Although known for more than 40 years (1, 21, the pathogenesis of the hyperdynamic circulatory state often associated with advanced liver disease remains poorly understood. The clinical observations of warm skin, capillary pulsations of the digits, bounding pulse, somewhat low blood pressure and wide pulse pressure, associated with a short circulation time in patients with Laennec's cirrhosis (3) led to hemodynamic studies that confirmed the presence of an abnormally high cardiac output and stroke volume, associated with a low peripheral vascular resistance, in about one third to one half of patients with advanced cirrhosis (1, 2, 4). This high-output state was associated with a narrow arteriovenous oxygen difference. Thus the cardiac output was increased out of proportion to the oxygen consumption (i.e., it was not justified metabolically). Although this state resembled that which had been described in beriberi, it was not associated with clinical evidence of thiamine deficiency and only rarely with heart failure (51, and it did not respond to thiamine therapy. Thus advanced liver disease was added to the list of high cardiac output states, which in addition to thiamine deficiency, include anemia, arteriovenous fistulas, some generalized skin disorders, Paget's disease of bone and thyrotoxicosis, as well as anxiety and pregnancy. These diseases and states all have in common lowered peripheral vascular resistance.
Many theories as to the pathogenesis of the hyperdynamic circulatory state in chronic liver disease have been proposed (Table 1). A meritorious theory would have to account for the lowered peripheral vascular resistance that is the physiological landmark of this altered circulatory state. Furthermore, in view of the magnitude of the changes seen in at least some patients, alterations in regional vascular beds, such as the splanchnic region, could hardly be the sole mechanism. The focus, then, on the systemic circulation is also justified by the clinical observations of warm and often blushed skin, the frequency of spider angiomata, the presence of capillary pulsations. Indeed, reported that in patients with cirrhosis, blood flow to the legs, measured with the duplex-Doppler method, was signifi-See related article on page 1343.