Key Words:
aortic trauma , iliac artery trauma , abdominal vascular trauma , visceral artery trauma
Introduction
Injuries to the major vessels in the abdomen are associated with a high mortality. Following penetrating abdominal trauma, vascular injuries are the most common causes of death. Intraabdominal hemorrhage can be catastrophic due to the difficulty of rapidly accessing the retroperitoneal vessels. It is for this reason that early recognition of a possible vascular injury is essential and transfer to a center capable of early surgical intervention is vital. The early diagnosis of these injuries has been facilitated with the increasing use of computed tomography (CT) angiography and with its availability close to the resuscitation room.
The majority of vascular trauma involves the extremities. By comparison, injuries to the abdominal vessels are less common, and hence it is difficult for a trauma center and its surgeons to accumulate large caseloads of specific arterial injuries. The incidence of injuries differs between military and civilian trauma. Although penetrating trauma is the more common mechanism for both civilian and military settings, blunt trauma resulting in abdominal vascular injuries is more common in the civilian setting. During the Vietnam War and World War II, the incidence of penetrating abdominal vascular injuries was less than 3%. In populations with a high incidence of knife crime, the incidence approaches 10%; and this figure doubles to more than 20% in populations with gun crime. For aortic penetrating injuries, the incidence still remains low and is less than 3% for penetrating trauma. In the context of blunt trauma, the incidence of abdominal vascular injury remains low at 3% and even lower (0.04%) for aortic injuries.
Mechanism of Injury
The vast majority of abdominal vascular injuries are a result of penetrating trauma. In the context of noniatrogenic injuries, penetrating injuries usually occur either from stab wounds or firearms. Injuries resulting from explosions (e.g., bomb blast) are complex, resulting in mixed patterns of penetrating and blunt trauma.
Stab wounds (e.g., knife wounds) result in localized injuries whereby the path of injury follows the track of the weapon. The type of injury that results from firearms is variable depending on the nature of the firearm. Gunshot wounds may be high-velocity or low-velocity. Low-velocity gunshot wounds are defined as wounds caused by projectiles such as a bullets or missiles with speeds of less than 600 m/s.) Low-velocity gunshot wounds such as those that occur with handguns cause localized injury to the structures that lie in the paths of the projectiles. They are associated with a lower transfer of energy compared with high-velocity gunshot wounds. Military wounds are more often a result of high-velocity (greater than 600 m/s) projectiles. A high-velocity projectile carries with it a significant amount of kinetic energy that is transferred to the surrounding tissue and results in extensive injury around the path of the projectile as well as the immediate damage to any tissue in the path of the projectile. The amount of energy transferred to the patient will be decided by a combination of factors including the energy carried by the missile, the cross-sectional area of the missile that comes into contact with the tissue, and the degree of retardation of the missile within the patient, that is, whether the missile passes through the tissue (delivering less energy) or comes to rest within the tissue (delivering all of its kinetic energy).
The injury that results from shotgun wounds is dependent on the range at which the shotgun is fired. If the range is less than 5 m, the chance of survival is approximately 10%. At this range, although shotgun is made up of multiple pellets, the lead shot projects as a single mass on impact and subsequently spreads out. When the shotgun is fired from a greater distance (e.g., 5 m to 15 m) the shot behaves as multiple low-energy missiles, resulting in less injury. At close range, vascular injuries tend to be multiple, complex, and frequently contaminated either with bowel contents or external contaminants such as the victims clothing.
Vascular injuries as a result of blunt trauma are far less common compared with penetrating trauma. The mechanism by which blunt trauma results in vascular injury is either by severe deceleration, by crush injuries, or by direct laceration from a fractured bone fragment. Severe deceleration can occur in the context of high-speed road traffic accidents or falls from significant heights. Crush injuries also occur in road traffic accidents and may result in an anteroposterior crush injury as seen in a seatbelt-restrained passenger. This can also be associated with shearing injuries of the aortic branches. Fractures of the spine or pelvis can result in direct laceration to the aorta and iliac vessels, respectively. Renal vessels may be damaged with acceleration—deceleration type injuries causing shearing forces to be applied to the renal pedicle.
While the adventitia is the most durable part of the arterial wall, the intima remains the least elastic and therefore most likely to be torn during blunt injury. Hence the artery is frequently injured from “inside to outside,” and the adventitia may remain intact. This creates a thrombogenic environment within the artery resulting in thrombosis and occlusion. Alternatively the intima may be sheared resulting in a dissection. If the adventitia remains intact the artery may still be weakened contributing to delayed aneurysmal degeneration. Total transmural injury can lead to perforation, hemorrhage, and false aneurysms.
Anatomy
Vascular injuries in the abdomen are classified according to geographical location ( Fig. 11-1 ). These are usually defined within three zones, albeit a fourth zone is occasionally included.
Zone I begins at the point of entry of the aorta through the diaphragm (i.e., the aortic hiatus) and extends down to the sacrum. The aorta enters the abdomen at the level of the twelfth thoracic vertebra passing behind the median arcuate ligament of the diaphragm. The aorta descends to the level of the fourth lumbar vertebra where it bifurcates into the left and right common iliac arteries. Zone I includes the central retroperitoneal area and the base of the mesentery. The area is further divided into the supramesocolic and inframesocolic areas. The supramesocolic and inframesocolic areas are defined by the levels of the renal arteries. The suprarenal aorta, celiac axis, superior mesenteric artery (SMA), renal arteries, inferior vena cava (IVC), and superior mesenteric vein all lie within this supramesocolic area. The inframesocolic area contains the infra renal aorta, the inferior mesenteric artery, and the IVC.
Zone II exists either side of zone I and contains the paracolic gutters, kidneys, and renal vessels. It is also referred to as the upper lateral retroperitoneum.
Zone III containing the iliac vessels is also known as the pelvic retroperitoneum.
The hepatic artery, portal vein, retrohepatic IVC, and hepatic veins all lie within an area occasionally referred to as zone IV.
Clinical Presentation
The patient should be inspected for signs of penetrating injury. Stab wounds in the abdomen should be obvious but be aware that stab wounds in the chest, back, and gluteal regions can result in injury to abdominal and pelvic vessels. With both penetrating and blunt trauma, examine for bruising in the flanks. This can be a sign of a retroperitoneal bleeding. With gunshot wounds, examine the patient for entry and exit wounds. An attempt to predict the trajectory may provide some idea of the vessels and organs injured. Do not assume that the injury is localized to the missile path. The presentation of arterial injuries may be early or late depending on the artery involved, as well as the type and mechanism of injury.
Early presentation is usually in the form of hemorrhage and hypovolemic shock. Urgent laparotomy will reveal either blood in the peritoneal cavity or a retroperitoneal hematoma. The zone should be defined according to Figure 11-1 . Some patients may respond to resuscitation but presentation with a distended abdomen should raise the suspicion of a vascular injury. Patients who are stabilized and taken for trauma CT of the abdomen revealing vascular injury may also be included as early presenters. Thrombosis, dissections, and occlusions may present with lower limb ischemia (absent or diminished femoral pulses; cold, pale limbs). This should be considered in the context of blunt injury resulting in pelvic fractures or abdominal crush. Be aware that the presentation may not be immediate with intimal tears, and repeated examinations are mandatory. Injuries to the renal pedicles may present with hematuria. Anuria as a result of bilateral renal artery thrombosis is rare.
Both penetrating and blunt trauma can result in vascular injuries that present late. With the increasing use of CT angiography, arterial injuries are being detected early reducing the incidence of late presentation. Pseudoaneurysms frequently present late. They may each present as a pulsatile mass compressing adjacent structures. Compression of the duodenum may present as bowel obstruction. The false aneurysm may erode into the bowel resulting in massive gastrointestinal hemorrhage. Similarly internal iliac pseudoaneurysms have presented with rectal bleeding. Pseudoaneurysm of the renal artery can present with hematuria. Arterial fistulas have been seen with hepatic artery injuries and penetrating liver injuries. These fistulas may present with hemobilia, right upper quadrant pain, and upper gastrointestinal hemorrhage. Injuries involving both arteries and veins can cause arteriovenous fistulas. The clinical manifestation may be obvious or subtle. Aortocaval fistulas are associated with lower limb edema and an abdominal bruit. Other arteriovenous fistulas may present later with high-output cardiac failure and lower limb chronic venous skin changes.
Investigations
The choice of investigation will depend on the patient’s hemodynamic stability and the available local facilities. CT has become the gold standard investigation. Availability close to the resuscitation room is an important factor in the planning of a major trauma center. Catheter angiography still maintains an important role in trauma and has the advantage of being coupled with therapeutic options such as stenting and embolotherapy. Early availability of experienced interventional radiologists and the location of the radiology suite often limit use to the hemodynamically stable patient. The use of ultrasound in trauma has increased in the form of focused assessment with sonography for trauma (FAST) scans. Bedside ultrasonography is able to detect intraabdominal free fluid, facilitating the decision for early exploratory laparotomy. The exploratory trauma laparotomy remains an important diagnostic tool and is coupled with the techniques of damage control surgery. Duplex scanning is less useful in the acute trauma presentation. It has a role in assessing neck trauma and can be used for surveillance to detect late pseudoaneurysms and arteriovenous fistulas. In the context of abdominal vascular injuries, its use is limited.
Surgical Techniques
The operative approach will be dependent on the location of the hematoma and the degree of urgency. The latter is dictated by the degree of hemodynamic shock.
When a decision is made to proceed to surgery, the patient should be prepared with sterile drape application allowing exposure of the abdomen, chest, and groins. This allows for incisions to be extended into the chest; and, if necessary, a thorocotomy can be utilized to gain control of the descending aorta. To facilitate distal control, exposure of the common femoral arteries may be required. The initial incision is a long midline laparotomy from the xiphisternum to the pubis. If further access is required, the incision may be extended in the midline to include a median sternotomy or through the 6th or 7th intercostal spaces for a lateral thorocotomy.
On initiating the laparotomy the surgeon may be presented with an abdominal cavity containing free blood. At this stage it may be difficult to establish the source of bleeding and the principles of damage control surgery should be applied. In order identify the source of bleeding, the surgeon should proceed with packing of the abdominal cavity, using large packs to either stop or slow the bleeding. These packs are then removed from each compartment until the source of bleeding is identified. The four-quadrant packing technique requires packs to be placed in the right upper quadrant over the right lobe of the liver, the left upper quadrant, the infracolic compartment (elevate the greater omentum and pack either side of the small bowel mesentery), and the pelvis. Pelvic packing is performed by lifting the small bowel out of the pelvis before applying the packs into the pelvis.
Exposure of the aorta and its branches is best achieved using the technique of a medial visceral rotation. This can be performed from either the left or right side; the decision will be dependent on which vessels need to be exposed. The medial visceral rotation can be a time-consuming technique, even in experienced hands; and temporary control may be required, especially if active hemorrhage is occurring from the supramesocolic aorta. Direct manual compression of the aorta against the spine may control the bleeding but frequently restricts exposure of the aorta and therefore subsequent repair. It can be a useful technique to control the inflow, but the ultimate aim should be to apply a clamp.
Division or creation of a window within the lesser omentum enables exposure of the supraceliac aorta. This technique is aided by retracting the stomach and the esophagus to the left. The liver is retracted in a cephalad direction. Division of the diaphragmatic crura further aids exposure, and then a supra celiac aortic clamp can be applied. This is the quickest way to apply a supraceliac clamp and to gain control of the bleeding abdominal aorta. Although inflow will be controlled, back-bleeding from the visceral vessels and lumbar arteries may be significant. The presence of visceral branches can make distal control challenging.
In order to perform a left-sided medial visceral rotation, the peritoneal attachments of the sigmoid and the descending colon are divided. The incision is started in the lateral avascular peritoneal reflection of the sigmoid colon and is continued proximally along the left paracolic gutter. The plane is developed by mobilizing the sigmoid colon and the descending colon to the midline. The retroperitoneal attachments of the left kidney, pancreatic tail, and spleen can be divided, mobilizing these organs to the midline and hence facilitating complete exposure of the abdominal aorta from its origin at the diaphragm to its bifurcation at the level of the fourth lumbar vertebra ( Figs. 11-2 and 11-3 ). This technique carries a significant risk of damage to the spleen, left kidney and left renal vessels. Developing a dissection plane anterior to the left kidney can reduce the risk of intraoperative renal injury.
If rapid proximal control of the abdominal aorta is required before the medial visceral rotation, a clamp can be applied to the distal descending thoracic aorta. This is especially useful with an expanding zone I hematoma. The aorta is exposed by division of the left crus of the diaphragmatic aortic hiatus. Incision is made at the 2 o’clock position exposing the descending thoracic aorta and hiatal aorta. This is the quickest way to achieve proximal control during a medial visceral rotation. The presence of celiac nerves and lymphatic tissue around the aorta, together with dense diaphragmatic muscle fibers, makes careful dissection of the most proximal abdominal aorta difficult, time consuming, and hence unsuitable for the severely hypotensive patient.
The advantage of this technique is that, after mobilizing the spleen and the tail of the pancreas, the anterior midline visceral branches of the aorta are well exposed and can be controlled, repaired, or ligated.
A right-sided medial visceral rotation is performed by dividing the peritoneal reflection lateral to the ascending colon ( Fig. 11-4 ). A dissection plane is developed anterior to the kidney, facilitating mobilization of the colon and terminal ileum to the midline. This allows exposure of the duodenum, which can then be kocherized. The duodenum and the pancreatic head are mobilized to the left, and the retroperitoneal tissue left of the IVC is divided to expose the suprarenal aorta, the celiac axis, and the SMA. If exposure of the diaphragmatic hiatal aorta is required, this technique should be avoided.
If injury is isolated to the infrarenal aorta, exposure to this part of the aorta can be achieved via an anterior approach that resembles that for an infrarenal abdominal aortic aneurysm. Peritoneal incision is made left of the duodenojejunal flexure, the peritoneum dissected off the aorta and an infrarenal aortic clamp applied. More proximal application of an infrarenal aortic clamp can be facilitated by ligation and division of the left renal vein, preferably preserving its adrenal and gonadal tributaries.
Surgical exposure of the celiac artery is either via a medial visceral rotation or via a direct dissection through the lesser sack. Fullen’s anatomical classification can be used for the purpose of describing injuries to the SMA. Exposure of the proximal SMA (Fullen’s zone I) is via a left medial visceral rotation. If severe bleeding dictates very rapid exposure, this part of the SMA can be exposed by dividing the neck of the pancreas. The easiest and quickest way of doing this is by using a stapling device; but, if this is not available, intestinal clamps should be applied before the division of the pancreatic neck to control any bleeding. The proximal infrapancreatic SMA can be exposed through root of the small bowel mesentery, and this may be facilitated further by mobilization of the duodenum and retraction of the pancreas. The more distal SMA may be exposed directly in the bowel mesentery.
The inferior mesenteric artery origin is easily exposed via an infrarenal approach to the aorta. The renal arteries can be exposed through respective medial visceral rotation techniques. In the presence of a large retroperitoneal hematoma, the application of a supraceliac aortic clamp should be used for proximal control. If the renal artery is bleeding from a more distal point (e.g., renal hilum), the renal artery can be exposed at its origin without the need for a visceral rotation. The small bowel is eviscerated to the right, and the aorta is approached anteriorly. The duodenojejunal flexure is mobilized as previously described. The left renal vein can be either divided as previously described or retracted proximally. The latter can be facilitated by division of the left gonadal and adrenal veins. This will allow exposure of the origin of the renal arteries.
The left renal artery can be seen following dissection of the surrounding peritoneal tissue. The right renal artery may require lateral retraction of the IVC to identify its origin. Additionally medial rotation of the duodenum and then of the pancreas may be required to visualize the right renal vein, which will need to be looped and retracted before the remaining right renal artery can be exposed. The presence of a large retroperitoneal hematoma around the right kidney and juxtarenal IVC can make this a challenging dissection. Identifying the IVC distally and then dissecting in a proximal direction along the course of the IVC through the hematoma is an alternative approach.
Although the focus of this chapter is on arterial injuries due to their close proximity, the veins may be injured with the artery in the patient with multiple injuries. Achieving hemostasis during combined venous and arterial bleeding can be challenging. The application of clamps to a large vein can further tear the vein and therefore should be avoided or used with extreme caution. Using mounted sponges or swabs to apply pressure above and below the injury can achieve hemorrhage control and is less likely to damage the vein. With the aid of an experienced assistant, the surgeon can repair or ligate the vein. An alternative technique is using Foley catheters within large veins to control the inflow and back-bleeding.
Aortic Injuries
The majority of injuries to the aorta are consequences of penetrating traumas. Blunt injuries are rare and may be associated with seatbelt injuries and thoracolumbar fractures of the spine. The majority of patients who experience a rupture do not survive transport to hospital.
The complex forces that are associated with blunt trauma can damage the aortic intima resulting in aortic dissection, thrombosis, and consequently end organ ischemia or limb ischemia. This may not be apparent at the initial presentation, and a high index of clinical suspicion is vital. Less commonly, patients may have delayed presentation with a pseudoaneurysm or arteriovenous fistula.
An aortic branch may be avulsed and present as a large retroperitoneal hematoma during the trauma laparotomy. Gunshot wounds appear to be associated with a higher incidence of aortic injuries than knife wounds. The clinical presentation will be dependent on a number of factors. If the injury results in bleeding into the peritoneal cavity, the patient presents in severe shock with peritonitis and a distended abdomen. Frequently these patients do not survive transfer to the hospital. If the injury is to the lateral wall and bleeding is confined to the retroperitoneum, hemorrhage may tamponade temporarily within the retroperitoneum.
Investigations
Hemodynamically unstable patients who do not respond to initial fluid resuscitation should be taken immediately to the operating room for a trauma laparotomy. Patients who are stable can be investigated with a trauma CT scan. This will identify significant bleeding or retroperitoneal hematomas. With the increasing availability of CT angiography, the use of catheter angiography as a diagnostic tool has diminished. Catheter angiography does, however, offer the possibility of combining both diagnostic and therapeutic options with the use of endovascular stents, occlusion balloons, and embolization techniques.
Treatment
The choice of treatment is dependent on patient factors and institutional factors. Patient factors include hemodynamic status, injuries to other intraabdominal organs, and degree of intraabdominal contamination. Institutional factors include the availability of local facilities (e.g., interventional radiology, CT imaging, and medical expertise).
Injuries to the infrarenal aorta have been successfully treated with endovascular techniques. These include endovascular stent-grafts for dissection flaps and aortocaval fistulas, as well as embolization (e.g., coiling) of aortic visceral branches.
The trauma laparotomy may reveal a retroperitoneal hematoma. Central hematomas require exploration, and the principles of gaining both proximal and distal arterial control should be applied. Exposure of the aorta and its branches has been previously described. Small aortic lacerations may be closed with a 3-0 or 4-0 Prolene suture using the technique of lateral aortorrhaphy. If there is a defect in the aorta and lateral aortorrhaphy is likely to narrow the aorta, consideration should be given to repairing the defect using a prosthetic patch or tube graft ( Fig. 11-5 ). Consideration must always be given to the principles of damage control surgery. The surgeon should avoid prolonged complex arterial repairs in the patient who is acidotic, hypothermic, and coagulopathic.
The decision to use prosthetic grafts will be affected by the degree of intraabdominal contamination from other injuries. Many surgeons will opt for an extra anatomical bypass in the presence of abdominal contamination. Some surgeons do not consider mild contamination as a contraindication to the use of prosthetic grafts in the trauma patient. Instead the contamination is dealt with, the peritoneum is washed out, and a graft is used if needed. Like many controversies in vascular trauma there is a lack of evidence in the literature to either support or negate the use of prosthetic grafts in this setting.
Follow-up
Young patients treated with endovascular stents will need to be in a long-term surveillance program, as the durability of these grafts in young patients remains unknown. If there has been abdominal contamination and a prosthetic graft used, the patient should be followed up for signs of graft infection.
Investigations
Hemodynamically unstable patients who do not respond to initial fluid resuscitation should be taken immediately to the operating room for a trauma laparotomy. Patients who are stable can be investigated with a trauma CT scan. This will identify significant bleeding or retroperitoneal hematomas. With the increasing availability of CT angiography, the use of catheter angiography as a diagnostic tool has diminished. Catheter angiography does, however, offer the possibility of combining both diagnostic and therapeutic options with the use of endovascular stents, occlusion balloons, and embolization techniques.
Treatment
The choice of treatment is dependent on patient factors and institutional factors. Patient factors include hemodynamic status, injuries to other intraabdominal organs, and degree of intraabdominal contamination. Institutional factors include the availability of local facilities (e.g., interventional radiology, CT imaging, and medical expertise).
Injuries to the infrarenal aorta have been successfully treated with endovascular techniques. These include endovascular stent-grafts for dissection flaps and aortocaval fistulas, as well as embolization (e.g., coiling) of aortic visceral branches.
The trauma laparotomy may reveal a retroperitoneal hematoma. Central hematomas require exploration, and the principles of gaining both proximal and distal arterial control should be applied. Exposure of the aorta and its branches has been previously described. Small aortic lacerations may be closed with a 3-0 or 4-0 Prolene suture using the technique of lateral aortorrhaphy. If there is a defect in the aorta and lateral aortorrhaphy is likely to narrow the aorta, consideration should be given to repairing the defect using a prosthetic patch or tube graft ( Fig. 11-5 ). Consideration must always be given to the principles of damage control surgery. The surgeon should avoid prolonged complex arterial repairs in the patient who is acidotic, hypothermic, and coagulopathic.
The decision to use prosthetic grafts will be affected by the degree of intraabdominal contamination from other injuries. Many surgeons will opt for an extra anatomical bypass in the presence of abdominal contamination. Some surgeons do not consider mild contamination as a contraindication to the use of prosthetic grafts in the trauma patient. Instead the contamination is dealt with, the peritoneum is washed out, and a graft is used if needed. Like many controversies in vascular trauma there is a lack of evidence in the literature to either support or negate the use of prosthetic grafts in this setting.
Follow-up
Young patients treated with endovascular stents will need to be in a long-term surveillance program, as the durability of these grafts in young patients remains unknown. If there has been abdominal contamination and a prosthetic graft used, the patient should be followed up for signs of graft infection.
Injuries to the Visceral Arteries
Celiac Artery and Branches
Isolated injuries to the celiac artery are rare. The majority of patients have other vascular injuries. It is for this reason that these injuries are associated with a high mortality. The majority of injuries to the celiac artery are a consequence of penetrating trauma.
Bleeding from the celiac trunk or its branches close to their origin can be difficult to control. This is because of the small size of the vessel, especially in a shocked patient where vasoconstriction makes exposure all the more difficult. The surrounding connective tissue and the location of the celiac trunk contribute to a difficult dissection. Urgent control may be needed with a supraceliac aortic clamp. This is best achieved as previously described via a window through the lesser omentum. Exposure of the celiac axis is best achieved via a left medial visceral rotation but this is time consuming and dependent on the hemodynamic status of the patient.
Injuries to the left gastric or splenic artery should not be repaired as these are small vessels and are better managed with ligation. The surgeon should be aware that the left hepatic artery may arise entirely from the left gastric artery in up to 10% of patients. If there is an injury to the celiac trunk, this can also be managed by ligation provided the SMA is patent and the ligation is proximal to the branches of the celiac trunk. Evidence from elective endovascular aneurysm repairs suggests that the risk of ischemic foregut complications is low in most.
If the common hepatic artery is injured, there are a number of options. The artery can be identified in the lesser omentum and its exposure facilitated by retracting the duodenum inferiorly. At the epiploic foramen, it lies anterior to the portal vein and medial to the common bile duct; and hence the Pringle maneuver may facilitate control of bleeding when the injury is at the porta hepatis. Ligation of the common hepatic artery proximal to the origin of the gastroduodenal artery is possible, again dependent on the patency of the inferior pancreaticoduodenal branch of the SMA. The common hepatic artery may have a sufficient diameter so that it is possible to perform arteriorrhaphy. Alternatively limited resection and an end-to-end anastomosis may be attempted. If end-to-end anastomoses is not possible, reconstruction with autologous vein graft or even prosthetic graft may be considered; however, in the young resuscitated patient with patent SMA, circulation and a well-developed gastroduodenal artery, primary ligation or embolization is unlikely to cause any long-term sequelae.
If the patient is stable and local facilities and expertise permit, endovascular options may be considered. Catheter angiography can be used to identify bleeding, and this procedure can be combined with coil embolization.
Superior Mesenteric Artery
The most common mechanism of injury to the SMA is penetrating trauma. This is frequently associated with other injuries. With the exception of the renal artery, the SMA is the most commonly injured aortic visceral branch following blunt trauma. Rapid deceleration can result in either avulsion of the SMA at its origin ( Fig. 11-6 ). Alternatively, deceleration injuries may present as an intimal tear, dissection and thrombosis. This comes as no surprise when consideration is given to the mobility of the small bowel and its mesentery. These injuries can present either early or late as intestinal ischemia.
