Vasoactive and Antiarrhythmic Drugs in the Catheterization Laboratory

Vasoactive and Antiarrhythmic Drugs in the Catheterization Laboratory

Gilbert Zoghbi MD, FACC, FSCAI




Nitroglycerin is a mainstay drug for the treatment of angina. In vascular smooth cells, nitroglycerin is metabolized to nitric oxide, which is converted to S-nitrosothiols, which in turn activate guanylate cyclase and generate cyclic guanosine monophosphate (GMP), resulting in smooth muscle relaxation and subsequent vasodilatation of venous beds, peripheral arteries, and coronary arteries. Nitroglycerin has a more pronounced effect on veins than on arteries, and thus its anti-ischemic effect is more related to venodilatation and preload reduction, which reduces myocardial wall stress that decreases myocardial oxygen demand, and indirectly improves subendocardial myocardial flow and collateral flow when present. Nitroglycerin dilates both normal and diseased coronary arteries, though this action is of uncertain clinical importance, except in patients who have vasospastic angina.

Nitroglycerin has a rapid onset and a short duration of action. It can be administered via the sublingual, intra-arterial, intravenous (IV), intracoronary, or intraventricular route. Nitroglycerin is commonly used in the catheterization laboratory during coronary angiography or percutaneous coronary interventions (PCIs) to improve coronary flow, prevent or alleviate coronary spasm, provoke myocardial bridging, relieve angina, or reduce preload in patients with elevated filling pressures. Prophylactic intracoronary nitroglycerin is commonly used before intravascular ultrasound or rotablation device activation. Nitroglycerin is also used in the pharmacological cocktail given via the radial artery to prevent or treat radial artery spasm during transradial procedures. Sublingual nitroglycerin is usually given as a 0.4-mg tablet or spray. Intracoronary, intra-arterial, or intraventricular nitroglycerine is commonly administered in 50 to 300 µg boluses. Higher doses can result in hypotension and reflex tachycardia without further augmentation in coronary blood flow. Nitroglycerin should not be administered to patients with a systolic blood pressure of <90 mm Hg or to patients who have taken phosphodiesterase inhibitors within 24 hours. Nitroglycerin should be administered very cautiously to patients with severe aortic stenosis, hypertrophic cardiomyopathy, severe left main disease, right ventricular infarctions, or volume depletion because of increased risk of causing deleterious hypotension (1, 2).

Calcium-Channel Blockers

Calcium-channel blockers inhibit the L-type calcium channel on vascular smooth muscle cells and slow-response myocardial cells. Calcium-channel blockers are divided into dihydropyridines and non-dihydropyridines. Dihydropyridines (such as amlodipine, felodipine, isradipine, nicardipine, and nifedipine) have a predominant vasodilator effect, with very little or no effect on cardiac contractility or conduction. In contrast, non-dihydropyridines (such as verapamil and diltiazem) have a lesser vasodilator effect and a more pronounced effect on reducing cardiac contractility and conduction. Nicardipine is the only dihydropyridine that can be given intravenously or intra-arterially. In general, calcium-channel blockers decrease peripheral vascular resistance, decrease blood pressure, alleviate coronary spasm, and increase coronary blood flow. Calcium-channel blockers can be used in the cardiac catheterization laboratory to treat supraventricular and atrial arrhythmias (non-dihydropyridines), radial or coronary spasm, and no-reflow (non-dihydropyridines and nicardipine) (3, 4, 5 and 6).

  • Diltiazem: IV bolus of 0.25 mg/kg (15 to 20 mg) over 2 minutes, followed by maintenance rate of 5 to 20 mg/hr for supraventricular tachycardia (SVT)/atrial tachycardia; 2.5 to 5 mg intra-arterial bolus for prophylactic treatment or treatment of radial artery spasm; and 0.5 to 2 mg intracoronary boluses for treatment of no-reflow.

  • Verapamil: IV bolus of 2.5 to 5 mg over 2 minutes; second dose of 5 to 10 mg (˜0.15 mg/kg) may be given 15 to 30 minutes later (for SVT/atrial tachycardia); 2.5 to 5 mg intraarterial bolus for prophylactic treatment or treatment of radial artery spasm; and 50 to 200 µg intracoronary boluses for 2 to 4 boluses if needed for treatment of no-reflow (60% to 100% success).

  • Nicardipine: IV infusion of 5 mg/hr (maximum dose of 15 mg/hr) for treating hypertension; 200 µg intracoronary bolus for 2 to 4 boluses for the treatment of no-reflow (99% success in one study; some benefit in prophylactic administration to prevent no-reflow in saphenous vein graft [SVG] PCIs and rotational atherectomy); 2.5 to 5 mg intra-arterial for prophylactic treatment or treatment of radial artery spasm during transradial angiography.


Papaverine is a potent arterial vasodilator whose mechanism of action is thought to be due to inhibition of a phosphodiesterase enzyme, which results in increased cyclic adenosine monophosphate (AMP) in smooth muscle cells with resultant smooth muscle relaxation and arterial vasodilatation. Intracoronary papaverine is used to induce coronary hyperemia for assessment of coronary flow reserve (CFR) or fractional flow reserve (FFR). Its onset of action is within 10 to 30 seconds, and its duration is for 45 to 60 seconds from time of administration. Commonly used intracoronary bolus doses are 12 to 16 mg for the right coronary artery (RCA) and 16 to 20 mg for the left coronary artery (LCA). Papaverine ??????(30 mg intrarenal bolus) was also used to “stress” the kidney and measure hyperemic renal artery FFR and hyperemic renal artery systolic gradients (HSG). An HSG of 21 mm Hg and a renal FFR of 0.90 have been considered to represent a hemodynamically significant renal artery stenosis. Papaverine can prolong the QT segment and cause torsades de pointes. Papaverine can cause crystallization when
combined with some of the ionic contrast agents, and can also increase coronary venous lactate production that may cause myocardial ischemia (7, 8, 9, 10 and 11).


Unlike nitroglycerin, nitroprusside is a direct nitric oxide donor that activates guanylate cyclase and generates cyclic GMP, resulting in smooth muscle relaxation and subsequent vasodilatation. Nitroprusside can be used in hypertensive emergencies and acute heart failure, particularly due to acute mitral regurgitation. The IV nitroprusside dose starts at 0.25 to 0.3 µg/kg/min and can be titrated by 0.5 µg/kg/min every few minutes to achieve the desired hemodynamic effects (maximum dose of 10 µg/kg/min). Nitroprusside has been used to treat no-reflow during PCIs, and is given in 25 to 200 µg intracoronary boluses up to 1000 µg (12, 13 and 14).

Adenosine Agonists

Adenosine is a nonselective adenosine receptor agonist that is used to produce coronary hyperemia in conjunction with myocardial perfusion imaging and for assessing CFR and FFR. For purposes of FFR or CFR evaluation, adenosine can be administered intracoronary (40 µg for the RCA and 60 µg for the LCA) or intravenously (140 µg/kg/min). Higher doses of intracoronary adenosine boluses (doses of 120, 180, 360, and 720 µg) were well tolerated, and progressively increased the frequency of patients with an FFR less than 0.75 from 30% with a dose of 60 µg to 51% with a dose of 720 µg (15). The peak hyperemic effect of intracoronary adenosine is achieved within a few seconds of its administration with a sustained plateau of hyperemia of about 5 seconds. The peak hyperemic effect of IV adenosine is reached within 2 minutes of its administration and lasts for less than 30 seconds from termination of drug administration. IV adenosine permits measuring a pullback FFR and has been shown in one study to cause more hyperemia than intracoronary adenosine (11). Adenosine has also been used in the catheterization laboratory in vasodilator testing in patients with pulmonary hypertension, where IV adenosine is infused at 50 µg/kg/min and is increased by 50 µg/kg/min every 2 minutes to a maximum dose of 250 µg/kg/min (16).

Regadenoson is a selective adenosine A2A receptor agonist that is administered as a single 400 µg IV bolus and is used as a stress agent in conjunction with myocardial perfusion imaging. Peak hyperemia is reached within seconds of its administration and lasts for about 2 minutes from its administration. One study compared an IV regadenoson bolus to an IV adenosine infusion at 140 µg/kg/min for evaluation of coronary stenoses using FFR (17). Regadenoson was as effective as adenosine in measuring FFR with a strong linear correlation with adenosine and similar frequency of 52% in detecting FFR ≤ 0.8. Regadenoson seems to be a promising agent for use in the catheterization laboratory owing to its ease of administration that obviates the use of an infusion pump. Intracoronary adenosine boluses of 10 to 20 µg have been used to treat no-reflow during coronary and SVG PCIs with a 90% success rate. Common side effects of adenosine include bronchospasm, chest pain, dyspnea, flushing, atrioventricular (AV) block, modest hypotension, and modest increase in heart rate. The side effects are short lived and can be reversed with 50 to 100 mg of IV aminophylline if they become severe and prolonged.

Adenosine is contraindicated in patients with heart transplantation or patients with second- or third-degree heart block in the absence of a functional pacemaker. Adenosine should be used cautiously in patients with bronchospastic lung disorders because of the risk of adenosine-induced bronchoconstriction (8, 15, 17, 18, 19 and 20).

Coronary Vasoconstrictors


Acetylcholine is an endogenous neurotransmitter that causes endothelial-dependent vasodilatation via release of nitric oxide and other vasoactive substances in the presence of a normal endothelium, and causes vasoconstriction via direct activation of receptors on smooth muscle cells in the presence of an abnormal endothelium. Intracoronary acetylcholine administration constricts diseased coronary arteries (endothelial dysfunction or atherosclerosis) and vasodilates normal coronary arteries (normal endothelial function). Acetylcholine has been used to diagnose variant (Prinzmetal) angina, particularly in patients who have normally apparent coronary arteries on coronary angiography. Acetylcholine has also been used to assess epicardial and microvascular vasomotor responses that can lead to ischemia in patients with stable angina who have normal or minimal coronary artery disease without features of variant angina. In one study of patients with stable angina and normal or minimal coronary artery disease, two thirds of patients had an abnormal test, where 45% of patients had epicardial spasm (≥75% coronary narrowing with symptom production) and 55% of patients had microvascular spasm (symptom reproduction with ischemic ECG changes and no epicardial spasm) (21). Intracoronary incremental doses of acetylcholine of 20, 50, and 80 µg are usually injected into the RCA, and 20, 50, and 100 µg doses are injected into the LCA. Spasm is defined as total or subtotal occlusion after acetylcholine administration. Spasm caused by low doses of acetylcholine is usually more proximal and focal and is associated with more ST elevation and the clinical findings of variant angina. Spasm caused by higher acetylcholine doses is associated with more distal and diffuse spasm and is associated with less ST elevation and less characteristics of variant angina. Acetylcholine is very short acting and rapidly inactivated. Continuous infusions of 0.02 to 2.2 µg (10-8, 10-7, 10-6 M) have been used to identify normal endothelial coronary artery function manifesting as vasodilatation. Marked bradycardia, heart block, and vasospasm are common with acetylcholine, and thus temporary pacing is recommended during its administration. Serious side effects such as sustained ventricular tachycardia (VT), shock, and cardiac tamponade occurred in 4 of 715 patients (0.56%) in one study, though no death or irreversible complications occurred (22, 23 and 24).


Ergonovine is an ergot derivative that causes smooth muscle cell contraction and is commonly used to induce uterine contractions to treat or prevent postpartum hemorrhage. It can also be used in the coronary tree to provoke coronary spasm and evaluate patients with angina pectoris who have normal coronaries or minimal coronary artery disease on coronary angiography. Ergonovine can be administered intracoronary as an infusion of 10 µg/min over 4 minutes for a maximal dose of 40 µg in the RCA and as 16 µg/min over 4 minutes for a total dose of 64 µg in the LCA (25). Alternatively, ergonovine can be administered by slow intracoronary injections over 1 minute each of sequential doses of 1, 5, 10, and 30 µg at 3- to 5-minute intervals, with a maximum cumulative dose of 50 µg (26). An ECG is obtained at the end of each interval or if the patient develops angina symptoms. Angiography of the RCA and LCA should be promptly performed when angina symptoms occur.
Diffuse coronary narrowing is a physiologic response to ergonovine, whereas a severe (more than 75% narrowing in some studies and subtotal to total occlusion in other studies) focal coronary narrowing is considered a response indicative of coronary spasm when associated with ischemic ECG changes or typical symptoms (25). Ergonovine-induced spasm can be reversed with the administration of intracoronary nitroglycerine. In one study, intracoronary acetylcholine-induced spasm (873 patients) was compared with intracoronary ergonovine-induced spasm (635 patients). In patients without ischemic heart disease, acetylcholine-induced spasm was significantly more common than ergonovine-induced spasm (11% vs. 6%). In addition, acetylcholine significantly provoked more spasm in patients without fixed stenosis than did ergonovine (36.2% vs. 25.5%). Major complications occurred in 1.4% of patients with the acetylcholine test and in 0.2% of patients with the ergonovine test, with no occurrence of any myocardial infarction or death with either test (25).

Vasopressors and Inotropes

Vasopressor drugs cause peripheral vasoconstriction leading to increase in the systemic vascular resistance (SVR) and mean arterial pressure (MAP). Inotropic drugs, on the other hand, increase cardiac contractility. Some of the vasopressor drugs have both vasopressor and inotropic effects, depending on the receptors they stimulate. Stimulation of peripheral α1 receptors causes vasoconstriction and that of cardiac α1 receptors augments inotropy. Stimulation of β1 receptors (located mainly on myocytes) augments inotropy and chronotropy. Stimulation of the β2 receptors (located mainly in the vasculature) augments vasodilatation. Stimulation of the dopaminergic receptors DA1 causes vasodilatation in the renal, splanchnic, and coronary beds (27, 28). These drugs can be used in the catheterization laboratory, depending on the situation encountered and the desired effect (Table 5-1) (27).

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May 28, 2016 | Posted by in CARDIOLOGY | Comments Off on Vasoactive and Antiarrhythmic Drugs in the Catheterization Laboratory

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