Scientists tackle mystery of brain

activity during cardiac arrest

A research project funded by the Austrian Science Fund FWF is attempting to provide scientific insights into an age-old mystery: what goes on in the brain of people who are on the brink of death due to cardiac arrest and have memories of the time when their heart had stopped after resuscitation? Although a very rare occurrence, such experiences are reported from time to time. From a scientific point of view they are hard to explain, since electrical activity in the brain is thought to cease seconds after the blood supply is interrupted. Scientists are still at a loss, but according to project head Roland Beisteiner, there are explanations for such events.

"Although no comprehensive evidence of brain activity during cardiopulmonary resuscitation (CPR) has been found so far, this doesn't mean that it doesn't exist," he said.

Beisteiner, a neurologist from the Medical University of Vienna said an increasing amount of data, for instance from coma patients or the realm of anesthesia, points to the fact that the brain has great capacities for regeneration and information processing invisible to outside observers.

"We need as much physiological data as we can get and better control of what happens during CPR," said Beisteiner. Together with the neuro-scientist Michael Berger and the emergency physician Fritz Sterz, Beisteiner is trying to collect such data for the first time in the ongoing international AWARE study, which is coordinated by New-York based emergency physician Sam Parnia.

Austrian researchers were previously involved in AWARE (AWAreness during REsuscitation) by evaluating questionnaires from patients "pulled back to life." In a subsequent step, emergency rooms of medical centers in the U.S., UK and Austria will be equipped with sensors to register blood flow and electrical activities in the frontal lobe. Researchers know from animal testing that brain activity declines rapidly upon cardiac arrest, but still remains at measurable levels for about 30 seconds. A recent study conducted in the U.S. suggests the brain may shift into something like a state of alert for this period and show signs of increased cognitive activity. There are also explanations for out-of-body experiences since visual-spatial perception can be manipulated, as has been demonstrated by experiments conducted by the Swiss neurologist Olaf Blanke.

"Blanke's experiments show that we can manipulate the feeling of mind and body being a single unit," said Beisteiner. "The brain seems to have a predisposition for disruption of this unity of space and body, and hence the sensation of leaving one's body may arise."

The three-year FWF project "Gedächtnisprozesse bei Herzstillstand-PatientInnen" (2015 - 2018, Memory processes in cardiac-arrest patients) is expected to lead to improvements in the technical aspects of resuscitation. "We need this research to understand what the brain can do. Above all, it is important for physicians to know whether patients perceive things even if one cannot tell that from the outside," Beisteiner said.

Blood test after heart surgery

helps assess stroke risk

The results of a blood test done immediately after heart surgery can be a meaningful indicator of postoperative stroke risk, according to a study by researchers at Wake Forest Baptist Medical Center (Winston-Salem, North Carolina). An acutely elevated level of blood urea nitrogen (BUN), a measure of kidney function detected through blood testing, was the most powerful predictor of postoperative stroke among the study's subjects.

Up to 9% of cardiac surgery patients suffer post-operative stroke, and these events are significantly more serious and more frequently fatal than those experienced in the general population.

"An elevated BUN level after surgery tells us that the kidneys aren't working well, which could mean that the blood vessels feeding the kidneys may be narrow," said Martinson Arnan, assistant professor of neurology at Wake Forest Baptist and lead author the study, published in the March online issue of the Annals of Thoracic Surgery. "We found that if kidney vessels aren't performing well, it is likely that other vessels in the body, including the brain, aren't working well either resulting in a higher risk of stroke."

In the case-controlled study, the researchers analyzed 5,498 adults ages 18 to 90 who underwent cardiac surgery from 2005 to 2010 and identified 180 who suffered a stroke within 10 days of surgery. An elevated BUN level was not only the most accurate predictor of stroke in this group, it greatly exceeded the predictive accuracy of more commonly recognized risk factors such as smoking, pre-operative high blood pressure and emergency surgery.

The test that measures BUN is inexpensive and routinely administered before and after all cardiac surgeries. However, the test is most effective as a predictor for stroke if it is administered immediately after surgery rather than at the discretion of the physician, which is the current practice, Arnan said.

"Based on our research, we need to more carefully monitor patients with high BUN postoperatively for any symptoms of stroke so that they may benefit from therapy immediately," he said. "Anything that can help us better assess that risk can help decrease the incidence of stroke, decrease disability and reduce expenses."

This research also suggests that there may be a role for evaluating the narrowness of blood vessels bringing blood to the kidneys prior to surgery as a means of decreasing stroke risk.

Catheter ablation beats

heart regulating drug

Among patients with heart failure and atrial fibrillation, those who underwent catheter ablation were less likely to die, be hospitalized or have recurrent atrial fibrillation than patients taking a heart rhythm regulating drug, according to a study led by Luigi Di Biase of St. David's Medical Center and the Albert Einstein College of Medicine at Montefiore Hospital (Bronx).

Catheter ablation was most successful in procedures where ablation was required in other areas in addition to the pulmonary vein, researchers said.

Heart failure and atrial fibrillation often co-occur and are two of the most common heart problems in older adults. In the new study, 71% of patients treated with catheter ablation were free of atrial fibrillation, the study's primary endpoint, after two years of follow-up, while only 34% of patients who took the antiarrhythmic drug Amiodarone were free of symptoms at that point.

"Even when it is effective, Amiodarone often needs to be discontinued after a while due to serious long-term side effects," Di Biase said. "Our study suggests that in patients with heart failure and atrial fibrillation, catheter ablation is an effective alternative treatment that can help patients avoid or discontinue this drug to reduce the risk of these long-term side effects."

The study included just over 200 patients treated in eight European and U.S. hospitals. All patients had heart failure, atrial fibrillation and either an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D).

The researchers randomly assigned half of the patients to undergo catheter ablation, a surgical procedure in which doctors thread thin, flexible wires into the heart through blood vessels in the arm, groin or neck. These wires are used to deliver energy or heat that destroys the areas of heart tissue that cause the abnormal heart rhythm. The rest of the patients were treated with Amiodarone.

In addition to having a higher rate of freedom from atrial fibrillation, participants who underwent catheter ablation also had lower rates of hospitalization and mortality during the two-year follow up. The authors noted that 31% of patients receiving ablation were subsequently hospitalized compared to 57% of patients taking Amiodarone. Also, 8% of patients receiving ablation died during the course of the study compared to 18% of patients taking Amiodarone.

Di Biase said the type and extent of the ablation procedure had a marked impact on the procedure's success rate.

"If the ablation is limited to the pulmonary vein alone, the success rate goes down, almost to the level of the Amiodarone treatment," Di Biase said. "The highest success rates were for procedures in which other areas (in addition to the pulmonary vein) were ablated."

The specific areas that benefit from additional ablation depend on each patient's individual condition. In addition, many patients in the study required more than one ablation procedure to achieve freedom from atrial fibrillation.

Researchers link gene mutations

to congenital heart disease

Fetal ultrasound exams on more than 87,000 mice that were exposed to chemicals that can induce random gene mutations enabled developmental biologists at the University of Pittsburgh School of Medicine (Pitt) to identify mutations associated with congenital heart disease in 61 genes, many not previously known to cause the disease. The study, published online in Nature, indicates that the antenna-like cellular structures called cilia play a critical role in the development of these heart defects.

The findings are the culmination of an effort to find the genetic determinants of structural heart disease in the "Bench to Bassinet" program, launched six years ago by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, led at Pitt by principal investigator Cecilia Lo, a professor and chair of the Department of Developmental Biology, Pitt School of Medicine.

"This project has given us new insights into the biological pathways involved in development of the heart," Lo said. "The genes and pathways identified in our study will have clinical importance for interrogating the genetic causes of congenital heart disease in patients."

For the study, Lo's team mated mice exposed to chemicals that could create random genetic mutations, resulting in 87,355 pregnancies. They scanned each fetus using noninvasive ultrasound and recovered over 3,000 independent cases of congenital heart defects, all incompatible with life. They sequenced the genes of mutant animals and compared them to those of unaffected offspring to identify 91 recessive mutations in 61 genes.

"We were surprised to learn many of these genes were related to the cilia, or cilia-transduced cell signaling," Lo said. "These findings suggest cilia play a central role in the regulation of heart development, including patterning left-right asymmetry in the cardiovascular system critical for efficient oxygenation of blood."

She added that pathways recovered in the mouse study show overlap with those associated with de novo, or spontaneous, mutations identified in congenital heart disease patients. Co-investigators of the project include other researchers from the University of Pittsburgh; the University of Massachusetts Medical School (Ann Arbor); the Jackson Laboratory (Sacramento); and Children's National Medical Center (Washington).