Predictors of inotropic and chronotropic effects of N G‐monomethyl‐l‐arginine

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.