[Endothelium-protective effects of epinine (N-methyldopamine) in myocardial ischemia-reperfusion in the isolated working rat heart].
The effect of cardiac dopaminergic receptors stimulation with epinine (N-methyldopamine) on reperfusion injury was investigated in isolated working rat heart submitted to 15 min of global ischemia. Isolated Wistar rat hearts (n = 75) were used and subdivided into five groups: Group A control hearts, Group B epinine 10 ng/ml, Group C epinine 20 ng/ml, Group D epinine 40 ng/ml, Group E epinine 80 ng/ml. The drug was added to the perfusion buffer at the beginning of experimental procedures. Hemodynamic parameters, heart rhythm (epicardial ECG), heart weight changes, coronary microvascular permeability (FITC-albumin diffusion) and myocytes damage (necrosis enzymes release, immunoperoxidase labeling anti-LDH antibody) were evaluated. After ischemia in groups B and C a significant reduction of functional alterations and myocytes damage was observed with respect to Group A associated with a significant reduction of reperfusion edema (heart weight: Group A +29 +/- 3.5%, Group B +15 +/- 3.8%, Group C 16 +/- 5%, Group D 27 +/- 5%, Group E 33 +/- 4%). At reperfusion time, a significant proarrhythmic effect occurred only in groups D and E. A significant reduction of postischemic endothelial FITC-albumin diffusion was also observed in groups B and C (FITC-albumin diffusion, Group A 32.8 +/- 6% area, Group B 16.33 +/- 5% area, Group C 21.7 +/- 4.5% area, Group D 30 +/- 5% area, Group E 35 +/- 7% area). Our data show that, in isolated working rat heart, the dopaminergic stimulation with low-doses epinine may exert a cardioprotective effect against ischemia-reperfusion damage by modulating endothelial permeability changes and improving coronary microcirculation. The importance of dopaminergic receptors is also suggested by the evidence that at higher doses, when alpha and beta-adrenoceptors stimulation occurs, this cardioprotective effect is significantly reduced or lost.
Di Napoli
P
P
Istituto di Clinica Cardiovascolare, Università degli Studi G D'Annunzio, Chieti.
Di Crecchio
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A
Di Muzio
M
M
Contegiacomo
G
G
Spoletini
L
L
Barsotti
A
A
D000818:Animals; D003846:Deoxyepinephrine / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D018491:Dopamine Agonists; D003846:Deoxyepinephrine
Effetto endotelio-protettivo dell'epinina (N-metildopamina) in corso di ischemia-riperfusione nel cuore isolato e lavorante di ratto.