| Vasospasm | |
|---|---|
| Classification and external resources | |
| ICD-9 | 443.9 |
Vasospasm refers to a condition in which blood vessels 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.
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Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to atherosclerosis. Vasospasm is the major cause of Prinzmetal angina
Normally endothelial cells release prostacyclin 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.
Ischemia in the heart due to coronary vasospasm can lead to angina, myocardial infarction and even death.
The occurrence of vasospams can be reduced by preventing the occurrence of atherosclerosis. 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.
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.
These drugs should not be taken with PDE5 inhibitors (i.e. sildenafil) 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 medications used to reduce the occurrence and severity of vasospams and ultimately ischemia include L-type calcium channel blockers (i.e. verapamil, diltiazem, nifedipine) and Beta-receptor antagonists (i.e. propranolol).
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.
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.
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 at the site of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is coronary artery bypass.
This information is a summary of a lecture given by a professor at Albany College of Pharmacy.