The Role of the False Neurotransmitter Octopamine in the Hypotension of Fulminant Hepatic Failure

Abstract

1. An investigation was carried out into the mechanism of unexplained hypotension in patients with fulminant hepatic failure. The cardiac output and peripheral resistance were compared in normotensive and hypotensive patients. In addition, the serum concentration of the false neurotransmitter octopamine and the pressor response to noradrenaline, and to the indirectly acting sympathomimetic agent tyramine, were measured in hypotensive and normotensive patients with fulminant hepatic failure and in healthy subjects. 2. The cardiac output and the peripheral resistance were decreased in the hypotensive patients, and their mean heart rate was slower than in the normotensive patients. Although the serum octopamine concentration was significantly elevated in the patients compared with the control subjects, the highest octopamine concentrations were unexpectedly found in the normotensive patients and a significant positive correlation could be demonstrated between the resting blood pressure and the serum octopamine concentration. The pressor response to tyramine and noradrenaline were similar in the hypotensive patients, the normotensive patients and control subjects. 3. These results suggest that neither increased serum concentrations of the false neurotransmitter octopamine, nor end-organ insensitivity to released noradrenaline are responsible for the hypotension. A more likely explanation is toxic depression of the vasomotor centre. The opening of peripheral arteriovenous shunts, possibly as a result of endotoxaemia, might be an additional factor.

Treatment of Lactic Acidosis with Dichloroacetate in Dogs

“…Others have documented cardiovascular collapse in liver failure, both in patients (36) and hepatectomized dogs (37). DCA administered to dogs with hepatectomy-lactic acidosis prevented further deterioration of cardiac index (Fig.…”

Serum octopamine, coma, and charcoal haemoperfusion in fulminant hepatic failure

“…We have previously described a positive relationship between sympathetic activity and serum octopamine levels in patients with FHF [13], and increased sympathetic drive following gastrointestinal haemorrhage may account for the raised octopamine levels seen in these patients. Such amino acids could either arise from intestinal absorption or be released from necrotic liver cells.…”

Plasma catecholamines in hepatic coma and liver cirrhosis: Role of octopamine

“…Therefore it seems unlikely that the depletion of the noradrenergic neuron of noradrenaline by tyramine or the substitute neurotransmitter octopamine plays a crucial role in the development of hypotension in patients with chronic liver disease or futminant hepatic failure as has been postulated [8,7,24]. Trewby et al (1977) [31] found on the other hand highest octopamine concentrations in those patients with a normal blood pressure. They suggested that neither increased concentrations of octopamine nor endorgan sensitivity to released noradrenaline are responsible for the hypotension.…”

“…Normal mean values of octopamine have been found to be 0.40 ng/ml [5], 0.24 ng/ml with a range of 0 to 1.91 ng/ml [16], 1.6 ng/ml [31], 1.9 ng/ml [20] and 4.6 ng/ml [23]. However compared with the normal range of noradrenaline in plasma from 0.1 to 0.7 ng/ml the above mentioned normal levels of octopamine are unexpectedly high.…”

“…In 1971 Fischer and Baldessarini found elevated urinary excretion of octopamine in patients with hepatic coma and suggested that the replacement of catecholamines by octopamine can account for the simultaneous alterations in central nervous, cardiovascular and renal system in patients with hepatic coma. Elevated levels of octopamine in plasma of patients with hepatic encephalopathy or hepatic coma have been reported subsequently by several authors [5,20,23,28,31].…”