Predictors of inotropic and chronotropic effects of NG-monomethyl-L-arginine.

Abstract

BACKGROUND:

The haemodynamic effects of intravenous infusion of the non-selective nitric oxide synthase (NOS) L-omega monomethyl arginine (L-NMMA) have previously been characterized in humans. Its effect of reducing cardiac index (CI) is an important reason for the increase in mortality in patients with septic shock receiving L-NMMA in a pivotal outcome trial for this indication. The mechanism for the reduction in CI however, is uncertain.

METHODS:

In this study, we investigated the haemodynamic and arterial stiffness response to a bolus intravenous infusion of L-NMMA (3 mg kg(-1) over 5 min) in 26 healthy human volunteers to clarify the likely cause of L-NMMA induced negative inotropic and chronotropic effects. Digital photoplethysmography (MicroMedical Pulse Trace) was used to derive two measures of arterial stiffness: stiffness index, a measure of large arterial stiffness, and reflection index (RI), a measure of small- to medium-sized arterial stiffness. Haemodynamic measurements of systolic blood pressure, diastolic blood pressure, heart rate, systemic vascular resistance index (SVRI), stroke index and CI were made using a bioimpedance monitor (BioZ Cardiodynamics).

RESULTS:

We found that changes in CI during L-NMMA are closely related to changes in RI and SVRI.

CONCLUSION:

The negative inotropic effect of L-NMMA may be a result of an increase in coronary vascular resistance and a resultant decrease in myocardial perfusion. The reduction in CI may also result from a direct reduction of the normal positive inotropic effect of NO by L-NMMA which is closely correlated with its effects on SVRI.

• Authors: D G Brillante, A J O'Sullivan, M T Johnstone, L G Howes
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 39 Issue 4 Pg. 273-9 (Apr 2009) ISSN: 1365-2362 [Electronic] England
• PMID: 19292882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• omega-N-Methylarginine
• Nitric Oxide Synthase

Topics

• Adult
• Arteries (drug effects)
• Blood Flow Velocity (drug effects)
• Enzyme Inhibitors (pharmacology)
• Female
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Humans
• Male
• Myocardial Contraction (drug effects)
• Nitric Oxide Synthase (pharmacology)
• Regression Analysis
• Young Adult
• omega-N-Methylarginine (pharmacology)