Although
arginine vasopressin and
terlipressin have been identified as useful nonadrenergic agents to increase systemic blood pressure in catchecholamine-resistant
septic shock, the impairments in cardiac index (CI) and global
oxygen transport may limit their clinical applicability. The present study was designed as a prospective controlled laboratory experiment to investigate the effects of
dobutamine as an adjunct to
terlipressin infusion on cardiopulmonary hemodynamics and global
oxygen transport in healthy and endotoxemic sheep. Nine adult ewes were instrumented for chronic study using an established protocol. After a baseline measurement in the healthy state had been performed, 1 mg
terlipressin was given as bolus infusion. Thirty minutes later,
dobutamine was continuously infused at incremental doses (2 and 5 microg x kg(1) x min(1), each for 1 h). After 24 h of recovery, a hypotensive-hyperdynamic circulation was induced and maintained by a continuous infusion of Salmonella typhosa
endotoxin (10 ng x kg(1) x min(1)). After 16 h of
endotoxemia, the six surviving sheep received
terlipressin and
dobutamine according to the same protocol that was used in healthy sheep. Compared with baseline,
terlipressin infusion was associated with a significant increase in MAP that, however, occurred at the expense of a compromised CI,
oxygen delivery index (DO(2)I), and mixed venous oxygen saturation (SvO(2), each P < 0.05).
Dobutamine infusion was followed by a dose-dependent increase in CI, DO(2)I, and SvO(2) in both health and
endotoxemia (each P < 0.05). Although the higher dosage of
dobutamine exerted favorable effects, such as a decrease in pulmonary vascular resistance index (P < 0.05), the associated onset of
tachycardia (P < 0.05) and arterial
hypotension (P < 0.05) may limit its
therapeutic use under septic conditions. This study provides evidence that
dobutamine in a dosage of 2 microg x kg(1) x min(1) is useful to reverse the
terlipressin-linked depressions in CI, DO(2)I and SvO(2) in ovine
endotoxemia without obvious side effects.