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The Heart of the Matter

Recent studies have found that the critical role played by mitochondria in cardiac cells lies at the heart of “myocardial preconditioning?. This term refers to the period of brief ischemia and reperfusion via revascularization and oxygenation of the heart that primes the mitochondria into a stress-resistant state so that prolonged periods of ischemia in the future are much more tolerable. Effective priming results in reduced risk for cardiac infarctions and reduced rates of cardiac cell death, perhaps because the mitochondria have acquired a protective phenotype in the ischemic area. Additionally, studies have suggested that generation of ROS or Reactive Oxygen Species may play a part in signaling cardiac cells in ischemic regions of the heart to undergo apoptosis or programmed cell death rather than necrosis, and in doing so, allow for partial or even full recovery of cardiac tissue. While conducting research with my mentor at the VA Medical Center over the past year, I found a significant decrease in generation of ROS in primary cardiac swine cells under hypoxic conditions (5% oxygen) as opposed to normoxic conditions (21% oxygen), results I had the opportunity to present at the Undergraduate Research Symposium this past spring. These conditions mimic in vitro what occurs in vivo in an ischemic heart, implying that ROS may act as a signaler or downstream regulator of a signaler in inducing the myocardium to hibernate.
In a similar experiment conducted by Vanden, T. et al., chick embryonic ventricular myocytes were exposed to hydrogen peroxide, a type of ROS, to mimic the effects of inducing hypoxic preconditioning. The researchers found a significantly lower level of cell death for these myocytes when hypoxia and reoxygenation were induced in the future.
Even more interesting, recent research concerning myocardial hibernation conducted by Levy R. et al. has shown its association with the septic heart. Sepsis, a systemic illness caused by bacteria and toxins and resulting in multi-organ failure, is the leading cause of death for critically ill patients in the U.S, making the hibernating model even more important. The study found that the changes seen during myocardial hibernation occur in the septic heart, and that during sepsis, cardiomyocytes (heart muscle cells) become “functionally hypoxic? even though plenty of oxygen is available and no ischemia occurs. So what appears to be multiple organ failure might actually be multiple organ hibernation, and play an adaptive or protective role.
I find this research fascinating and highly applicable to cardiac care as well as my future career area of interest, cardiothoracic surgery. Over the last few weeks, I’ve been working on ring studies with my mentor. The LAD or left anterior descending artery (the site of constrictor placement to induce ischemia) and circumflex were isolated from revascularized pig hearts, and vascular constriction was measured at resting conditions and stressed conditions with the addition of ET-1, a well-established vasoconstrictor. What we’re seeing is amazing and difficult to interpret. In the coming weeks, I’m hoping to try to get a handle on how to analyze iTRAC data and proteomics in order to begin to get an understanding of what we’re observing – should be exciting!


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