Researchers working with guinea pigs have created what is believed to be the first biologic cardiac pacemaker, according to an article in the September 12th issue of Nature.

"Most applications of gene therapy try to cure a disease caused by a single defective or missing gene, but we used the cells' genes as a tool box to tweak its function," said investigator Eduardo Marban, M.D., Ph.D.

After the researchers genetically altered the balance of potassium within guinea pig myocardial cells, the cells spontaneously and rhythmically fired. Such a biopacemaker is a potentially important option for patients at too high a risk for infection from implanted electronic pacemakers or too small for an implanted device, said the researchers.

"We've created a biologic pacemaker in the guinea pig, but now the hard work comes," says Marban. "We need to fine tune it -- develop controlling strategies, find the optimum place to re-engineer the cells in the heart, control the frequency of the new pacemaker. But there is light at the end of the tunnel."

The American team had hypothesized that altering the cellular potassium balance might allow heart cells to regain intrinsic excitability. Previous researchers had discovered a number of years ago that if just three specific building blocks of the myocardial potassium channel are altered, the potassium balance is disrupted.

In the current work, researchers attached the gene for the defective channel to a virus, and virus-infected cells faithfully transcribed the genes. Three to four days after injecting the gene-carrying virus into the heart muscle of guinea pigs, Junichiro Miake, Ph.D., lead author, saw that the myocardial cells had begun making the defective potassium channel. Even more important, a new, faster, pace-setting impulse was clearly visible on their electrocardiograms.

"This potassium channel acts like an anchor, keeping heart muscle cells from developing pacemaker-like abilities," explained Marban. "By blocking the channel, we effectively lifted the anchor, freeing the muscle cells to re-establish abilities they last held in the developing embryo."

"When this channel is blocked, heart muscle cells that normally have to wait for stimulation begin to beat on their own," added Marban. "In many important ways the guinea pig is similar to humans. Its cardiac electrophysiology is very similar, and this channel is as common in human heart muscle as in the guinea pig. We believe the same principles will prevail in humans."