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Ultrastructural and cytochemical effect of PAF-acether and its antagonist BN-52021 on the guinea pig heart
J
Mol
PFlg
Cell
Cardiol
22 (Supplement
III)
(1990)
MECHANICAL UNLOADING OF THE HEART DUAlNO l!?CHEMA AND REPEAFUSION FAILS TO WIT INFARCT SIZE IN THE RABBIT. Allson C. Cave, *John G. Klngme Jr, David J. Hearse. CardovascularResearch,The Rayne Institute,St. Thomas’Hospital,
London,U.K.and *QuebecHeart Institute,Lava1Hospital,Quebec,Canada. it hasbeen suggestedthat unloadingthe heartduring ischaemiaand/or reperlusionmaylimit infarctsize.We have investigated this pessibilii using heterotcqichearttransplantiin wfthregional ischaemiawherebythe transplantedheart is unloadedand the recipient’sown heartservesas a loaded control.Inthis waythe extentof myocardialinfarctionwascomparedin two heartsin the same animal under similarexperimentalcondilions. Donor heartswere excised,arrestedwith St. Thomas’Hosptalcardiiplegic solutionand maintained at 15% for 1 h during whichtimethey weretransplantedintothe necksof recipientrabbits(usingend to skie anastomosesof &nor aortato recipientcarotidarteryanddonor pulmonaryarteryto recipientjugularvein).Oneday later(when functionand metabolismhad recoveredin the transplantedhearts)rabbitswerere-anaesthetisedand the left circumflexcoronary artery in both the transolantedand recfoienthearts.After 1 h of reoional ischaemiaheartswere reoerfusedfor 3 h. The _ lioated L&led Unloided transplanted heart was paced at 205bpm throughout to overcome any Risk zone (cml) 3.4io.4 3.Mo.3 differencesin heart rate due to denewation.Infarctsize was assessedby Vol. of necrosis (cml) 2.4ti.3 2.2io.2 triphenyltetrazoliumchloridestainingand wasexpressedasa percentageof Infarct size (%) 75zt6 73*4 the risk zone (as measuredby autoradiiraphy) and the left ventricular LV welghf (g) 4.4M.2 volume. As shown, no significantdkferenceswere seen in any of the 5.w.3 Risk zone (% LV) 29.9k3.2 29.2236 measuredparametersbetweentheloadedandunbadedhearts. Inconclusion, Vol. of necrosis (%LV) 21.&l .7 21.ztl.9 our resultssuggestthatthe amountof workperformedby the heartdoesnot appearto be a principalfactor in determiningultimateinfarctsize. Data are meanfsem (n=6)
pF20
ASSOCIATION
B33!WER?
ANTIANGINAL
AND
CARDIOPROTECTIVE
ACTIVITY
OF
PF21
ULTRASTRUCTURAL AND CYTOCHRMICAL EFFECT OF PAF-ACETHER AND ITS ANTAGONIST BN-52021 ON THE GUINEA PIG HEART of Pharmacology and Forensic Susanna &ertess,Istvan BaloghTValeria Kecskem&i.Depts. Medicine, Semmelweis University of Medicine, Budapest,Hungary. Progressive calcium and nickel cytocheaical changes have been quantitated in muscle of guinea pig heart by PAF-acether/Sigma/ and its antagonist BN-52021/the gift of P. Braquet/.Hearts were perfused according to Langendorff and they were incubated in Tyrode solution containing 10e7M PAF-acether alone or after pretreatment of 10-k BN52021.Samples were taken for routine electrnmicroscopic technlque,for calcium cytochemistry/K pyroantimonate,Pb acetate/and nickel cytochemistry/dimethylglioxime/.PAF caused the following changes:a thrombocytic adhesion and aggregation in capillary; separation between the coronary endothelial and smooth muscle layers; ischemic-like BN-52021 prevented the intraalteration in perivascularly localated muscle cells. cellular and intramitochondrial swelliug,the changes in permeability,the separation between eodothelial and middle layers of coronary caused by PAF. PAF resulted in a depletion of calcium deposits from the cytoplasma and sarcolemma.The latter depletion can be prevented by BN-52021.Ni-dimethylglioxime canplexes could be observed in the vessel lumina,platelets,endothelial cellular pynocytic vesicles,smooth muscle layers of coronary artery,SR and subsarcolemmalvesicles wall by PAF perfusion.BN-52021 was not able to prevent the appereance of Ni particles but it could decrease their number This work was supported by OTKA Eu.Min.622.
ENERGYYIELDING AGENTS Vladimir v.Gatsura,Yurij B.RosonoV, Leo W.Sernov. National Scientific Centre of Biologically Active Compounds. Moscow Region,142450, USSR. Antianginal effect of drugs was estimated according to their influence on dynamics of *lischemicll ECG after gradual compression of coronar? artery of the nonanaesthetized rabbits. Cardloprotective activity was determined by the restriction of myccardial infarct zone 4 hours after occlusion of the coronary artery of rats. All drugs were administered intravenous1 Sodium malate (100 m&kg), ascorbic acid f5 mg/kg 5' , dehydroascorbit acid (5 mg/kgl were active as sntianginal end cardioprotective drugs. Fructose-1,6-diphoephate (100 mg/kg) and qytochrome C (20 mg/kg) decreased sizes of infarct zone to 59 and 5% of control value respectively.without any positive effects on angina1 syndrome. Antienginal and cardioprotective activity of noted above agents correlates with sarcolemmal permeability of ischemic cardiomyocytea.
S.62
Mol
PFlg
Cell
Cardiol
22 (Supplement
III)
(1990)
MECHANICAL UNLOADING OF THE HEART DUAlNO l!?CHEMA AND REPEAFUSION FAILS TO WIT INFARCT SIZE IN THE RABBIT. Allson C. Cave, *John G. Klngme Jr, David J. Hearse. CardovascularResearch,The Rayne Institute,St. Thomas’Hospital,
London,U.K.and *QuebecHeart Institute,Lava1Hospital,Quebec,Canada. it hasbeen suggestedthat unloadingthe heartduring ischaemiaand/or reperlusionmaylimit infarctsize.We have investigated this pessibilii using heterotcqichearttransplantiin wfthregional ischaemiawherebythe transplantedheart is unloadedand the recipient’sown heartservesas a loaded control.Inthis waythe extentof myocardialinfarctionwascomparedin two heartsin the same animal under similarexperimentalcondilions. Donor heartswere excised,arrestedwith St. Thomas’Hosptalcardiiplegic solutionand maintained at 15% for 1 h during whichtimethey weretransplantedintothe necksof recipientrabbits(usingend to skie anastomosesof &nor aortato recipientcarotidarteryanddonor pulmonaryarteryto recipientjugularvein).Oneday later(when functionand metabolismhad recoveredin the transplantedhearts)rabbitswerere-anaesthetisedand the left circumflexcoronary artery in both the transolantedand recfoienthearts.After 1 h of reoional ischaemiaheartswere reoerfusedfor 3 h. The _ lioated L&led Unloided transplanted heart was paced at 205bpm throughout to overcome any Risk zone (cml) 3.4io.4 3.Mo.3 differencesin heart rate due to denewation.Infarctsize was assessedby Vol. of necrosis (cml) 2.4ti.3 2.2io.2 triphenyltetrazoliumchloridestainingand wasexpressedasa percentageof Infarct size (%) 75zt6 73*4 the risk zone (as measuredby autoradiiraphy) and the left ventricular LV welghf (g) 4.4M.2 volume. As shown, no significantdkferenceswere seen in any of the 5.w.3 Risk zone (% LV) 29.9k3.2 29.2236 measuredparametersbetweentheloadedandunbadedhearts. Inconclusion, Vol. of necrosis (%LV) 21.&l .7 21.ztl.9 our resultssuggestthatthe amountof workperformedby the heartdoesnot appearto be a principalfactor in determiningultimateinfarctsize. Data are meanfsem (n=6)
pF20
ASSOCIATION
B33!WER?
ANTIANGINAL
AND
CARDIOPROTECTIVE
ACTIVITY
OF
PF21
ULTRASTRUCTURAL AND CYTOCHRMICAL EFFECT OF PAF-ACETHER AND ITS ANTAGONIST BN-52021 ON THE GUINEA PIG HEART of Pharmacology and Forensic Susanna &ertess,Istvan BaloghTValeria Kecskem&i.Depts. Medicine, Semmelweis University of Medicine, Budapest,Hungary. Progressive calcium and nickel cytocheaical changes have been quantitated in muscle of guinea pig heart by PAF-acether/Sigma/ and its antagonist BN-52021/the gift of P. Braquet/.Hearts were perfused according to Langendorff and they were incubated in Tyrode solution containing 10e7M PAF-acether alone or after pretreatment of 10-k BN52021.Samples were taken for routine electrnmicroscopic technlque,for calcium cytochemistry/K pyroantimonate,Pb acetate/and nickel cytochemistry/dimethylglioxime/.PAF caused the following changes:a thrombocytic adhesion and aggregation in capillary; separation between the coronary endothelial and smooth muscle layers; ischemic-like BN-52021 prevented the intraalteration in perivascularly localated muscle cells. cellular and intramitochondrial swelliug,the changes in permeability,the separation between eodothelial and middle layers of coronary caused by PAF. PAF resulted in a depletion of calcium deposits from the cytoplasma and sarcolemma.The latter depletion can be prevented by BN-52021.Ni-dimethylglioxime canplexes could be observed in the vessel lumina,platelets,endothelial cellular pynocytic vesicles,smooth muscle layers of coronary artery,SR and subsarcolemmalvesicles wall by PAF perfusion.BN-52021 was not able to prevent the appereance of Ni particles but it could decrease their number This work was supported by OTKA Eu.Min.622.
ENERGYYIELDING AGENTS Vladimir v.Gatsura,Yurij B.RosonoV, Leo W.Sernov. National Scientific Centre of Biologically Active Compounds. Moscow Region,142450, USSR. Antianginal effect of drugs was estimated according to their influence on dynamics of *lischemicll ECG after gradual compression of coronar? artery of the nonanaesthetized rabbits. Cardloprotective activity was determined by the restriction of myccardial infarct zone 4 hours after occlusion of the coronary artery of rats. All drugs were administered intravenous1 Sodium malate (100 m&kg), ascorbic acid f5 mg/kg 5' , dehydroascorbit acid (5 mg/kgl were active as sntianginal end cardioprotective drugs. Fructose-1,6-diphoephate (100 mg/kg) and qytochrome C (20 mg/kg) decreased sizes of infarct zone to 59 and 5% of control value respectively.without any positive effects on angina1 syndrome. Antienginal and cardioprotective activity of noted above agents correlates with sarcolemmal permeability of ischemic cardiomyocytea.
S.62