Patients receiving donated lungs may develop arrhythmias, including atrial fibrillation. Researchers from Baylor College of Medicine in Texas reviewed the charts of all lung transplant recipients in 2006 and 2007. Of the 75 patients who underwent lung transplant, 38 percent developed arrhythmias within 30 days of transplantation. The most common arrhythmia was atrial fibrillation, followed by atrial flutter. Researchers speculate that the donor-derived tissue (atrial cuff or pulmonary vein) is a likely source of the arrhythmias passed to lung recipients.

Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California San Francisco (UCSF) have identified a genetic factor critical to the formation of chambers in the developing heart. The discovery of the role of a microRNA called miR-138, could offer strategies for the treatment of congenital heart defects.The heart is one of the first and most important organs to develop. In fact, embryos cannot survive long with a functioning heart. In vertebrates (animals with backbones), special cells form a heart tube; that tube loops back on itself to form the atrium and ventricle and the canal and valve that separates them. This requires a complicated sequence of genes turning on and off. MicroRNAs are very small RNAs of 20 to 25 nucleotides that regulate numerous gene functions. Approximately 650 human miRNAs are known, but only a few have yet been studied to determine what they actually do in a cell.

Researchers, led by Sarah Morton, an MD/PhD student at UCSF and GICD Director Deepak Srivastava MD, examined zebrafish, which are an ideal model system for understanding genetic functions. Zebrafish are small, reproduce fast, and are essentially transparent so that that events of heart formation can be studied while they are still alive. Yet many of their systems are quite similar to those of humans. For example, miR-138 is exactly the same in zebrafish and humans.

“What’s interesting is that a single microRNA is responsible for setting up the distinct patterning of a developing heart into separate chambers,” said Dr. Srivastava, senior author of the study. “Since many congenital heart defects involve abnormalities in the formation of the chambers, this is important information in finding ways of treating or avoiding those defects.”

The GICD scientists reported in today’s issue of the Proceedings of the National Academy of Sciences USA, that miR-138 is present in the zebrafish heart at specific times and in specific places in the developing heart. Furthermore, they showed that it is required to insure that the cardiac chambers develop properly. When the scientists used genetic engineering techniques to eliminate miR-138, cardiac function was disrupted, and the ventricles did not develop correctly, with the muscle precursor cells failing to mature properly.

“The miR-138 function was required during a discrete developmental window that occurred 24-34 hours after fertilization,” said Sarah Morton. The team also showed that the miRNA controlled development by regulating numerous factors that function jointly to define the chambers, including a key enzyme that makes retinoic acid.

Recent studies indicate that infusing hearts with stem cells taken from bone marrow could improve cardiac function after myocardial infarction (tissue damage that results from a heart attack).  But in a recent systematic review, Cochrane Researchers concluded that more clinical trials are needed to assess the effectiveness of stem cell therapies for heart patients, as well as studies to establish how these treatments work.

In a heart attack, blocked arteries can cut off the blood supply to areas of heart tissue.  This leads to myocardial infarction severe tissue damage caused by lack of oxygen, which is transported in the blood.

“We need more studies that look at the long term effects of these interventions, as well as at the types of cells that are used and how they actually repair the heart tissue,” says lead researcher Dr. Enca Martin-Rendon, who works in the Stem Cell Research Department, NHS Blood and Transplant, at the John Radcliffe Hospital in Oxford, UK.

The team drew together data from 13 different trials involving 811 patients.  Although these trials show that treatment with bone marrow stem cells (BMSCs) may lead to a moderate improvement in cardiac function, the researchers say there is still not enough evidence to confirm this.  They also found that BMSC treatment did not reduce the measurable area of damaged heart tissue.

Only three trials looked to see if effects lasted for more than six months after BMSC treatment.  The researchers discovered that in these trials, there was no evidence of any benefit 12 months after treatment.

Quite how BMSCs cause this short term benefit is uncertain.  One theory is that they enable extra blood vessels to develop, while another is that they release chemicals that encourage the growth of healthy heart muscle cells while decreasing the development of scar tissue in the damaged area.

“If it turns out these treatments are beneficial in any way, they could be made available to all heart attack patients.  We think infusion with stem cells may help increase blood flow into damaged heart tissues, but without more investment in this area of research, we can’t be sure,” says Martin-Rendon.

Scientists have discovered a compound that could lead to new treatments for heart attacks as well as methods to protect hearts during open heart surgery and other situations in which blood flow to the heart is interrupted.In the process, the researchers uncovered cellular mechanisms that help explain how alcohol can protect against heart attack damage. In addition, they have uncovered a possible key to reducing chest pain and the heart attack damage among millions of people of East Asian descent who are genetically unable to respond to nitroglycerin and other cardiovascular treatments.

A research team of scientists at Stanford and Indiana universities schools of medicine reports in the Sept. 12 issue of the journal Science that by jump-starting a particular enzyme they were able to significantly reduce the amount of cell death caused by lack of blood flow to the heart.

The group, led by Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford, found that administering a compound called Alda-1 activated the enzyme, reducing heart muscle damage in experiments involving rats.

First, however, the researchers studied various mechanisms known to provide cardioprotection to heart muscle cells, including the use of ethanol, to better understand how those mechanisms worked. That work revealed a cellular signaling system that activated a particular enzyme called ALDH2.

“The idea was to find a small molecule that could bypass the signaling process and activate the enzyme directly,” said Thomas D. Hurley, Ph.D., professor of biochemistry and molecular biology and director of the Center for Structural Biology at the IU School of Medicine. Hurley’s research has included years of study of the ALDH2 enzyme.

Although the Alda-1 molecule reduced heart tissue damage in laboratory tests, years of work will be necessary to refine the compound into a version that would be potentially effective and safe for human use, Dr. Hurley said. That benefit could extend to about 40 percent of people of East Asian descent who carry a mutated form of the ALDH2 enzyme, which puts them at increased risk of cardiovascular damage.

Sounding the chest with a cold stethoscope is probably one of the most commonly used diagnostics in the medical room after peering down the back of the throat while the patient says, “Aaaah”. But, research published in the inaugural issue of the International Journal of Medical Engineering and Informatics looks set to add an information-age approach to diagnosing heart problems. The technique could circumvent the problem of the failing stethoscope skills of medical graduates and reduce errors of judgment

Listening closely to the sound of the beating heart can reveal a lot about its health. Healthcare workers can identify murmurs, palpitations, and other anomalies quickly and then carry out in-depth tests as appropriate. Now, Samit Ari and Goutam Saha of the Indian Institute of Technology in Kharagpur have developed an analytical method that can automatically classify a much wider range of heart sounds than is possible even by the most skilled stethoscope-wielding physician.

Their approach is based on a mathematical analysis of the sound waves produced by the beating heart known as Empirical Mode Decomposition (EMD). This method breaks down the sounds of each heart cycle into its component parts. This allows them to isolate the sound of interest from background noise, such as the movements of the patient, internal body gurgles, and ambient sounds.

The analysis thus produces a signal based on twenty five different sound qualities and variables, which can then be fed into a computer-based classification system. The classification uses an Artificial Neural Network (ANN) and a Grow and Learn (GAL) network. These are trained with standardized sounds associated with a specific diagnosis.

The team then tested the trained networks using more than 100 different recordings of normal heart sounds, sounds from hearts with a variety of valve problems, and different background noises. They found that the EMD system performs more effectively in all cases than conventional electronic, wavelet-based, approaches to heart sound classification.

A disturbing percentage of medical graduates cannot properly diagnose heart conditions using a stethoscope, the researchers explain, and the poor sensitivity of the human ear to low frequency heart sounds makes this task even more difficult. The automatic classification of heart sounds based on Ari and Saha’s technique could remedy these failings.

New data, generated by David Ornitz and colleagues, at Washington University School of Medicine, St. Louis, have indicated a crucial role for signaling pathways that involve the protein sonic hedgehog in maintaining the blood vessels that supply the mouse heart and keep it beating.  These data have implications for drug development as they suggest that antagonists of hedgehog signaling pathways, such as those being developed as anticancer therapeutics, might have unwanted side effects.

In the study, mice lacking the ability to mediate hedgehog signaling in cells that form part of the blood vessels that supply the heart were found to die of heart failure.  This was because in the absence of hedgehog signaling the blood vessels of the heart were lost, meaning that the heart cells were no longer supplied with enough oxygen and died.  Although these data indicate a need for caution when developing clinical antagonists of hedgehog signaling, it is possible that the degree of inhibition needed to have a clinical effect on tumor development might not have the effect on blood vessels of the heart that completely eliminating expression of the protein does.

Researchers at the University of Cincinnati (UC) are looking for ways to reduce or prevent heart damage by starting where the problem often begins: in the genes.

Following a heart attack, cells die, causing lasting damage to the heart.

Keith Jones, PhD, a researcher in the department of pharmacology and cell biophysics, and colleagues are trying to reduce post-heart attack damage by studying the way cells die in the heart—a process controlled by transcription factors.

Transcription factors are proteins that bind to specific parts of DNA and are part of a system that controls the transfer of genetic information from DNA to RNA and then to protein.  Transfer of genetic information also plays a role in controlling the cycle of cells—from cell growth to cell death.

“We call it ‘gene regulatory therapy,’” says Jones.

So far, studies have identified the role for an important group of interacting transcription factors and the genes they regulate to determine whether cells in the heart survive or die after blood flow restriction occurs.

Often, scientists use virus-like mechanisms to transfer DNA and other nucleic acids inside the body.

The “virus” takes over other healthy cells by injecting them with its DNA.  The cells, then transformed, begin reproducing the virus’ DNA.  Eventually they swell and burst, sending multiple replicas of the virus out to conquer other cells and repeat the process.

Now, UC researchers are further investigating new, non-viral delivery mechanisms for this transfer of DNA.

“We can use non-viral delivery vehicles to transfer nucleic acids, including transcription factor decoys, to repress activation of specific transcription factors in the heart,” Jones says, adding that the researchers have made this successfully work within live animal models.  “This means we can block the activity of most transcription factors in the heart without having to make genetically engineered mice.”

Jones will be presenting these results at the International Society for Heart Research in Cincinnati, June 17-20.

He says this delivery mechanism involves flooding the cells with “decoys” which trick the transcription factors into binding to the decoys rather than to target genes, preventing them from activating those genes.

“We can use this technology to identify the target genes and then investigate the action of these genes in the biological process,” Jones says.

He says that this delivery has limitations and advantages.

“It can be used to block a factor at any point in time and is reversible,” he says.  “However, right now, a specific delivery route must be used to target the tissue or cell.”

Jones and other researchers are hoping that this new technology will allow them to directly address the effects of gene regulation in disease, as opposed to using classical drugs that treat symptoms or have significant adverse outcomes.

“So far, this seems to cause no adverse effects in animals,” he says.  “We are hopeful and are working toward pre-clinical studies.”

The increased beating of the heart that one experiences when in a stressful situation is just one part of the body’s response to stress, something often known as the “fight-or-flight response”. Another component of the fight-or-flight response is the suppression of pain, also known as stress-induced analgesia (SIA). Some of the nerves and nerve-produced peptides that are responsible for SIA have been identified, but much remains to be discovered. In a new study, a team of researchers in California, from AfaSci, Inc., Burlingame, and SRI International, Menlo Park, has revealed that nerves producing the peptide N/ORQ and nerves producing the peptide Hcrt are key in regulating SIA in mice.

The research team, which was led by Xinmin Xie and Thomas Kilduff, showed that in the brain of normal mice, Hcrt-producing nerve cells (Hcrt neurons) and N/ORQ-producing nerve cells interacted. N/ORQ affected the electrical current across Hcrt neurons and the release of neurotransmitters by these cells. Furthermore, administration of N/ORQ blocked SIA in normal mice, but this was overcome by administration of Hcrt at the same time. The authors therefore conclude that N/ORQ likely influences a variety of Hcrt-mediated processes, in addition to SIA, and suggest that these pathways might contribute to medical conditions caused by excessive stress, such as anxiety and post-traumatic stress disorder.

The world’s first optical pacemaker is described in an article published today in Optics Express, the Optical Society’s open-access journal. A team of scientists at Osaka University in Japan show that powerful, but very short, laser pulses can help control the beating of heart muscle cells.”If you put a large amount of laser power through these cells over a very short time period, you get a huge response,” says Nicholas Smith, who led the research. The laser pulses cause the release of calcium ions within the cells, Smith explains, and this action forces the cells to contract.

This technique provides a tool for controlling heart muscle cells in the laboratory, a breakthrough that may help scientists better understand the mechanism of heart muscle contraction.

One potential application of this technology is in studying uncoordinated contractions in heart muscle. Normally, heart muscle contracts in a highly coordinated fashion, and this is what allows the heart to pump blood through the vasculature. But in some people, this coordinated beating breaks down, and the heart twitches irregularly—a condition known as fibrillation.

The new laser technique may allow scientists to create a form of fibrillation in the test tube. The lasers can destabilize the beating of the cells in laboratory experiments by introducing a beat frequency in one target cell distinct from the surrounding cells. This would allow scientists to study irregular heart beats on a cellular level and screen anti-fibrillation drugs.

Outside the laboratory, exposing heart muscle cells to powerful laser pulses can have its drawbacks. Although the laser pulses last for less than a trillionth of a second, damaging effects can build up over time and this currently limits the possibility of clinical applications.