Heart abnormal conduction

Inhalation of certain hydrocarbons, including some anesthetics, can make the mammalian heart abnormally sensitive to epinephrine, resulting in ventricular arrhythmias, which in some cases can lead to sudden death (Reinhardt et al. 1971). The mechanism of action of cardiac sensitization is not completely understood but appears to involve a disturbance in the normal conduction of the electrical impulse through the heart, probably by producing a local disturbance in the electrical potential across cell membranes. The hydrocarbons themselves do not produce arrhythmia the arrhythmia is the result of the potentiation of endogenous epinephrine (adrenalin) by the hydrocarbon. 

By these mechanisms, antiarrhythmic drugs can suppress ectopic automaticity and abnormal conduction occurring in depolarized cells— rendering them electrically silent—while minimally affecting the electrical activity in normally polarized parts of the heart. However, as... 

Spach MS (1982) The electrical representation of cardiac muscle based on discontinuities of axial resistivity at a microscopic and macroscopic level. In de Carvalho A Paes, Hoffman BE, Lieber-man M (eds) Normal and Abnormal Conduction in the Heart, Mt. Kisco NY Futura Publishing Co. 

Laboratory studies-. The patient has a slight normo-cytic anemia. Sestamibi nucleotide imaging disclosed abnormal uptake in muscle tissue of the thighs, and the heart. Nerve-conduction studies show a sensory-motor mixed dysneuronal dys-schwannian polyneuropathy. BMG showed in distal... 

Multiform PVCs look different from one another (see shaded areas) and arise either from different sites or from the same site via abnormal conduction. Multiform PVG may indicate severe heart disease or digoxin toxicity. 

While the ECG is an invaluable tool for the observation of heart rate and rhythm, as well as for the diagnosis of conduction abnormalities, ischaemia, and infarcts, its detailed interpretation is not without pitfalls. One reason for this is that different changes in cardiac cellular behaviour may give rise to very similar effects on the ECG. This makes it difficult to draw conclusions from a patient s ECG to the underlying (sub-)cellular mechanisms. This issue is usually referred to as the inverse problem. ... 

Do not exceed a rate of 25 mg/min in elderly patients or in the presence of atherosclerotic heart disease or conduction abnormalities... 

Abnormal initiation of electrical impulses occurs as a result of abnormal automaticity. If the automaticity of the SA node increases, this results in an increased rate of generation of impulses and a rapid heart rate (sinus tachycardia). If other cardiac fibers become abnormally automatic, such that the rate of initiation of spontaneous impulses exceeds that of the SA node, other types of tachyarrhythmias may occur. Many cardiac fibers possess the capability for automaticity, including the atrial tissue, the AV node, the Purkinje fibers, and the ventricular tissue. In addition, fibers with the capability of initiating and conducting electrical impulses are present in the pulmonary veins. Abnormal atrial automaticity may result in premature atrial contractions or may precipitate atrial tachycardia or atrial fibrillation (AF) abnormal AV nodal automaticity may result in junctional tachycardia (the AV node is also sometimes referred to as the AV junction). Abnormal automaticity in the ventricles may result in ventricular premature depolarizations (VPDs) or may precipitate ventricular tachycardia (VT) or ventricular fibrillation (VF). In addition, abnormal automaticity originating from the pulmonary veins is a precipitant of AF. 

Diltiazem and verapamil can cause cardiac conduction abnormalities such as bradycardia, AV block, and heart failure. Both can cause anorexia, nausea, peripheral edema, and hypotension. Verapamil causes constipation in about 7% of patients. 

Side effects from /1-blockade in the myocardium include bradycardia, AV conduction abnormalities, and acute heart failure. Blocking / -receptors in arteriolar smooth muscle may cause cold extremities and aggravate PAD or Raynaud s phenomenon because of decreased peripheral blood flow. 

The isolate is penicillin sensitive (MIC less than or equal to 0.1 mcg/mL). / There are no cardiovascular risk factors such as heart failure, aortic insufficiency, or conduction abnormalities. 

Regulatory guidance for non-clinical cardiovascular safety pharmacology testing is given in the ICH S7A and B.25,42 The effects of an NCE on blood pressure, heart rate, and the ECG should be evaluated. Furthermore, in vivo, in vitro, and ex vivo evaluations, including methods for (assessing) repolarization and conductance abnormalities, should... 

The ICH guideline lists the assessment of effects on blood pressure, heart rate and ECG. In vivo, in vitro and/or ex vivo evaluations, including methods for electrical repolarisation and conductance abnormalities, should also be considered. These abnormalities can be associated with risks for fatal ventricular arrhythmias called Torsade de pointes. 

Hypersensitivity or idiosyncrasy to quinidine or other cinchona derivatives manifested by thrombocytopenia, skin eruption or febrile reactions myasthenia gravis history of thrombocytopenic purpura associated with quinidine administration digitalis intoxication manifested by arrhythmias or AV conduction disorders complete heart block left bundle branch block or other severe intraventricular conduction defects exhibiting marked QRS widening or bizarre complexes complete AV block with an AV nodal or idioventricular pacemaker aberrant ectopic impulses and abnormal rhythms due to escape mechanisms history of drug-induced torsade de pointes history of long QT syndrome. 

Cardiovascular effects If a ventricular pacemaker is operative, patients with seconder third-degree heart block may be treated with mexiletine if continuously monitored. Exercise caution in such patients or in patients with preexisting sinus node dysfunction or intraventricular conduction abnormalities. 

Concomitant use of calcium channel blockers (atenolol) Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta-blockers are administered with verapamil or diltiazem. Patients with preexisting conduction abnormalities or left ventricular dysfunction are particularly susceptible. Recent acute Ml (sotalol) Sotalol can be used safely and effectively in the long-term treatment of life-threatening ventricular arrhythmias following an Ml. However, experience in the use of sotalol to treat cardiac arrhythmias in the early phase of recovery from acute Ml is limited and at least at high initial doses is not reassuring. 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

Intraventricular conduction delay often leads to late activation of the left ventricular free wall with significant mechanical consequences. The mechanical consequences of abnormal electrical activation of the heart have long been recognized [58, 60, 86]. These include dyssynchrony between the atria. 

A series of pilot studies began with multisite pacing for patients with heart failure and dilated cardiomyopathy in the early 1990s [52, 105-111]. An improvement in LV function and symptoms of heart failure were demonstrated. This provided the interest in biventricular pacing for heart failure. The term cardiac resynchronization therapy was coined to refer to pacing therapies that attempt to enhance cardiac performance by using pacing to correct electrical conduction abnormalities in the heart. The most common form of this therapy is atrial-synchronous... 

Flecainide (Tambocor) is a fluorinated aromatic hydrocarbon examined initially for its local anesthetic action and subsequently found to have antiarrhythmic effects. Flecainide inhibits the sodium channel, leading to conduction slowing in all parts of the heart, but most notably in the His-Purkinje system and ventricular myocardium. It has relatively minor effects on repolarization. Flecainide also inhibits abnormal auto-maticity. 

Direct effects on the heart are determined largely by Bi receptors, although B2 and to a lesser extent a receptors are also involved, especially in heart failure. Beta-receptor activation results in increased calcium influx in cardiac cells. This has both electrical and mechanical consequences. Pacemaker activity—both normal (sinoatrial node) and abnormal (eg, Purkinje fibers)—is increased (positive chronotropic effect). Conduction velocity in the atrioventricular node is increased (positive dromotropic effect), and the refractory period is decreased. Intrinsic contractility is increased (positive inotropic effect), and relaxation is accelerated. As a result, the twitch response of isolated cardiac muscle is increased in tension but abbreviated in duration. In the intact heart, intraventricular pressure rises and falls more rapidly, and ejection time is decreased. These direct effects are easily demonstrated in the absence of reflexes evoked by changes in blood pressure, eg, in isolated myocardial preparations and in patients with ganglionic blockade. In the presence of normal reflex activity, the direct effects on heart rate may be dominated by a reflex response to blood pressure changes. Physiologic stimulation of the heart by catecholamines tends to increase coronary blood flow. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

Arrhythmias are caused by abnormal pacemaker activity or abnormal impulse propagation. Thus, the aim of therapy of the arrhythmias is to reduce ectopic pacemaker activity and modify conduction or refractoriness in reentry circuits to disable circus movement. The major mechanisms currently available for accomplishing these goals are (1) sodium channel blockade, (2) blockade of sympathetic autonomic effects in the heart, (3) prolongation of the effective refractory period, and (4) calcium channel blockade. 

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