Cardiovascular system cardiac function

Mean arterial pressure and cardiac output, an expression of the amount of blood that the heart pumps each minute, are the key Indicators of the normal functioning of the cardiovascular system. Mean arterial pressure is strictly controlled, but by changing the cardiac output, a person can adapt, e.g., to increased oxygen requirement due to increased workload. Blood flow in vital organs may vary for many reasons, but is usually due to decreased cardiac output. However, there can be very dramatic changes in blood pressure, e.g., blood pressure plummets during an anaphylactic allergic reaction. Also cytotoxic chemicals, such as heavy metals, may decrease the blood pressure. 

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

The substrate specificity of ACE is low. ACE cleaves a variety of pairs of amino acids from the carboxy-terminal part of several peptide substrates. The conversion of ANGI to ANGII and the degradation of bradykinin to inactive fragments are considered the most important functions of ACE. Both peptides have profound impact on the cardiovascular system and beyond. ACE is thus an important target for ACE inhibitors. These compounds are frequently and efficiently used in the treatment of hypertension and cardiac failure. 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

For many drugs, at least part of the toxic effect may be different from the therapeutic action. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures the body s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, 13 blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and any other drugs that may be given. 

The function of the cardiovascular system is to maintain adequate tissue perfusion. Cardiac output is the product of heart rate (rhythm) and cardiac contractility (giving rise to stroke volume). These factors are under neuronal, hormonal and mechanical control systems. Pharmacological manipulation of any of these contributors will result in changes in cardiovascular function and hence peripheral blood flow. In human medicine, the primary goal is to increase life expectancy, while maintenance of performance and quality of life are the main priorities in equine medicine. 

Nonclinical safety pharmacology studies submitted to regulatory agencies are outlined in ICH Guidance S7A (2001), and the basic package includes evaluation of a drug candidate s effects on the central nervous system, respiration, and the cardiovascular system. Cardiovascular system evaluation includes assessment of cardiac function and cardiac electrophysiological activity. 

---