2023 UCI Institute for Clinical & Translational Science
PI: Yama Akbari, MD, PhD
Co-I: Michael Rochon-Duck, MD
Brain-heart connections during cardiac arrest for early stage prognosis and treatments to improve outcome
Spreading depolarization (SD) is a massive release of ions and energy that travels across the brain surface and is detectable using electrical recordings. SD is sometimes called a “brain tsunami,” alluding to the fact that they are the largest and most powerful brain waves detected. The most common causes of SD include migraine auras (sensory disturbances that can precede the headache), seizures, traumatic brain injuries (TBI), strokes, and cardiac arrest (CA) which starves the brain of oxygen. Understanding SD is important to physicians because SD can cause brain tissue to swell and release toxic chemicals that can trigger the death of neurons.
While previous investigations have looked at how SD affects brain tissue directly, we want to see if SD can also have impacts on organ systems beyond the brain. Using a rat model of CA, our lab was the first to show SD may change the rate at which blood pressure drops off as the heart becomes progressively weaker. This may not be as surprising as it appears since the heart and brain are interconnected through a variety of pathways called the autonomic nervous system, the most famous such pathway being the vagus nerve. We suspect that SD alters how the vagus nerve communicates with the heart, perhaps triggering arrhythmias (irregular heart rhythms) that can be detected by monitoring the electrical activity of the heart. Other researchers have found that stimulating the vagus nerve with electrodes can make it harder for SD to happen in the brain, but no one has yet done experiments to see if stopping SDs can also stop arrhythmias in the heart.
Our lab specializes in a rat model of CA and cardiopulmonary resuscitation (CPR), and we want to be the first to test the hypothesis that SD induces arrhythmias due to vagus nerve signaling. We induce CA in a rat by stopping its air supply (done as humanely as possible and approved by veterinarians), which mimics choking, drowning, or drug overdoses in humans. We then will use electrical and optical recordings of brain activity and metabolism, as well as recordings of heart activity and blood pressure. This will allow us to correlate SD events in the brain to arrhythmias in the heart by using computational algorithms to extract detailed statistics. After we establish whether SD is correlated with arrhythmias, we will experimentally block or stimulate the vagus nerve with electrodes or drugs to test this relationship between the heart and brain.
Doing these experiments in animals will tell us what to look for in human patients. In parallel to these animal experiments, we will use a database of brain recordings during CA in the hospital to see if the same signatures of SD and arrhythmia occur simultaneously in patients. Even after successful CPR, most people who have CA are left in comas or have permanent brain damage. Understanding how the brain interacts with the heart during the process of dying may be the first step to allow doctors to develop better, targeted resuscitation methods.
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