The Fight Against Heart Disease: Helping the Heart Fight Back
How to prevent heart disease.
Posted April 15, 2021 | Reviewed by Lybi Ma
Eugene Braunwald, MD (1929-) is regarded as the premier cardiologist of the last 100 years. Born in Vienna, Austria, he and his family barely escaped a Nazi concentration camp. Braunwald rose to fame for his work on the normal function of the human heart, and the effect of heart attacks leading to many new treatments. He began his academic career at the National Institute of Health in the 1950s, and for many years was the Chairman of Internal Medicine at the Brigham and Women’s Hospital of Harvard Medical School. His textbook Heart Disease has been the “gold standard” for cardiovascular medicine for almost 40 years.
In 1968, invigorated by a new facility on the West Coast, Braunwald and his team1 did meticulous research on the effect of blood pressure on the function of the normal heart and a heart damaged by a heart attack. The blood pressure is the resistance in the arteries that the left ventricle needs to pump against to push the blood to reach the tissues; the higher the resistance, that is the more constricted the blood vessels, the harder the heart muscle cells need to work. The resistance to blood flow is named “afterload.” The lower the afterload, the blood pressure of the arterial side of the circulation, the easier it is for the left ventricle to pump more efficiently. But the research showed that there was a range of blood pressure that was optimal for the performance of the heart. If medications dropped the resistance in the arteries too much, then the heart could not deliver enough blood and oxygen to the organs.
What about the other side of the circulation? The veins empty blood into the right side of the heart where it is pumped through the lungs and returns to the left side. Braunwald knew that the pressure in the veins and the right side of the heart must have a significant effect on how much blood could be “loaded” into the left side of the heart to be pumped forward. If there was not enough blood and pressure in the right heart, there was less blood to “prime the pump” on the left side of the heart and then less output of the heart. Here is an engine metaphor—the cylinders of the engine might be fine, but if the fuel pump is faulty, the cylinders can’t do their job well. This influence of the veins on the heart is called “preload.” Preload, just like afterload, is tricky. The right amount of blood entering the heart from the vein will stretch the heart muscle cells a bit more and create more actin and myosin bridges.2 The heart is like a rubber band—stretch the right distance and it will snap back more with more force. But don’t over-stretch it.
If the heart muscle is weak from disease, often there is too much blood or liquid in the veins. In the short term, this retention of fluid is beneficial; the heart muscle stretches and the effect helps improve the heart’s function. But this improvement in function comes at a cost: as the left ventricle expands, the inner lining of the cells of the ventricle use more oxygen. The ventricle is like a plastic balloon; the larger it gets, the more pressure is placed on its cells. This “wall tension” was the third key driver of the demand of the heart for oxygen. The demand was not just from the heart rate and the intrinsic contractility of the sarcomeres. In people with damaged hearts, too often the right and left sides of the heart reach their limit of adaptation, and excess fluid ends up in the lungs as “pulmonary edema” or in the lower part of the body as “edema,” swelling of the legs and abdomen. Doctors were aware of this effect of all types of heart disease for centuries, but now with sophisticated animal experiments, Braunwald and his colleagues demonstrated how and why these physical findings arose.
1 Braunwald agreed to move to San Diego, California, to lead the Department of Medicine of a brand-new medical school. Many of his key collaborators followed him to the West Coast.
2 This effect of the volume of blood on the heart is called the Frank-Starling Relationship, first discovered by physiologists of the late nineteenth century.