Tilarginine is L-N-monomethyl
arginine (
L-NMMA) or N(G)-monomethyl-
L-arginine HCL, a non-selective inhibitor of
nitric oxide synthase (NOS), which has been studied in the treatment of
septic shock and
cardiogenic shock complicating
myocardial infarction. Despite strong evidence that excessive
nitric oxide (NO) production plays a pivotal role in the pathogenesis of
septic shock and may contribute to the pathogenesis of
cardiogenic shock complicating
myocardial infarction, outcome studies in these two disorders have proved disappointing.
L-NMMA therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg h), in
septic shock whereas the effects of a lower dose (1 mg/(kg h)) in
cardiogenic shock complicating
myocardial infarction were neutral. The excess mortality in patients with
septic shock was almost certainly the result of unfavourable haemodynamic changes induced by
L-NMMA (decreased cardiac output, increased pulmonary vascular resistance and reduced tissue
oxygen delivery) whereas the lack of benefit in patients with
cardiogenic shock complicating
myocardial infarction may have been because the dose of
L-NMMA was too low. Further studies of
L-NMMA at doses < 5 mg/(kg h) in conjunction with inotrope support may produce more beneficial results. Conversely, the use of a selective inducible NOS inhibitor to reduce the pathological effects of excessive NO production although leaving the beneficial effects of vascular NO production by endothelial NOS unaltered may prove to be of value.