Antibiotic-induced cardiac arrhythmias.

This review aims to clarify the underlying risk of arrhythmia associated with the use of macrolides and fluoroquinolones antibiotics. Torsades de pointes (TdP) is a rare potential side effect of fluoroquinolones and macrolide antibiotics. However, the widespread use of these antibiotics compounds the problem. These antibiotics prolong the phase 3 of the action potential and cause early after depolarization and dispersion of repolarization that precipitate TdP. The potency of these drugs, as potassium channel blockers, is very low, and differences between them are minimal. Underlying impaired cardiac repolarization is a prerequisite for arrhythmia induction. Impaired cardiac repolarization can be congenital in the young or acquired in adults. The most important risk factors are a prolonged baseline QTc interval or a combination with class III antiarrhythmic drugs. Modifiable risk factors, including hypokalemia, hypomagnesemia, drug interactions, and bradycardia, should be corrected. In the absence of a major risk factor, the incidence of TdP is very low. The use of these drugs in the appropriate settings of infection should not be altered because of the rare risk of TdP, except among cases with high-risk factors.

Lack of central effects of peripherally administered adenosine A(1) agonists on synaptic transmission in the rat hippocampus.

Peripheral administration of adenosine A(1) receptor selective agonists is generally thought to protect the hippocampus against ischemic damage via central actions. We examined the effects of two peripherally administered A(1) agonists, cyclohexyladenosine (CHA) and adenosine amine congener (ADAC), on synaptic transmission in the hippocampus and on indices of cardiovascular function. We conclude that the permeability of these agonists is not sufficient to result in concentrations necessary to activate central adenosine A(1) receptors within the hippocampus.

Adenosine-mediated activation of Akt/protein kinase B in the rat hippocampus in vitro and in vivo.

Adenosine is considered an endogenous neuroprotective metabolite that through activation of the A(1) receptor results in reduction of neuronal damage following cerebral ischemia. Protein kinase B, also known as Akt/PKB, is part of an endogenous pathway that exerts effective neuroprotection from both necrotic and apoptotic cell death. Using a rat model of unilateral common carotid artery occlusion coupled with hypoxia, and using in vitro rat hippocampal slices, we examined the ability of adenosine to directly activate Akt/PKB. Western blot analysis revealed that levels of phosphorylated Akt/PKB were elevated in vivo under ischemic conditions in an adenosine A(1)-dependent manner and elevated in hippocampal slices treated with an adenosine A(1) agonist. We conclude from these studies that the activation of an adenosine A(1) receptor-mediated signal transduction pathway, either by endogenous adenosine (in vivo) or by an adenosine A(1) agonist (in vitro), results in the activation of the neurotrophic kinase Akt/PKB.