What are the primary molecules and cellular signals associated with prolonged hypertensive stress that cause adverse myocardial tissue remodeling, and what strategies that prevent or reverse adverse remodeling can be developed and tested?

We now can create critical cell types like cardiomyocytes etc. from stem cells. Additionally, we are learning the rules of using these cells to rebuild tissues. A major gap in our knowledge relates to the immunobiology of these cells. Lessons from transplantation medicine are only partially applicable, because solid organs are more complex and likely more immunogenic than defined cell populations.

How does the immune... more »

There remain many differences between women and men in the risk of myocardial infarction (MI or “heart attack”), manifestations of MI and outcomes after MI. The time in which the facts about differences between the sexes were unknown or ignored has passed. However, there are many basic answers women and their physicians need, such as: a) Why are younger women with MI at such high risk of death as compared to their male... more »

Identify the immune cell phenotype responsible for myocyte damage post infarction.

What are the critical mechanisms that account for progression from reversible to irreversible ischemia and reperfusion injury?

Acute cardiovascular complications are frequent in critical illness and injury, occurring on a spectrum that includes troponin leak or demand ischemia to acute occlusive coronary events and lethal arrhythmias. They arise in the course of similar acute illnesses but they epidemiology, pathogenesis, treatment and long-term consequences are unknown. Are they the result of a generalized inflammatory state that persists... more »

The introduction of troponin assays has changed the criteria for myocardial infarction (MI), with much smaller myocardial damage now classified as an MI. Since to date, the FDA has not approved new agents based on their decreasing size of an MI, regulatory approval has required endpoints like death or heart failure that require large numbers of patients and long periods of time. Thus, it is difficult to attract industry... more »

There is compelling evidence that pre-hospital therapy of both stroke and MI can improve outcomes and yet, with the exception of aspirin for MI, almost no care is administered pre-hospital in the U.S. NHLBI has a major stake in improving pre-hospital care because there already are sufficient data to show that currently available interventions would improve outcomes if they could be administered in the prehospital setting.... more »

Which therapy or combination of therapies to reduce injury from acute myocardial infarction (AMI) will be most efficacious for future clinical trials?

What is an appropriate mechanism and study design to evaluate the beneficial effects of hypothermia following acute myocardial infarction?

What is needed to develop the technologies that will allow reparative interventions to be performed on excised natural hearts that have been overhauled ex vivo and replanted?

 

This will involve keeping the myocardium alive and sterile for extended periods that are long enough to complete the interventions while being able to also perform the necessary reparative interventions.

What are the mechanisms of ischemia-independent mechanisms contributing to the infarct size in patients with acute myocardial infarction?

Infarct size is the single most important prognostic factor for short- and long-term outcomes.

The success in reperfusion strategies have shown that prompt reperfusion leads to a reduction in infarct size, and to improved outcomes.

Despite effective reperfusion, however, a secondary... more »