Free radicals and cardioplegia: organic anti-oxidants as additives to the St Thomas' Hospital cardioplegic solution.
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)
Chambers
D J
DJ
Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, UK.
Astras
G
G
Takahashi
A
A
Manning
A S
AS
Braimbridge
M V
MV
Hearse
D J
DJ
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
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