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Marcello Malpighi (1628-1694), using the newly invented microscope, discovered and made the initial descriptions of the "missing link" in Harvey's description of the circulation: the previously invisible small capillaries that connect the arteries and veins. Other scientists made the first conclusions that the purpose of the circulation through the lungs was to "aerate" the blood (oxygen was not yet discovered), a process that changed it from dark to bright red.

In the later part of the 18th century, knowledge about the heart and vessels continued to grow, especially as it applied to disease. Descriptions of heart failure, pericardial disease, disease of the heart valves, thickening of blood vessel walls, chest pain, palpitations and slow heartbeat, and the phenomenon of blood pressure all emerged during this time.

Not unexpectedly, as knowledge about diseased organs (the science of pathology) grew, the effort to diagnose the nature of the disease in ill patients began to take precedence. This attempt to correlate clinical conditions with pathologic states was the thrust of progress in the early 1800s. The first suggestions that angina pectoris is chest pain related to an inadequate -supply of blood to the heart muscle were made at this time. Many of the basic aspects of the physical examination of the patient were developed, including methods of visual inspection, examination by touch (palpation), percussion (for example, tapping on the chest), and auscultation (listening, especially trough the stethoscope).