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Minto and Schnider (1) have pointed out that “Rapidly evolving changes in health care economics and consumer expectation make it unlikely that traditional drug development approaches will succeed in the future. A shift away from the narrow focus on rejecting the null hypothesis toward a bro ...

Cardiovascular disease remains the leading cause of death in industrialized countries and despite major progress in drug development, morbidity and mortality has not significantly changed over the last couple of decades. Today, still more than half a million people are diagnosed with ...

Cardiac arrhythmias are major causes of morbidity and mortality, including sudden cardiac death. Sudden cardiac death in the United States occurs with a reported incidence of greater than 300,000 persons per year (1). Although coronary heart disease is a major cause of death, other etiologi ...

Statistics from the American Heart Association show that the total number of arrhythmia-related mortalities is approx 500,000 of an estimated 2,000,000 US deaths per year, or nearly one-quarter of all cardiovascular-related deaths (1). The majority of such deaths, which have remained at a n ...

Assessment of patients with acute coronary syndromes (ACS), including chest pain, is often a diagnostic challenge to physicians. Biochemical markers of myocardial injury have become routine in assisting clinicians in confirming the diagnosis of acute myocardial infarction (AM ...

It is known that the administration of drugs can relieve or prevent many of the consequences of myocardial ischemia; this is the basis for the current therapy of angina of effort by, for example, organic nitrites and nitrates and β adrenoceptor-blocking drugs. These are effective in the short term; p ...

From even the most basic physiological observations, it is obvious that parts of the heart can generate their own intrinsic contractile rhythm. With the development of techniques to record electrical activity from tissues, it became clear that contraction of the heart is triggered by an act ...

Action potential waveforms in the mammalian myocardium reflect the synchronized activation (and inactivation) of multiple types of membrane ion channels (1) contributing inward (depolarizing) or outward (repolarizing) ionic currents (Fig. 1). These (inward and outward) curr ...

Drugs acting at the cardiac ion channel level, such as antiarrhythmics, have been in clinical use for several decades, well before the understanding that cardiac excitability was indeed a delicate equilibrium among the activity of specific ion channel classes and that the intimate mecha ...

Sudden cardiac death is a euphemism for ventricular fibrillation (VF) in the majority of cases of ischemic heart disease. It occurs most commonly during acute (

The purpose of this chapter is to ask why there has been so little success in developing new antiarrhythmic drugs and what can we do to increase our chances of success. Failure has been a fairly common theme in attempts to produce new antiarrhythmic drugs, particularly for lethal ventricular arrhyt ...

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and involves irregular and extremely rapid activation of the atria (approx 400 beats per min ; ref. 1). The prevalence of AF increases with age, with an incidence of 0.5% in patients less than 50 yr of age and an incidence of more than 5% in patients g ...

In a healthy heart, an increase in myocardial oxygen demand induces an increase in coronary artery blood flow and oxygen delivery. When obstructive coronary artery disease occurs, there is an abnormal diminished coronary blood supply relative to the myocardial oxygen demand known as hyp ...

Sodium-hydrogen exchange (NHE) is among the most important processes involved in pH regulation in the cardiac cell, especially under ischemic conditions. There is now excellent evidence that stimulation of NHE contributes to paradoxical induction of cell injury. The mechanism for t ...

Platelets are not only responsible for primary hemostasis (1), but also for the thrombi that produce the morbidity and mortality of arterial vascular disease (2). Although considerable effort has been expended to associate augmented platelet function with arterial thrombosis, it is m ...

Apoptotic cell death is a genetically regulated process and the balance between death and survival signals determines the fate of a cell. Apoptosis is important in development and in a number of pathological conditions including cancer and autoimmune diseases. Many transcription fac ...

The Genome Project and the technological innovations that it spawned have dramatically altered the future course of all biological research. The Genbank database already harbors billions of base pairs of DNA sequences derived from millions of individual sequence entries http://ww ...

Apoptosis as a distinct pathologic process has been recognized for decades. Its importance in many disease processes has become increasingly appreciated as new techniques for detecting and quantifying it have been developed with almost exponential rapidity. While all these techn ...

One of the major goals in applications of cytometry in analysis of apoptosis is to identify and quantify dead cells and often to discriminate between apoptosis and necrosis. Recognition of dead cells relies on the presence of a particular biochemical or molecular marker that is characteris ...

Enzyme-linked imMunosorbent assays (ELISAs) have long been used to quantify cytokines and other proteins that are secreted from cells. ELISAs enable the user to assay multiple samples, to obtain reproducible quantitative results, and to design studies with quantifiable endpoints. ...