Syndrome of Severe Bradycardia and Hypotension following Sublingual Nitroglycerin Administration

Abstract

Severe bradycardia associated with profound systemic arterial hypotension was observed in 3 patients following sublingual nitroglycerin administration. All patients had clinical evidence of active ischemic heart disease. In 1 patient, third-degree heart block was observed several hours later, requiring pacemaker therapy. Radionuclide ventriculography in 1 patient during the bradycardia revealed no significant change in regional wall motion or in left or right ventricular ejection fraction. Review of the literature shows no consistent predictors as to which patients are at risk for developing this syndrome. Possible pathophysiologic mechanisms are discussed. These case reports illustrate an unpredictable and serious complication of nitroglycerin administration, and emphasize the need for caution in use of this drug for ischemic heart disease.

Side effects of using nitrates to treat angina

“…Cardiovascular side effects of nitrates more commonly include hypotension with reflex tachycardia, flushing and palpitations [7,12,26]. A less common, but potentially life-threatening, adverse effect is that of nitroglycerin-induced hypotension with paradoxical bradycardia, for which there have been several documented case reports in the literature [29][30][31][32][33][34][35]. Bradycardia associated with nitrates is uncommon, but may range in severity from simple sinus bradycardia to atrioventricular block, asystole and syncope.…”

Nitroglycerin Induced Syncope Occurs in Subjects with Delayed Phase Shift of Baroreflex Action

“…7 A majority of described cases of severe bradycardia with hypotension occurred in subjects with acute or chronic ischemic heart disease. 2,3 This reaction occurred in patients with acute inferior infarction, but also in patients with anterior myocardial infarction, 2 suggesting that diminished left ventricular filling due to ischemic right ventricular dysfunction was not the main mechanism. Only four reports of this reaction in subjects without heart disease have been published.…”

“…Interestingly, some patients who developed bradycardia and hypotension received NTG previously without apparent adverse effect. 3 Thus, it seems that predisposition to the development of bradycardia hypotension after NTG is not permanent and may change in time. The role of abnormal autonomic balance has been discussed, but no data exist on that issue because of the unexpected nature of the event.…”

“…Severe hypotension with paradoxical bradycardia after nitroglycerin (NTG) administration has been repeatedly described. [1][2][3][4][5][6][7][8] This reaction occurs not only in patients with ischemic heart disease, but also in patients with normal hearts. Clinically, the reaction resembles vasovagal syncope.…”

Nesiritide (hbNP): A New Class of Therapeutic Peptide for the Treatment of Decompensated Congestive Heart Failure

“…The autonomic effects of natriuretic peptides appear to be mediated by both inhibition of sympathetic‐mediated reduction in parasympathetic neurotransmission and central inhibition of sympathetic neurotransmission 44,45 . Vagally mediated hypotension may not be specific to natriuretic pep‐tides, as nitroglycerin, another cGMP‐dependent vasodilating agent, is also rarely associated with episodes of bradycardia and hypotension 46 …”