Comparative anthracycline cardiotoxicity and CO Q10

81 PATTERNS OF FLOW AND METABOLISM AND EARLY VENTRICULAR ARRHYTHMIAS OF MYOCARDIAL ISCHAEMIA: 3-DIMENSIONAL MAPPING. D.C.Russell, J.S.Lawrie, R.A.Riemersnn and M.F.Oliver. Cardiovascular Research Unit, University EDINBURGH, EH8 gXF, SCOTLAND. of Edinburgh, George Square, Heterogeneity of regional metabolism and flow may provide the basis for re-entrant excitation and hence early ventricular arrhythmias of This has been examined by construction of myocardial ischaemia. 34imensional computer maps of regional metabolism, blood flow and epicardial activation at onset of arrhythmias following proximal occlusion of the left anterior descending coronary artery in 12 dogs. Flow was assessed using tracer microspheres and epicardial activation by multiplexing signals from an 80-point electrode grid over the ischaemic zone. The heart was then excised, rapidly frozen and 160 tissue samples (~mm2) taken from endocardium and epicardium for analysis of lactate and 3H20 content (derived from pre-infused 2-3H-glucose) as an index of glycolytic activity. Maps of 3H20 content showed maximal values in "border" regions with normal conduction and marked heterogeneity in the Maps of tissue lactate showed marked spatial central ischaemic zone. heterogeneity in both epicardium and epicardium but correlated with regional flow. It is suggested that variability in residual regional glycolysis may influence energy dependent "slow response" delayed conduction and thus be a critical determinant of spatial patterns of re-entry at this time. (Supported by the British Heart Foundation).

COIMPARATIVE ANTHRACYCLINE CARDIOTOXICITY AND CO QlO. S. Saman, L.H. Opie, P. Jacobs. MRC Ischaemic Heart Disease Research Unit, Departments of University of Cape Town, South Africa. Medicine & Haematology, Cardiotoxicity limits the use of daunomycin, a potent antimitotic drug. A new analogue, carminomycin, is claimed to have less cardiotoxicity and equal antimitotic activity at lower concentrations. We compared the effects of daunomycin and carminomycin on the isolated working rat heart. One group of hearts was pretreated with QlO. Mechanical function was determined by cardiac output (CO). Release of lactate dehydrogenase (17H) into the medium was taken as a nonspecific index of myocardial cell membrane damage. The results (meansfSEM) at 55 min after addition of drug: Control Daunomycin Carminomycin QlO + carminomycin 17.5umol,/f

10~mol/i?

17.5~mol/E

17.5pmol/E

CO ml,'min 57.9kl.O 32k2.4 44.3+1.6* 24.922.1 24.8k2.2 ATP pmol/g 4.7f0.2 3.2kO.2 3.320.2 2.9+0.2** 4.320.1 5.akO.8 3.2kO.8 PCR )Jmol/g 4.020.4 4.5+4 4.6kO.2 LDH mU/g/mn 7.8f0.8 6.821.0 4.92o.a 4.7t1.3 3.liO.S *P