Acute haemodynamic effects of lipolysis-induced increase of free fatty acids in healthy men.
Circulating free fatty acids (FFA) are elevated in subjects with insulin resistance and Type II diabetes, and increase during myocardial ischaemia, but their haemodynamic effects are incompletely understood. During an investigation of the effects of FFA on endothelial function, we administered lipid emulsion (150 mg x min(-1) of soybean oil) with heparin (0.2 unit x kg(-1) x min(-1)) intravenously to eight healthy men for 2 h. This increased circulating FFA to 3.1+/-0.5 mmol/l. Forearm blood flow was measured by venous occlusion plethysmography during brachial artery infusions of saline, acetylcholine and nitroprusside before, and at 1 and 2 h. Lipid/heparin infusion had no significant effect on vasodilation to nitroprusside but progressively increased responses to acetylcholine (from 6.3+/-2.0 during 30 microg x min(-1) before-lipid infusion to 7.9+/-1.3 at 1 h and 12.2+/-1.1 ml x min(-1) x 100 ml(-1) at 2 h, P<0.001). Basal flow increased from 2.7+/-0.7 to 4.7+/-0.8 ml x min(-1) x 100 ml(-1) from 0 to 2 h. We performed a second study to clarify this effect on basal blood flow. Healthy men (n=8) received, on separate occasions, 4 h intravenous infusions of lipid emulsion with heparin and, as a control, saline with heparin. Lipid with heparin increased mean arterial blood pressure (maximum increment 8.2+/-2.7 mm Hg, P<0.01 compared with saline/heparin control) and forearm blood flow (from 1.7+/-0.2 to 2.9+/-0.3 ml x min(-1) x 100 ml(-1), P<0.01) without a significant effect on heart rate, and reduced calculated forearm vascular resistance (from 49.1+/-5.4 to 31.3+/-3.9 arbitrary units, P<0.01). In conclusion, acute elevation of FFA in healthy men increases arterial blood pressure and reduces vascular resistance. These haemodynamic changes could be clinically relevant.
Kearney
Mark T
MT
Department of Cardiology, GKT School of Medicine, Denmark Hill, Bessemer Road, London SE5 9PJ, UK. mark.kearney@kcl.ac.uk
Chowienczyk
Philip J
PJ
Brett
Sally E
SE
Sutcliffe
Angela
A
Ritter
James M
JM
Shah
Ajay M
AM
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D010991:Plethysmography; D012039:Regional Blood Flow; D014664:Vasodilation / Q000187:drug effects
D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified