Ischemia associated arrhythmias

Cardiomyopathy is the most common chemotherapy-associated cardiac toxicity. Myocardial ischemia, pericarditis, arrhythmias, miscellaneous electrocardiogram (ECG) changes, and angina occur much less frequently. The anthracyclines (da-unorubicin, doxorubicin, epirubicin, and idarubicin) have the highest consistent risk for cardiomyopathy, which is cumulative dose related. There is evidence that high-dose cyclophosphamide, mitoxantrone, and fluorouracil also pose an increased risk of cardiac damage. The concurrent use of traztuzu-mab with an anthracycline and cyclophosphamide is associated with a risk of cardiac dysfunction, but the consequences of sequential use are not yet known. 

Cocaine can have marked effects on the heart and cardiovascular system. Adverse actions may include myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular events, and a hyperco-agulable state (24,40). By 1997 more than 250 cases of myocardial infarction related to the recreational use of cocaine had been documented in the literature (41). Although less common, aortic dissection related to use of cocaine-free base ("crackcocaine") has also been documented (42). Seizures also can be associated with cocaine use (43). 

Low-dose dopamine is not without adverse reactions and most studies have failed to evaluate its potential toxicities. Adverse reactions that may be associated with low-dose dopamine include tachycardia, arrhythmias, myocardial ischemia, depressed respiratory drive, and gut ischemia. Low-dose dopamine has also been postulated to impair resistance to infection through a reduction in prolactin concentrations.21 Furthermore, significant overlap in receptor activation occurs. Therefore, doses considered to activate only dopamine receptors may increase cardiac output and blood pressure through dopamine s effect on 3- or a-adrenergic receptors. 

Terbutaline has been shown to prolong pregnancy but has not been associated with decreased neonatal morbidity.36 It is contraindicated for use in women with preexisting cardiac arrhythmia. Potentially serious adverse effects include pulmonary edema, cardiac arrhythmia, or myocardial ischemia in the mother. Reported fetal and neonatal adverse effects include tachycardia, hyperglycemia, and hyperinsulinemia.41... 

Most effective against arrhythmias associated with digitalis toxicity and exercise, particularly if the latter is related to ischemia. 

As for the cardiovascular system, the cardioprotective effects of selective H3-receptor agonists, demonstrated in models of protracted myocardial ischemia (Imamura et al., 1994, 1995, 1996a Hatta et al., 1996, 1997), could be predictive of beneficial effects in coronaropatic patients. Hence, the attenuation of carrier-mediated noradrenaline release in hypoxic and/or ischemic myocardium by H3-agonists would limit the sympathetic overactivity and the associated incidence of ventricular arrhythmias and angina, as well as the increase of metabolic demand by the myocardium, thus preventing further damage and cardiac failure. 

Proarrhythmic effects of antiarrhythmic drugs In the Cardiac Arrhythmia Suppression Trial (CAST) treatment with encainide and flecainide, two class IC antiarrhythmic agents, successfully prevented ventricular ectopic beats in patients who had myocardial infarction. However, continued therapy with either drug was associated with a two- to three-fold increase in death due to cardiac arrhythmias. Similar results were reported for moricizine. Increased death was probably due to drug-induced fatal arrhythmias triggered by recurrent myocardial ischemia. 

Cocaine is a central nervous system stimulant that inhibits the peripheral reuptake of catecholamines, leading to increased sympathomimetic activity [129]. Its abuse is associated with a variety of medical problems. These include acute myocardial infarction, cardiac arrhythmias, cerebrovascular accidents, hyperpyrexia and stimulated sympathetic activity, seizures and coma, obstetrical comphcations, intestinal ischemia and a variety of psychiatric complications [128-131]. A number of reports in the mid to late 1980 s described patients who developed rhabdomyolysis while using cocaine [132-134]. Some of these patients experienced acute kidney injury [135-139]. While the exact incidence of acute kidney injury secondary to cocaine rhabdomyolysis is unknown, in one reported series it occurred... 

Arrhythmias are observed during the ischemic phase as well as at reperfusion in most of the animal models. In the first 2-10 min of ischemia, a burst of irregular ventricular tachycardia occurs but evolution to ventricular flbrillation is rare. These arrhythmias are mainly of a reentry nature. A second phase of arrhythmias is evident after 20-30 min of ischemia. The percentage of animals that show this delayed phase of arrhythmias is small and the evolution to ventricular flbrillation is more frequent and the animals can die. This phase is associated with a massive release of catecholamines, changes in calcium overload and an increase in extracellular potassium, reviewed by Carmeliet.55... 

Preischemic activation of a-adrenergic signaling also results in cardioprotection. Pretreatment with norepinephrine induces bimodal (early and delayed) myocardial functional adaptation to ischemia in rats. PKC appears to be involved in the early response. Delayed protection was shown to be associated with the expression of genes encoding fetal contractile proteins (increase in P-MHC mRNA).94 However, a-receptor agonists can trigger arrhythmias in the setting of ischemia and reperfusion.55... 

A. Systemic intoxication associated with stonefish envenomation can include the rapid onset of hypotension, tachycardia, cardiac arrhythmias, myocardial ischemia, syncope, diaphoresis, nausea, vomiting, abdominal cramping, dyspnea, pulmonary edema, cyanosis, headache, muscular weakness, and spasticity. 

They antagonize the positive inotropic and chronotropic effects of catecholamines. Cardiac arrhythmias associated with excessive adrenergic stimulus, released endogenous catecholamines or sensitization of the heart by anes-thetics or cardiac glycosides may effectively be treated by 6-blockade. Some B-blockers also possess membrane or local anesthetic action and are effective against arrhythmias due to ischemia or cardiac glycoside toxicity as well. This membrane action was shown to be independent of 6-blockade since resolved isomers of B-blockers possessed equal antiarrhythmic potency but unequal B-blocking action. 

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