- Email: [email protected]
In vivo antibody therapy for intercellular adhesion molecules limits infarct size in myocardial ischemia-reperfusion
J hlol
Crll
(hrdiol
23 (Supplemmt
II) ( 1Wl )
16
IN VIVO ANTIBODY THERAPY FOR INTERCELLULAR ALJHESION MOLECULES LmIMITti INFARC'I ? i SI,:l. IN MYOCARDIAL ISCHEMIA-REPERFUSION. T. Yamazakt 11 , Y. Svko 11 , T. 'Tdmdt,inl ', 2) Thy 'Third Departmerlt ot Irrterrldl Meiiv 111., , K. Okumura 31, Y , Yazakl'). M. Mlyasaka of Immunology, Tokyo Metri7rpol;;ar Inst~tlite <,I Unlverslty of Tokyo 1) , Department Medical Scxnce2), Department r~f Immunology, Juntendo Unlvijrslty , l'akyci, .Japor Leukocytes play a crltlcal role ln myocardlal lschemla-reperfuslon lrl]ury ,+,riri PrnLobar~lt,~>I the essential first step 1s adherence to capillary endothelld. anestheslzed rats were sub]ected to 30 mlrl nt left ariterlor dt,scerldlrlq cnron?r'/ artery occlusion followed by 48 hrs iif reperfuslor,. w:e fOUild l,y slgnlflcantly enhanced lmmunofluoroescence that myocardial ischemia-reperfuslon the expresslorl of CD54 in capllldry endothella and that most of the inflltratlllg MAbs aqairrst leukocytes were positive for CDlla, CDllb+c and CD18. Next, functional epltope of CDlla (WT.11, CDllb+c (0X42), CD18 (WT.31 and CD54 (lA29) were given (5mg/kg) as a bolus I.". MAb-trr3tc,d 5 nun before myocardial lscheml
17
EFFECTS OF ANTIARRHYTHMIC AGENTS CLASSIFIED AS CLASS III GROUP ON ISCHEMIAINDUCED MYOCARDIAL DAMAGE IN CANINE HEARTS. Hanakl, T. Ogawa. K. Take*. S. Suglyama**. T. Ozawa**. Y. Departments of internal Med~clne, Surgical Operation Center+ and Blomedlcal Chemistry'**, Faculty of Medicine, Un1versit.y of Nagoya, Nagoya 466, Japan. To clarify the cardloprotectlve effects of antiarrhythmlc agents classified as class III on lschemlc hearts, 2 hour occluzlon of coronary artery was performed after either physiological saline (iv). amlodarone 1~1, (3 w/kg sotalol (1 mg/kg 1~). or E-4031 (2.5 ug/kg/min cll) admin,stratlon. Electrocardiogram was monitored throughout the experiment. Heart mitochondrla were prepared from both the lschemlc and nonlschemlc areas, and their function was estimated polarographically. Activltles of the lysosomal enzymes, N-acetyl-Bglucosaminidase Two hour and a-glucuronidase, were measured in each fraction. occlusion induced ventricular arrhythmias, and all drugs greatly suppressed the of arrhythmias. development All drugs significantly protected mltochondria against lschemia, and prevented lschemia-induced leakage of lysosomal enzymes. These results Indicate that antlarrhythmic agents classified as class III show cardloprotective effects, which might participate in their ant,arrhythm?c effect.
ia
THE EFFECT OF LP-805 ON THE ISCHEMIC MYOCARDIAL ACIDOSIS IN DOGS. K. T. Morimoto', T. Shiba#, M. Tsujitani*, Y. Abiko. Ichihara, Department of Pharmacology, Asahikawa Medical College, Asahikaswa, *POLA Pharmaceutical R & D Laboratory, Yokohama, #Biological Research Laboratorles, Lederle (Japan), Shikl, Japan. We examined whether LP-805, a newly developed coronary attenuates the myocardial acidosis induced by Ischemla. vasodiiator, Ischemia was induced by occluding the left anterior descending coronary artery (LAD) in anesthetized open-chest dogs. LAD flow was artificially reduced to about l/3 of the original flow. Hyocardial pH micro pH electrode inserted into the left was measured by a glass ventricle perfused by the occluded artery. Myocardial pH was decreased from about 7.5 to about 6.9 after the onset of ischemia and was kept at the low level until the occluded artery was released. After 30 min of ischemia, either the vehicle or 10, 30, or 100 ug/kg of ~~-805 was injected iv. LP-805 attenuated the decrease in myocardlal ph' induced by ischemia in a dose dependent manner. In conclusion, LP-805 may reduce the lschemic influence on the myocardium. s.22
Crll
(hrdiol
23 (Supplemmt
II) ( 1Wl )
16
IN VIVO ANTIBODY THERAPY FOR INTERCELLULAR ALJHESION MOLECULES LmIMITti INFARC'I ? i SI,:l. IN MYOCARDIAL ISCHEMIA-REPERFUSION. T. Yamazakt 11 , Y. Svko 11 , T. 'Tdmdt,inl ', 2) Thy 'Third Departmerlt ot Irrterrldl Meiiv 111., , K. Okumura 31, Y , Yazakl'). M. Mlyasaka of Immunology, Tokyo Metri7rpol;;ar Inst~tlite <,I Unlverslty of Tokyo 1) , Department Medical Scxnce2), Department r~f Immunology, Juntendo Unlvijrslty , l'akyci, .Japor Leukocytes play a crltlcal role ln myocardlal lschemla-reperfuslon lrl]ury ,+,riri PrnLobar~lt,~>I the essential first step 1s adherence to capillary endothelld. anestheslzed rats were sub]ected to 30 mlrl nt left ariterlor dt,scerldlrlq cnron?r'/ artery occlusion followed by 48 hrs iif reperfuslor,. w:e fOUild l,y slgnlflcantly enhanced lmmunofluoroescence that myocardial ischemia-reperfuslon the expresslorl of CD54 in capllldry endothella and that most of the inflltratlllg MAbs aqairrst leukocytes were positive for CDlla, CDllb+c and CD18. Next, functional epltope of CDlla (WT.11, CDllb+c (0X42), CD18 (WT.31 and CD54 (lA29) were given (5mg/kg) as a bolus I.". MAb-trr3tc,d 5 nun before myocardial lscheml
17
EFFECTS OF ANTIARRHYTHMIC AGENTS CLASSIFIED AS CLASS III GROUP ON ISCHEMIAINDUCED MYOCARDIAL DAMAGE IN CANINE HEARTS. Hanakl, T. Ogawa. K. Take*. S. Suglyama**. T. Ozawa**. Y. Departments of internal Med~clne, Surgical Operation Center+ and Blomedlcal Chemistry'**, Faculty of Medicine, Un1versit.y of Nagoya, Nagoya 466, Japan. To clarify the cardloprotectlve effects of antiarrhythmlc agents classified as class III on lschemlc hearts, 2 hour occluzlon of coronary artery was performed after either physiological saline (iv). amlodarone 1~1, (3 w/kg sotalol (1 mg/kg 1~). or E-4031 (2.5 ug/kg/min cll) admin,stratlon. Electrocardiogram was monitored throughout the experiment. Heart mitochondrla were prepared from both the lschemlc and nonlschemlc areas, and their function was estimated polarographically. Activltles of the lysosomal enzymes, N-acetyl-Bglucosaminidase Two hour and a-glucuronidase, were measured in each fraction. occlusion induced ventricular arrhythmias, and all drugs greatly suppressed the of arrhythmias. development All drugs significantly protected mltochondria against lschemia, and prevented lschemia-induced leakage of lysosomal enzymes. These results Indicate that antlarrhythmic agents classified as class III show cardloprotective effects, which might participate in their ant,arrhythm?c effect.
ia
THE EFFECT OF LP-805 ON THE ISCHEMIC MYOCARDIAL ACIDOSIS IN DOGS. K. T. Morimoto', T. Shiba#, M. Tsujitani*, Y. Abiko. Ichihara, Department of Pharmacology, Asahikawa Medical College, Asahikaswa, *POLA Pharmaceutical R & D Laboratory, Yokohama, #Biological Research Laboratorles, Lederle (Japan), Shikl, Japan. We examined whether LP-805, a newly developed coronary attenuates the myocardial acidosis induced by Ischemla. vasodiiator, Ischemia was induced by occluding the left anterior descending coronary artery (LAD) in anesthetized open-chest dogs. LAD flow was artificially reduced to about l/3 of the original flow. Hyocardial pH micro pH electrode inserted into the left was measured by a glass ventricle perfused by the occluded artery. Myocardial pH was decreased from about 7.5 to about 6.9 after the onset of ischemia and was kept at the low level until the occluded artery was released. After 30 min of ischemia, either the vehicle or 10, 30, or 100 ug/kg of ~~-805 was injected iv. LP-805 attenuated the decrease in myocardlal ph' induced by ischemia in a dose dependent manner. In conclusion, LP-805 may reduce the lschemic influence on the myocardium. s.22