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Electrophysiology of Normal Cardiac Rhythm01:19

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The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase...
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Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
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Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
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Lower respiratory tract disorders present challenges that often require skilled and nuanced approaches for effective management. Common ailments, such as asthma and chronic obstructive pulmonary disease (COPD), have prompted the development of intricate treatment strategies involving bronchodilators and anti-inflammatory drugs, each tailored to ease breathing and revitalize the lungs.
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Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms.

Joachim Alexandre1, Javid J Moslehi2, Kevin R Bersell3

  • 1CHU Caen, PICARO Cardio-oncology Program, Department of Pharmacology, F-14033 Caen, France; Normandie Univ, UNICAEN, CHU Caen, EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, 14000 Caen, France.

Pharmacology & Therapeutics
|April 27, 2018
PubMed
Summary

Cancer therapies can cause heart rhythm disorders, including arrhythmias and QTc prolongation, even without heart muscle damage. These cardiac complications are often overlooked and challenging to link directly to specific anticancer drugs.

Keywords:
Atrial fibrillationCardiotoxicityChemotherapyKinase inhibitorsQTc intervalVentricular tachycardia

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Area of Science:

  • Cardiology
  • Oncology
  • Pharmacology

Background:

  • Cancer treatments have improved survival, but can lead to cardiovascular diseases.
  • Cardiotoxicity from cancer therapy includes heart failure and cardiac rhythm disorders.
  • Cardiac rhythm disorders can occur independently of cardiomyopathy in cancer patients.

Purpose of the Study:

  • To highlight anticancer drug-induced cardiac rhythm disorders as an underappreciated complication.
  • To discuss mechanisms and specific anticancer agents associated with arrhythmias.
  • To address challenges in establishing causal links between drugs and arrhythmias.

Main Methods:

  • Review of literature on anticancer drug-induced cardiotoxicity and arrhythmias.
  • Identification of specific chemotherapy agents and kinase-inhibitors linked to arrhythmias.
  • Discussion of mechanisms including hERG and phosphoinositide-3-kinase inhibition.

Main Results:

  • Supraventricular and ventricular arrhythmias, including torsades de pointes, are reported.
  • QTc prolongation is a key factor, associated with kinase-inhibitors, arsenic trioxide, and others.
  • Causation is complex due to comorbidities and polypharmacy in cancer patients.

Conclusions:

  • Anticancer drug-induced cardiac rhythm disorders are an underappreciated adverse effect.
  • Further investigation into incidence, significance, and mechanisms is warranted.
  • Clinical awareness and research are crucial for managing these cardiotoxicities.