Traumatic injury to an extremity may produce partial or total occlusion of a vessel from compression, shearing or laceration. Acute arterial occlusion may develop as a result of arterial dissection in the carotid artery or aorta or as a result of iatrogenic arterial injury (e.g., after angiography).

The thrombi may dislodge and may travel anywhere in the circulatory system, where they may lead to pulmonary embolus, an acute arterial occlusion causing the oxygen and blood supply distal to the embolus to decrease suddenly. The degree and extent of symptoms depend on the size and location of the obstruction, the occurrence of clot fragmentation with embolism to smaller vessels, and the degree of peripheral arterial disease (PAD).

- Thromboembolism (blood clots)

- Embolism (foreign bodies in the circulation, e.g. amniotic fluid embolism)

The major cause of acute limb ischaemia is arterial thrombosis (85%), while embolic occlusion is responsible for 15% of cases. In rare instances, arterial aneurysm of the popliteal artery has been found to create a thrombosis or embolism resulting in ischaemia.

Risk factors contributing to PAD are the same as those for atherosclerosis:

- Smoking – tobacco use in any form is the single most important modifiable cause of PAD internationally. Smokers have up to a tenfold increase in relative risk for PAD in a dose-response relationship. Exposure to second-hand smoke from environmental exposure has also been shown to promote changes in blood vessel lining (endothelium) which is a precursor to atherosclerosis. Smokers are 2 to 3 times more likely to have lower extremity peripheral arterial disease than coronary artery disease. More than 80%-90% of patients with lower extremity peripheral arterial disease are current or former smokers. The risk of PAD increases with the number of cigarettes smoked per day and the number of years smoked.

- Diabetes mellitus – causes between two and four times increased risk of PAD by causing endothelial and smooth muscle cell dysfunction in peripheral arteries. The risk of developing lower extremity peripheral arterial disease is proportional to the severity and duration of diabetes.

- Dyslipidemia – a high level of low-density lipoprotein (LDL cholesterol) and a low level of high-density lipoprotein (HDL cholesterol) in the blood) - elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAD. Correction of dyslipidemia by diet and/or medication is associated with a major improvement in rates of heart attack and stroke.

- Hypertension – elevated blood pressure is correlated with an increase in the risk of developing PAD, as well as in associated coronary and cerebrovascular events (heart attack and stroke). Hypertension increased the risk of intermittent claudication 2.5- to 4-fold in men and women, respectively.

- Risk of PAD also increases in individuals who are over the age of 50, male, obese, heart attack, or stroke or with a family history of vascular disease.

- Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, fibrinogen, hyperviscosity, hypercoagulable state.

Diabetes mellitus increases the risk of stroke by 2 to 3 times. While intensive blood sugar control has been shown to reduce small blood vessel complications such as kidney damage and damage to the retina of the eye it has not been shown to reduce large blood vessel complications such as stroke.

Peripheral arterial disease is more common in the following populations of people:

- All people who have leg symptoms with exertion (suggestive of claudication) or ischemic rest pain.

- All people aged 65 years and over regardless of risk factor status.

- All people between the age of 50 to 69 and who have a cardiovascular risk factor (particularly diabetes or smoking).

- Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia).

- Individuals with an abnormal lower extremity pulse examination.

- Those with known atherosclerotic coronary, carotid, or renal artery disease.

- All people with a Framingham risk score 10%-20%

- All people who have previously experienced chest pain

Nutrition, specifically the Mediterranean-style diet, has the potential for decreasing the risk of having a stroke by more than half. It does not appear that lowering levels of homocysteine with folic acid affects the risk of stroke.

The fact that the ischemic cascade involves a number of steps has led doctors to suspect that neuroprotectants such as calcium channel blockers or glutamate antagonists could be produced to interrupt the cascade at a single one of the steps, blocking the downstream effects. Though initial trials for such neuroprotective drugs led many to be hopeful, until recently, human clinical trials with neuroprotectants such as NMDA receptor antagonists were unsuccessful.

On October 7, 2003, a U.S. patent number 6630507 entitled "Cannabinoids as Antioxidants and Neuroprotectants" was awarded to the United States Department of Health and Human Services, based on research carried out at the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). This patent claims that cannabinoids are "useful in the treatment and prophylaxis of wide variety of oxidation associated diseases such as ischemia, inflammatory ... and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma..."

On November 17, 2011, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR part 404.7(a)(1)(i), the National Institutes of Health, Department of Health and Human Services, published in the Federal Register, that it is contemplating the grant of an exclusive patent license to practice the invention embodied in U.S. Patent 6,630,507, entitled “Cannabinoids as antioxidants and neuroprotectants” and PCT Application Serial No. PCT/US99/08769 and foreign equivalents thereof, entitled “Cannabinoids as antioxidants and neuroprotectants” [HHS Ref. No. E-287-1997/2] to KannaLife Sciences Inc., which has offices in New York, U.S. This patent and its foreign counterparts have been assigned to the Government of the United States of America. The prospective exclusive license territory may be worldwide, and the field of use may be limited to: The development and sale of cannabinoid(s) and cannabidiol(s) based therapeutics as antioxidants and neuroprotectants for use and delivery in humans, for the treatment of hepatic encephalopathy, as claimed in the Licensed Patent Rights.

Therapeutic hypothermia has been attempted to improve results post brain ischemia . This procedure was suggested to be beneficial based on its effects post cardiac arrest. Evidence supporting the use of therapeutic hypothermia after brain ischemia, however, is limited.

A closely related disease to brain ischemia is brain hypoxia. Brain hypoxia is the condition in which there is a decrease in the oxygen supply to the brain even in the presence of adequate blood flow. If hypoxia lasts for long periods of time, coma, seizures, and even brain death may occur. Symptoms of brain hypoxia are similar to ischemia and include inattentiveness, poor judgment, memory loss, and a decrease in motor coordination. Potential causes of brain hypoxia are suffocation, carbon monoxide poisoning, severe anemia, and use of drugs such as cocaine and other amphetamines. Other causes associated with brain hypoxia include drowning, strangling, choking, cardiac arrest, head trauma, and complications during general anesthesia. Treatment strategies for brain hypoxia vary depending on the original cause of injury, primary and/or secondary.

When a limb is ischemic in the non-acute (chronic) setting, the condition is alternatively called peripheral artery disease or critical limb ischemia, rather than ALI. In addition to limb ischemia, other organs can become ischemic, causing:

- Renal ischemia (nephric ischemia)

- Mesenteric ischemia

- Cerebral ischemia

- Cardiac ischemia

Brain ischemia has been linked to a variety of diseases or abnormalities. Individuals with sickle cell anemia, compressed blood vessels, ventricular tachycardia, plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of heart attack, and congenital heart defects have a higher predisposition to brain ischemia in comparison their healthy counterparts.

Sickle cell anemia may cause brain ischemia associated with the irregularly shaped blood cells. Sickle shaped blood cells clot more easily than normal blood cells, impeding blood flow to the brain.

Compression of blood vessels may also lead to brain ischemia, by blocking the arteries that carry oxygen to the brain. Tumors are one cause of blood vessel compression.

Ventricular tachycardia represents a series of irregular heartbeats that may cause the heart to completely shut down resulting in cessation of oxygen flow. Further, irregular heartbeats may result in formation of blood clots, thus leading to oxygen deprivation to all organs.

Blockage of arteries due to plaque buildup may also result in ischemia. Even a small amount of plaque build up can result in the narrowing of passageways, causing that area to become more prone to blood clots. Large blood clots can also cause ischemia by blocking blood flow.

A heart attack can also cause brain ischemia due to the correlation that exists between heart attack and low blood pressure. Extremely low blood pressure usually represents the inadequate oxygenation of tissues. Untreated heart attacks may slow blood flow enough that blood may start to clot and prevent the flow of blood to the brain or other major organs. Extremely low blood pressure can also result from drug overdose and reactions to drugs. Therefore, brain ischemia can result from events other than heart attacks.

Congenital heart defects may also cause brain ischemia due to the lack of appropriate artery formation and connection. People with congenital heart defects may also be prone to blood clots.

Other events that may result in brain ischemia include cardiorespiratory arrest, stroke, and severe irreversible brain damage.

Recently, Moyamoya disease has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood circulation to the brain, consequently leading to oxygen deprivation.

Risk factors for thromboembolism, the major cause of arterial embolism, include disturbed blood flow (such as in atrial fibrillation and mitral stenosis), injury or damage to an artery wall, and hypercoagulability (such as increased platelet count). Mitral stenosis poses a high risk of forming emboli which may travel to the brain and cause stroke. Endocarditis increases the risk for thromboembolism, by a mixture of the factors above.

Atherosclerosis in the aorta and other large blood vessels is a common risk factor, both for thromboembolism and cholesterol embolism. The legs and feet are major impact sites for these types. Thus, risk factors for atherosclerosis are risk factors for arterial embolisation as well:

- advanced age

- cigarette smoking

- hypertension (high blood pressure)

- obesity

- hyperlipidemia, e.g. hypercholesterolemia, hypertriglyceridemia, elevated lipoprotein (a) or apolipoprotein B, or decreased levels of HDL cholesterol)

- diabetes mellitus

- Sedentary lifestyle

- stress

Other important risk factors for arterial embolism include:

- recent surgery (both for thromboembolism and air embolism)

- previous stroke or cardiovascular disease

- a history of long-term intravenous therapy (for air embolism)

- Bone fracture (for fat embolism)

A septal defect of the heart makes it possible for paradoxical embolization, which happens when a clot in a vein enters the right side of the heart and passes through a hole into the left side. The clot can then move to an artery and cause arterial embolisation.

A study showed that those who quit smoking reduced their risk of being hospitalized over the next two years.

Smoking increases blood pressure, as well as increases the risk of high cholesterol. Quitting can lower blood pressure, and triglyceride levels.

Secondhand smoke is also bad for the heart health.

Diet is a very important factor in getting coronary ischemia or coronary artery disease and preventing it.

A heart healthy diet is low in saturated fat and cholesterol and high in complex carbohydrates.

Complex carbohydrates include fruits, vegetables, and whole grains. These food choices can reduce the risk of a heart attack or any other congestive heart failure event.

A heart healthy diet also includes low sodium intake and a higher potassium intake. A low potassium intake raises blood pressure, as does a diet high in sodium.

Causes include:

- Thrombosis (approximately 40% of cases)

- Arterial embolism (approximately 40%)

- arteriosclerosis obliterans

Another cause of limb infarction is "skeletal muscle infarction" as a rare complication of long standing, poorly controlled diabetes mellitus.

With treatment, approximately 80% of patients are alive (approx. 95% after surgery) and approximately 70% of infarcted limbs remain vital after 6 months.

Non-occlusive disease has a poor prognosis with survival rate between 40-50%.

The ischemic (ischaemic) cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia (inadequate blood supply). This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the activation of chemicals produced during and after ischemia. The ischemic cascade usually goes on for two to three hours but can last for days, even after normal blood flow returns.

A cascade is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:

1. Lack of oxygen causes the neuron's normal process for making ATP for energy to fail.

2. The cell switches to anaerobic metabolism, producing lactic acid.

3. ATP-reliant ion transport pumps fail, causing the cell to become depolarized, allowing ions, including calcium (Ca), to flow into the cell.

4. The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.

5. The presence of calcium triggers the release of the excitatory amino acid neurotransmitter glutamate.

6. Glutamate stimulates AMPA receptors and Ca-permeable NMDA receptors, which open to allow more calcium into cells.

7. Excess calcium entry overexcites cells and causes the generation of harmful chemicals like free radicals, reactive oxygen species and calcium-dependent enzymes such as calpain, endonucleases, ATPases, and phospholipases in a process called excitotoxicity. Calcium can also cause the release of more glutamate.

8. As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.

9. Mitochondria break down, releasing toxins and apoptotic factors into the cell.

10. The caspase-dependent apoptosis cascade is initiated, causing cells to "commit suicide."

11. If the cell dies through necrosis, it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby neurons, and glutamate can overexcite them.

12. If and when the brain is reperfused, a number of factors lead to reperfusion injury.

13. An inflammatory response is mounted, and phagocytic cells engulf damaged but still viable tissue.

14. Harmful chemicals damage the blood–brain barrier.

15. Cerebral edema (swelling of the brain) occurs due to leakage of large molecules like albumins from blood vessels through the damaged blood brain barrier. These large molecules pull water into the brain tissue after them by osmosis. This "vasogenic edema" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases).

The prognosis depends on prompt diagnosis (less than 12–24 hours and before gangrene) and the underlying cause:

- venous thrombosis: 32% mortality

- arterial embolism: 54% mortality

- arterial thrombosis: 77% mortality

- non-occlusive ischemia: 73% mortality.

In the case of prompt diagnosis and therapy, acute mesenteric ischemia can be reversible.

An arterial embolism is caused by one or more emboli getting stuck in an artery and blocking blood flow, causing ischemia, possibly resulting in infarction with tissue death (necrosis). Individuals with arterial thrombosis or embolism often develop collateral circulation to compensate for the loss of arterial flow. However, it takes time for sufficient collateral circulation to develop, making affected areas more vulnerable for sudden occlusion by embolisation than for e.g. gradual occlusion as in atherosclerosis.

CT angiography would be helpful in differentiating occlusive from non-occlusive causes of mesenteric ischaemia.

Mesenteric ischemia is a medical condition in which injury of the small intestine occurs due to not enough blood supply. It can come on suddenly, known as acute mesenteric ischemia, or gradually, known as chronic mesenteric ischemia. Acute disease often presents with sudden severe pain. Symptoms may come on more slowly in those with acute on chronic disease. Signs and symptoms of chronic disease include abdominal pain after eating, unintentional weight loss, vomiting, and being afraid of eating.

Risk factors include atrial fibrillation, heart failure, chronic renal failure, being prone to forming blood clots, and previous myocardial infarction. There are four mechanisms by which poor blood flow occurs: a blood clot from elsewhere getting lodged in an artery, a new blood clot forming in an artery, a blood clot forming in the superior mesenteric vein, and insufficient blood flow due to low blood pressure or spasms of arteries. Chronic disease is a risk factor for acute disease. The best method of diagnosis is angiography, with computer tomography (CT) being used when that is not available.

Treatment of acute ischemia may include stenting or medications to break down the clot provided at the site of obstruction by interventional radiology. Open surgery may also be used to remove or bypass the obstruction and may be required to remove any intestines that may have died. If not rapidly treated outcomes are often poor. Among those affected even with treatment the risk of death is 70% to 90%. In those with chronic disease bypass surgery is the treatment of choice. Those who have thrombosis of the vein may be treated with anticoagulation such as heparin and warfarin, with surgery used if they do not improve.

Acute mesenteric ischemia affects about five per hundred thousand people per year in the developed world. Chronic mesenteric ischemia affects about one per hundred thousand people. Most people affected are over 60 years old. Rates are about equal in males and females of the same age. Mesenteric ischemia was first described in 1895.

In cardiology, stunned myocardium is a state when some section of the myocardium (corresponding to area of a major coronary occlusion) shows a form of contractile abnormality. This is a segmental dysfunction which persists for a variable period of time, about two weeks, even after ischemia has been relieved (by for instance angioplasty or coronary artery bypass surgery). In this situation, while myocardial blood flow (MBF) returns to normal, function is still depressed for a variable period of time.

Myocardial stunning is the reversible reduction of function of heart contraction after reperfusion not accounted for by tissue damage or reduced blood flow.

After total ischemia occurs, the myocardium switches immediately from aerobic glycolysis to anaerobic glycolysis resulting in the reduced ability to produce high energy phosphates such as ATP and Creatinine Phosphate. At this point, the lack of the energy and lactate accumulation results in cessation of contraction within 60 seconds of ischemia (i.e. Vessel Occlusion). Subsequent to this is a period of "myocardial stunning," in which reversible ischemic damage is taking place. At approximately 30 minutes after the onset of total ischemia the damage becomes irreversible, thereby ending the phase of myocardial stunning.

Clinical situations of stunned myocardium are:

- acute myocardial infarction (AMI)

- after percutaneous transluminal coronary angioplasty (PTCA)

- after cardiac surgery

- 'neurogenic' stunned myocardium following an acute cerebrovascular event such as a subarachnoid hemorrhage

Some evidence suggests that magnesium sulfate administered to mothers prior to early preterm birth reduces the risk of cerebral palsy in surviving neonates. Due to the risk of adverse effects treatments may have, it is unlikely that treatments to prevent neonatal strokes or other hypoxic events would be given routinely to pregnant women without evidence that their fetus was at extreme risk or has already suffered an injury or stroke. This approach might be more acceptable if the pharmacologic agents were endogenously occurring substances (those that occur naturally in an organism), such as creatine or melatonin, with no adverse side-effects.

Because of the period of high neuronal plasticity in the months after birth, it may be possible to improve the neuronal environment immediately after birth in neonates considered to be at risk of neonatal stroke. This may be done by enhancing the growth of axons and dendrites, synaptogenesis and myelination of axons with systemic injections of neurotrophins or growth factors which can cross the blood–brain barrier.

Carotid stenosis is a narrowing or constriction of the inner surface (lumen) of the carotid artery, usually caused by atherosclerosis.