Getting a Grip

A non-invasive method gets right to the heart of the matter.

By: Ellen Beth Levitt
Date: May 20, 2011

The endothelium that lines coronary arteries is like a canary in a coal mine. Changes in the function of endothelial cells are the early warning signs of the effects of smoking, hypertension, lipid disorders and diabetes, and are harbingers of dangers to come, such as atherosclerosis, inflammation, calcium deposits, and heart attacks.

The quest to noninvasively assess the endothelium of tiny coronary arteries has been a challenging one. In past studies, for example, researchers used ultrasound to look at the brachial artery in response to stress, such as immersing the arm in ice water or briefly restricting arm circulation. Those methods did reveal some important clues about the vessel’s ability to dilate.

But instead of using the brachial artery as a proxy for the coronary arteries, Hopkins cardiologists Allison Hays, Robert Weiss and colleagues wanted to study endothelial function in the coronary arteries themselves to assess a patient’s early risk of a heart attack and to follow the vessels over time. After all, it is disease within the coronary arteries themselves that leads to heart attacks.

In the first-ever use of magnetic resonance imaging to look at the endothelial function of coronary vessels, the team conducted a study involving 20 healthy volunteers and 17 patients with established coronary artery disease that had been documented by coronary catheterization within the past six months. To create a form of stress that would test the function of the endothelial cells, the researchers asked all participants to continuously squeeze a handgrip device—a dynamometer—for four minutes while the MRI machine zeroed in on their coronary arteries.

“We measured coronary artery size and rate of blood flow using MRI before and during the isometric hand grip exercise,” Hays explains. “In healthy individuals, the stress caused an increase in vessel diameter and blood flow. In patients with coronary artery disease, the vessels did not dilate normally and there was no increase in blood flow.”

Adds Weiss, “Most people would not have predicted that you could see changes in these 2- to 3-millimeter arteries in the beating heart in a non-invasive way. But our findings were entirely consistent with information from the patients’ cardiac catheterization studies.”

To prove that the scientists were truly assessing endothelial function responses, the researchers gave some study participants a tab of nitroglycerin while they were still in the MRI machine. Everyone’s arteries dilated. However, that same dilation was only seen among the healthy volunteers during the hand-grip exercise, indicating that researchers were, indeed, gauging endothelial responses.

In a subset of patients, the researchers measured two of the coronary vessels using MRI. Each patient had one vessel with mild disease (as revealed in the cardiac catheterization) and another vessel with severe disease. “We found that the extent of coronary endothelial dysfunction was related to the degree of stenosis in that artery,” says Hays, “showing a spectrum of endothelium dysfunction within heart arteries in each individual patient—something that had not been established before.” Ellen Beth Levitt