Chapters authored
Inflammation and Diabetic Cardiomyopathy
Diabetes mellitus (DM) is a metabolic syndrome that manifests a low grade of systemic inflammation that contributes to the development of cardiovascular diseases (CVDs). DM is a predominant risk factor for CVDs inducing structural changes in the heart, infiltration of fibrosis, apoptosis, and cardiac remodeling, all leading to myocardial infarction (MI), heart failure (HF), and sudden cardiac death. Furthermore, more than 80% of diabetic patients usually die from heart diseases or diabetic cardiomyopathy (DCM). Currently, HF is one of the main causes of mortality in the world despite advances in drug treatments. According to literature, a strong association exists between chronic inflammation and the development of DCM. In order to have a better appreciation of the effect of diabetes and inflammation on the cardiovascular system (CVS), it is of paramount importance to have a better understanding of diabetes, the physiology of the CVS, and the pathophysiology of DM. Thus, the present review highlights the role of chronic inflammation in the complex interplay between the development of DM and DCM. Our understanding of the process is critical in the discovery of new targeted therapies for DCM and other forms of HF.
Part of the book: Inflammatory Heart Diseases
Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death
More than 450 million people worldwide have diabetes mellitus (DM), a metabolic disorder characterized by an increase in blood glucose level (hyperglycemia) that arises from insufficient insulin secretion or resistance to insulin’s action. More than 70% of individuals with chronic DM will develop cardiovascular diseases (CVDs) including atherosclerosis and coronary artery diseases (CADs), hypertension, cardiac arrhythmias, cardiomyopathy (heart failure), stroke, and chronic kidney disease. A significant number of these individuals will also succumb to sudden cardiac death (SCD). SCD usually occurs in early morning from abnormal heart rhythms or arrhythmias and ventricular fibrillation. When the pumping action of the heart becomes erratic, a reduction in oxygenated blood to the brain leads to unconsciousness and brain damage. SCD is independent of age and sex and positively correlates with impairment in cardiac metabolism, muscle damage, fibrosis, apoptosis, hypertrophy, ischemia, and deranged cation signaling. This review centers on mechanisms by which intracellular cations (Na+, K+, and Ca2+) handling, inflammation, and oxidative and carbonyl stresses due to diabetes-induced hyperglycemia can lead to the deterioration of excitation/contraction coupling (ECC), impaired contractility, arrhythmias, and SCD in DM patients. It also discusses the beneficial effects of exercise training to attenuate the risk of SCD.
Part of the book: Sudden Cardiac Death
Effects of Diabetes Mellitus on the Conduction System of the Heart: Mini-Review
Diabetes mellitus can induce substantial damage to the conduction system of the heart, especially the sinoatrial node. This is due to hyperglycemia leading to bradyarrhythmia. DM, via the elevation of HG, generates the production of a number of insulting agents in the myocardium known as reactive oxygen species and reactive carbonyl species, which elicit direct damage to neuro-filament-M and β2-adrenergic receptors in the conducting system as well as a number of cardiac contractile, cation transporting and channel proteins. One cation channel protein is the hyperpolarization-activated cyclic nucleotide-gated potassium channel. It encodes the protein responsible for the hyperpolarizing-activated current or the “funny current” that participates in spontaneous diastolic membrane depolarization in sinoatrial node cells. Gene expression of these proteins and their physiological functions are decreased in the diabetic heart, which affects the generation of electrical impulses or action potentials resulting in increases in RR and PR intervals and QRS complex duration of the electrocardiogram. The heart rate and force of contraction of the myocardium are decreased leading to bradyarrhythmia and sudden cardiac death. This review attempts to explain the cellular mechanism(s) involved in diabetes-induced bradyarrhythmia with emphasis on cation-transporting proteins, especially the hyperpolarization-activated cyclic nucleotide-gated channels pacemaker current channels.
Part of the book: New Insights on Cardiomyopathy