医学研究：电刺激可帮助控制大鼠出血（二）
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.
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.
![Peak voltage required to induce 25% and 50% constriction (V25 and V50) with pulse durations of 1, 10, 100, and 1000[emsp14][mgr]s/phase (MEAN +/- SE, n = 6).](http://www.nature.com/srep/2013/130704/srep02111/images_article/srep02111-f3.jpg)
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.
Extent of vasoconstriction increased not only with the stimulus amplitude but also with the pulse repetition rate, for both the arteries (Figure 4a) and veins (Figure 4b). In this set of measurements, stimulation was applied during 2 minutes, but the vessels constricted to the minimum diameter within about a minute. After the end of stimulation, the blood vessel slowly dilated back to its original width within about 10 minutes (Figure 4). The recovery time to 90% of the original diameter increased with pulse repetition rate. For example, for 1 Hz it was about 4 minutes, while for 103 Hz it was about 8 minutes.
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.
Response of blood vessels to continuous stimulation was measured during 10 minute intervals, with the frequency increasing with each step, as shown in Figure 5. Again, the vessels reached the minimum size at each particular frequency within about a minute, and then remained at approximately steady state, with the extent of constriction dependent on the repetition rate. Vasoconstriction was stronger in arteries than in veins for each pulse frequency with both transient (Figure 4) and continuous (Figure 5) stimulation, and the difference was more pronounced at higher repetition rates. Maximum response to continuous stimulation (Figure 5) was smaller than to the transient stimulation regime (Figure 4), especially at higher 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).
Mesenteric blood vessels (Figure 6) had similar kind of response to that of the femoral arteries and veins. For the same pulse parameters, the extent of vasoconstriction in mesenteric arteries was higher than in femoral arteries (Figure 2), and the difference increased with larger amplitudes. For example, with 1 μs pulses at 200 V mesenteric arteries constricted by 76%, compared to 49% reduction in femoral arteries. Mesenteric veins constricted more than the femoral veins at low amplitudes, while this ratio reversed at higher amplitudes.
![Constriction of mesenteric arteries (a) and veins (b) in response to stimulation with pulses of 1 and 100[emsp14][mgr]s/phase in duration.](http://www.nature.com/srep/2013/130704/srep02111/images_article/srep02111-f6.jpg)
Vessels were stimulated at repetition rate of 1 Hz during 10 seconds, with 20 minutes recovery between sessions. (MEAN +/− SE, n = 10).
Hemorrhage control during vascular injury
Complete cut of a femoral artery represents a model of traumatic injury leading to profound loss of blood by the animal. Applying 100 μs pulses of 150 V (corresponding to 75% constriction at 1 Hz repetition rate) at a repetition rate of 10 Hz for 30 seconds rapidly decreased the bleeding rate. In all 6 cases treated with this regime, a nearly complete hemorrhage arrest has been achieved within a few seconds. The average blood loss from the femoral artery measured during 30 seconds of treatment and 30 seconds after that was about 7 times less than that of a non-treated control (0.14 vs. 1.05 ml, p = 0.001) (Figure 7). In all untreated animals, bleeding still continued after the 1 minute-long blood collection, and the animal died within minutes if bleeding was not mechanically stopped at the end of the measurements. When treated with pulse amplitude of 30 V at 1 Hz (corresponding to 50% constriction threshold), there was no complete hemorrhage arrest, and therefore reduction in blood loss was less pronounced: (0.35 vs 1.05 ml, p = 0.005), as shown in Figure 7). Strong decrease in blood loss was also observed in the severed mesenteric arteries treated with 100 μs pulses of 40 V at 1 Hz (corresponding to 75% constriction threshold), as shown in Figure 7.
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.
