A preliminary double-blind study of intravenous nitroglycerin in acute myocardial infarction

Abstract

A preliminary double-blind, placebo-controlled study of the effects of a 48-h intravenous infusion of nitroglycerin (NG) in 140 patients with acute myocardial infarction has been carried out. The patients were randomised to placebo or active treatment within 12 h of the onset of symptoms. Those patients treated with nitroglycerin showed a significant reduction on both days in systolic blood pressure, haemoglobin concentration, and packed cell volume. There was also a significant reduction in diamorphine usage in the first 24 h. There was a higher incidence (non-significant) of dysrhythmia in the placebo group despite an increased usage of antidysrhythmic therapy. The mortality rate in the placebo group was 13%, and 7.8% in the active treatment group, but this difference was not significant. At the 3-month follow-up, 83% of treated patients as opposed to 60% of placebo group were able to resume normal or near-normal activities. Preliminary findings suggest that intravenous NG may be useful treatment for patients with acute myocardial infarction and a larger-scale trial is warranted.

N‐acetylcysteine fails to attenuate haemodynamic tolerance to glyceryl trinitrate in healthy volunteers.

“…In addition, mechanisms other than the depletion of SH groups may be important in the development of tolerance. In particular the activation of neurohumoral reflexes such as the renin-angiotensin system resulting in volume expansion and vasoconstriction in response to nitrate induced vasodilation have been implicated (Lis et al, 1984;Packer et al, 1985Packer et al, , 1987. Finally nitrates exert their haemodynamic actions to differing extents in different vascular beds.…”

“…Current hypotheses include activation of the renin-angiotensin system (Fahmy & Gavras, 1985), plasma volume expansion (Lis et al, 1984) and at a cellular level, diminished availability of reduced sulphydryl (SH) groups in vascular smooth muscle cells (Needleman & Johnson, 1973). These SH groups are thought to react with the nitric oxide generated from organic nitrates to form the active intermediates, snitrosothiols, which in turn activate the enzyme soluble guanylate cyclase, elevating levels of cyclic guanosine monophosphate (cGMP) leading to smooth muscle relaxation (Ignarro et al, 1981).…”

Chronic administration of N‐acetylcysteine fails to prevent nitrate tolerance in patients with stable angina pectoris.

“…Nitrate tolerance may be due to mechanisms other than sulphydryl group-depletion. Activation of the renin-angiotensin system (Fahmy & Gavras, 1985) and plasma volume expansion (Lis et al, 1984) may limit the systemic vasodilatory effects of glyceryl trinitrate responsible for some aspects of its action. In conclusion this study demonstrates that daily dosing with N-acetylcysteine 400 mg three times daily failed to prevent significantly or ameliorate the development of nitrate tolerance in a group of patients with chronic stable angina during treatment with transdermal glyceryl trinitrate.…”

“…The mechanism by which this tolerance to nitrates develops is unclear. Current hypotheses include activation of neurohumoral reflexes (Fahmy & Gavran, 1985), haemodilution (Lis et al, 1984) and, at a cellular level, depletion of cytosolic sulphydryl groups in vascular smooth muscle (Ignarro et al, 1981;Needleman et al, 1983).…”

Update on nitrate tolerance.

“…Studies have shown elevation of plasma catecholamines and activation of the renin-angiotensin system (Miller et al, 1977). In the other studies, intravenous infusions of GTN lead to a reduction in haematocrit suggesting that haemodilation and plasma volume expansion may play a role in nitrate tolerance (Lis et al, 1984).…”