TY - JOUR
T1 - Perfusate sodium during ischemia modifies post-ischemic functional and metabolic recovery in the rabbit heart
AU - Renlund, Dale G.
AU - Gerstenblith, Gary
AU - Lakatta, Edward G.
AU - Jacobus, William E.
AU - Kallman, Clayton H.
AU - Weisfeldt, Myron L.
N1 - Funding Information:
Complete functional and metabolic recovery does not occur if the myocardium is reper-fused following 30 to 60 min of severe ischemia \[2, 3, 13, 19, 20, 27, 30\]. Attempts to improve recovery have been directed towards main- taining intracellular conditions as close to normal as possible during ischemia. Myocardial ischemia is accompanied in part by a fall in intracellular pH and high energy phosphates and interventions during ischemia which result in increased intracellular pH and high * This study was supported in part by National Heart, Lung, and Blood Institute Specialized Center of Research Grant No. P-50-HL 17655-08, Bethesda, Maryland and Coronary Heart Disease Research, a program of the American Health Assistance Foundation. Computational assistance was received from CLINFO, sponsored by a grant (5 M01 RR35-20) from the National Institutes of Health. t To whom correspondence should be addressed at: Carnegie 591, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21205, USA.
PY - 1984/9
Y1 - 1984/9
N2 - Metabolic and functional recovery following 60 minutes of low flow (0.1 ml/min) ischemia were compared in rabbit hearts perfused with normal sodium and potassium, low sodium (120 mm NaCl replaced by 120 mm LiCl), or zero potassium perfusate during ischemia. During the control, pre-ischemic, and reperfusion periods, all hearts were perfused identically with normal sodium and potassium. 31P NMR was used to monitor intracellular pH (pHi), ATP, and phosphocreatine (PCr). Developed pressure, end diastolic pressure, pHi, and the integrated areas of ATP and PCr were equivalent in the three groups in the pre-ischemic period. The fall in pHi, PCr, ATP, and developed pressure and the rise in end diastolic pressure during 60 min ischemia also did not differ among the three groups. In contrast to the lack of an effect of perfusate sodium and potassium on the decline in parameters of metabolism and function during ischemia, there was a marked difference in the recovery of these indices during reperfusion. Hearts perfused with low sodium during ischemia exhibited the best recovery (expressed as percent of control) of developed pressure (95±4%), PCr (106±6%), and ATP (51±2%) and the smallest rise in end diastolic pressure (229±50%); hearts perfused with normal sodium and potassium during ischemia had intermediate recovery values for developed pressure (53±10%), PCr (78±9%), ATP (45±4%) and end diastolic pressure (487±73%) and the hearts perfused with zero potassium solution during ischemia exhibited the poorest recovery of developed pressure (23±6%), PCr (49±6%), ATP (39±5%) and end diastolic pressure (968±185%). These results indicate that interventions which do not alter PCr, ATP or pHi during ischemia but which can diminish or enhance intracellular sodium accumulation can respectively improve or impair metabolic and functional recovery during reperfusion. The most likely mechanism to explain these findings is a sodium-dependent calcium influx occurring during reperfusion. This suggests that interventions which lower intracellular sodium or inhibit or reverse the direction of sodium-calcium exchange at the onset of reperfusion may lessen injury following reperfusion of ischemic myocardium.
AB - Metabolic and functional recovery following 60 minutes of low flow (0.1 ml/min) ischemia were compared in rabbit hearts perfused with normal sodium and potassium, low sodium (120 mm NaCl replaced by 120 mm LiCl), or zero potassium perfusate during ischemia. During the control, pre-ischemic, and reperfusion periods, all hearts were perfused identically with normal sodium and potassium. 31P NMR was used to monitor intracellular pH (pHi), ATP, and phosphocreatine (PCr). Developed pressure, end diastolic pressure, pHi, and the integrated areas of ATP and PCr were equivalent in the three groups in the pre-ischemic period. The fall in pHi, PCr, ATP, and developed pressure and the rise in end diastolic pressure during 60 min ischemia also did not differ among the three groups. In contrast to the lack of an effect of perfusate sodium and potassium on the decline in parameters of metabolism and function during ischemia, there was a marked difference in the recovery of these indices during reperfusion. Hearts perfused with low sodium during ischemia exhibited the best recovery (expressed as percent of control) of developed pressure (95±4%), PCr (106±6%), and ATP (51±2%) and the smallest rise in end diastolic pressure (229±50%); hearts perfused with normal sodium and potassium during ischemia had intermediate recovery values for developed pressure (53±10%), PCr (78±9%), ATP (45±4%) and end diastolic pressure (487±73%) and the hearts perfused with zero potassium solution during ischemia exhibited the poorest recovery of developed pressure (23±6%), PCr (49±6%), ATP (39±5%) and end diastolic pressure (968±185%). These results indicate that interventions which do not alter PCr, ATP or pHi during ischemia but which can diminish or enhance intracellular sodium accumulation can respectively improve or impair metabolic and functional recovery during reperfusion. The most likely mechanism to explain these findings is a sodium-dependent calcium influx occurring during reperfusion. This suggests that interventions which lower intracellular sodium or inhibit or reverse the direction of sodium-calcium exchange at the onset of reperfusion may lessen injury following reperfusion of ischemic myocardium.
KW - Intracellular pH
KW - Ischemia
KW - Myocardial energy metabolism
KW - Reperfusion of ischemic myocardium
KW - Sodium-dependent calcium influx
UR - http://www.scopus.com/inward/record.url?scp=0021591776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021591776&partnerID=8YFLogxK
U2 - 10.1016/S0022-2828(84)80003-6
DO - 10.1016/S0022-2828(84)80003-6
M3 - Article
C2 - 6492172
AN - SCOPUS:0021591776
SN - 0022-2828
VL - 16
SP - 795
EP - 801
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 9
ER -