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Long term hypothermic preservation of the heart: The optimal concentration of calcium in the St. Thomas' Hospital cardioplegic solution
J Mol
361
Cell
Cardiol
21 (Supplement
II) (1989)
LONG TERM HYPOTHERMIC PRESERVATION OF THE HEART : THE OPTIMAL CONCENTRATION OF A Takahashi, D J Chambers, CALCIUM IN THE ST. THOMAS HOSPITAL CARDIOPLEGIC SOLUTION. M V Braimbridge, D J Hearse. Cardiovascular Research, The Rayne Institute, St. Thomas’ Hospital, London, UK. The optimal concentration of calcium in the St Thomas’ Hospital cardioplegic solution (STH) has been reported to be 1.2 mM (Yamamoto et.al, 1984);however, this study used a short period (35min) of normothermic (3PC) ischemia. During heart transplantation, donor hearts are maintained in a globally ischemic state at 4-10% whereas during open-heart surgery the heart is usually kept at lo-15%. We used the isolated perfused working rat heart to investigate the effectof calcium concentration of STH on post-ischemic recoveryafter long-term hypothermic storage. Hearts (n=Wgroup)were aerobically perfused with bicarbonate buffer (20 min) prior to cardioplegic infusion (3 min, 7.5%) and storage for 6h immersed in cardioplegic solution at 7.5%. Hearts were then reperfused in the Langendorff mode (30 min) during which time creatine kinase leakage was measured.The hearts were then converted to the working mode (20 min). and postischemic functional recoverywas measured and expressed as a percent of pre-ischemic control values. (*:p&O5 when comparedwith controlIl.2 mM1) 2.1 2.4 Calcium concentration (mM)in STH 0 0.3 0.6 0.9 1.2 1.5 1.6 Recovery of cardiacoutput(%) 29.3k2.2 46.4k3.5 63.1k4.9' 51.1+8.1 39.9ir7.6 43.8k4.8 45.9ti.2 41.8k4.8 36.5zk6.6 CK leakage(IUI30minheart) 24.2k3.2' 6.5kO.8 5.7kl.0 6.2kO.9 7.8k2.0 7.6kl.3 12.6k4.6 9.8kl.7 9.M2.7 Further investigationsat calcium concentrations of 0.4,0.5,0.6,0.7and 0.8mMrevealed a relativelysharp cut offbetween 0.6and 0.7mM,such that recoveries of cardiac output were 50.4ti.5,56.7+7.5,57.4-15.0,46.4&4.4 and 50.9M.l% respectively. Thus, with rat hearts (i) the optimal calcium concentration for the STHat hypothermia (7.5”~) is in the range 0.5-0.6mM, (ii) increasing the calcium concentration above 0.7 mM had no further deleterious effect on functional recovery.
362MYOCARDIAL PROTECTION WITH BROMO-ADENOSINE MONOPHOSPHATE(Br-AMP)AS AN ADJUNCT TO CARDIOPLEGIC SOLUTION. T. Okamura, N. Nakagawa, A. Suzuki. Deparetment of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan. ATP synthesis after myocardial ischemia is limited by availability of precursor for ATP synthesis, especially adenoscine. The present study was aimed to evaluate the effect of Br-AMP which repertedly blocks adenosine transport across cell membrane by Isolated working rat hearts were used for this inhibiting 5-nucleotidase activity. cardioplegic solution (20 ml4 KCL added to experiment. After 10 min. of working model, Krebs-Henseleit buffer) was infused for 2 min. Hearts were subjected to 30 min. of global ischemia at 37 C followed by 30 min. of reperfusion. Hearts were treated with either 100,uM Br-AMF(B Group,n=9) or Br-AMP vehicle(C Group,n=Y) as adjunct to cardioplegic solution. Hemodynamic functions such as heart rate(HR), systolic pressure(SP), coronary flow(CF), aortic flow(AF) and cardiac output(C0) were assessed at pre and post ischemic conditions. Percentile recovery of AF at 30 min. of reperfusion was 69.8t5.7 % in Group B as compared with 50.6f 6.7% in Group C (~~05). CO was 75.5f4.5% in Group B and 60.3+5.1% in Group C (~~05). HR, SP, and CF were no significant different between Group B and Group C. These results suggest that Bromo-Adenosine Monophosphate protects ischemic myocardium and enhances recovery of post-ischemic cardiac function.
363
NUCLEOSIDE-ENRICHED CARDIOPLEGIA: METABOLIC PROTECTION DURING ISCHEMIA. L.A. Robinson and D.L. Harwood. Departments of Surgery and Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska, USA. The potential for improved myocardial protection during ischemia by substrate-enhanced cardioplegic solution (CPS) was investigated in the isolated working rat heart. Inosine triphosphate (ITP), adenosine triphosphate (ATP), and inosine were evaluated with dose-response studies in St. Thomas’ Hospital CPS. Protection after 60 min of normothermic ischemia was improved with ITP and ATP but greatest with inosine. Optimal Dosane % Recoverv Aortic Flow Control ---21.925.1 ITP O.lmM 41.3+3.6 p
s.121
361
Cell
Cardiol
21 (Supplement
II) (1989)
LONG TERM HYPOTHERMIC PRESERVATION OF THE HEART : THE OPTIMAL CONCENTRATION OF A Takahashi, D J Chambers, CALCIUM IN THE ST. THOMAS HOSPITAL CARDIOPLEGIC SOLUTION. M V Braimbridge, D J Hearse. Cardiovascular Research, The Rayne Institute, St. Thomas’ Hospital, London, UK. The optimal concentration of calcium in the St Thomas’ Hospital cardioplegic solution (STH) has been reported to be 1.2 mM (Yamamoto et.al, 1984);however, this study used a short period (35min) of normothermic (3PC) ischemia. During heart transplantation, donor hearts are maintained in a globally ischemic state at 4-10% whereas during open-heart surgery the heart is usually kept at lo-15%. We used the isolated perfused working rat heart to investigate the effectof calcium concentration of STH on post-ischemic recoveryafter long-term hypothermic storage. Hearts (n=Wgroup)were aerobically perfused with bicarbonate buffer (20 min) prior to cardioplegic infusion (3 min, 7.5%) and storage for 6h immersed in cardioplegic solution at 7.5%. Hearts were then reperfused in the Langendorff mode (30 min) during which time creatine kinase leakage was measured.The hearts were then converted to the working mode (20 min). and postischemic functional recoverywas measured and expressed as a percent of pre-ischemic control values. (*:p&O5 when comparedwith controlIl.2 mM1) 2.1 2.4 Calcium concentration (mM)in STH 0 0.3 0.6 0.9 1.2 1.5 1.6 Recovery of cardiacoutput(%) 29.3k2.2 46.4k3.5 63.1k4.9' 51.1+8.1 39.9ir7.6 43.8k4.8 45.9ti.2 41.8k4.8 36.5zk6.6 CK leakage(IUI30minheart) 24.2k3.2' 6.5kO.8 5.7kl.0 6.2kO.9 7.8k2.0 7.6kl.3 12.6k4.6 9.8kl.7 9.M2.7 Further investigationsat calcium concentrations of 0.4,0.5,0.6,0.7and 0.8mMrevealed a relativelysharp cut offbetween 0.6and 0.7mM,such that recoveries of cardiac output were 50.4ti.5,56.7+7.5,57.4-15.0,46.4&4.4 and 50.9M.l% respectively. Thus, with rat hearts (i) the optimal calcium concentration for the STHat hypothermia (7.5”~) is in the range 0.5-0.6mM, (ii) increasing the calcium concentration above 0.7 mM had no further deleterious effect on functional recovery.
362MYOCARDIAL PROTECTION WITH BROMO-ADENOSINE MONOPHOSPHATE(Br-AMP)AS AN ADJUNCT TO CARDIOPLEGIC SOLUTION. T. Okamura, N. Nakagawa, A. Suzuki. Deparetment of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan. ATP synthesis after myocardial ischemia is limited by availability of precursor for ATP synthesis, especially adenoscine. The present study was aimed to evaluate the effect of Br-AMP which repertedly blocks adenosine transport across cell membrane by Isolated working rat hearts were used for this inhibiting 5-nucleotidase activity. cardioplegic solution (20 ml4 KCL added to experiment. After 10 min. of working model, Krebs-Henseleit buffer) was infused for 2 min. Hearts were subjected to 30 min. of global ischemia at 37 C followed by 30 min. of reperfusion. Hearts were treated with either 100,uM Br-AMF(B Group,n=9) or Br-AMP vehicle(C Group,n=Y) as adjunct to cardioplegic solution. Hemodynamic functions such as heart rate(HR), systolic pressure(SP), coronary flow(CF), aortic flow(AF) and cardiac output(C0) were assessed at pre and post ischemic conditions. Percentile recovery of AF at 30 min. of reperfusion was 69.8t5.7 % in Group B as compared with 50.6f 6.7% in Group C (~~05). CO was 75.5f4.5% in Group B and 60.3+5.1% in Group C (~~05). HR, SP, and CF were no significant different between Group B and Group C. These results suggest that Bromo-Adenosine Monophosphate protects ischemic myocardium and enhances recovery of post-ischemic cardiac function.
363
NUCLEOSIDE-ENRICHED CARDIOPLEGIA: METABOLIC PROTECTION DURING ISCHEMIA. L.A. Robinson and D.L. Harwood. Departments of Surgery and Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska, USA. The potential for improved myocardial protection during ischemia by substrate-enhanced cardioplegic solution (CPS) was investigated in the isolated working rat heart. Inosine triphosphate (ITP), adenosine triphosphate (ATP), and inosine were evaluated with dose-response studies in St. Thomas’ Hospital CPS. Protection after 60 min of normothermic ischemia was improved with ITP and ATP but greatest with inosine. Optimal Dosane % Recoverv Aortic Flow Control ---21.925.1 ITP O.lmM 41.3+3.6 p
s.121