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Cryoprotective Perfusion

灌注冷冻保护液

At Alcor major blood vessels are connected to a perfusion circuit by a physician or veterinary surgeon. The preferred vascular access points are the aortic arch and right auricle of the heart, which are accessed by thoracic surgery (median sternotomy). Traditionally, neuropreservation patients have been treated by this same procedure, except that the descending aorta was clamped. In 2000, Alcor began treating

neuropreservation patients by directly accessing the carotid and

vertebral arteries. This requires careful surgical transection of the spinal column because vertebral arteries are located within the column. Alcor通过外科医师将主要血管连接到灌注回路。首选的接入位置是主动脉弓和右心房,可以通过胸外科手术接入(在胸骨正中进行手术)。传统上,仅保存大脑的病人也采用相同的手术过程,唯一不同的是将主动脉夹住。在2000年,对仅保存大脑的病人,Alcor开始通过直接对颈动脉和椎动脉的灌注来进行冷冻。由于椎动脉位于脊柱内,这就要求脊柱外科手术中须格外小心脊柱横断。

A base perfusate similar to the preservation solution used during

transport is circulated through the patient at a temperature near 0°C (the freezing point of water) for several minutes. This washes out any

remaining blood. The cryoprotectant concentration is then linearly increased over 2 hours to one half the final target concentration. This slow introduction minimizes osmotic stress, and allows time for the cryoprotectant concentration to equilibrate (become the same) inside and outside cells. A rapid increase to the final concentration is then made, and the final concentration is held until the venous outflow concentration equals the target concentration (approximately one hour). Temperature, pressure, and cryoprotectant concentration data are continuously monitored and acquired by computer.

在运输过程中,病人的温度接近0°(水的冰点),采用类似于保存液的一种基本灌洗液在病人体内循环几分钟,从而冲洗出所有的剩余血液。冷冻保护剂的浓度在两小时内线性增加,最终达到目标浓度的二分之一。这种缓慢的推入可以将渗透压降为最小,并使得细胞内外冷冻保护剂的浓度有足够的时间达到平衡(变成相同)。之后将保护液的浓度快速升为最终浓度,之后一直保持最终浓度,直到静脉流出浓度等于目标浓度(时间约需1小时)。计算机将连续监测温度、压力和冷冻保护剂浓度的数据。

The status of the brain is visually monitored through two small holes in the skull made using a standard neurosurgical tool (14 mm Codman perforator). This permits verification of brain perfusion by dye

injection, and observation of the osmotic response of the brain. A healthy brain slightly retracts from the skull in response to cryoprotectant perfusion. An injured brain swells, indicating that the blood-brain barrier has been compromised. This injury is often seen in patients who suffered a long period of untreated cardiac arrest.

采用标准外科手术工具(14mm可德曼穿孔器)在颅骨上钻两个小孔,通过这两个小孔可由肉眼观测大脑状态。这样一来,结合染色注射就可以检测大脑的灌注情况,并且可以观察大脑的渗透压变化。当一个健康的大脑被灌注冷冻剂时,它会从头骨缩回。受伤的大脑则会膨胀,这说明血-脑屏障已经受到的损伤。这种损伤常见于在心脏骤停后长时间未能开始进行冷冻手术的病人。

The cryoprotectant solution Alcor uses to prevent freezing is a mixture of chemicals developed by mainstream cryobiologists for long-term banking of transplantable organs. The solution has beenspecifically validated for structural preservation of the brain. At the end of perfusion, these chemicals are present at a concentration of

approximately 60%. In tissues adequately penetrated by the solution, the small amount of remaining water is not able to freeze. Instead of freezing, tissues vitrify when they are cooled to cryogenic temperatures.

Variable penetration of the solution appears to result in a combination of vitrification and partial freezing in various body tissues, but total vitrification (ice-free preservation) of the brain, at least under ideal conditions.

Alcor采用的冷冻保护剂是一种化学混合物,由权威低温生物学家研发用于移植器官的长期保存的液体。已经有专业机构验证这种溶液可以良好的保护大脑结构。在灌注结束时,这些化学试剂的浓度到将达约60%。在保护剂充分渗透到人体组织后,组织中剩余的少量水不足以结冰。当人体组织被降温到低温下时,它们不会结冰,而是被玻璃化。不同的溶液渗透率,决定了在不同人体组织中玻璃化和结冰的比例,但至少在理想条件下,可实现大脑的全部玻璃化(无冰保存)。 Cooling

降温

After cryoprotective perfusion, patients are cooled under computer control by fans circulating nitrogen gas at a temperature near -125°C. The goal is to cool all parts of the patient below -124°C (the glass transition temperature) as quickly as possible to avoid any ice formation. This requires approximately three hours, at the end of which the patient will have "vitrified" (reached a stable ice-free state). The patient is then further cooled to -196°C over approximately two weeks.

在灌注冷冻保护剂后,计算机控制的风扇将氮气循环,将患者冷冻至-125°C,这样做的目的是将患者所有组织器官尽快玻璃化而防止结冰(玻璃化温度为-124°

C)。这大约需要三个小时,结束后,病人达到玻璃化(一种稳定的无冰状态)。接下来将病人进一步冷却至-196°C,约需要耗时两周至数周时间。

Patients are monitored by sensitive "crackphone" instruments during this long cooling period to detect fracturing events that tend to occur when large objects are cooled below the glass transition temperature. Contrary to media reports, fracturing is not a result of mishandling. It is a universal problem for large organs cooled to liquid nitrogen

temperature. The federal government recently awarded $1.3 million dollars to specifically study the problem of fracturing during cryopreservation.

大型器官在被冷却到低于玻璃化温度时容易发生压裂。在长时间的冷冻期间,采用敏感的破裂麦克风设备对压裂进行实时监测。与媒体所报道相反的是,破裂不是处理不当的结果。这是大器官冷却到液氮温度的常见一个问题。联邦政府最近已经拨款130万美元,用于研究低温保存过程中的破裂问题。

Long-Term Care

长期护理

Currently Alcor patients are stored under liquid nitrogen at a temperature of -196°C. The liquid nitrogen is held in vacuum-insulated dewars that require replenishment every few weeks. Liquid nitrogen is used because it is inexpensive and reliable.

目前,Alcor患者都存储在液氮中,温度为-196°C。液氮在真空绝缘的杜瓦瓶中保存,每隔几个星期就需要进行补给。之所以使用液氮是因为它便宜又可靠。 Alcor is currently experimenting with an alternative "vapor phase" storage system that would retain the safety and reliability advantages of liquid nitrogen, but allow patients to be maintained at controlled temperatures warmer than liquid nitrogen. This will reduce or eliminate fracturing injury.

Alcor正在尝试用一个“汽相”的存储系统作为替代品,它不仅保持了液态氮的安全性和可靠性等优点,还可以使得在患者在比液态氮温暖的受控温度下进行保存。这将减少或消除压裂伤害。

Cases without Cardiopulmonary Support

无心肺支持的案例

Unfortunately not all Alcor members can be reached at the moment their heart stops. In cases of sudden illness or serious injury, blood

circulation may stop for hours before any cryonics procedures are possible. If a physician determines that an Alcor member in cardiac arrest cannot be resuscitated by current technology (i.e. declares legal death), the most important actions are administration of heparin (a drug that prevents blood clotting) followed by chest compressions to circulate the heparin, cooling with ice, and prompt shipment on ice to Alcor. Alcor will cooperate with local funeral directors in making these arrangements. Alcor will also negotiate with authorities to limit the extent of any autopsy that may be required. (Alcor recommends that all members execute a Religious Objection to Autopsy).

不幸的是,并非所有的Alcor成员都可以在他们的心脏停止的瞬间接受手术。如果是突发疾病或严重受伤的情况下,冷冻手术开始前血液循环可能会停止几个小时。如果某位心脏停搏的Alcor成员经医生确定,无法采用现有技术得到恢复(即在法律上已经死亡),最重要的操作是施用肝素(一种防止凝血的药物);并紧接着通过胸部按压,使肝素在人体中循环;同时用冰冷却,并立即在冰中保存运送至Alcor。Alcor将和当地殡葬官员合作完成上述安排。Alcor还会与当局协商,尽可能限制需要尸检的程度(Alcor建议所有成员都以宗教信仰为由避免尸检)。