Cardiac function

Several chemical compounds can have an adverse effect on the heart and the vascular system. The effect may first appear as a transient change in the cardiac function. However, prolonged exposure increases the risk of permanent effects. Occasionally, functional effects such as cardiac arrhythmias may even lead to death. Furthermore, in many cases the effects of chemicals... 

Mechanisms of Cardiotoxicity Chemical compounds often affect the cardiac conducting system and thereby change cardiac rhythm and force of contraction. These effects are seen as alterations in the heart rate, conduction velocity of impulses within the heart, and contractivity. For example, alterations of pH and changes in ionic balance affect these cardiac functions. In principle, cardiac toxicity can be expressed in three different ways (1) pharmacological actions become amplified in an nonphysiological way (2) reactive metabolites of chemical compounds react covalently with vital macromolecules... 

Catecholamines are also intimately involved in cardiac function, with 3-sympathetic agonists having a generally stimulant action on the heart. Some effort has thus been devoted to the synthesis of agents that would act selectively on the heart. (Very roughly speaking, 3 -adrenergic... 

The narrow therapeutic range of digitalis related cardiotonic agents has resulted in an extensive effort to identify compounds in other structural classes which will improve cardiac function. The discovery of the heterocyclic cardiotonic drug, amrinone, led to research on other heterocyclic compounds for that indication. The imidazopyridine, isomazole (57), is representa-... 

FIGURE 2.17 Differential efficiency of receptor coupling for cardiac function, (a) Guinea pig left atrial force of contraction (inotropy, open circles) and rate of relaxation (lusitropy, filled circles) as a function (ordinates) of elevated intracellular cyclic AMP concentration (abscissae). Redrawn from [6]. 

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. 

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

U (No CaM) i PKA t PKCo/S Heart, brain (striatum) Cardiac function, Ca2+-dependent regulation... 

All or only some of these symptoms may be present. Anaphylactic shock can be fatal if the symptoms are not identified and treated immediately. Treatment is to raise the blood pressure improve breathing, restore cardiac function, and treat other symptoms as they occur. 

Both carvedilol and labetalol are contraindicated in patients with hypersensitivity to the drag, bronchial asthma, decompensated heart failure, and severe bradycardia The drugs are used cautiously in patients with drag-controlled congestive heart failure, chronic bronchitis, impaired hepatic or cardiac function, in those with diabetes, and during pregnancy (Category C) and lactation. 

An arrhythmia may occur as a result of heart disease or from a disorder that affects cardiovascular function. Conditions such as emotional stress, hypoxia, and electrolyte imbalance also may trigger an arrhythmia An electrocardiogram (ECG) provides a record of the electrical activity of the heart. Careful interpretation of the ECG along with a thorough physical assessment is necessary to determine the cause and type of arrhythmia The goal of antiarrhythmic drug therapy is to restore normal cardiac function and to prevent life-threatening arrhythmias. 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

Clearly, cardiac function may not be addressed exclusively on the basis of describing the working mechanisms of single cells. Both normal and disturbed heart rhythms are based on a spreading wave of electrical excitation, the meaningful investigation of which requires conduction pathways of at least hundreds if not thousands of cells in length. 

Cardiac function (i.e., can the patient tolerate negative inotropic medications)... 

Impaired cardiac function (poor ejection fraction) o Amiodarone... 

Normal baseline QT interval and normal cardiac function o Treat ischemia... 

Heart failure (HF) is defined as the inadequate ability of the heart to pump enough blood to meet the blood flow and metabolic demands of the body.1 High-output HF is characterized by an inordinate increase in the body s metabolic demands, which outpaces an increase in cardiac output (CO) of a generally normally functioning heart. More commonly, HF is a result of low CO secondary to impaired cardiac function. The term heart failure will refer to low-output HF for purposes of this chapter. 

A basic grasp of normal cardiac function sets the stage for understanding the pathophysiologic processes leading to HF and selecting appropriate therapy for HF. Cardiac output is defined as the volume of blood ejected per unit of time (liters per minute) and is a major determinant of tissue perfusion. Cardiac output is the product of heart rate (HR) and stroke volume (SV) CO = HR x SV. The following describes how each parameter relates to CO. 

To assess for prevention of disease progression, practitioners may utilize serial echocardiograms every 6 months to assess cardiac function and evaluate the effects of drug therapy. 

Other diagnostic tests should also be obtained in order to rule out precipitating factors (chest radiograph) and to evaluate cardiac function (ECG). 

Dosing and Administration Mitoxantrone is infused intravenously over 30 minutes to reduce the chance of cardiotoxicity.46 Mitoxantrone is administered every 3 months, if cardiac function and laboratory values are normal (Table 26-6). 

Reduced lean body mass Reduced muscle strength Reduced exercise performance Thin, dry skin cool peripheries poor venous access Depressed affect, labile emotions Impaired cardiac function... 

Cardiac transplantation is one option for patients with severe heart failure. Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III or IV symptoms and have an ejection fraction of less than 25%.1,3 The general indications for cardiac transplantation include rapidly declining cardiac function and a projected 1-year mortality rate of greater than 75%. Mechanical support with an implantable left ventricular assist device may be appropriate while patients await the availability of a viable organ.1,3 Some additional reasons for heart transplant include ... 

The outcome from intraabdominal infection is not determined solely by what transpires in the abdomen. Unsatisfactory outcomes in patients with intraabdominal infections may result from complications that arise in other organ systems. A complication commonly associated with mortality after intraabdominal infection is pneumonia.26 A high APACHE (Acute Physiology And Chronic Health Evaluation) II score, a low serum albumin, and a high New York Heart Association cardiac function status were significantly and independently associated with increased mortality from intraabdominal infection.27... 

Dopamine is a a- and P-adrenergic agent with dopaminergic activity Low doses of dopamine (1 to 5 mcg/kg per minute) maintain renal perfusion, higher doses (greater than 5 mcg/kg per minute) exhibit a- and P-adrenergic activity and are frequently utilized to support blood pressure and to improve cardiac function. Low doses of dopamine should not be used for renal protection as part of the treatment of severe sepsis.24,27-28... 

It has been proposed that NO mediates the myocardial depression associated with sepsis (F6, L14). NO synthesis induced by endotoxin blunts beta-adrenergic responsiveness (B2). In vivo, the use of NO synthase inhibitors led to conflicting results (M26), with a general decreased cardiac output and oxygen delivery being observed. NO synthase inhibition improved left ventricular contractility in endo-toxemic pigs but also increased ventricular afterloads, which ultimately is detrimental to cardiac function (H20). Possible sources of NO in the heart may be the vascular cells, the endothelial cells, and the cardiac myocytes (P6). 

---