Stopping the heartache

A significant fraction of damage to heart muscle occurs after blood flow is restored following myocardial infarction, or heart attack.  This type of damage, called ischemia reperfusion injury, is a contributor to ongoing cardiac health issues for heart attack survivors. Given that approximately 750,000 Americans experience heart attacks every year and one in eight will experience a heart attack in their lifetime, effective strategies to prevent lasting damage to the heart are needed.  Currently, most therapeutic interventions target blood clots that cause the ischemia but do little to prevent tissue damage once blood flow is re-established.

In the current issue of Critical Care Medicine, Dr. Mark Roth and colleagues in the Basic Sciences Division show that the essential nutrient iodide can protect heart tissue when administered prior to re-establishing the blood supply or reperfusion of the heart.  Building on previous studies with selenide, another protective micronutrient, and with iodide in mice, the authors used two animal models, rats and pigs, believed to be more relevant to human cardiovascular function and sensitivity to ischemia reperfusion injury, to determine whether iodide might be the sought-after protective agent. 

Roth and colleagues sought to demonstrate that a reduction/oxidation, or redox, buffering agent such as iodide could make a clinically significant difference in the amount of heart tissue damage once blood flow was reestablished.  Iodide is one of the many nutrients we obtain from a normal diet; iodide-rich foods include green vegetables, fish and seaweed.  The body’s requirement for iodide arises primarily from incorporation of iodide into thyroid hormones T3 (tri-iodothyronine) and T4 (thyroxine).  These hormones are secreted from the thyroid and regulate metabolism throughout the body.  The daily dietary requirement is miniscule, about 150 micrograms for adults, hence the micronutrient moniker.

Roth and colleagues administered 1 mg/kg sodium iodide, almost 500-times the minimum daily dietary requirement, before myocardial infarction was induced by cutting off blood flow through the coronary artery.  Iodide was given intravenously after ischemia was induced and 5 minutes before blood flow was reestablished.  Without protective therapy extensive cardiac damage would result.  Cardiac damage was quantified after an hour of ischemia by measuring the release of cardiac troponin, a tissue injury biomarker, tissue histology and echocardiography.  Iodide, when given pre-reperfusion reduced the release of troponin and infarct size by 45% in pigs and 60% in rats.  Says Roth “Administration of electron buffers such as iodide may be an effective and safe way to reduce the incidence of and improve outcome after heart attack.” 

The mechanism by which iodide protects cardiac tissue from injury may be due to its ability to act as a “buffering” agent for redox chemistry.  When oxygen-rich blood re-enters a tissue that has been starved for oxygen, a dramatic shift in the redox potential occurs.  Iodide, with its swarming cloud of electrons can readily surrender electrons to quench reactive oxygen species and prevent oxidative damage.  Since iodide has been around since the beginning of time on Earth, the protective effect in ischemia/reperfusion injury “… raises the idea that primordial electron buffers play a fundamental role in maintaining homeostasis as they likely did when life first appeared on earth” according to Roth, lead author on the study.  Interestingly, intravenous administration of iodide also increased the peroxide scavenging ability in blood, supporting the “redox buffer” mechanism of action.  The authors will “… continue to try to understand how electron buffers work and to harness them as medicines.”

Iodide is an exceptionally safe nutrient.  Iodized table salt, or sodium chloride supplemented with either potassium iodide or potassium iodate, provides approximately 45 micrograms of iodide per gram of salt.  This form of iodide can more than adequately supply the body’s iodide needs while staying below the daily recommended salt intake limit (1.5 grams for adults).  The results reported by Roth and colleagues raise an interesting question: could higher levels of dietary iodide intake lead to better long-term outcomes for coronary artery disease sufferers before heart attacks happen?  Future research will determine the answer.

Morrison, M.L., Iwata, A., Keyes, C.C, Langston, W., Insko, M.A., Langdale, L.A. and Roth, M.B., Critical Care Medicine, 2018 Jul 30 [Epub ahead of print]

Research was supported by the Army Research Office.