Researchers at the Johns Hopkins University School of Medicine have found that a chemical commonly used in the production of such medical plastic devices as intravenous (IV) bags and catheters can impair heart function in rats. Appearing online this week in the American Journal of Physiology, these new findings suggest a possible new reason for some of the common side effects—loss of taste, short term memory loss—of medical procedures that require blood to be circulated through plastic tubing outside the body, such as heart bypass surgery or kidney dialysis. These findings also have strong implications for the future of medical plastics manufacturing.
In addition to loss of taste and memory, coronary bypass patients often complain of swelling and fatigue. These side effects usually resolve within a few months after surgery, but they are troubling and sometimes hinder recovery.
His personal experience with coronary bypass surgery propelled his search for a root cause for the loss of taste phenomenon, reports principal investigator Artin Shoukas, Ph.D., professor of biomedical engineering, physiology and anesthesiology and critical care medicine at Johns Hopkins. "I'm a chocoholic, and after my bypass surgery everything tasted awful, and chocolate tasted like charcoal for months."
Shoukas and Caitlin Thompson-Torgerson, Ph.D., a postdoctoral fellow in anesthesiology and critical care medicine suspected that the trigger for these side effects might be a chemical compound of some kind.
To test their theory, Shoukas and his team of researchers took liquid samples from IV bags and bypass machines before they were used on patients. The team analyzed the fluids in another machine that can identify unknown chemicals and found the liquid to contain a chemical compound called cyclohexanone. The researchers thought that the cyclohexanone in the fluid samples might have leached from the plastic. Although the amount of cyclohexanone leaching from these devices varied greatly, all fluid samples contained at least some detectable level of the chemical.
The researchers then injected rats with either a salt solution or a salt solution containing cyclohexanone and measured heart function. Rats that got only salt solution pumped approximately 200 microliters of blood per heartbeat and had an average heart rate of 358 beats per minute, while rats injected with cyclohexanone pumped only about 150 microliters of blood per heartbeat with an average heart rate of 287 beats per minute.
In addition to pumping less blood more slowly, rats injected with cyclohexanone had weaker heart contractions. The team calculated that cyclohexanone caused a 50 percent reduction in the strength of each heart contraction. They also found that the reflex that helps control and maintain blood pressure is much less sensitive after cyclohexanone exposure. Finally, the team observed increased fluid retention and swelling in the rats after cyclohexanone injections.
According to Thompson-Torgerson and Shoukas, they would like to figure out how these side effects—decreased heart function and swelling—occur and to what degree cyclohexanone is involved. Despite the findings in this study, they emphasize that patients should listen carefully to the advice of their physicians. "We would never recommend that patients decline this type of treatment if they need it," says Shoukas. "On the contrary, such technologies are life-saving medical advances, and their benefits still far outweigh the risks of the associated side effects. As scientists, we are simply trying to understand how the side effects are triggered and what the best method will be to mitigate, and ultimately remedy, these morbidities."
This study was funded by the Bernard A. & Rebecca S. Bernard Foundation, the American Heart Association, the W.W. Smith Foundation, the National Institutes of Health, the Pulmonary Vascular Research Institute, the American College of Cardiology, the Shin Chun-Wang Young Investigator Award, the American Physiological Society, the Joyce Koons Family Cardiac Endowment Fund, and funds from Dr. Shoukas.
Authors on the paper are Caitlin S. Thompson-Torgerson, Hunter C. Champion, Lakshmi Santhanam, Z. Leah Harris and Artin A. Shoukas, all of Johns Hopkins University School of Medicine.