Comparison of elimination and cardiovascular effects of adenine nucleosides administered intrapericardially or intravenously in anesthetized dog.
Intrapericardial (IP) administration of certain cardioactive agents allows investigation of local pharmacological actions on the heart and may carry potential benefit to influence myocardial function. The cardioprotective adenosine (ADO) and inosine (INO) may be the most representative candidates. Elimination and cardiovascular effects of IP and intravenously (IV) applied ADO and INO were compared on anesthetized dogs. Their pericardial and systemic concentrations were measured after consecutive administration of increasing ADO and INO doses. In the case of IP administration at the end of the incubation period, pericardial concentrations of adenine nucleosides significantly exceeded the control values. However, the IV applied ADO and INO were rapidly metabolized in the systemic plasma. As characteristic hemodynamic effects, small but sustained decrease in heart rate (IP ADO) and increase in myocardial contractility (IP INO) were observed. During IV administration, ADO and INO exerted remarkable effects on all hemodynamic variables, which then gradually disappeared in 15 minutes. In summary, the elimination of ADO and INO was significantly slower in the pericardial fluid than in the plasma. Considering the balanced cardiac actions and lack of strong systemic hemodynamic effects, IP administration of adenine nucleosides may suggest a promising approach in the local treatment of the diseased heart.
Nagy
Andrea
A
Heart Center, Semmelweis University, Budapest 1122, Hungary. andi.nagy@gmail.com
Sax
Balázs
B
Entz
László
L
Barát
Erzsébet
E
Toma
Ildikó
I
Becker
Dávid
D
Merkely
Béla
B
Kékesi
Violetta
V
D000241:Adenosine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007288:Inosine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D009200:Myocardial Contraction / Q000187:drug effects; D010496:Pericardium / Q000187:drug effects / Q000378:metabolism*
D002316:Cardiotonic Agents; D007288:Inosine; D000241:Adenosine