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The effect of drugs with ion channel-blocking activity on the early embryonic rat heart

Abela, D (författare)
Ritchie, H (författare)
Ababneh, D (författare)
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Gavin, C (författare)
Nilsson, Mats F (författare)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Division of Toxicology
Niazi, M Khalid Khan (författare)
Uppsala universitet,Centrum för bildanalys
Carlsson, K (författare)
Webster, WS (författare)
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 (creator_code:org_t)
2010-10-08
2010
Engelska.
Ingår i: Birth defects research. Part B. Developmental and reproductice toxicology. - : Wiley. - 1542-9733 .- 1542-9741. ; 89:5, s. 429-440
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the IKr/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or IKr/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing.

Ämnesord

NATURVETENSKAP  -- Data- och informationsvetenskap -- Datorseende och robotik (hsv//swe)
NATURAL SCIENCES  -- Computer and Information Sciences -- Computer Vision and Robotics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Nyckelord

embryo/fetal physiology
in vitro screens
mechanisms of teratogenesis
pharmaceuticals
Image analysis
Bildanalys
PHARMACY
FARMACI
Computerized Image Processing
Datoriserad bildbehandling

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ref (ämneskategori)
art (ämneskategori)

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