Cardiac function is compromised by reduction of coronary blood flow which deprives the heart muscle of the energy it needs to contract and pump blood.  Temporary or permanent loss of coronary blood flow leads to insufficient cardiac performance as well as injury and death of heart muscle cells.  When cardiac function is inadequate other vital organs, including the brain, kidneys and lungs, do not receive sufficient blood supply to sustain function.  Thus, inadequate cardiac function causes other organs to fail, too.  Cardiac failure is a life-threatening condition and over 400,000 Americans die from heart failure each year.  Catecholamine drugs such as adrenaline increase cardiac performance and are potentially life-saving interventions for treatment of inadequate cardiac function in patients with heart failure.  Unfortunately, the doses of these drugs necessary to restore cardiac function deplete the heart muscle cells of critically important energy reserves.  This energy depletion can worsen cardiac injury and cell death and also can cause irregular heart beat and cardiac arrest.  These problems have severely limited the therapeutic use of catecholamine drugs to only the most dire emergencies.  A means of increasing the potency of catecholamine drugs is needed to enable lower doses to be used to improve cardiac function while avoiding the dangerous side effects of these drugs.

          I have demonstrated that pyruvate increases the potency of catecholamine drugs in failing guinea-pig hearts.  When administered with pyruvate, lower doses of catecholamines were needed to produce a desirable increase in cardiac function.  These findings raise the possibility that pyruvate could be used to safely augment catecholamine potency in heart failure patients.  However, the isolated guinea-pig heart differs fundamentally from human heart.  In human heart disease, some parts of the heart remain well supplied with blood despite the loss of blood supply to other areas.  Moreover, in heart patients drugs are often administered only to the diseased portions of the heart.  Thus, in order to demonstrate the potential for pyruvate as a catecholamine-enhancing medication in patients it is essential to test the combination of pyruvate and catecholamine drugs in a heart model more representative of human heart disease: a large mammal heart, within the animal’s body and supplied with its own blood, in which failure of a portion of the heart is produced by blockade of only one major coronary artery.  The proposed investigation will define the ability of pyruvate to safely enhance the potency of catecholamine drugs in the heart of a large mammal, the dog, which will serve to validate the use of this therapy in human heart patients.  A pyruvate:catecholamine formulation would likely prove far more effective and considerably safer than catecholamine alone for improving cardiac performance.  Thus, the results of this investigation could greatly expand the clinical use of catecholamine drugs for treating heart failure.

©Cardiovascular Research Institute, February 2000
An Institute of Discovery at the University of North Texas Health Science Center at Fort Worth