Stem cell therapy can regenerate heart muscle in primates, according to a 91爆料-led study. The scientists on this and related projects are seeking way to repair hearts weakened by myocardial infarctions. This all-too-common type of heart attack blocks a major artery and deprives heart muscle of oxygen.

People who survive a severe episode often continue their lives in poor health because their hearts no longer work properly. The researchers hope eventually to restore such failing hearts to normal function. Their approach uses heart cells created from human embryonic stem cells

The researchers tested the possibility of producing enough of these cardiac muscle cells to remuscularize damaged hearts in a large animal whose heart size and physiology are human-like.

Their results are reported today, April 30, in the advanced online edition of Nature. See .

Dr. Charles Murray, professor of pathology and bioengineering, and Dr. Michael LaFlamme, assistant professor of pathology, are the senior authors of the paper.

Read the details of their project and its outcomes in, and watch a video describing the research.

On Oct. 15, Dr. Graham Nichol, 91爆料 professor of medicine and director of the 91爆料-Harborview Center for Prehospital Emergency Care, launched MyHeartMap Seattle. This was a month-long, city-wide scavenger hunt to discover all of Seattle鈥檚 automated external defibrillators, or AEDs. The winner or winning team would be awarded $10,000 provided to Nichol鈥檚 research efforts by the Food and Drug Administration and several AED companies. Thirty-two teams signed up to participate. The AED sightings started rolling in.

On Twitter, teams posted selfies with AEDs, asked for hints, and celebrated when they found 鈥済olden AEDs,鈥� which were worth $50 extra. The contest was extremely close.

One month later, Nichol announced the winning team: Team HeartMarket, a group of six 20-somethings with a serious love for scavenger hunts, had found 800 AEDs.

Rebecca Bridge heard about the contest through a Google alert for the phrase 鈥渟cavenger hunt.鈥� She described the four frantic weeks her team spent searching: 鈥淗ealth clubs, dentist offices, hotels, office buildings. Sometimes they were locked up somewhere.鈥�

The contest required some sleuthing.聽 One evening, while having dinner on Capitol Hill, Rebecca and her teammate Mike Pantoliano walked by Seattle Academy鈥檚 open house for parents. They just looked at other and proceeded inside to what turned out to be a gold mine of defibrillators.

Fellow HeartMarket teammates were Ben Estes, Lara Petersburg, Megan Singley, Miranda Rensch, and Aaron Wheeler. Mike said that often the folks he encountered at the front desk of a business didn鈥檛 know what an AED was, or were immediately suspicious.

鈥淭hey thought we were there to ticket or fine them for not having one,鈥� he said.

In some cases, employees would direct Team HeartMarket to an area of the building where they might have an AED. The searchers would find a fire extinguisher instead.

鈥淲e developed an irrational hatred of fire extinguishers,鈥� joked Mike.

Although there is currently no legal penalty associated with not having an AED, keeping one on hand in areas frequented by many people is a good idea.聽 These medical devices are extremely important in saving lives. When combined with CPR, the use of an AED improves survival rates for sudden cardiac arrest by almost half. Before the contest began, Nichol and his team knew of roughly 250 registered AEDs in various public locations like schools and public buildings. Now his team is sorting through over 2,000 reportings. After eliminating duplicates, they expect a potential database of at least 1,500.

MyHeartMapSeattle was the second of two AED hunts in the United States. The first, in Philadelphia, was orchestrated by Dr. Raina Merchant, assistant professor of emergency medicine at the University of Pennsylvania. Both contests arose from the need to map and monitor defibrillators. The FDA has publicly stated a desire to monitor these devices to see how often they are used and how they affect the survival rate of sudden cardiac arrest. So, rather than sending one person or even a team of hourly-paid individuals to search each city building by building, researchers decided to hold a contest to capitalize on the recent success of crowdsourcing. Eventually, the FDA hopes to place unique labels (QR codes) on each defibrillator.

The inspiration for the HeartMap project was the DARPA Red Balloon Challenge, 聽a 2009 contest/experiment that offered $40,000 to the person or team that was able to submit the exact locations of 10 large red, weather balloons hidden in plain sight all around the United States. The winning team located all 10 balloons in just under 9 hours. Armed with this knowledge, researchers were able to secure funding from the FDA and several AED companies to offer the $10,000 reward.

Of course, the other purpose for tracking and mapping AEDs is that they are designed for public use. Any person can follow the directions correctly and deliver the electrical current that could correct an irregular heartbeat and save a person鈥檚 life. CPR can sustain a victim鈥檚 life, but without an AED the survivor could still suffer brain damage or death. Having a map of AEDs will allow 911 operators to pinpoint a location and relay that information to a bystander before a first-responder can make it to the scene. With modern technology, it鈥檚 possible that each city could have a comprehensive location-based smartphone app that would allow a bystander to find the nearest AED with the swipe of a finger.

For now, Nichol and Merchant and their teams have inspired other cities to hold their own scavenger hunts, and they鈥檙e taking the show on the road. There鈥檚 no word yet as to exactly where the next HeartMapChallenge will be, but we can bet $10,000 it will be a fruitful endeavor.

Oh, and Seattle, if you鈥檙e wondering鈥� 聽After downtown, HeartMarket鈥檚 guess is that Capitol Hill is the next best heart-friendly neighborhood.

AEDs are electronic briefcase-size devices designed to allow bystanders on scene at a medical emergency to help someone who has collapsed with loss of mechanical activity of the heart, or cardiac arrest.

鈥淥ur list of AED locations may be incomplete. We are seeking the public鈥檚 help to learn where more of these devices are,鈥� said Dr. Graham Nichol, 91爆料 professor of medicine in the Center for Pre-Hospital Emergency Care at 91爆料 Medicine鈥檚 Harborview Medical Center.

AEDs are cost-effective lifesavers that are often placed where cardiac arrests are most likely, such as airports, sports clubs and shopping malls, according to Nichol, who explained why it is important for a bystander聽to be able to locate an AED immediately.

鈥淐ardiac arrests are a leading cause of death in the United States but can be treated if recognized and responded to quickly with an AED.鈥�

Often cardiac arrest is due to ventricular fibrillation, in which the lower chambers of the heart quiver instead of contracting in a steady beat. AEDs simplify analysis of the heart rhythm. This enables lay people to recognize and treat ventricular fibrillation before emergency medical services providers arrive. Each device has voice and visual prompts that guide bystanders through the necessary steps.

More than 1.2 million AEDs are now in public places in the United States, and about 180,000 more are installed each year. Sometimes bystanders cannot find the nearest AED during a medical emergency. That鈥檚 where the My HeartMap Seattle challenge comes in.聽Game players will assist 91爆料 clinicians by reporting the location of AEDs in community settings throughout Seattle.

Here are the basic rules of the game.

• 聽 The contest starts Tuesday, Oct.15, and ends Friday, Nov. 15.
• 听听 to participate in the contest.
• 聽 When you locate an AED in Seattle, report a brief description of it on the contest website, including the building address for the AED, its location within the building, and whether the device appears to be ready for use.
• 聽 A $10,000 grand prize will be awarded to the individual or team that identifies the most unique AEDs. 鈥淯nique鈥� means no other player or team has already found the AED. The grand prize will be 鈥渦nlocked鈥� when at least one individual or team identifies 500 AEDs or all contest participants collectively identify 750 AEDs.
• 聽 Twenty $50 prizes are also available. Twenty AEDs in the city of Seattle have been pre-selected by the research team as 鈥淕olden AEDs.鈥� These are unmarked, and those who are first to report a 鈥淕olden AED鈥� will win $50.
• 聽 You can follow MyHeartMap Seattle on twitter (@cprnation, #MyHeartMapSeattle) or at the .

The AED scavenger hunt aims to build public awareness about AEDs, which are commonly contained in a clear glass wall box, sometimes near a fire extinguisher. The spot is generally marked with a symbol of an electrical charge passing through a heart shape.

The contest is modeled after a similar Philadelphia County project at the University of Pennsylvania, which in turn adapted an approach from the Defense Advanced Research Projects Agency for its Red Balloon Challenge. Dr. Raina Merchant, University of Pennsylvania assistant professor of emergency medicine, directed the My HeartMap Philadelphia Challenge. She is the director of the Penn Medicine Social Media Lab and an expert in the use of digital strategies to educate the public on at-the-scene emergency aid. Merchant is collaborating with 91爆料 scientists on the My HeartMap Seattle Challenge.

鈥淭his is an exciting collaboration that could have a real impact on access to emergency care in Seattle and other regions throughout the country,鈥� noted Merchant.

During the MyHeartMap Philadelphia challenge, participants submitted data about AED locations via a website and a phone app. Some 313 individuals and teams reported more than 1,400 AEDs. Prizes were given for reporting the most AEDs found or for being the first to report the location of specific previously selected devices.

鈥淢ost people realize that AEDs are simple enough to use,鈥� Nichol said.聽鈥淛ust follow the voice and visual prompts. They are designed to provide a shock only when needed.鈥�

An AED is usually activated by opening its lid.聽The commands then begin with visual, recorded and text instructions for baring the patient鈥檚 chest and sticking on the pads.聽Then the machine asks everyone to step back while it analyzes the heart rhythm. It repeats the request to stand clear if it decides to administer a shock. If the rhythm suddenly normalizes before a shock is delivered, the machine will report a rhythm change and announce that no shock will occur.

Most machines also instruct in CPR and coach the timing of compressions and breaths.

鈥淢y HeartMap Seattle will help us improve care for patient with out of hospital cardiac arrest,鈥� Nichol said. 鈥淭he methods and results of this AED scavenger hunt in Seattle will be applied to scavenger hunts in other large cities throughout the United States. In the future, we will have a comprehensive record of AED locations throughout the country.鈥�

My HeartMap Seattle is funded by the U.S. Food and Drug Administration, Zoll Medical Inc., Philips Healthcare Inc., Physio-Control Inc., HeartSine Technologies Inc. and Cardiac Science Inc.

The collaborating sponsors include the American Heart Association, Medic One Foundation, Nick of Time Foundation, University of Pennsylvania and 91爆料.

Growing evidence has suggested that low blood levels of 25-hydroxyvitamin are associated with higher risk of developing coronary heart disease among whites. Few of these studies included substantial numbers of people from other races.

Vitamin D levels tend to be lower among people from other racial and ethnic minority groups, and some of these populations have higher rates of heart disease. However, after correcting for other risk factors for heart disease in their large, multi-ethnic study group, the researchers did not find an association between low vitamin D and cardiovascular events in their black and Hispanic study participants.

鈥淥ur study suggests that the results of ongoing vitamin D clinical trials conducted in white populations should be applied cautiously to people of other racial and ethnic backgrounds,鈥� said Cassianne Robinson-Cohen, the lead author for the JAMA paper. The senior author is Ian deBoer, 91爆料 assistant professor of medicine, Division of Nephrology.

Robinson-Cohen is an affiliate instructor in epidemiology at the 91爆料 School of Public Health and a researcher at the Kidney Research Institute, where her team explores the genetic, metabolic and epidemiological factors related to heart and kidney disease.

She noted that the findings in their recent JAMA paper came from an observational study, not a randomized clinical trial, and could not guarantee cause and effect.

鈥淥ur future studies will examine the genetics affecting the levels and use of vitamin D in the body to try to figure out why the link between low vitamin D blood levels and heart disease varies by race and ethnicity,鈥� she said.聽 鈥淲e don鈥檛 know for sure, but perhaps genes affecting the need for and use of vitamin D could have evolved to adapt to different levels of sun exposure in places where various ethnic subgroups of people originated.鈥�

Her team plans to聽look for variations in genes known to mediate vitamin D activation and metabolism. She said these genes have been identified, but at present scientists haven鈥檛 determined how gene variation influences susceptibility to the adverse effects of low vitamin D.

The report published this week was from one of the projects within the Multi-Ethnic Study of Atherosclerosis. MESA is a major, long-term medical research effort supported by the National Heart Lung and Blood Institute, part of the National Institutes of Health. More than 6,800 men and women from six regions across the United States are participating in MESA. The diverse study group that was 38 percent white, 28 percent black, 22 percent Hispanic, and 12 percent Chinese. Robinson-Cohen and her team studied 6,436 MESA participants who enrolled between July 2000 and September 2002.

All participants were free of any known cardiovascular diseases at the time they enrolled, and had their blood levels of V25-hydroxyvitamin D measured. The mean age of participants at the start of the study was 62 (range 45 to 84 years) and slightly more than half were women.

The mean blood concentrations for whites was 30.1 ng/ml, Chinese 26.7, Hispanic 24.6, and blacks 19.2, The researchers tested the association of Vitamin D levels with the first incidence of coronary heart disease events 鈥� myocardial infarction, angina, cardiac arrest, or death from coronary heart disease 鈥� occurring from the start of the study until May 2012. During the eight-and-a-half year study, 361 participants had such an event. The researchers used several statistical risk analyses to check to see if links between blood vitamin D levels and coronary heart disease differed among white, black, Chinese and Hispanic populations.
鈥淭his report underscores the value of conducting studies that include participants from diverse backgrounds,鈥� said Dr. Michael Lauer, director of the National Heart Lung and Blood Institute’ Division of Cardiovascular Sciences. 鈥淭he MESA investigators have presented a finding that could serve as a foundation for future research on the possible link between vitamin D blood levels and heart disease.鈥�

鈥淭he differences in associations across race-ethnicity groups were consistent for both a broad and restricted definition of coronary heart disease and persisted after adjustment for known risk factors for coronary heart disease,鈥� the researchers noted in their paper.

Robinson-Cohen believes the strengths of the study are its size, duration,聽 the use of several statistical analyses, the rigorous definition of heart disease events, and the efforts made to control for many confounding risk factors, such as age, gender, smoking, diabetes, blood pressure, cholesterol levels, physical activity, kidney disease,C-reactive protein concentrations, educational attainment, income聽 and so on.聽 A main weakness of the study, she said, is that it is observational, and therefore can鈥檛 be ascertain cause and effect.

鈥淭o determine cause and effect, a large, multiethnic, randomized control clinical trial would need to be conducted,鈥� she said.

Robinson-Cohen pointed out, that beyond these specific results, the nature of the findings show the importance of designing medical research that includes a diverse ethnic and racial makeup of participants. Such multi-ethnic studies would help prevent cases where findings from one group are incorrectly applied to other groups.

鈥淲e need to make a bigger effort to design and fund medical studies with large enough representation of various racial and ethnic backgrounds that we don鈥檛 draw ungrounded conclusions based on one group,鈥� Robinson-Cohen said.

The study, 鈥淩acial Differences in the Association of Serum 25-hydroxyvitamin D Concentration with Coronary Heart Disease Events鈥� was supported with grants and contracts N01-HC-95159聽 and N01-HC-95169 from the National Heart Lung and Blood Institute and聽 R01DK088762 from the National Institute of Diabetes and Digestive and Kidney Diseases.

Read the .

Exposure to diesel exhaust may render friendly, cholesterol-fighting molecules incapable of performing their important job. A new study suggests that the traffic air pollutant may prevent good cholesterol from battling the bad, artery-clogging cholesterol that promotes heart attack and stroke.

The study鈥檚 team included environmental health scientists led by Michael E. Rosenfeld at the 91爆料 School of Public Health and heart disease specialist Jesus Araujo and his colleagues in the Division of Cardiology at the University of California, Los Angeles. Their , published in the June issue of Arteriosclerosis, Thrombosis, and Vascular Biology, is the first to report that exposure to traffic sources of air pollution 鈥� diesel exhaust from combustion engines 鈥� can alter the protective nature of normal high-density lipoprotein, or HDL, and set in motion biological mechanisms that lead to cardiovascular disease.

Best known for its ability to scavenge harmful 鈥渂ad鈥� cholesterol from blood vessels and excrete it from the body, HDL is also an antioxidant powerhouse. Set against bad cholesterol 鈥� low-density lipoprotein or LDL 鈥� HDL blocks oxidation, a process that induces inflammation in the blood vessels and leads to the hardening of arteries, explained Rosenfeld, professor of environmental and occupational health sciences. But that鈥檚 not all. An additional virtue of HDL鈥檚 鈥済oodness鈥� lies in its ability to prevent inflammation caused by white blood cell patrols honing in tissues antagonized by air pollution particulates.

All of this adds up. Scoring high levels of HDL in blood tests at the doctor鈥檚 office has generally been accepted as protective against cardiovascular disease. Higher levels of HDL mean less risk of heart attack and stroke. That is, until now.

Researchers found that exposure to diesel exhaust led to the loss of the anti-oxidant and anti-inflammatory properties of the HDL.

鈥淚t turned the good cop into a bad cop,鈥� said study co-author Timothy Larson, 聽91爆料 professor of environmental and occupational health sciences.

HDL normally performs protective functions, but if the molecules are exposed to pollution, they lose their protective quality.

In the arm of the study completed at the 91爆料, mice were exposed to diesel exhaust over a two-week period at levels comparable to those we encounter everyday. The lab is one of the few in the country that can accurately simulate ambient air pollution exposures in a controlled environment. Results of the mice鈥檚 exposure were compared to a control group that received only clean filtered air. In a second experiment, a third group was exposed to diesel exhaust for two weeks and filtered air for an additional week. Researchers wanted to assess whether a week was sufficient time for the HDL to return to normal.

鈥淲hat was really surprising: the one week of recovery time was not sufficient,鈥� said Rosenfeld, who is also a 91爆料 professor of pathology. 鈥淭his has some pretty significant implications for how exposure to air pollution can impact development of cardiovascular disease. Even short-term exposures to pollution can have pretty long-term effects.鈥�

The National Institute of Environmental Health Sciences, one of the National Institutes of Health, supported the research through grant number R01 ES016959/ES/NIEHS.

The potential of gene therapy to boost heart muscle function was explored in a recent 91爆料 animal study. The findings suggest that it might be possible to use this approach to treat patients whose hearts have been weakened by heart attacks and other heart conditions.

Michael Regnier, 91爆料 professor and vice chair of bioengineering, Charles Murry, director of the Center for Cardiovascular Biology and co-director of the Institute for Stem Cell and Regenerative Medicine, and Sarah Nowakowski, a 91爆料 graduate student in bioengineering, led the study. The findings appeared online March 25 in the Proceedings of the National Academy of Sciences.

Normally, muscle contraction is powered by a molecule, the nucleotide called adenosine-5′-triphosphate, or ATP. Other naturally occurring nucleotides can also power muscle contraction, but in most cases they have proven to be less effective than ATP.

In an earlier study of isolated muscle, however, Regnier, Murry and their colleagues had found that one naturally occurring molecule, called 2 deoxy-ATP, or dATP, was actually more effective than ATP in powering muscle contraction.聽 dATP 聽increased both the speed and force of the contraction, at least over the short-term.

In the new study, the researchers wanted to see whether this effect could be sustained. To do this, they used genetic engineering to create a strain of mice whose cells produced higher-than-normal levels of an enzyme called ribonucleotide reductase. This enzyme converts the precursor of聽 ATP, adenosine-5鈥�-diphosphate or ADP, to dADP, which, in turn, is rapidly converted to dATP.

鈥淭his fundamental discovery, that dATP can act as a 鈥榮uper-fuel鈥� for the contractile machinery of the heart, or myofilaments, opens up the possibility to treat a variety of heart failure conditions,鈥� Regnier, an established investigator of the American Heart Association, said. 鈥淎n exciting aspect of this study and our ongoing work is that a relatively small increase in dATP in the heart cells has a big effect on heart performance.鈥�

The researchers found that increased production of the enzyme ribonucleotide reductase increased the concentration of dATP within heart cells approximately tenfold. Even though this level was still less than one to two percent of the cell鈥檚 total pool of ATP, the increase led to a sustained improvement in heart muscle function. The genetically engineered hearts contracted more quickly and with greater force.

鈥淚t looks as though we may have stumbled on an important pathway that nature uses to regulate heart contractility,鈥� Murry added. 鈥淭he same pathway that heart cells use to make the building blocks for DNA during embryonic growth makes dATP to supercharge contraction when the adult heart is mechanically stressed.鈥�

Importantly, the elevated dATP effect was achieved without imposing additional metabolic demands on the cells. That observation suggests that the modification would not harm the cell鈥檚 functioning over the long-term.

The study鈥檚 findings, the authors write, suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for heart failure.

Read the PNAS scientific , “Transgenic overexpression of ribonucleotide reductase improves cardiac performance.”

The work was supported by grants from the National Institutes of Health and the National Science Foundation Graduate Research Fellowship Program.

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BEAT BioTherapeutics, a private company spinout from the 91爆料, has entered into an exclusive global license agreement covering聽 this technology and is moving forward with clinical development. For more information, visit