Blood and power: How to prevent a heart from dying
This story begins in the time of cholera. The year was 1831, and a disease structured to drain its host of water was infecting Europe. Doctors were at a loss for how to stop the sickness, but they devised a partial solution to help alleviate the symptoms of the illness. Doctors gave a saline solution to patients with the hope that the mixture could replenish the liquids leached by the disease without drowning the blood. It worked. Blood pressure increased, people felt better, and some of them even survived for a bit.
Saline solution is still used today, and it’s still effective. But it could be better, according to Steven Poelzing, an associate professor at the Virginia Tech Carilion Research Institute.
“Intravenous saline solutions could do more than improve blood pressure. They could help prevent sudden cardiac death,” said Poelzing, also an associate professor at the Virginia Tech–Wake Forest University School of Biomedical Engineering and Sciences. Sudden cardiac death occurs when the electrical conduction of the heart is interrupted, and it’s a significant cause of death in many groups, particularly young athletes.
Poelzing came to this conclusion after several studies were conducted in his laboratory, each building on the previous experiment’s results. His team has published several culminating papers in the past year, the most recent of which was published in the European Journal of Physiology. Poelzing’s team found that the composition of different solutions could drastically affect the speed at which the heart could conduct electricity – the pace of which needs to be kept within a certain range and at a steady rate in order to sustain life.
“Scientists and clinicians know that when your heart gets sick, gap junctions uniformly downregulate. They start to disappear until the heart stops working,” Poelzing said. Gap junctions connect cells, transporting information and conducting electricity. “If you block the gap junctions, conduction slows, but there’s not a magical threshold for sudden cardiac death.”
In fact, in rodent studies, animals with only half the gap junctions as their healthy counterparts are just as likely to live normal lives. The problem, Poelzing said, is whether the rodents have the same rate of electrical conduction. One research camp claimed that conduction was slowed in mice with fewer gap junctions, while the other research camp claimed that there was no measurable variation in conduction.
Why the difference?
“Experimental techniques in science are handed down like your great-grandmother’s secret recipe,” Poelzing said. “Every generation introduces little quirks into the recipe. Each research group bathed their samples in a slightly different solution, the components of which either caused more water or less water in the heart.”
Neither group was wrong, according to Poelzing. The fluid hydration state of the heart dictated the rate of conduction velocity—that much was obvious. But the data were pointing to something else surprising.
“It was the opposite of what we had hypothesized,” Poelzing said. “The heart with the smaller vascular space – the one with less water – should have faster electrical conduction than the heart with the larger vascular space. We saw the opposite.”
For roughly the past century, scientists have worked on the assumption that all electricity activity goes through gap junctions, and there is no other mechanism through which cells conduct electricity. In recent years, however, things have become more complicated.
“The body has many alternative mechanisms to sustain life,” Poelzing said. “In the case of electrical conduction in cardiac cells, gap junctions might not be the only path.”
There’s a pocket, called the perinexus, near the gap junctions between cardiac cells. Poelzing’s colleague Robert Gourdie, who is a professor at the Virginia Tech Carilion Research Institute, discovered the pocket in 2011, and they found that it is chockfull of sodium channels. Poelzing and his team hypothesized that by decreasing the number of sodium ions in their solution, they could reduce the size of the pocket, and the electrical current could jump the cleft between cells quickly, speeding the rate of conduction. They were partly right.
“The solutions contain a mix of sodium, potassium, and calcium,” Poelzing said. “One solution with adjusted sodium levels would speed the rate of conduction, while another, with the same levels of sodium, would slow conduction.”
Poelzing’s team made 16 different solutions, adjusting for sodium, calcium, and potassium levels and ratios.
“We concluded that they all interact to affect cardiac conduction, but it’s a stacked effect,” Poelzing said. “One change won’t affect your heart that much, but changes to all three minerals can make all the difference.”
Imagine an elementary school orchestra concert, Poelzing said. One or two children may be out of sync or unable to hit the right notes, but, in general, the audience can recognize the piece as it continues playing. But, those bad notes can become distracting and knock the rest of the students out of tune. The piece becomes unrecognizable.
“That’s what I think causes sudden cardiac death,” Poelzing said. “Enough things go bad simultaneously that you start to see the loss of gap junctions, you start to see the loss of calcium, the loss of sodium and potassium. The electrical conductivity can’t jump from cell to cell anymore, and you get an abnormal electrical storm on your heart.”
Poelzing said a major step in the fight against sudden cardiac death is to consider changing the solutions used in ambulances and hospitals.
“The first thing they do for a medical procedure is hook you up to a bag of saline,” Poelzing said. “It’s okay – it’ll get your blood pressure up. But what if that bag of saline could be optimized? What if it could be designed to prevent sudden cardiac death?”
Like diabetics monitor their insulin levels, perhaps doctors could monitor the calcium, sodium, and potassium levels of their patients. Based on the results, doctors could administer solutions best suited to the patient – to restore the levels to the recognizable orchestral piece.
“These solutions could offer much more than they do now,” Poelzing said. “They could help people reach beautiful chords and be at equilibrium.”
Written by Ashley WennersHerron