New Strategies for the Treatment of Atrial Fibrillation

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the clinical practice. It significantly contributes to the morbidity and mortality of the elderly population. Over the past 25–30 years intense effort in basic research has advanced the understanding of the relationship between the pathophysiology of AF and atrial remodelling. Nowadays it is clear that the various forms of atrial remodelling (electrical, contractile and structural) play crucial role in initiating and maintaining the persistent and permanent types of AF. Unlike in ventricular fibrillation, in AF rapid ectopic firing originating from pulmonary veins and re-entry mechanism may induce and maintain (due to atrial remodelling) this complex cardiac arrhythmia. The present review presents and discusses in detail the latest knowledge on the role of remodelling in AF. Special attention is paid to novel concepts and pharmacological targets presumably relevant to the drug treatment of atrial fibrillation.

Regional Anesthesia in the Prevention of Chronic Postoperative Pain

Chronic postsurgical pain (CPSP) develops after a surgical procedure but increases its intensity and persists beyond the healing process without another cause to explain it. The incidence ranges from 5–85%, according to the type of surgery. Patients who develop CPSP may have a protracted ambulation, cardiac and pulmonary complications and increased morbidity and mortality. Several risk factors have been found related to the development of CPSP: female gender, young age, genetic predisposition, and psychosocial problems, hence prevention, early identification and treatment of these factors is essential. Several guidelines recommend the use of multimodal analgesia to treat postoperative pain, and the perioperative management seems to have a preventive role in the development of CPSP. Regional anesthesia (RA) either neuraxial or peripheral nerve blocks, by modulating signaling created by a surgical incision, play a key role in the prevention of CPSP. Local anesthetics have anti-inflammatory properties which decrease sensitization, reduce ectopic firing of neurons, cytokines expression and decrease neutrophil priming. RA reduces pain signals to the spinal cord and supraspinal and cortical nociceptive centers. RA along with other pharmacologic interventions can improve the CPSP as well as the physical and social functionality.

Optimising risk factors for atrial fibrillation post-cardiac surgery

Postoperative atrial fibrillation (POAF) is an ongoing complication following cardiac surgery, with an incidence of 15%–60%. It is associated with substantial mortality and morbidity, as well increased hospital stays and healthcare costs. The pathogenesis is not fully understood, but the literature suggests that POAF occurs when transient, postoperative triggers act on vulnerable atrial tissue produced by preoperative, procedure-induced and postoperative processes such as inflammation, oxidative stress, autonomic dysfunction and electrophysiological remodelling of the atrial tissues. This sets the stage for arrhythmogenic mechanisms, such as ectopic firing secondary to triggered activity and re-entry mechanisms generating POAF. Preoperative factors include advanced age, sex, ethnicity, cardiovascular risk factors, preoperative drugs, electrocardiogram and echocardiogram abnormalities. Procedural factors include: the use of cardiopulmonary bypass and aortic cross clamp, type of cardiac surgery, use of hypothermia, left ventricular venting, bicaval cannulation and exclusion of the left atrial appendage. Postoperative factors include postoperative drugs, electrolyte and fluid balance and infection. This review explores the pathogenesis of POAF and the contribution of these perioperative factors in the development of POAF. Patients can be risk stratified for targeted treatment and prophylaxis, and how these factors can be attenuated to improve POAF outcomes following cardiac surgery.

Bone Cancer Pain, Mechanism and Treatment

The world health organization (WHO) has predicted a global amount of 19 million cancer cases by 2025. Breast, prostate and lung cancer are common cancer types and show metastasis in 60 to 84% of the cases, with 75 to 90% experiencing life-altering cancer-induced bone pain (CIBP), characterized by continuous, dull progressive pain with movement-induced incident peaks and random breakthrough spikes. Therefore, it is the most difficult pain condition to treat. CIBP is a unique type of pain with neuropathic and nociceptive components. Briefly, an invading tumor cell disturbs the healthy balance of the bone resulting in an acidic microenvironment, activating sensory fibers in the bone. The invaded tumor cell and adjacent stromal cells secrete mediators initiating an immune response with transcriptional signaling, resulting in increased cytokines and growth factors. Sensory nerve fibers are damaged and start to sprout, causing ectopic firing, and as tumors grow in size they activate mechanoreceptors. Aside from bisphosphonates and antibody therapy, CIBP is treated by a range of NSAIDs to strong opioids, but remains undertreated in one-third of cases. This chapter discusses the accompanying CIBP of bone tumors, the mechanism of action and current treatments.

Autotomy

The landmark paper discussed in this chapter is ‘Autotomy following peripheral nerve lesions: Experimental anaesthesia dolorosa’, published by Wall et al. in 1979. This paper was the culmination of a series of studies in which Wall, together with a number of colleagues, investigated the underlying causes of neuropathic pain following peripheral nerve injury. In this paper, the authors used a variety of nerve injury models to show that the extent of resultant anaesthesia combined with ectopic firing from damaged axons in nerve-end neuromas correlated with the severity of self-mutilation (termed ‘autotomy’) observed in the affected hindlimb. The authors therefore suggested that these simple models might be suitable for studies of the prevention of irritations originating from chronic lesions of peripheral nerves. Indeed, this proved to be the case, sparking the development of numerous animal models of spontaneous pain following nerve injury and spawning a new field of neuropathic pain research.