The objective of this clinical trial is to better understand how lactate, a naturally occurring energy substance, can be used to lessen damage to the vascular system in adults with a high cardiovascular disease risk.
The main questions it aims to answer are:
1. Does giving lactate intravenously reduce injury to the vascular system? 2. Does giving lactate intravenously together with blood flow occlusion - known as ischemic preconditioning, reduce vascular injury better than blood flow occlusion by itself? 3. How does lactate help the vascular system?
Researchers will compare lactate to a placebo (a look-alike substance that contains no lactate) to see if lactate works to lessen vascular injury.
Researchers will also compare lactate to blood flow occlusion to see which one is better at preventing vascular injury.
Researchers will also compare lactate and blood flow occlusion together to see if combining them works better than either one alone.
In one visit to the laboratory, participants will:
Obtain a measurement of vascular health in an arm Be given liquid lactate, a liquid placebo, and/or arm blood flow occlusion Obtain a second measurement of vascular health in an arm.
Sedentary men and women between the ages of 18-65 years of all races and ethnicity
Diet and weight stable for the past 3 months
Non-smoking and not using tobacco or electronic cigarettes
Use of medications known to affect cardiovascular function
Hyperlactemia
Type A lactic acidosis
Type B lactic acidosis
Parallel
Ischemic preconditioning
Procedure/SurgeryThe objective of this Intervention is to show that ischemic preconditioning (IPC) protects against endothelial ischemia/reperfusion injury. Baseline endothelium-dependent vasodilation to reactive hyperemia will be performed on the nondominant arm, followed by 3 × 5-minute cycles of IPC in the opposite arm. IPC will be induced using a blood pressure cuff placed on the opposite upper arm and inflated to 220 mmHg for 5 min, followed by 5 min of deflation. This procedure will be repeated two additional times taking about 30 minutest to complete. Following a 10-minute rest phase, endothelial injury will be induced using a blood pressure cuff that will be inflated to stop blood flow through the nondominant arm for 20 minutes, followed by 15 minutes of cuff deflation. Endothelium-dependent vasodilation measurements will be repeated immediately after the 15-minute cuff deflation phase.
Intravenous lactate infusion
DrugThe objective of this Intervention is to show that an intravenous infusion of lactate protects against endothelial ischemia/reperfusion injury. Baseline endothelium-dependent vasodilation to reactive hyperemia will be performed on the nondominant arm. Thereafter, a continuous intravenous infusion of lactate will be delivered in the contralateral arm. After systemic lactate reaches \~3 mmol/L, endothelial injury will be induced using a blood pressure cuff that will be inflated to stop blood flow through the nondominant arm for 20 minutes, followed by 15 minutes of cuff deflation. Endothelium-dependent vasodilation measurements will be repeated immediately after the 15-minute cuff deflation phase.
No ischemic preconditioning (control)
Procedure/SurgeryThe objective of this Intervention is to show that a control experiment without ischemic preconditioning does not provide protection against endothelial ischemia/reperfusion injury. Baseline endothelium-dependent vasodilation to reactive hyperemia will be performed on the nondominant arm, followed by 3 × 5-minute cycles of no upper arm occlusion in the opposite arm. To avoid upper arm occlusion, a blood pressure cuff will be placed on the upper arm and inflated to a low pressure of 20 mmHg pressure to not influence blood flow through the arm. This control procedure will be repeated two additional times taking about 30 minutes to complete. Following a 10-minute rest phase, endothelial injury will be induced using a blood pressure cuff that will be inflated to stop blood flow through the nondominant arm for 20 minutes, followed by 15 minutes of cuff deflation. Endothelium-dependent vasodilation measurements will be repeated immediately after the 15-minute cuff deflation phase.
Normal Saline Infusion (Placebo)
DrugThe objective of this Intervention is to show that a placebo intravenous infusion does not protect against endothelial ischemia/reperfusion injury. Baseline endothelium-dependent vasodilation to reactive hyperemia will be performed on the nondominant arm. Thereafter, a continuous infusion of normal saline that does not contain lactate will be delivered in the contralateral arm. After 20 minutes of the placebo infusion, endothelial injury will be induced using a blood pressure cuff that will be inflated to stop blood flow through the nondominant arm for 20 minutes, followed by 15 minutes of cuff deflation. Endothelium-dependent vasodilation measurements will be repeated immediately after the 15-minute cuff deflation phase.
Ischemic preconditioning and intravenous lactate
Combination productThe objective of this Intervention is to show that combining ischemic preconditioning (IPC) with an intravenous infusion of lactate provides the best protection against endothelial injury. First, baseline endothelial function to reactive hyperemia will be performed on the nondominant arm. Thereafter, a continuous intravenous infusion of lactate will be delivered in the contralateral arm. After that investigators will administer IPC using a blood pressure cuff placed on the same upper arm and inflated to 220 mmHg for 5 min, followed by 5 min of deflation. This procedure will be repeated two more times taking about 30 minutes to complete. The intravenous lactate infusion will be maintained. After a 10-minute rest phase and while lactate is still being infused, endothelial injury will be induced using a blood pressure cuff inflated to stop blood flow through the opposite arm (nondominant arm) for 20 minutes, followed by 15 minutes of cuff deflation. Endothelial function will be repeated.
Baseline value of the mean peak forearm blood flow response to reactive hyperemia.
Endothelium-dependent vasodilation will be assessed in the experimental (nondominant) arm by the forearm blood flow response to reactive hyperemia using strain-gauge venous occlusion plethysmography. Data are reported in ml of blood per 100 mL arm volume per minute.
Mean peak forearm blood flow response to reactive hyperemia at 3 hours.
Endothelium-dependent vasodilation will be assessed in the experimental (nondominant) arm by the forearm blood flow response to reactive hyperemia using strain-gauge venous occlusion plethysmography. Data are reported in ml of blood per 100 mL arm volume per minute.
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Gary Van Guilder
Lead sponsor
Western Colorado University
Sponsor institution
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