ST elevation myocardial infarction nitrate therapy
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Nitrates are widely used in the management of patients with myocardial infarction. Historically, there were concerns in the distant past that nitrates would precipitate "coronary steal": as a result of vasodilating epicardial arteries and resistance vessels, it was hypothesized that nitrates would cause the shunting of blood flow to healthy tissue and away from infarcting tissue. This concern does not appear to be well founded. While nitrates can be of benefit in STEMI, caution should be exercised in their administration to patients with right ventricular infarct physiology (hypotension, ST elevation in right sided leads).
Mechanism(s) of Benefit
In determining whether nitrates should be administered and in determining the dose, the following mechanisms of benefit (as well as potential for harm) associated with nitrate administration should be kept in mind:
- Reduction in preload via venodilation: While this may be of benefit in many STEMI patients, this may lead to hypotension and hypoperfusion in those patients with right ventricular infarction with ST segment elevation in lead V4R.
- Reduction in afterload via arterial dilation: This may be of particular relevance in the patient with pulmonary edema or papillary muscle rupture or other mechanical complications.
- Vasodilation of epicardial coronary arteries: While a modest component of vasoconstriction may be present in the majority of STEMI patients, relief of vasospasm may be particularly important in those rare patients with coronary spasm as the precipitating event.
- Dilation of collateral vessels: This vasodilatory benefit must, however, be balanced against the load dependence of collateral filling and optimization of the subendocardial to epicardial flow ratio 
Clinical Trial Data Supporting Nitrate Administration
A large randomized trial (ISIS 4) of nitrate administration (1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo) demonstrated no significant mortality benefit of nitrate administration in the setting of STEMI.  Similarly, when data were pooled from 22 trials enrolling more than 80,000 patients treated with nitrates either intravenously or orally, mortality rates were 7.7% in the control group and 7.4% in the nitrate group. Taken together, randomized and pooled data are consistent with a possible, but very modest treatment effect of nitrates such that only 3 to 4 deaths might be prevented for every 1,000 patients treated. Despite this lack of mortality benefit, nitrates may imporve a patient's quality of life by relieving pain and easing breathing by reducing the pulmonary capillary wedge pressure.
Contraindications to Nitrate Administration
- Right ventricular infarction in which the patient is critically dependent upon preload for RV filling and cardiac output 
- Viagra and other phosphodiesterase inhibitors within 24 hours (48 hours for tadalafil). Nitrates and these agents share a common mechanism of action in facilitating the release of nitric oxide. Both clases of agent also increase cyclic guanosine monophosphate (cGMP) .
- Systolic blood pressure 30 mm Hg less than usual
- Systolic blood pressures less than 90 mm Hg
- Severe bradycardia 
Dosing of Nitrates
Initial sublingual Dosing
Before administering nitrates, contraindications to nitrate administration should be assessed first (see above: presence of hypotension, RV infarct, ingestion of phosphodiesterase inhibitors, profound bradycardia). The standard initial dose of nitroglycerin at the time of presentation of STEMI is 0.4 mg administered sublingually.
Intravenous nitroglycerin offers an advantage over sublingual administration in so far as it allows careful titration of the dosing in response to the patient’s blood pressure. The standard approach to dosing intravenous nitroglycerin is to begin the infusion rate at 5 to 10 mcg per minute. The infusion rates is increased by 5 to 20 mcg per minute until either:
- Symptoms are relieved
- The mean arterial blood pressure (MAP) is reduced by 10% of its baseline level in normotensive patients
- The mean arterial blood pressure (MAP) is reduced by up to 30% for hypertensive patients
In dosing nitrates, the following should be avoided:
- The systolic blood pressure is lowered below 90 mm Hg
- The systolic blood pressure drops greater than 30 mm Hg below baseline. 
Nitrates versus Beta-Blocker Administration
In so far as the mortality benefits of nitrates are limited, their dosing should be titrated to a blood pressure that does not limit the co-administration of beta-blockers, which have, in contrast, been associated with advantages in mortality and infarct size reduction.
2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (DO NOT EDIT) 
|"1. Patients with ongoing ischemic discomfort should receive sublingual nitroglycerin (0.4 mg) every 5 minutes for a total of 3 doses, after which an assessment should be made about the need for intravenous nitroglycerin. (Level of Evidence: C) "|
|"2.Intravenous nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion. (Level of Evidence: C) "|
|Class III (Harm)|
|"1. Nitrates should not be administered to patients with systolic blood pressure less than 90 mm Hg or greater than or equal to 30 mm Hg below baseline, severe bradycardia (less than 50 beats per minute [bpm]), tachycardia (more than 100 bpm), or suspected RV infarction. (Level of Evidence: C) "|
|"2. Nitrates should not be administered to patients who have received a phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (48 hours for tadalafil). (Level of Evidence: B) "|
- The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction 
- ↑ Abrams J (July 1985). "Hemodynamic effects of nitroglycerin and long-acting nitrates". Am. Heart J. 110 (1 Pt 2): 216–24. PMID 3925741.
- ↑ Winbury MM (January 1971). "Redistribution of left ventricular blood flow produced by nitroglycerin. An example of integration of the macro- and microcirculation". Circ. Res. 28: Suppl 1:140–7. PMID 5541112.
- ↑ Gorman MW, Sparks HV (September 1980). "Nitroglycerin causes vasodilatation within ischaemic myocardium". Cardiovasc. Res. 14 (9): 515–21. PMID 6783307.
- ↑ (March 1995) "ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group". Lancet 345 (8951): 669–85. PMID 7661937.
- ↑ Kinch JW, Ryan TJ (April 1994). "Right ventricular infarction". N. Engl. J. Med. 330 (17): 1211–7. PMID 8139631.
- ↑ Cheitlin MD, Hutter AM, Brindis RG, et al (January 1999). "ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association". J. Am. Coll. Cardiol. 33 (1): 273–82. PMID 9935041.
- ↑ Come PC, Pitt B (October 1976). "Nitroglycerin-induced severe hypotension and bradycardia in patients with acute myocardial infarction". Circulation 54 (4): 624–8. PMID 822962.
- ↑ Antman EM, Hand M, Armstrong PW, et al (January 2008). "2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee". Circulation 117 (2): 296–329. doi:10.1161/CIRCULATIONAHA.107.188209. PMID 18071078.
- ↑ Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M et al. (2004). "ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction).". Circulation 110 (5): 588-636. doi:10.1161/01.CIR.0000134791.68010.FA. PMID 15289388.
- ↑ Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK (August 2004). "ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction)". Circulation 110 (9): e82–292. PMID 15339869.
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