Medical research: Electrical stimulation helps control bleeding in rats
本期Scientific Reports上發表的一項研究提出，用微秒脈沖對大鼠的靜脈和動脈進行電刺激，也許能幫助控制出血和減少不能通過壓迫止血的傷口中的失血。還需要進一步的研究來確定該方法對人類患者是否有效，但該方法對于在外傷中或手術過程中控制不能通過壓迫止血的出血也許會有用。
用止血帶止血在戰場上能幫助降低創傷死亡率，但該方法無法用于不能通過壓迫止血的出血，包括流入體腔（如腹腔）中的出血，也不能用于軀干與四肢或頸部接合部的傷口。上個世紀70年代，人們發現給一個被夾住的血管施加直流電幾分鐘時間可誘導產生血栓。然而，這樣所導致的熱損傷使得該技術無法用在臨床實踐中。
Yossi Mandel和來自Daniel Palanker實驗室的同事將微秒脈沖的電流施加到大鼠的大腿（腹股溝）區域和腹腔內的靜脈和動脈上。這樣使得這些血管中在幾秒內發生血管收縮，但幾分鐘內血管又擴張回它們的本來大小。增強電流強度，血管被完全地、永久性地阻斷。大鼠股動脈和腹部動脈中的血流速度降低，出血被迅速止住，股動脈的失血量與未經處理的大鼠相比減少7倍。作者在血管收縮后長達3.5小時未發現組織受到損傷，盡管還需要進行更長時間的跟蹤觀察來評估對組織是否會有任何潛在的長期影響。
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.
Trauma is the leading cause of death among US individuals younger than 44 years. Hemorrhagic shock accounts for 30–40 percent of traumatic mortality1, 2. Bleeding is also the most common preventable cause of death on battlefield3. Applications of tourniquets to compressible hemorrhages4, 5, 6, 7, 8 caused a marked decrease in limb exsanguinations3, 4, 9. As a result, according to the US army, hemorrhage not amenable to truncal tourniquets (also called non-compressible hemorrhage) is now the leading cause of preventable death3. Part of the non-compressible hemorrhages occur due to bleeding into body cavities (such as the abdomen or chest), while others are caused by wounds in the junction between the trunk and the limbs or neck. The latter ones, called junctional hemorrhages, are recognized as a care gap, and those of the pelvic, buttock and groin area are of highest prevalence10. Though Combat Gauze? is endorsed by the US Army for bleeding care in areas not amenable to a tourniquet, it is often ineffective in junctional hemorrhages such as groin, gluteal, axilla, shoulder and others9, 4, 3, 10. A novel mechanical compressing device, the Combat Ready Clamp, was recently introduced into the US Army3, 11, but has not yet been proven clinically. This device cannot be applied to wounds of the head, neck, abdomen and chest.
Effective prevention of blood loss in the pre-hospital arena offers the best opportunity to save soldiers with non-compressible injuries12, therefore major efforts are undertaken to develop technologies for this unmet need. In early 70 s, it was demonstrated that thrombosis can be induced in a clamped blood vessel by minutes-long application of direct electric current13, 14, 15. However, associated thermal damage precluded the use of this technology in clinical practice. Reduction in blood perfusion during electro-chemotherapy was also noted previously, and it was found to enhance the antitumor effect of the chemotherapy16, 17. More recently, constriction of blood vessels and thrombosis without thermal damage have been achieved with short (μs-ms) electric pulses18. However, these techniques have not been characterized in mammals, nor have they been evaluated for clinical use in various bleeding scenarios.
Recently we described significant decrease in blood loss from liver injury in rabbits treated by sub-millisecond electrical pulses19. The current study evaluates the effect of microsecond pulses on blood vessels in two areas non-amenable to truncal tourniquets: the groin area (femoral) and the abdominal cavity (mesenteric). We demonstrate significant vasoconstriction and decrease in blood loss following injury of these blood vessels. These results indicate a possibility of controlling non-compressible hemorrhage using non-thermal pulsed electrical stimulation.
Stimulation current was applied to the exposed blood vessel via 2 mm diameter pipette electrode filled with saline, while a large pad return electrode was applied to skin on the back side on the animal via conductive gel. Biphasic (symmetric, anodic-first square) pulses of electric current with duration of 1 μs per phase, amplitude of 250 V and repetition rate of 10 Hz caused, within seconds, a very pronounced local constriction of both femoral (Figure 1a,b) and mesenteric (Figure 1c,d) arteries and veins. Extent of the constriction of femoral vessels in response to 10 seconds long stimulation at 1 Hz repetition rate is plotted in Figure 2, as a function of stimulus amplitude and duration. Vasoconstriction increased with higher pulse amplitude and longer duration for both arteries and veins. For all pulse durations tested, vessels diameter decreased with increasing pulse amplitude along a sigmoid curve, having a response threshold on the lower end, and reaching a minimum size of about 20–25% of the original diameter on the high end (Figure 2). Strength-duration dependence of the 25% and 50% constriction thresholds could be approximated by a power dependence t?a, where a was approximately 0.3 for femoral arteries and veins (Figure 3). For all pulse durations, lower voltage was required to reach similar constriction in arteries, compared to veins, although the difference decreased at longer durations.