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

Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor

Nerve growth factor (NGF) causes a rapid sensitisation of nociceptive sensory neurones to painful thermal stimuli owing to an action on the heat and capsaicin receptor TRPV1 (formerly known as VR1). We have developed a new technique to study this rapid sensitisation of TRPV1 by monitoring the effects of NGF on the increase in intracellular calcium concentration ([Ca2+]i) following exposure to capsaicin. Brief applications of capsaicin caused a rise in [Ca2+]i, and NGF was found to enhance this rise in 37 % of capsaicin-responsive neurones within 2 min. Pathways responsible for transducing the sensitisation of TRPV1 by TrkA, the NGF receptor, were characterised by observing the effects of inhibitors of key members of NGF-activated second messenger signalling cascades. Specific inhibitors of the ras/MEK (mitogen-activated protein and extracellular signal-regulated kinases) pathway and of phospholipase C did not abolish the NGF-induced sensitisation, but wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), totally abolished the effect of NGF. Pharmacological blockade of protein kinase C (PKC) or calcium-calmodulin-dependent protein kinase II (CaMK II) activation also prevented NGF-induced sensitisation, while blockade of protein kinase A (PKA) was without effect. These data indicate that the crucial early pathway activated by NGF involves PI3K, while PKC and CaMK II are also involved, probably at subsequent stages of the NGF-activated signalling pathway

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>