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Cardioprotection by A1-adenosine mediated effects
J Mol
Cell
Cardiol
22 (Supplement
III)
(1990)
plasma proteins (necessitating very high doses) and to its oral bioavailability. The more recent analogs of mioflazine, such as R 75 231, are much more appropriate, maybe unique, prove - or disprove - the concept.
Ljj
;;:;;;;y:
J Schrader, Germany.
;;;EVOt;;ARDIAL
Physiologisches
PROTECTION;
Institut,
EFFECTS
ON CORONARY
Moorenstrasse
5,
BLOOD
Dusseldorf
poor to
FLOW AND
1,
West
L12
CARDIOPROTECTION BY A -ADENOSINE MEDIATED EFFECTS. Luiz Belardinelli, Dept. of Medicine and pharmacology, Co1 i ege of Medicine, University of Florida, Gainesville FL 32610. It is now well established that the cardiac effects of adenosine are due to activation of specific extracellular receptors, t.haL is, Al ,nnd 2 subtypes. In the heart, activation of the Al-receptor subtype 1) causes atria1 s owrng (chronotroplc effect), 2) reduces contractllitp, 3) slows conduction through the atrioventricular (AV) and 4) depresses ventricular automaticity. Activation of the node (dromotropic effect), receptor also attenuates the cardiac stinulatory actions of catecholamines in heart rate and contractility). On the other hand, activation of the these actions of coronary vasodilation. Thus, altogether, (0 ) balance, an improvement in myocardial oxygen i.e., demand (reduce hear. i rate). In this increase 0 supply (vasodilation) and decrease O2 study carr l ed out in isolated perfused gui.nea pig hearts, we demonstrated that adenosine During is a significantly more potent vasodilator than as a bradycardic substance. infusion of adenosine. maximal or near maximal coronary vasodilation occurs before A,The ICI0 value for coronary dilation was 0.05 uM whereas for medi.ated actions are noted. the negative chronotropic and drontotropic effects were 5 and 4 PM, respectively. We then showed that when coronary vasodilation alone fails to restore an imbalance between 0 the production of adenosine reaches sufficient levels to caus & supply and demand, ventricular rate decreases, 0 cousumpt bradycardia or AV block. Consequently, ion is This would have the e I feet of sparing reduced, and Ol supply/demand balance improves. the ventricular myocardium from work and hence retard cell ihjury, when O2 supply does not meet demand.
Ll3
MYOCARDIAL TISSW PROTKCTION BY ENDOGELJOOS PPOSTAGL4NDINS Kareten SchrBr, Thomas Hohlfeld, Isabelle Woditsch. Institut fur Pharmakologie, Heinrich-Heine-Universitgt Dusseldorf, Moorenstr. 5, D-4000 Dusseldorf 1, PRG A transiently enhanced generation of endogenous proetaglandine (PGI2) is freInhibition of this prostaglandin formation by quently found in myocardial ischaemia. indomethacin aggravates ischaemic injury while exogenous supplementation with PGI2attenuate8 myocardial injury. Beneficial results type compounds, such a8 iloproet. using compounds euch a8 were alao found by stimulation of endogenous PO12 formation dsfibrotide. These data suggest that a “cytoprotectfve” effect of prostacyclins might be involved and contributes to improved tissue preservation. Cytoprotection in myocardial ischaamfa is probably an non-specific rssponse which involves etabilisation of ischaemically injured myocardial tissue including endothelium, myocytes and adrenergic nerve terminals. Evidence is presented that irrchaemia-induced catecholamine redistribution is prevented by prostacyclina and that endothelial injury, determined by measuring NO release from reperfused ischaemic rabbit hearte, tend8 to be further aggravated by elimination of endogenous proetaglandln production. Alternatfvely, beneficial action8 of prostacycline might be further enhanced by improved local perfusion and inhibition of PMN- and platelet function. It is concluded that generation of endogenoua PGIx-like compound8 in the ischaemic myocerdium appear8 to be an important protective factor for jeopardized tissue.
S.130
Cell
Cardiol
22 (Supplement
III)
(1990)
plasma proteins (necessitating very high doses) and to its oral bioavailability. The more recent analogs of mioflazine, such as R 75 231, are much more appropriate, maybe unique, prove - or disprove - the concept.
Ljj
;;:;;;;y:
J Schrader, Germany.
;;;EVOt;;ARDIAL
Physiologisches
PROTECTION;
Institut,
EFFECTS
ON CORONARY
Moorenstrasse
5,
BLOOD
Dusseldorf
poor to
FLOW AND
1,
West
L12
CARDIOPROTECTION BY A -ADENOSINE MEDIATED EFFECTS. Luiz Belardinelli, Dept. of Medicine and pharmacology, Co1 i ege of Medicine, University of Florida, Gainesville FL 32610. It is now well established that the cardiac effects of adenosine are due to activation of specific extracellular receptors, t.haL is, Al ,nnd 2 subtypes. In the heart, activation of the Al-receptor subtype 1) causes atria1 s owrng (chronotroplc effect), 2) reduces contractllitp, 3) slows conduction through the atrioventricular (AV) and 4) depresses ventricular automaticity. Activation of the node (dromotropic effect), receptor also attenuates the cardiac stinulatory actions of catecholamines in heart rate and contractility). On the other hand, activation of the these actions of coronary vasodilation. Thus, altogether, (0 ) balance, an improvement in myocardial oxygen i.e., demand (reduce hear. i rate). In this increase 0 supply (vasodilation) and decrease O2 study carr l ed out in isolated perfused gui.nea pig hearts, we demonstrated that adenosine During is a significantly more potent vasodilator than as a bradycardic substance. infusion of adenosine. maximal or near maximal coronary vasodilation occurs before A,The ICI0 value for coronary dilation was 0.05 uM whereas for medi.ated actions are noted. the negative chronotropic and drontotropic effects were 5 and 4 PM, respectively. We then showed that when coronary vasodilation alone fails to restore an imbalance between 0 the production of adenosine reaches sufficient levels to caus & supply and demand, ventricular rate decreases, 0 cousumpt bradycardia or AV block. Consequently, ion is This would have the e I feet of sparing reduced, and Ol supply/demand balance improves. the ventricular myocardium from work and hence retard cell ihjury, when O2 supply does not meet demand.
Ll3
MYOCARDIAL TISSW PROTKCTION BY ENDOGELJOOS PPOSTAGL4NDINS Kareten SchrBr, Thomas Hohlfeld, Isabelle Woditsch. Institut fur Pharmakologie, Heinrich-Heine-Universitgt Dusseldorf, Moorenstr. 5, D-4000 Dusseldorf 1, PRG A transiently enhanced generation of endogenous proetaglandine (PGI2) is freInhibition of this prostaglandin formation by quently found in myocardial ischaemia. indomethacin aggravates ischaemic injury while exogenous supplementation with PGI2attenuate8 myocardial injury. Beneficial results type compounds, such a8 iloproet. using compounds euch a8 were alao found by stimulation of endogenous PO12 formation dsfibrotide. These data suggest that a “cytoprotectfve” effect of prostacyclins might be involved and contributes to improved tissue preservation. Cytoprotection in myocardial ischaamfa is probably an non-specific rssponse which involves etabilisation of ischaemically injured myocardial tissue including endothelium, myocytes and adrenergic nerve terminals. Evidence is presented that irrchaemia-induced catecholamine redistribution is prevented by prostacyclina and that endothelial injury, determined by measuring NO release from reperfused ischaemic rabbit hearte, tend8 to be further aggravated by elimination of endogenous proetaglandln production. Alternatfvely, beneficial action8 of prostacycline might be further enhanced by improved local perfusion and inhibition of PMN- and platelet function. It is concluded that generation of endogenoua PGIx-like compound8 in the ischaemic myocerdium appear8 to be an important protective factor for jeopardized tissue.
S.130