The Impact of Zinc Supplementation on Left Ventricular Function in Nonischemic Cardiomyopathy
Status:
Completed
Trial end date:
2011-06-01
Target enrollment:
Participant gender:
Summary
Heart failure affects over 5.3 million Americans and, while other cardiovascular diseases
have enjoyed a reduction in mortality rates over the last decade, the mortality from heart
failure continues to rise[1]. Thus, identifying novel therapies that can reduce heart failure
development and/or progression are warranted. Unifying to most cardiomyopathic processes is
an impaired handling of reactive oxygen species (ROS)[2-4]. Reactive oxygen species are
generated as byproducts of inflammation and oxidative stress that occur in the setting of
normal myocardial aerobic metabolism. Metallothionein, glutathione reductase, and superoxide
dismutase are major antioxidants in the myocardium that help combat oxidative stress and
prevent myocardial damage. In certain clinical settings, including cardiac ischemia,
diabetes, and heavy metal excess (copper, iron), myocardial oxidative stress levels are
greatly increased. When pro-oxidant levels exceed myocardial antioxidant capabilities,
ROS-induced membrane, protein, and DNA inactivation can lead to the development of cardiac
dysfunction.
One means of preventing the development or progression of cardiomyopathy is to reduce
oxidative stress through up-regulation of intramyocardial antioxidants. Murine studies of
cardiomyopathy have shown that oral administration of zinc acetate may succeed as an indirect
myocardial anti-oxidant because zinc sufficiently up-regulates the intramyocardial production
of superoxide dismutase (a zinc-dependant anti-oxidant enzyme) and metallothionein (a "super
antioxidant") [5-8]. Zinc also directly reduces prooxidant Cu levels by reducing
gastrointestinal zinc absorption. However, to date, no studies have examined the impact of
zinc acetate supplementation in subjects with cardiomyopathy and systolic failure on
antioxidant capacity and remodeling.
The hypothesis of this pilot study is that administration of oral zinc acetate to humans with
cardiomyopathy will lead to an up-regulation of myocardial anti-oxidant capabilities,leading
to a favorable reduction in oxidative stress. This study will provide preliminary data to
support a randomized, placebo-controlled trial of zinc therapy in heart failure as a means of
improving or preventing the progression of systolic dysfunction in subjects with
mild-moderate heart failure.