Disease relevance of digitoxin

• Hyperthermia potentiates doxorubicin-related cardiotoxic effects [1].
• Toxicity studies further indicate that DXR-MAb 9.2.27 conjugate is less toxic in vivo than the freely administered DXR, which is known to cause considerable cardiotoxic effects [2].
• To test the hypothesis that mismatch between myocardial fatty acid uptake and utilization leads to the accumulation of cardiotoxic lipid species, and to establish a mouse model of metabolic cardiomyopathy, we generated transgenic mouse lines that overexpress long-chain acyl-CoA synthetase in the heart (MHC-ACS) [3].
• The absence of erbB2 signaling in cardiac myocytes results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects observed in a subset of breast cancer patients treated with the anti-Her2 antibody herceptin [4].
• Since endothelin may contribute to hemodynamic deterioration by potent vasoconstrictory and cardiotoxic actions, increased plasma levels may be associated with an unfavorable prognosis after myocardial infarction [5].

Psychiatry related information on digitoxin

• Among the depressive symptoms, hopelessness (HR=3.44; 95% CI=1.65-7.19) was the most cardiotoxic symptom [6].
• TCAs are also cardiotoxic in overdosage, and panic disorder patients with comorbid depression are at high risk of attempted suicide [7].
• The S(-) isomer is known to be less neuro- and cardiotoxic, but demonstrates a lower potency to block motor activity than RS(+/-) bupivacaine [8].
• Patients with coronary artery disease, hypertension, diabetes mellitus, exposure to cardiotoxic drugs, alcohol abuse, or a family history of cardiomyopathy are at high risk for heart failure and may benefit from routine screening [9].

High impact information on digitoxin

• Sarafotoxins, a group of 21-residue cardiotoxic peptides from snake venom that induce coronary vasoconstriction, show high-affinity binding to rat atrial and brain membranes and activate the hydrolysis of phosphoinositides [10].
• Amoxapine overdose. Coma and seizures without cardiotoxic effects [11].
• Less cardiotoxic chemosensitizers are needed to reverse multidrug resistance in cancer [12].
• Underlying pathogenetic mechanisms may include free-radical-mediated myocyte damage, adrenergic dysfunction, intracellular calcium overload, and the release of cardiotoxic cytokines [13].
• HERG is likely to be the primary target for the known cardiotoxic effects of other, related antihistamines [14].

Chemical compound and disease context of digitoxin

• These experiments show, for the first time, that 3NPA has important cardiotoxic effects as well as neurotoxic effects, and that cardiac toxicity possibly resulting from inhibition of the succinate dehydrogenase in heart mitochondria, contributes to the cause of death in 3NPA poisoning in acute and subacute/chronic studies in mice [15].
• Cocaine is also a cardiotoxic agent and can induce cardiac arrhythmia and ventricular fibrillation [16].
• Reboxetine is not cardiotoxic, and it is not associated with an increased risk of seizures or of orthostatic hypotension [17].
• If epirubicin proves to be less cardiotoxic than doxorubicin, this combination would merit further evaluation as potential adjuvant therapy for early breast cancer [18].
• It is concluded that selective alpha 1-receptor stimulation and alpha 2-receptor blockade increases the cardiotoxic effects of ouabain and selective alpha 2-receptor stimulation and alpha 1-receptor blockade inhibits ouabain-induced arrhythmias and cardiac arrest in guinea-pigs [19].

Biological context of digitoxin

• The purpose of this investigation was to compare the cardiotoxic potential of these compounds and to characterize the myocardial pharmacokinetics in order to provide a possible explanation for differences in cardiotoxicity [20].
• Doxorubicin, a cardiotoxic antineoplastic, disrupts the cardiac-specific program of gene expression (Kurabayashi, M., Dutta, S., Jeyaseelan, R., and Kedes, L [21].
• During cardiac ischaemia activation of ATP-sensitive K(+) (K(ATP)) channels contributes to action potential (AP) shortening which is either cardiotoxic by inducing re-entrant ventricular arrhythmias or cardioprotective by inducing energy-sparing effects or ischaemic preconditioning (IPC) [22].
• In terms of safety issues, the current second generation grouping includes compounds with proven cardiotoxic effects and others with the potential for adverse drug interactions [23].
• Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy [24].

Anatomical context of digitoxin

• In patients with endomyocardial disease and eosinophilia, the eosinophil may be directly cardiotoxic or a primary mediator of cardiac damage; therapeutic attempts to reduce the number of eosinophils might be benefit [25].
• Cardiotoxic effects of the plasticizer metabolite, mono (2-ethylhexyl)phthalate (MEHP), on human myocardium [26].
• The key and possibly initiating role of the exogenous NADH dehydrogenase of cardiac mitochondria in this reaction pathway provides a rationale to explain the selective cardiotoxic potency of the cytostatic anthraquinone glycosides [27].
• Biochemical and pharmacological properties of a cardiotoxic factor isolated from the blood serum of burned patients [28].
• An indirect effect of ALS by release of cardiotoxic substances from damaged blood cells seems to be a more probable explanation than a direct action of ALS on cardiac cell membranes [29].

Associations of digitoxin with other chemical compounds

• Electron microscopy of the mouse hearts demonstrated conclusively that doxorubicin was cardiotoxic after 13 weeks of exposure, showing mitochondrial degeneration and disruption of the myofibrillar organization [30].
• We tested antitumor activity, tolerability, and pharmacokinetics of the lesser cardiotoxic epirubicin (EPI) and PTX (ET combination) [31].
• Hence cyclosporine might be cardiotoxic already at concentrations below the pharmacological dosages while azathioprine influences the myocytes only at concentrations much higher than the therapeutic level [32].
• Metabolic perturbations in the endocardium produced by cardiotoxic doses of isoprenaline were prevented or reduced by propranolol pretreatment [33].
• The indicator dilution method was used to measure the single-pass maximum extraction (Emax) and net extraction (Enet(t)) of 201Tl and 99mTc-Q12 over 15 min during control perfusion (n = 11) and during normal (1 microM, n = 6) and high cardiotoxic (50 microM, n = 11) dose infusions of the digitalis glycoside, ouabain [34].

Gene context of digitoxin

• In the present study, we assessed the hypothesis that cardiotoxic effects of proinflammatory cytokines are mediated by the activation of NF-kappaB [35].
• Previous in vivo data show a markedly enhanced cardiotoxic response to doxorubicin in beta2-/- mice, which is rescued by the additional deletion of the beta1-AR [36].
• In conclusion, the differential cardioprotective/cardiotoxic effects mediated by beta1 vs. beta2-AR subtypes in knockout mice are recapitulated in myocytes isolated from these mice. beta2-ARs appear to play a cardioprotective role, whereas beta1-ARs a cardiotoxic role [36].
• In healthy human subjects and in patients with atherosclerotic vascular diseases, the effect of COX-2 inhibition on coagulation is equally unclear as no prospective, randomized, double-blinded studies sufficiently powered to investigate cardiovascular endpoints have been performed to directly investigate a potentially cardiotoxic effect of coxibs [37].
• This hypothesis predicts that improved SERCA2 function would provide protection from cardiotoxic effects of anthracycline administration [38].

Analytical, diagnostic and therapeutic context of digitoxin

• In the present study, we tested the hypothesis that ONOO(-) is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts [39].
• CONCLUSION: RCTs have shown clear evidence of biologic activity for the protective agents, but this does not imply therapeutic benefit as compared with alternative strategies such as avoidance of prolonged use of cardiotoxic agents or use of standard doses of chemotherapy [40].
• PURPOSE: We conducted a phase I crossover study of escalating doses of both paclitaxel (Taxol; Bristol-Myers, Squibb, Princeton, NJ) and r-verapamil, the less cardiotoxic stereoisomer, in heavily pretreated patients with metastatic breast cancer [41].
• Cardiotoxic effects were measured from electrocardiogram changes up to 2 weeks after treatment [42].
• They also were less cardiotoxic in cell culture [43].

References