Mathematical Modeling and Simulation of Ventricular Activation Sequences: Implications for Cardiac Resynchronization Therapy

Next to clinical and experimental research, mathematical modeling plays a crucial role in medicine. Biomedical research takes place on many different levels, from molecules to the whole organism. Due to the complexity of biological systems, the interactions between components are often difficult or impossible to understand without the help of mathematical models. Mathematical models of cardiac electrophysiology have made a tremendous progress since the first numerical ECG simulations in the 1960s. This paper briefly reviews the development of this field and discusses some example cases where models have helped us forward, emphasizing applications that are relevant for the study of heart failure and cardiac resynchronization therapy

Cardiac arrhythmias and electrolyte disturbances in colic horses

BACKGROUND: Despite increased focus on cardiac arrhythmias in horses, the nature and prevalence is still poorly described. Case reports suggest that arrhythmias occurring secondary to systemic disease are seen more commonly in the clinic than arrhythmias caused by cardiac disease. The aim of this study was to investigate the prevalence of arrhythmias in colic horses referred for hospital treatment. Associations between electrolyte disturbances and arrhythmias were also investigated. The study population consisted of eight control horses and 22 referred colic horses. A Holter electrocardiography (ECG) was recorded during the first 24 hours of admission. The ECG’s were analysed by a software program followed by manual visual inspection. Arrhythmias registered included second degree atrioventricular (AV) blocks, supraventricular premature complexes (SVPCs), and ventricular premature complexes (VPCs). Blood was collected at admission and again between 12 and 24 hours after ECG was applied, and analysed for concentrations of potassium, sodium, ionised calcium, chloride, glucose, and L-lactate. RESULTS: Heart rate was 37.4 ± 3.7 bpm in the control group, and 51.6 ± 11.8 bpm, in the colic group, which was significantly different (P < 0.0001). AV blocks and SVPCs were found in both groups, however only colic horses showed VPCs. No significant difference between the two groups was found for AV blocks, SVPCs, and VPCs (P = 0.08 - 0.76). The mean levels of potassium, sodium, ionized calcium, and chloride were significantly lower in the colic group compared to the control group at admission. Mean levels of glucose and L-lactate were significantly elevated in the colic group (P < 0.05). CONCLUSIONS: This study describes prevalence of cardiac arrhythmias and electrolytes concentrations in colic horses compared to healthy controls. Although we only observed VPCs in the colic horses, no significant differences between colic horses and controls were found. Despite the colic horses having electrolyte changes at admission no correlation was found between the electrolyte disturbances and cardiac arrhythmias. Although no clear conclusions can be drawn from the present study, the results indicate that relatively mild colic per se is not pro-arrhythmogenic, whereas severe colic probably are more likely to result in ventricular arrhythmia

Role of Appetite-Regulating Peptides in the Pathophysiology of Addiction: Implications for Pharmacotherapy

Food intake and appetite are regulated by various circulating hormones including ghrelin and glucagon-like-peptide 1 (GLP-1). Ghrelin, mainly released from the stomach, increases food intake, induces appetite, enhances adiposity as well as releases growth hormone. Hypothalamic “ghrelin receptors” (GHS-R1A) have a critical role in food intake regulation, but GHS-R1A are also expressed in reward related areas. GLP-1 is produced in the intestinal mucosa as well as in the hindbrain in response to nutrient ingestion. This gut-brain hormone reduces food intake as well as regulates glucose homeostasis, foremost via GLP-1 receptors in hypothalamus and brain stem. However, GLP-1 receptors are expressed in areas intimately associated with reward regulation. Given that regulation of food and drug intake share common neurobiological substrates, the possibility that ghrelin and GLP-1 play an important role in reward regulation should be considered. Indeed, this leading article describes that the orexigenic peptide ghrelin activates the cholinergic–dopaminergic reward link, an important part of the reward systems in the brain associated with reinforcement and thereby increases the incentive salience for motivated behaviors via this system. We also review the role of ghrelin signaling for reward induced by alcohol and addictive drugs from a preclinical, clinical and human genetic perspective. In addition, the recent findings showing that GLP-1 controls reward induced by alcohol, amphetamine, cocaine and nicotine in rodents are overviewed herein. Finally, the role of several other appetite regulatory hormones for reward and addiction is briefly discussed. Collectively, these data suggest that ghrelin and GLP-1 receptors may be novel targets for development of pharmacological treatments of alcohol and drug dependence