Myocardial Protection: The Science and Pathophysiology of Myocardial Ischemic Injury.

All right. Thanks again. I’m glad you guys are awake, and here, and present. I’ll try to keep you all engaged as much as I can. So let’s go through some of the slides. The first thing I’ll go through is an overview of coronary blood flow, how that contributes to cardiovascular disease, and myocardial infarction, and really, how did we get to this point? I’ll go through a little bit about the current medical treatments, which you all are probably more, even, familiar with than I am. Then, I’ll go into a little bit about my expertise about cell therapy, and really, the importance of timing for that. And then, I’ll finish up with the future areas of research. This is a slide I used yesterday, but I think it emphasizes how important and unique the heart is, compared to other organs. Coronary blood flow is tightly coupled to cardiac metabolism. Since the heart already has a high oxygen extraction rate at rest, that really leaves very little wiggle room in terms of ischemic tolerance. So the heart is very unique, but really, it only has about 20% room to go from basal to maximum oxygen extraction, compared to a skeletal muscle, which really can increase by about 70% in its blood flow and ability to deliver oxygen to the tissue. So I highlight this again, because I think it’s important. We are seeing a decrease in the mortality rates for men, shown in the blue. We see this blue line, back from 1979, decreasing all the way to 2004, in terms of deaths for men. However, for females, shown here in the red, we’re really still at the same spot we were back in 1979 (1) (Figure 1). The current clinical treatments for an myocardial infarction (MI), if a person were to come in, they would be diagnosed through an angiograph. It would show narrowing of a large artery, and typically, this mostly happens with men. They would show this narrowing of a large artery shown here in the yellow circle. And then from there, what they typically will do is a percutaneous coronary intervention, so they would go in and stent this large artery. Another thing they can do is a coronary bypass. These patients would be put on thrombolytic therapy, beta-blockers, angiotensinconverting enzyme (ACE) inhibitors, anticoagulants, and really, they get a whole tirade of drugs put at them after this point. However, there is a post-myocardial infarction prognosis that’s termed “no-reflow,” which is very typically found in women. And what happens is that they have reopened a large artery that was blocked and shown on an angiograph, and they’re still not getting distal flow to the tissue. And what they’re thinking is that it’s an adverse manifestation of coronarymicrovascular dysfunction. I talked about it yesterday, how the microvascular bed could really determine how much blood flow gets into the endocardial tissue. So, we’ve got a couple of things going on here. We’ve got the large arteries that can be blocked and then openedup, and hopefully can reperfuse the tissue, but if not, we still have this microcirculatory bed that’s dysfunctional. So in an angiograph, of course, what you’re seeing here is the large arteries. However, an angiograph is unable to tell you anything, really, about the microcirculation, and the microcirculatory bed of the cardiac tissue is very profuse and very profound. So what we’re seeing is that the microcirculation is key for a lot of patients. Not just women, but men as well. In terms of the anatomical differences between men and women, really, in terms of a vascular bed, they look exactly the same. We always have an artery coming in, branching off into smaller arterials. This is the area, as we can see, that blood flow distribution occurs in the arterials. Going down into the capillaries, where that oxygen extraction actually occurs, and then of course going into the venules, and then out into the veins. So nothing’s different there, in the hearts of men and women. But, it’s the function of those vessels that are involved that are different, typically, between men and women. When you develop coronary artery disease, for men, typically you’ve got that open artery. Over time, the plaque builds up, and that’s when you get that hardened Address correspondence to: Amanda Jo LeBlanc, PhD, Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40292. E-mail: ajbell01@louisville.edu