Role of Nitric Oxide in Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 84

a continuing analysis of patients treated with BiDil ® , which suggest that BiDil ®
decreases systolic blood pressure (SBP) in black heart failure patients with higher
baseline SBP but not in those with lower baseline SBP. The beneficial effects of
BiDil on clinical outcomes in A-HeFT were shown to be independent of baseline
SBP. When differentiating patients by baseline SBP above or below the median
(126 mmHg) in A-HeFT, the significant benefits demonstrated for BiDil on mortality
and morbidity were similar for both groups.
NO-Based Therapy for Management of Cardiogenic Shock
Cardiogenic shock (CS) is the leading cause of death among patients hospitalized
with acute myocardial infarction (AMI). It is defined as tissue hypoperfusion
resulting from ventricular pump failure in the presence of adequate intravascular
volume. Rapid assessment and triage of patients presenting in CS followed by
appropriate institution of supportive therapies including vasopressor and inotropic
agents, mechanical ventilatory support, and intra-aortic balloon pump counterpul-
sation are usually employed in the management of these patients. However, emer-
gency percutaneous coronary intervention or coronary artery bypass graft surgery
may be required, but the mortality from CS, approximately 50%, remains high
despite reperfusion therapy. There is a dire need for therapies to treat CS more
effectively. One approach is based on the role of NO in CS as the balance of NO
production and regulation of cardiac function is disrupted. Abnormal NO produc-
tion inhibits cardiac contractility in failing myocardium.
Tilarginine, L-N-monomethyl arginine (L-NMMA) or N(G)-monomethyl-L-
arginine HCL, a nonselective inhibitor of NOS, has been studied in clinical trials
for the treatment of CS complicating myocardial infarction. Despite evidence that
excessive NO production may contribute to the pathogenesis of CS complicating
myocardial infarction, the results of these studies proved disappointing because of
lack of benefit and excess mortality. Further studies using a selective iNOS inhibi-
tor to reduce the pathological effects of excessive NO production while leaving the
beneficial effects of vascular NO production by eNOS unaltered may prove to be
of value (Howes and Brillante 2008 ).
NO-Based Therapy for Cardiac Arrhythmias
Paroxysmal supraventricular tachycardia (PSVT), one of the most common cardiac
arrhythmias, is a rapid, regular heart rate originating in the atria. Currently, adenos-
ine is the only approved treatment for PSVT in the USA. Although both ATP and
adenosine inhibit atrioventricular nodal conduction, ATP is believed to have dual
inhibitory action; one mediated by adenosine, the product of its rapid enzymatic
degradation, and the other a triggered vagal reflex. Vagal maneuvers aimed at