Vasospasm
Encyclopedia
Vasospasm refers to a condition in which blood vessel
s spasm
, leading to vasoconstriction
. This can lead to tissue ischemia
and death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage
. Symptomatic vasospasm or delayed cerebral ischemia
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.
. Vasospasm is the major cause of Prinzmetal angina
and nitric oxide
(NO) which induce relaxation of the smooth muscle
cells, and reduce aggregation of platelets. Aggregating platelets stimulate ADP
to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also stimulate TXA-2
and 5-HT which can induce contraction of the smooth muscle cells. In general the relaxations outweighs the contractions.
During atherosclerosis a dysfunctional endothelium is observed during 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, 5-HT, and TXA-2. However the 5-HT and the TXA-2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations.
. This can be done in several ways, most important being lifestyle modifications — decreasing bad cholesterol, quitting smoking. Pharmacological therapy include hypolipidemics, thrombolytics and anticoagulants. Pharmacological options for reducing the severity and occurrence of ischemic episodes that is medications classified as organic nitrates which include long acting (i.e. isosorbide dinitrate
) and short acting (i.e. nitroglycerin) durations of action.
The way these drugs work is by increasing nitric oxide
levels in the blood and inducing coronary vasodilation
which will allow for more coronary blood flow due to a decreased coronary resistance. Therefore, there should be more oxygen supply to the vital organs (myocardium). The nitric oxide increase in the blood seen by 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. And it is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina.
) 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.
, diltiazem
, nifedipine
) and Beta-receptor antagonists (i.e. propranolol).
L-type calcium channel blockers induce coronary dilation as well as decrease the heart's demand for oxygen by reducing contractility, heart rate, and wall stress.
Again some calcium channel blocker should be avoided with some Beta-receptor blockers since they may cause severe bradycardia and other potential side effects.
at the site of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is coronary artery bypass.
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s spasm
Spasm
In medicine a spasm is a sudden, involuntary contraction of a muscle, a group of muscles, or a hollow organ, or a similarly sudden contraction of an orifice. It is sometimes accompanied by a sudden burst of pain, but is usually harmless and ceases after a few minutes...
, leading to vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
. This can lead to tissue ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
and death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage
Subarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
. Symptomatic vasospasm or delayed cerebral ischemia
Cerebral ischemia
Brain ischemia, also known as cerebral ischemia, is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus 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
Subarachnoid space
In the central nervous system, the subarachnoid cavity is the interval between the arachnoid membrane and pia mater....
hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.
General information
Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. Vasospasm is the major cause of Prinzmetal angina
General pathophysiology of vasospasms
Normally endothelial cells release prostacyclinProstacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...
and nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
(NO) which induce relaxation of the smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
cells, and reduce aggregation of platelets. Aggregating platelets stimulate ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also stimulate TXA-2
Thromboxane A2
Thromboxane A2 is a thromboxane. It is produced by activated platelets and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of...
and 5-HT which can induce contraction of the smooth muscle cells. In general the relaxations outweighs the contractions.
During atherosclerosis a dysfunctional endothelium is observed during 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, 5-HT, and TXA-2. However the 5-HT and the TXA-2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations.
Symptoms
Ischemia in the heart due to coronary vasospasm can lead to angina, myocardial infarction and even death.Therapy options
The occurrence of vasospams can be reduced by preventing the occurrence of atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. This can be done in several ways, most important being lifestyle modifications — decreasing bad cholesterol, quitting smoking. Pharmacological therapy include hypolipidemics, thrombolytics and anticoagulants. Pharmacological options for reducing the severity and occurrence of ischemic episodes that is medications classified as organic nitrates which include long acting (i.e. isosorbide dinitrate
Isosorbide dinitrate
Isosorbide dinitrate is a nitrate used pharmacologically as a vasodilator, e.g. in angina pectoris but also for anal fissure, a condition which is known to involve decreased blood supply leading to poor healing...
) and short acting (i.e. nitroglycerin) durations of action.
The way these drugs work is by increasing nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
levels in the blood and inducing coronary vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
which will allow for more coronary blood flow due to a decreased coronary resistance. Therefore, there should be more oxygen supply to the vital organs (myocardium). The nitric oxide increase in the blood seen by 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. And it is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina.
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, tachycardia, headaches and palpitations. Tolerance may also develop overtime 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.Contraindications
These drugs should not be taken with PDE5 inhibitors (i.e. sildenafilSildenafil
Sildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
) 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.
Other pharmacological options
Other medications used to reduce the occurrence and severity of vasospams and ultimately ischemia include L-type calcium channel blockers (i.e. verapamilVerapamil
Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
, diltiazem
Diltiazem
Diltiazem is a non-dihydropyridine member of the class of drugs known as calcium channel blockers, used in the treatment of hypertension, angina pectoris, and some types of arrhythmia....
, nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...
) and Beta-receptor antagonists (i.e. propranolol).
How they work
Beta-receptor antagonists do not cause vasodilation but they do decrease the heart's demand for oxygen. This decrease is caused by a reduction in heart rate, afterload and wall stress, leading to less contraction force needed by the myocardium. B-antagonists also increase coronary blood flow since they reduce heart rate.L-type calcium channel blockers induce coronary dilation as well as decrease the heart's demand for oxygen by reducing contractility, heart rate, and wall stress.
ADRs include
- VerapamilVerapamilVerapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
: hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, bradycardiaBradycardiaBradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, constipationConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation... - DiltiazemDiltiazemDiltiazem is a non-dihydropyridine member of the class of drugs known as calcium channel blockers, used in the treatment of hypertension, angina pectoris, and some types of arrhythmia....
: hypotension, bradycardia - NifedipineNifedipineNifedipine is a dihydropyridine calcium channel blocker...
: hypotension - Propranolol: asystoleAsystoleIn medicine, asystole is a state of no cardiac electrical activity, hence no contractions of the myocardium and no cardiac output or blood flow...
, asthma attacks
Contraindications
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.Again some 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 stentStent
In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...
at the site of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is coronary artery bypass.
See also
- Raynaud's phenomenonRaynaud's phenomenonIn medicine, Raynaud's phenomenon is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other areas. This condition can also cause nails to become brittle with longitudinal ridges. Named for French physician Maurice Raynaud , the phenomenon is believed to be the...
, a vasospastic disorder - Coronary artery vasospasm
- Reversible cerebral vasoconstriction syndrome