Pette.
The Irish and German groups are involved in understanding the transformation process, how back muscle can be changed to act like heart muscle, Dr Ohlendieck stated. They use animal-derived muscle "models" and examine the biochemical alterations that follow the change in biological stimulation.
The proteins expressed inside the cells vary depending on the input signals they receive, he said, but all muscle contraction is based on the transfer of calcium ions around the cell. "Calcium is the overriding second message inside the muscle which dictates the contractal state of the muscle. There are at least 10 proteins dictating that."
The surgical procedure is a remarkable undertaking. The doctors first isolate a piece of a back muscle, the latissimus dorsi, but leave both its blood supply and its nerve connections intact.
They connect an electrical device, like a pace-maker, to the nerve and override the normal signal, changing it to the kind of signal that controls the heartbeat, Dr Ohlendieck explained.
"The biggest difference between the heart and skeletal muscle is the heart is completely fatigue resistant," he stated. The cell transformation takes between two and six weeks but signs of the change inside the cells come much more quickly. "We see after only three days a drastic change," he said. "They change in colour from white to red, they become much smaller and change to contract much slower."
Once transformed, the muscle, still connected to its own blood supply and nerves, is wrapped around the heart of patients with severe heart disease. The transformed back muscle is connected to a pace-maker which controls its contractions. This is synchronised with the patient's own heartbeat.
The muscle gives the diseased heart an extra push, enabling it to circulate more blood with less effort. The technique, he added, is mostly for people on waiting lists for heart transplants, and helps them to stay healthy longer as they await their surgery.
"The biggest advantage is it doesn't cause any problems with rejection," he said. "You use the body's own tissue without causing any immune problem."
UCD's role is to find the best way to do the transformation, "to get the right condition without damaging the muscle fibres", he explained. Variables include the mix of stimulation versus rest and how much stimulation is given at any one time.
The transformation comes in three stages, he said. First the "very fast" fibres are destroyed by the change in signal. Soon after, "true trans-differentiation" from fast to slow muscle takes hold and begins to develop. The final stage, he said, was when emerging new cells took on the shape and function of slow muscle.
UCD's biochemical focus on the movement of calcium ions through the cell has given the team important new insights into heart disease generally, Dr Ohlendieck explained. The group's October paper was an examination of a heart disease called dilated cardiomyopathy, caused by an abnormal regulation of calcium ions within heart cells.
Understanding the biochemistry of the disease opens up opportunities for developing new medication and treatments of this type of chronic heart disease.