Preliminary research suggests that optogenetics could eventually replace electric shocks in the treatment of atrial fibrillation.
Preliminary research suggests that optogenetics could eventually replace electric shocks in the treatment of atrial fibrillation (AF).
At present, electric shocks can often restore normal function to patients whose hearts have just begun to beat irregularly, but the process is painful, even when performed using expensive and risky anesthesia.
Researchers from the Netherlands, however, have developed an alternative defibrillation method that uses optogenetics to insert depolarizing ion channels into the heart and then activating them with LEDs. Testing is still at very early stages, but the results so far have been promising.
Rather than start with three-dimensional animal hearts and be unable to monitor events under the surface, the study team started by isolating cardiac muscle cells from a rat atrium, replating them in culture dishes and allowing them to form intercellular connections.
Researchers induced atrial fibrilaltion in 31 of these nearly two-dimensional hearts and then used a lentivirus to insert the calcium-translocating channel rhodopsin (CatCh) gene into the hearts.
Finally, they turned a light onto the genetically modified hearts, hoping to activate the CatCh gene, which is a light sensitive depolarising channel, and restore normal cardiac function. All 31 hearts responded.
“This is the first evidence of a shockless defibrillation,” said the study’s lead researcher, Brian O. Bingen, MD, in a news release that accompanied the announcement of the study results. Bingen is also a PhD candidate at Leids Universitair Medisch Centrum.
“Our method of using optogenetics to defibrillate by light is completely painless and looks promising but more research is needed before it can be applied in patients,” said Bingen.
Bingen presented the findings and demonstrated the technique earlier this month at the Frontiers in CardioVascular Biology 2014 meeting, which was held in Barcelona, Spain. He then announced plans for getting back to work. “We now have to test our method in the 3D setting,” he said.
Bingen also noted that “In that scenario we won't be able to see the defibrillating mechanism in as much detail, but we hope that it will be possible to terminate AF in the complete heart. We will also test other types of light or energy sources that penetrate the body more deeply and could be applied externally, avoiding the need for an implanted device.”
Animal trials will come first and, if the technique keeps working, human trials will likely follow because the optogenetic method has several potential advantages over electric shocks.
The anesthesia necessitated by electric shocks is expensive and potentially dangerous. Worse, because of the pain, some patients hesitate to undergo the procedure as quickly or as frequently as they should, which can cause their AF to get worse.
AF usually progresses from a paroxysmal form, in which episodes of irregular heartbeat last from several minutes to several days, to a persistent and eventually a chronic form. Once the disease becomes chronic, the heart can no longer be shocked (or lit) back into normal rhythm.
Thus, frequent treatments that prevented the progression from paroxysmal AF to chronic AF — or at least delayed it — would extend patient lives and improve the quality of those lives.
And the optogentic technique could, potentially, enable far more frequent treatments delivered in a timelier manner.
“In theory, the patient could be given an implantable device with a mesh of light emitting diodes and when AF occurs you turn the light on and the AF stops,” Bingen said.