Vasospasm refers to a condition in which an

arterial An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pul ...

spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle ...

leads to

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

. This can lead to tissue

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...

and tissue death (necrosis). Cerebral vasospasm may arise in the context of

subarachnoid hemorrhage Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of cons ...

. Symptomatic vasospasm or delayed

cerebral ischemia Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. ...

is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage. Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...

. Vasospasm is the major cause of

Prinzmetal's angina Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable angina ...

Pathophysiology

Normally

endothelial cells The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...

release

prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosteno ...

and

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ch ...

(NO) which induce relaxation of the smooth muscle cells, and reduce aggregation of

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ...

. Aggregating platelets stimulate ADP to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also stimulate

thromboxane A2 Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by act ...

and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

which can induce contraction of the smooth muscle cells. In general, the relaxations outweighs the contractions. In atherosclerosis, a dysfunctional endothelium is observed on examination. It does not stimulate as much prostacyclin and NO to induce relaxation on smooth muscle cells. Also there is not as much inhibition of aggregation of platelets. In this case, the greater aggregation of platelets produce ADP, serotonin, and thromboxane A2. However the serotonin and the thromboxane A2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations.

Complications

Vasospasm can occur in a wide variety of peripheral vascular beds under poorly understood mechanisms. Prinzmetal angina, Buerger's disease, contrast mediated selective renal vasospasm, hypercoagulability and cryoglobulinemia likely represent just a few of the known pieces of this puzzling phenomena. Ischemia in the heart due to prolonged

coronary vasospasm Coronary vasospasm refers to when a coronary artery suddenly undergoes either complete or sub-total temporary occlusion. In 1959, Prinzmetal et al. described a type of chest pain resulting from coronary vasospasm, referring to it as a variant form ...

can lead to

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstru ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tra ...

and even death. Vasospasm in the hands and fingers due to prolonged exposure to vibration (30 – 300 Hz) and triggered by cold can lead to

Hand-arm vibration syndrome Vibration white finger (VWF), also known as hand-arm vibration syndrome (HAVS) or dead finger, is a secondary form of Raynaud's syndrome, an industrial injury triggered by continuous use of vibrating hand-held machinery. Use of the term ''vibration ...

in which feeling and manual dexterity are lost.

Angiography

In angiography, vascular access through femoral and axillary arteries are preferred because they are less prone to vasospasm. Meanwhile, brachial artery is more prone to vasospasm during instrumental access.

Hypothermia Rewarming

In a case study in 2000, following surgery for head trauma, a patient developed mild

hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe h ...

, a typical defense mechanism the brain uses to protect itself after injury. After the hypothermia rewarming period, the patient died from increased intracranial pressure and anisocoria. A sample of the cerebrospinal fluid and autopsy results indicated cerebral vasospasm.

Treatment

The occurrence of vasospasm can be reduced by preventing the occurrence of

. This can be done in several ways, the most important being lifestyle modifications—decreasing

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

(LDL),

quitting smoking Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often make ...

physical activity Physical activity is defined as any voluntary bodily movement produced by skeletal muscles that requires energy expenditure.Global Recommendations on Physical Activity for Health, 2009. World Health Organization. Geneva, Switzerland. Accessed 13/ ...

, and control for other risk factors including

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

, and

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

. Pharmacological therapies include

hypolipidemic agent Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins such as cholester ...

s, thrombolytics and

anticoagulants Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...

. Pharmacological options for reducing the severity and occurrence of ischemic episodes include the organic nitrates, which are rapidly metabolized to release

in many tissues, and are classified as having either long-acting (i.e.

isosorbide dinitrate Isosorbide dinitrate is a medication used for heart failure, esophageal spasms, and to treat and prevent chest pain from not enough blood flow to the heart. It has been found to be particularly useful in heart failure due to systolic dysfunctio ...

) or short-acting (i.e.

nitroglycerin Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating gl ...

) durations of action. These drugs work by increasing

levels in the blood and inducing coronary

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...

which will allow for more coronary blood flow due to a decreased coronary resistance, allowing for increased oxygen supply to the vital organs (myocardium). The nitric oxide increase in the blood resulting from these drugs also causes dilation of systemic veins which in turn causes a reduction in venous return, ventricular work load and ventricular radius. All of these reductions contribute to the decrease in ventricular wall stress which is significant because this causes the demand of oxygen to decrease. In general organic nitrates decrease oxygen demand and increase oxygen supply. It is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina. Other medications used to reduce the occurrence and severity of vasospasm and ultimately ischemia include L-type

calcium channel blockers Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

(notably

nimodipine Nimodipine, sold under the brand name Nimotop among others, is calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral hemorrhage). It was originally developed within the calcium channel bl ...

, as well as

verapamil Verapamil, sold under various trade names, is a calcium channel blocker medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia. It may also be use ...

diltiazem Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be us ...

nifedipine Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, R ...

) and beta-receptor antagonists (more commonly known as

beta blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...

or β-blockers) such as

propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance an ...

. L-type calcium channel blockers can induce dilation of the coronary arteries while also decreasing the heart's demand for oxygen by reducing

contractility Contractility refers to the ability for self- contraction, especially of the muscles or similar active biological tissue *Contractile ring in cytokinesis *Contractile vacuole *Muscle contraction ** Myocardial contractility *See contractile cell f ...

, heart rate, and wall stress. The reduction of these latter three factors decreases the contractile force that the myocardium must exert in order to achieve the same level of

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...

. Beta-receptor antagonists do not cause vasodilation, but like L-type calcium channel blockers, they do reduce the heart's demand for oxygen. This reduction similarly results from a decrease in heart rate, afterload, and wall stress.

Adverse effects

Like most pharmacological therapeutic options, there are risks that should be considered. For these drugs in particular, vasodilation can be associated with some adverse effects which might include orthostatic hypotension, reflex

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (s ...

, headaches and palpitations. Tolerance may also develop over time due compensatory response of the body, as well as depletion of -SH groups of glutathione which are essential for the metabolism of the drugs to their active forms. Potential side effects: *

Verapamil Verapamil, sold under various trade names, is a calcium channel blocker medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia. It may also be use ...

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

Diltiazem Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be us ...

: hypotension, bradycardia, risk of heart block *

Nifedipine Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, R ...

: hypotension *

Propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance an ...

asystole Asystole (New Latin, from Greek privative a "not, without" + ''systolē'' "contraction") is the absence of ventricular contractions in the context of a lethal heart arrhythmia (in contrast to an induced asystole on a cooled patient on a heart-lung ...

asthma attacks Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coug ...

Contraindications

Organic nitrates should not be taken with PDE5 inhibitors (i.e.

sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...

) since both NO and PDE5 inhibitors increase cyclic GMP levels and the sum of their pharmacodynamic effects will greatly exceed the optimal therapeutic levels. What you could see upon taking both medications at the same time, as caused by the much higher induction of relaxation of smooth muscle cells, include a severe drop in blood pressure. Beta-receptor antagonists should be avoided in patients with reactive pulmonary disease to avoid asthma attacks. Also Beta-receptor antagonists should be avoided in patients with AV node dysfunction and/or patients on other medications which might cause bradycardia (i.e. calcium channel blockers). The potential for these contraindications and drug-drug interaction could lead to asystole and cardiac arrest. Certain calcium channel blocker should be avoided with some beta-receptor blockers since they may cause severe bradycardia and other potential side effects.

Corrective therapy

Since vasospasms can be caused by atherosclerosis and contribute to the severity of ischemia there are some surgical options which can restore circulation to these ischemic areas. Regarding coronary vasospasm, one surgical intervention, referred to as percutaneous coronary intervention or angioplasty, involves placing a

stent In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandab ...

at the site of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is coronary artery bypass.

References

External links

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