title: Free radicals and cardioplegia: organic anti-oxidants as additives to the St Thomas' Hospital cardioplegic solution.
abstract: The isolated perfused working rat heart model of cardiopulmonary bypass and ischaemic cardiac arrest has been used to investigate whether addition of various organic anti-oxidants to the St Thomas' Hospital cardioplegic solution can enhance the recovery of function of the rat myocardium after normothermic (37 degrees C) global ischaemic arrest. Five anti-oxidants were studied: (i) ascorbate (1.0 and 10.0 mmol.litre-1), (ii) methionine (1.0 and 10.0 mmol.litre-1), (iii) reduced glutathione (1.0 and 10.0 mmol.litre-1), (iv) dimethylthiourea (0.1, 1.0, 10.0 and 50.0 mmol.litre-1), (v) N-2-mercaptopropionyl glycine (0.1, 1.0 and 10.0 mmol.litre-1). The recovery of aortic flow in control hearts which were free of anti-oxidant was 50.7(SEM 0.5)%; ascorbate (1.0 or 10.0 mmol.litre-1) improved this recovery to 72.1(1.7) and 70.2(0.3)% respectively; methionine (1.0 and 10.0 mmol.litre-1) improved the recovery to 74.1(5.7)% and 67.7(1.7)%, respectively; reduced glutathione (1.0 and 10.0 mmol.litre-1) improved the recovery to 66.7(1.4)% and 74.0(1.7)% respectively. In further studies, the addition of dimethylthiourea (0.1, 1.0 and 10.0 mmol.litre-1) to the cardioplegic solution failed to improve recovery of aortic flow [47.3(8.0), 24.6(7.3), 48.0(7.7)% respectively] when compared to its anti-oxidant free control value of 40.4(6.1)% and at a concentration of 50.0 mmol.litre-1 a very poor recovery of aortic flow of 7.7(4.8)% was observed. Mercaptopropionyl glycine (0.1, 1.0 and 10.0 mmol.litre-1) also failed to improve the recovery of aortic flow [34.7(1.6), 34.7(7.7) and 25.6(5.4)% respectively.2+ Since biological membranes are highly permeable to dimethylthiourea and mercaptopropionyl glycine, it is possible that they accumulate in the intracellular compartment.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Chambers
authors.forename: G
authors.initials: G
authors.lastname: Astras
authors.forename: A
authors.initials: A
authors.lastname: Takahashi
authors.forename: A S
authors.initials: AS
authors.lastname: Manning
authors.forename: M V
authors.initials: MV
authors.lastname: Braimbridge
authors.forename: D J
authors.initials: DJ
authors.lastname: Hearse
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D001639:Bicarbonates / Q000627:therapeutic use; D002122:Calcium Chloride / Q000627:therapeutic use; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D005609:Free Radicals; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008274:Magnesium / Q000627:therapeutic use; D008297:Male; D008715:Methionine / Q000627:therapeutic use; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011189:Potassium Chloride / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000627:therapeutic use; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use; D008625:Tiopronin / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D001639:Bicarbonates; D002314:Cardioplegic Solutions; D005609:Free Radicals; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; C038983:1,3-dimethylthiourea; D008715:Methionine; D008625:Tiopronin; D013890:Thiourea; D008274:Magnesium; D002122:Calcium Chloride; D001205:Ascorbic Acid