Cardiovascular Therapeutics - Applications of Biotechnology in Cardiovascular Therapeutics - page 16

the electrophysiological consequences of ischemia in isolated myocardial cells.
Glibenclamide is also effective in preventing the development of ventricular fibril-
lation in isolated heart preparations under conditions of low intracellular ATP.
Potassium loss during ischemia/hypoxia is attributed to activation of K AT P channel
and this is partially blocked by the action of glibenclamide. Many of the sequelae
of metabolic stress in the cardiac muscle are related to loss of sensitivity of these
channels to glibenclamide as observed in the canine model of congestive heart
failure. The underlying mechanism of this is not known but a reduction in sensitiv-
ity of these channels contributes to postinfarct electrophysiologic disturbances of
the heart.
Long Q-T Interval Syndrome as an Ion Channel Disorder
Long Q-T interval syndrome (LQTS) is an inherited cardiac disorder characterized
by a prolonged Q-T interval on ECG due to slow repolarization of the action
potential. Individuals with this syndrome are at risk of sudden death due to
ventricular arrhythmias. Mutations of the human HERG (ether-a-go-go related
gene), an inward rectifier potassium channel have been shown to cause a form
of LQTS.
Role of Plasminogen Activator Inhibitor-1
in the Cardiovascular System
Plasminogen activator inhibitor-1 (PAI-1) is critical in thrombus formation and
inflammation and plays a role in the progression of various cardiovascular diseases.
To date, a novel PAI-1 inhibitor have been reported to suppress the development of
experimental autoimmune myocarditis, vascular remodeling after arterial injury,
and heart transplant rejection using rodent models (Suzuki et al. 2011 ). Pathologically,
the PAI-1 inhibitor improved histological remodeling of myocardium and arteries
with suppression of inflammation and thrombus formation. Thus PAI-1 inhibitors
appear to exhibit potent effects on the prevention of adverse tissue remodeling.
However, PAI-1 is a multifunctional protein and more research is needed to further
elucidate the association between PAI-1 expression and cardiovascular disease.
Biotechnology and Therapy of Cardiovascular Diseases
Optimal use of existing therapeutics and discovery of new treatments for cardiovas-
cular disorders would involve improved methods of biotechnology. Interrelationships
of drug biotechnology and therapy of cardiovascular diseases are shown in
Fig. 1.1 .