Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

Fernando Sabia Tallo
* ,
Patrícia Oliveira Santana
,
Sandra Augusta Gordinho Pinto
,
Rildo Yamaguti Lima
,
Erisvaldo Amarante De Araújo
,
José Gustavo Padrão Tavares
,
Marcelo Pires-Oliveira
ORCID logo ,
Lucas Antonio Duarte Nicolau
,
Jand Venes Rolim Medeiros
ORCID logo ,
Murched Omar Taha
,
André Ibrahim David
,
Bráulio Luna-Filho
,
Carlos Eduardo Braga Filho
ORCID logo ,
Adriano Henrique Pereira Barbosa
,
Célia Maria Camelo Silva
,
Almir Gonçalves Wanderley
,
Adriano Mendes Caixeta
,
Afonso Caricat-Neto
,
Francisco Sandro Menezes-Rodrigues
* ORCID logo
Version 1 : Received: 18 September 2023 / Approved: 19 September 2023 / Online: 20 September 2023 (08:45:21 CEST)

A peer-reviewed article of this Preprint also exists.

Tallo, F.S.; de Santana, P.O.; Pinto, S.A.G.; Lima, R.Y.; de Araújo, E.A.; Tavares, J.G.P.; Pires-Oliveira, M.; Nicolau, L.A.D.; Medeiros, J.V.R.; Taha, M.O.; David, A.I.; Luna-Filho, B.; Filho, C.E.B.; Barbosa, A.H.P.; Silva, C.M.C.; Wanderley, A.G.; Caixeta, A.; Caricati-Neto, A.; Menezes-Rodrigues, F.S. Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction. Pharmaceuticals 2023, 16, 1473. Tallo, F.S.; de Santana, P.O.; Pinto, S.A.G.; Lima, R.Y.; de Araújo, E.A.; Tavares, J.G.P.; Pires-Oliveira, M.; Nicolau, L.A.D.; Medeiros, J.V.R.; Taha, M.O.; David, A.I.; Luna-Filho, B.; Filho, C.E.B.; Barbosa, A.H.P.; Silva, C.M.C.; Wanderley, A.G.; Caixeta, A.; Caricati-Neto, A.; Menezes-Rodrigues, F.S. Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction. Pharmaceuticals 2023, 16, 1473.

Abstract

Characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR), acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide. To investigate the cardioprotective role of cardiac Ca2+/cAMP/adenosine signaling in AMI, the effects of L-type Ca2+ channels (LTCC) blocker Nifedipine (NIF) and Verapamil (VER), in the absence and presence of A1-adenosine receptors (A1R) blocker (DPCPX), on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) induced by CIR in rats were evaluated. CIR was induced in adult male Wistar rats (290-320 g) by occlusion of the left anterior descendent coronary artery (10 min) followed by reperfusion (75 min). VA, AVB and LET incidences were evaluated by ECG analysis and compared between control (CIR group) and intravenously treated 5 min before CIR with NIF 1, 10, and 30 mg/kg (NIF+CIR groups) or DPCPX 100 µg/kg plus NIF 10 mg/kg (DPCPX+NIF+CIR group) and VER 1 mg/kg (VER+CIR group) or DPCPX 100 µg/kg plus VER 1 mg/kg (DPCPX+VER+CIR group). Serum levels of cardiac injury biomarkers (TCK and CK-MB) were quantified. In CIR group, VA, AVB and LET incidences were 90, 80 and 70%, respectively. In NIF+CIR group, incidence of VA was reduced to 50, 30 and 30%, AVB to 25, 10 and 20%, and LET to 25, 20 and 20%, and respectively. In DPCPX+NIF+CIR group, these incidences were not different from CIR group. TCK and CK-MB levels were similar in all groups. These results indicate that pharmacological modulation of the Ca2+/cAMP/adenosine signaling in cardiac cells by LTCC blockade and A1R stimulation could be a new strategy cardioprotective for human AMI therapy.

Keywords

cardiac ischemia-reperfusion; cardiac arrhythmias; pharmacological cardioprotection; Ca2+ channels; adenosine receptors

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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