Electrical modalities beyond pacing for the treatment of heart failure

In this review, we report on electrical modalities, which do not fit the definition of pacemaker, but increase cardiac performance either by direct application to the heart (e.g., post-extrasystolic potentiation or non-excitatory stimulation) or indirectly through activation of the nervous system (e.g., vagal or sympathetic activation). The physiological background of the possible mechanisms of these electrical modalities and their potential application to treat heart failure are discussed

Prostaglandin E2 inhibits calcium current in two sub-populations of acutely isolated mouse trigeminal sensory neurons

Prostaglandins are important mediators of pain and inflammation. We have examined the effects of prostanoids on voltage-activated calcium currents (ICa) in acutely isolated mouse trigeminal sensory neurons, using standard whole cell voltage clamp techniques. Trigeminal neurons were divided into two populations based on the presence (Type 2) or absence (Type 1) of low voltage-activated T-type ICa. The absence of T-type ICa is highly correlated with sensitivity to μ-opioid agonists and the VR1 agonist capsaicin. In both populations of cells, high voltage-activated ICa was inhibited by PGE2 with an EC50 of about 35 nm, to a maximum of 30 %. T-type ICa was not inhibited by PGE2. Pertussis toxin pre-treatment abolished the effects of PGE2 in Type 2 cells, but not in Type 1 cells, whereas treatment with cholera toxin prevented the effects of PGE2 in Type 1 cells, but not in Type 2 cells. Inhibition of ICa by PGE2 was associated with slowing of current activation and could be relieved with a large positive pre-pulse, consistent with inhibition of ICa by G protein βγ subunits. Reverse transcription-polymerase chain reaction of mRNA from trigeminal ganglia indicated that all four EP prostanoid receptors were present. However, in both Type 1 and Type 2 cells the effects of PGE2 were only mimicked by the selective EP3 receptor agonist ONO-AE-248, and not by selective agonists for EP1 (ONO-DI-004), EP2 (ONO-AE1–259) and EP4 (ONO-AE1–329) receptors. These data indicate that two populations of neurons in trigeminal ganglia differing in their calcium channel expression, sensitivity to μ-opioids and capsaicin also have divergent mechanisms of PGE2-mediated inhibition of calcium channels, with Gi/Go type G proteins involved in one population, and Gs type G proteins in the other

Electrical neuromodulation for patients with cardiac diseases

<p>In this review we discuss the position of electrical neuromodulation as a safe and reversible adjuvant therapy for treatment of patients with chronic cardiac diseases who have become refractory to conventional strategies. In patients with chronic refractory angina, electrical neuromodulation, independent of the applied modality, has shown to reduce complaints of angina, to enhance exercise capacity, to improve quality of life and to employ anti-ischaemic effects. To date, electrical neuromodulation seems to be one of the best adjuvant therapies for these patients. In addition, neuromodulation in the treatment of heart failure and resistant arrhythmias is the subject of several ongoing studies.</p>