Vasoconstriction by electrical stimulation: new approach to control of non-compressible hemorrhage

Abstract

Non-compressible hemorrhage is the most common preventable cause of death on battlefield and in civilian traumatic injuries. We report the use of microsecond pulses of electric current to induce rapid constriction in femoral and mesenteric arteries and veins in rats. Electrically-induced vasoconstriction could be induced in seconds while blood vessels dilated back to their original size within minutes after stimulation. At higher settings, a blood clotting formed, leading to complete and permanent occlusion of the vessels. The latter regime dramatically decreased the bleeding rate in the injured femoral and mesenteric arteries, with a complete hemorrhage arrest achieved within seconds. The average blood loss from the treated femoral artery during the first minute after injury was about 7 times less than that of a non-treated control. This new treatment modality offers a promising approach to non-damaging control of bleeding during surgery, and to efficient hemorrhage arrest in trauma patients.

Figure 1. Localized vasoconstriction in arteries and veins.

Femoral vessels before (a) and after (b) stimulation with 1 μs/phase pulses of 250 V at 10 Hz repetition rate for 30 seconds. Mesenteric vessels before (c) and after (d) stimulation with 1 μs pulses of 80 V at 1 Hz for 30 seconds. Lumens of the femoral and mesenteric arteries and veins are indicated by the red and blue arrows, respectively.

Figure 2. Normalized diameter of the femoral arteries (a) and veins (b) in response to electrical stimulation with various amplitudes and pulse durations.

Vessels sizes were measured after each stimulation session of 10 seconds in duration. Stimulation pulses were applied at 1 Hz. Vessels were allowed to recover for 20 minutes between the sessions.

Figure 3. Peak voltage required to induce 25% and 50% constriction (V₂₅ and V₅₀) with pulse durations of 1, 10, 100, and 1000 μs/phase (MEAN +/− SE, n = 6).

Analytical fit demonstrated that V₅₀ and V₂₅ thresholds for both types of blood vessels scale with pulse duration as a power function of approximately ~t^−0.3.

Figure 4. Dynamics of the vasoconstriction and recovery of a femoral artery (a) and vein (b) following stimulation with various repetition rates.

A single site on the vessel was stimulated at V₂₅ (80 V) with 1 μs pulses for 2 minutes and allowed to recover without stimulation during 13 minutes. Repetition rate increased from 1 to 10⁴ Hz with increments of a factor of 10.

Figure 5. Dynamics of vasoconstriction and recovery of a femoral artery (a) and vein (b) during continuous stimulation with various pulse repetition rates.

Blood vessels were stimulated at V₂₅ (80 V) with 1 μs pulses for 10-minute periods at each repetition rate. (MEAN +/− SE, n = 4).

Figure 6. Constriction of mesenteric arteries (a) and veins (b) in response to stimulation with pulses of 1 and 100 μs/phase in duration.

Vessels were stimulated at repetition rate of 1 Hz during 10 seconds, with 20 minutes recovery between sessions. (MEAN +/− SE, n = 10).

Figure 7. Blood loss following a complete cut of femoral and mesenteric arteries.

After cutting, the femoral artery was stimulated for 30 seconds with 100 μs pulses of 150 V at 10 Hz (white bar), or at 30 V and 1 Hz (pink bar). Blood was collected during stimulation and for an additional 30 seconds after stimulation. Control vessels were exposed and severed in a similar fashion, and the stimulation probe was placed above the vessel, but no stimulation was applied. Mesenteric vessels were treated with 100 μs pulses of 40 V (right white bar) at 1 Hz for 30 seconds, or not treated (red bar). In both vessels types, treatment caused decrease or even complete stoppage of bleeding after stimulation, while continuous bleeding was observed in the untreated arteries. Statistical significance of the differences between groups was evaluated using Student t-test: *p = 0.001,**p = 0.047 ***p = 0.005,****p < 0.001.

Figure 8. Histology of the treated (a) and untreated (b) femoral artery following complete vessel dissection.

(a) Femoral artery treated with 100 μs pulses of 150 V at 10 Hz for 30 seconds. Treatment caused complete occlusion of the vessel and termination of hemorrhage within a few seconds. Constricted lumen is filled with acute blood clot attached to the endothelium (solid arrow). Constriction is evident by round shape of the vessel and folding in the internal elastic lamina (dashed arrow). (b) Control femoral artery from the other side of the same animal was cut and left bleeding for 60 seconds. Free flowing blood in the control artery formed a detached clot during sample fixation.