Acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide and is characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR). However, the molecular mechanisms involved in these arrhythmias are still little understood. To investigate the cardioprotective role of the cardiac Ca²⁺/cAMP/adenosine signaling pathway in AMI, L-type Ca²⁺ channels (LTCC) were blocked with either nifedipine (NIF) or verapamil (VER), with or without A₁-adenosine (ADO), receptors (A₁R), antagonist (DPCPX), or cAMP efflux blocker probenecid (PROB), and the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by CIR in rats was evaluated. 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 and VER 1 mg/kg in the presence or absence of PROB 100 mg/kg or DPCPX 100 µg/kg. The serum levels of cardiac injury biomarkers total creatine kinase (CK) and CK-MB were quantified. Both NIF and VER treatment were able to attenuate cardiac arrhythmias caused by CIR; however, these antiarrhythmic effects were abolished by pretreatment with PROB and DPCPX. The total serum CK and CK-MB were similar in all groups. These results indicate that the pharmacological modulation of Ca²⁺/cAMP/ADO in cardiac cells by means of attenuation of Ca²⁺ influx via LTCC and the activation of A₁R by endogenous ADO could be a promising therapeutic strategy to reduce the incidence of severe and fatal arrhythmias caused by AMI in humans.

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.

Acute myocardial infarction (AMI), which is characterized by severe and fatal arrhythmias resultant from cardiac ischemia/reperfusion (CIR), is the leading cause of morbidity and mortality in the world. Considering that epiisopiloturin (EPI), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus produded anti-inflammatory and antioxidant effects in an animal model of peritonitis, paw edema and peritonitis in mice, we decided to investigate the potential cardioprotective activity of EPI in animal model of CIR. Then, adult rats submitted to CIR pretreated with EPI 10 mg/kg (EPI10+CIR group) or 15 mg/kg (EPI15+CIR group) were compared to control animals submitted to CIR treated with saline solution 0.9% (CIR group). To evaluate the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) induced by CIR in these rats, the ECG analysis was performed. Serum levels of cardiac damage markers, total creatine kinase (CK) and CK-MB, were measured. The results showed that the AVB incidence was reduced from 80% to 30%, and LET incidence was reduced from 70% to 20%, compared to CIR group. Serum levels of LDH, total CK and, CK-MB was similar in all groups studied. These results indicate that the treatment with EPI (15 mg/kg, IV) before CIR was effective to produce cardioprotective effects. Thus, the use of EPI could be a promisse strategy to reduce the incidence of severe and fatal arrhythmias associated with AMI.