Heart attacks are an unfortunately common occurrence across the country. One of the biggest consequences of a heart attack comes from ischemic reperfusion (IR). This is when tissue that has not had access to oxygen, in this case, due to a heart attack, gets flooded with oxygenated blood. The oxygen then kickstarts the stalled mitochondrial energy production.
The issue is that when this kickstart happens, it happens too quickly. The energy production system of the mitochondria is robust but constantly needs to maintain a balance of what is called reactive oxygen species (ROS). If ROS levels in a cell reach a certain point, that cell undergoes cell death. This cell death translates into tissue damage of oxygen-depleted tissues after heart attack recovery.
Preventing this tissue damage is a goal of researchers studying the cardiovascular system. Many methods revolve around the inhibition or regulation of the mitochondrial energy production system. The inhibition of the proteins malate aspartate shuttle (MAS) and succinate dehydrogenase (SDH) are current leads. Other studies have found already found them to be effective in preventing IR to a small degree. A team from the Aarhus University Hospital in Denmark wanted to know how inhibition of SDH affected the recovery of diabetic patients versus non-diabetic patients post-heart attack. Diabetes is associated with mitochondrial dysfunction and may change the way patients react to treatment via mitochondrial regulation.
Using both human and mouse models, they found that diabetes did indeed reduced the effectiveness of the SDH inhibitor in IR recovery. Even then, diabetic tests required larger doses of the inhibitor to produce an effect and only worked in animal models. In non-diabetic experiments, the SDH inhibitor protected cardiological tissue from IR damage, in line with observations from other studies.
The group goes on to point out that the inhibitors used to treat IR and prevent damage could be physiological instead of synthetic. There are a few natural compounds that could replace their synthetic inhibitor that maintain the same SDH inhibition. They also note that IR is not simple to treat and will require a combination of therapies to completely protect tissues from IR damage.
The team concludes, “SDH inhibition may provide a pharmacological target to counteract IR injury. However, synthetic agents have narrow therapeutic range and efficacy may be influenced by diabetes.”