Newswise — HOUSTON -- ( April 9, 2012 ) -- Heart cells starved of nutrients are less likely to be damaged during periods of decreased blood flow and sudden influxes of blood, known as ischemia and reperfusion, and are also less likely to get out of synch with their cellular neighbors, the damaging phenomenon called arrhythmia.
Methodist DeBakey Heart & Vascular Center scientists learned that starved heart cells maintain normal calcium cycling and basic mitochondrial function far longer than non-starved cells during periods of extreme stress.
The findings, which will appear in an upcoming issue of Cell Calcium, add to a growing body of scientific evidence that suggests the consumption of less energy -- while maintaining balanced nutrition -- can benefit tissues by enhancing cell performance and reducing DNA damage associated with the aging process.
"We are connecting several loose facts about calorie restriction and heart function, in particular, arrhythmias," said cardiac electrophysiologist Miguel Valderrábano, M.D., the study's principal investigator. "We have shown why nutrient restriction protects the cells from ischemia and reperfusion. Normal function means less risk of arrhythmias, during which heart cells stop communicating properly with each other, and which can cause further damage, even sudden cardiac death."
Heart disease remains the number one cause of death in the U.S. and around the world. About 400,000 cases of sudden cardiac death occur annually in the U.S. Coronary artery heart disease, which causes ischemia and reperfusion arrhythmias, is the leading cause.
The scientists studied cultured heart cells originally derived from young rats. The cells were grown in a 2 cm-by-2 cm monolayer, to allow ease of study. The researchers mapped intracellular calcium ions and mitochondrial membrane potential with the help of fluorescent tags. Ischemia was simulated by placing a 1.8 cm-by-1.8 cm cover slip over the center of the cell culture, which limited oxygen and nutrient flow to that portion of the culture. Reperfusion was simulated by the removal of the cover slip.
All cells were raised for two to three days in a blood-serum medium containing glucose. One group of cells was subjected to a low-nutrient medium for 24 hours prior to the ischemia-reperfusion experiments.
Nutrient-restricted cells were more likely to maintain normal mitochondrial action potentials (the capacity to produce energy) and normal calcium cycling across the cellular membrane (required for normal, synchronized heart beats) than cells that had access to nutrients all along.
Nutrient-restricted cells maintained normal pulsing about eight minutes longer than unrestricted cells during ischemia, and nutrient-restricted cells maintained mitochondrial action potentials and calcium cycling activity throughout simulated ischemia and reperfusion events, compared to unrestricted cells, which lost significant action potentials during reperfusion.
"These experiments are not yet telling us whether we can emulate the effects of nutrient restriction in humans to lessen the damage of ischemia-reperfusion," Valderrábano said. "But we have shown one way nutrient restriction may be acting to reduce heart tissue damage, a subject of interest to many laboratories."
Cell Calcium is published by Elsevier.
Sufen Wang and Jiexiao Chen of the Methodist DeBakey Heart & Vascular Center also contributed to this work. It was supported by The Methodist Hospital Research Institute and continuing funding from the National Institutes of Health.