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Gene expression is markedly changed in stunned and preconditioned myocardium
J Mel Cell Cardiol 24 (Supplement O-16
II) (1992)
ELECTRICAL STUNNING AND METABOLIC VIABlLITY OF REPERFUSED MYOCARDILJM Mamoru Miura, Takashi Saito, and Hitoshi Matsu-oka. Second Dept. of Internal Medicine, Akita University School of Medicine, Akita, Japan In order to know the pathphysiology of electrical stunning , continuity and accumulation of ischemic myocardial damage after reperfusion was studied in open-chest dogs, with epicardial surface ECG (AC-, DC-coupled), regional myocardial function (% systolic shortening (%SS)), and myocardial metabolism (tissue PCO,, pH and extracellular K concentration(Ke)). LAD was occluded for 2min (Trial l:Tl), following by 15min of reperfusion. After that, in control group(G-C) reperfusion was continued for another 95min, while in others 5min(G-5) or 15min(G-15) ofLAD occlusion followed by 9Omin or 8Omin of reperfusion was introduced. Then, LAD was again occluded for 2min (T2) in all groups. The differences in all variables above between Tl and T2 were compared in all 3 groups. As the results, reduction of %SS and ST deviation accompanied by decrease of PCO,, pH and Ke changes during T2 was noted in G-5 and G- 15. Correlation between Ke change and ST elevation was observed in both groups. Therefore, electrical stunning consisted of two components. One was characterized as altered metabolic response, such as decrease of tissue PCO, and proton production which was related to reduced Ke elevation. The other consisted of altered electrical properties of cardiac membrane. This phenomenon, continuity of ‘latent’ myocardial damage, was thought to be very important to myocardial stunning and preconditioning.
0-17 GENE EXPRESSION
IS MARKEDLY CHANGED IN STUNNED AND PRECONDITIONED MYOCARDKJM. Wolfgan S&per, Thomas Brand, Oliver Fm6, Hari S. Sharma, Rend Zimmermatm, Pieter Verdouw Janusx An&e; hfax-Plan&Institute Dad Nauheim, F.R.G. Brief corona& occlusions alter the isehemic tole&ce of the heart in favor of prolonged survival. We ah&d the question whether these beneficial effects are caused or accompanied by changes in gene expression. We oc&ded the distal LAD for 2xlOmin (interrupted by 3Omin of reperfusion) in anesthetized open-cheated pigs (n=lO) where regional function was reduced to 10 96 of normal. RNA was extracted from stunued and normal myoeardium, electrophomsed and blotted on Nylon membranes. Northern blot hybridization (GAPDH used as a reference) showed: lt- Ca2+-ATPase (porcine probe) t - Ubiquitin (porcine probe) t Ubiquitin AE (porcine probe) - Calsequestrin (porcine probe) - Phospholamban (porcine probe) t - c-fos (rat probe) t -+ - Cahnodulin (porcine probe) - c-myc (human probe) t t - Hsp 70 (human probe) t - egr-1 (mouse probe) t= newspecies) --unchanged. 0 = uPfegulated, We conchuie that brief coronary occlusions lead to a generalized stress response (c-fos, c-myc, egr-1), to regulatory changes (Ca 2+-binding proteins), but also to repair processe s (hsp 70, ubiquitin).
I
O-16
EFFECT OF INCREASED H+ BUFFERING CAPACITY OF PERFUSATE ON FUNCTIONAL RECOVERY OF STUNNED MYOCARDIDM IN ISOLATED RAT HEART. M. Tani, K. Shinmura, Y. Ebihara, Y. Asakura, S. Handa and Y. Nakamura. Keio University School of Medicine, Tokyo Japan This study investigated whether perfusate with an increased H+ buffering capacity Hearts were preperfused with would reduce myocardial stunning in isolated rat heart. oxygenated buffer (pH 7.4) containing either 1.25 or 2.5 mM free Ca2+ and 100 ?&I of either sucrose (S) or Hepes (H) for 10 min followed by 20 min of total ischemia and 30 min of reperfusion. In some hearts hypoxic buffer was used for 10 min of preperfusion to determine whether an additional protective effect can be obtained by Preperfusion with oxygenated buffer containing depressing glycolysis during ischemia. H and 1.25 or 2.5 mM Ca2+ caused an increase in high energy phosphate recovery and an increase in left ventricular function and a decrease in myocardial 45Ca2+ uptake. Hypoxic preperfusion with S and 1.25 mM Ca2+ provided a similar protective effect whereas no protective effect was observed when [Ca2+] was raised to 2.5 mM. Interestingly the protective effect of each intervention was lost when hypoxic preperfusion was combined with H and 1.25 mM Ca2+. These observations suggest that the perfusate with the increased H + buffering capacity improved funcitonal recovery and energy metabolism, and reduced Ca2+ overload independently of buffer [Ca'+]. The combination of hypoxic preperfusion with H canceled the protective effect of each intervention on myocardial stunning by unknown mechanism(s).
II) (1992)
ELECTRICAL STUNNING AND METABOLIC VIABlLITY OF REPERFUSED MYOCARDILJM Mamoru Miura, Takashi Saito, and Hitoshi Matsu-oka. Second Dept. of Internal Medicine, Akita University School of Medicine, Akita, Japan In order to know the pathphysiology of electrical stunning , continuity and accumulation of ischemic myocardial damage after reperfusion was studied in open-chest dogs, with epicardial surface ECG (AC-, DC-coupled), regional myocardial function (% systolic shortening (%SS)), and myocardial metabolism (tissue PCO,, pH and extracellular K concentration(Ke)). LAD was occluded for 2min (Trial l:Tl), following by 15min of reperfusion. After that, in control group(G-C) reperfusion was continued for another 95min, while in others 5min(G-5) or 15min(G-15) ofLAD occlusion followed by 9Omin or 8Omin of reperfusion was introduced. Then, LAD was again occluded for 2min (T2) in all groups. The differences in all variables above between Tl and T2 were compared in all 3 groups. As the results, reduction of %SS and ST deviation accompanied by decrease of PCO,, pH and Ke changes during T2 was noted in G-5 and G- 15. Correlation between Ke change and ST elevation was observed in both groups. Therefore, electrical stunning consisted of two components. One was characterized as altered metabolic response, such as decrease of tissue PCO, and proton production which was related to reduced Ke elevation. The other consisted of altered electrical properties of cardiac membrane. This phenomenon, continuity of ‘latent’ myocardial damage, was thought to be very important to myocardial stunning and preconditioning.
0-17 GENE EXPRESSION
IS MARKEDLY CHANGED IN STUNNED AND PRECONDITIONED MYOCARDKJM. Wolfgan S&per, Thomas Brand, Oliver Fm6, Hari S. Sharma, Rend Zimmermatm, Pieter Verdouw Janusx An&e; hfax-Plan&Institute Dad Nauheim, F.R.G. Brief corona& occlusions alter the isehemic tole&ce of the heart in favor of prolonged survival. We ah&d the question whether these beneficial effects are caused or accompanied by changes in gene expression. We oc&ded the distal LAD for 2xlOmin (interrupted by 3Omin of reperfusion) in anesthetized open-cheated pigs (n=lO) where regional function was reduced to 10 96 of normal. RNA was extracted from stunued and normal myoeardium, electrophomsed and blotted on Nylon membranes. Northern blot hybridization (GAPDH used as a reference) showed: lt- Ca2+-ATPase (porcine probe) t - Ubiquitin (porcine probe) t Ubiquitin AE (porcine probe) - Calsequestrin (porcine probe) - Phospholamban (porcine probe) t - c-fos (rat probe) t -+ - Cahnodulin (porcine probe) - c-myc (human probe) t t - Hsp 70 (human probe) t - egr-1 (mouse probe) t= newspecies) --unchanged. 0 = uPfegulated, We conchuie that brief coronary occlusions lead to a generalized stress response (c-fos, c-myc, egr-1), to regulatory changes (Ca 2+-binding proteins), but also to repair processe s (hsp 70, ubiquitin).
I
O-16
EFFECT OF INCREASED H+ BUFFERING CAPACITY OF PERFUSATE ON FUNCTIONAL RECOVERY OF STUNNED MYOCARDIDM IN ISOLATED RAT HEART. M. Tani, K. Shinmura, Y. Ebihara, Y. Asakura, S. Handa and Y. Nakamura. Keio University School of Medicine, Tokyo Japan This study investigated whether perfusate with an increased H+ buffering capacity Hearts were preperfused with would reduce myocardial stunning in isolated rat heart. oxygenated buffer (pH 7.4) containing either 1.25 or 2.5 mM free Ca2+ and 100 ?&I of either sucrose (S) or Hepes (H) for 10 min followed by 20 min of total ischemia and 30 min of reperfusion. In some hearts hypoxic buffer was used for 10 min of preperfusion to determine whether an additional protective effect can be obtained by Preperfusion with oxygenated buffer containing depressing glycolysis during ischemia. H and 1.25 or 2.5 mM Ca2+ caused an increase in high energy phosphate recovery and an increase in left ventricular function and a decrease in myocardial 45Ca2+ uptake. Hypoxic preperfusion with S and 1.25 mM Ca2+ provided a similar protective effect whereas no protective effect was observed when [Ca2+] was raised to 2.5 mM. Interestingly the protective effect of each intervention was lost when hypoxic preperfusion was combined with H and 1.25 mM Ca2+. These observations suggest that the perfusate with the increased H + buffering capacity improved funcitonal recovery and energy metabolism, and reduced Ca2+ overload independently of buffer [Ca'+]. The combination of hypoxic preperfusion with H canceled the protective effect of each intervention on myocardial stunning by unknown mechanism(s).