Related Experiment Videos
Synthetic 8-ornithine-vasopressin, a clinically used vasoconstrictor, causes cardiac effects mainly via changes in
Background:
8-ornithine-vasopressin (ornipressin, POR-8) is used as a potent peripheral vasoconstrictor mainly in combination with local anaesthetics. Because ornipressin causes vasoconstriction, any myocardial depressive effects could be caused indirectly by reduced myocardial perfusion secondary to coronary vasoconstriction, or directly by effects on myocardial tissue.
Methods:
On isolated guinea pig hearts, we compared direct effects of ornipressin by perfusion at constant flow with indirect effects by perfusion at constant pressure by Langendorff technique. Ornipressin concentrations tested were 0.05, 0.1, 0.25, 0.5 and 1.0 IU/L (1 International Unit (IU) ornipressin = 2.8 micrograms)
Results:
Coronary flow decreased significantly (P < 0.001) in concentration-dependent manner with ornipressin at constant pressure while AV conduction time and percentage O2 extraction (%O2E) increased and heart rate (HR), systolic left ventricular pressure (LVP) and myocardial O2 consumption (MVO2) decreased. Coronary perfusion pressure increased significantly with increasing ornipressin at constant coronary flow while HR and AV time were unchanged and LVP decreased only at the higher concentrations. At an identical or slightly reduced HR LVP product (RPP), MVO2 increased up to 27 +/- 6% at 1.0 IU/L ornipressin during constant flow perfusion.
Conclusion:
An increase in %O2E coupled with a decrease in coronary flow at constant pressure is consistent with myocardial depression secondary to reduced tissue perfusion. These ornipressin-induced effects are not evident at constant coronary flow except for a small but direct myocardial depressant effect on LVP at higher concentrations. The increase of MVO2 at constant flow, despite equal or even reduced work, is described as Gregg's phenomenon and it is probably due to an increase in coronary perfusion pressure during coronary vasoconstriction. Even though extrapolation of our results in humans is questionable, the current indication for use of ornipressin as vasoconstrictor may need to be reconsidered, especially in patients with reduced coronary reserve.