Jaipaul Singh

By Manal M.A. Smail, Chris F. Howarth, Jaipaul Singh and Abla Mohamed Ismail

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

By Manal M.A. Smail, Frank C. Howarth, Jaipaul Singh, Sunil Rupee, Khemraj Rupee, Carlin Hanoman, Abla Mohammed Ismail, Farah Ahmed Sleiman, Samar Abdulkhalek and Keshore Bidasee

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

By Manal Smail, Sunil Rupee, Khemraj Rupee, Abla Mohammed Ahmed Ismail, Sara Sultan, Frank Christopher Howarth, Ernest A. Adeghate and Jaipaul Singh

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

By Manal Smail, Khemraj Rupee, Sunil Rupee, Carlin Hanoman, Abla Ismail, Ernest Adeghate, Raphael Singh, Emanuel Cummings, Chris Sawh and Jaipaul Singh

Cardiomyopathies (CMPs) encompass a heterogeneous group of cardiac disorders affecting mainly many of the elderly populations globally. Clinical presentation of cardiomyopathy varies among patients, based on the type and severity of the disorder. Preventing cardiomyopathy involves a multifaceted approach. Management strategies for cardiomyopathy encompass a spectrum of interventions. Medications, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics, and anti-arrhythmic drugs, are commonly prescribed to patients. Device implantation, including pacemakers, implantable cardioverter-defibrillators (ICDs), and ventricular-assist devices (VADs), is necessary in some cases. Lifestyle changes, including dietary modifications. Reduction in alcohol consumption, smoking and stress level, weight management, and regular exercise programmes, are essential components of adherence to self-care. Surgical interventions may be considered, including cardiac surgery and, in severe cases, heart transplantation. This review provides a thorough understanding of cardiomyopathy, covering a wide range of crucial aspects, including epidemiology, risk factors, types, subcellular and molecular mechanisms, clinical presentation, diagnostic approaches, treatment modalities, and prevention strategies, a profound understanding of these aspects is essential for healthcare professionals and researchers to enhance patient health care.

Part of the book: Etiology, Prevention and Management of Cardiomyopathy [Working title]

By Ernest A. Adeghate, Sahar Mohsin, Ahmed Bin Amar, Suhail AlAmry, Mariam AlOtaiba, Omobola Awosika Oyeleye and Jaipaul Singh

Diabetes mellitus (DM) is a condition of abnormal carbohydrate metabolism, leading to persistent hyperglycemia. It is defined as a fasting blood glucose over 7.0 mmol/L, a 2-hour plasma post-meal of 11.1 mmol/L, or HbA1C values over 6.5% (48 mmol/L). DM affects almost 600 million people globally with an annual cost of around three trillion US dollars. These data indicate that DM is a global health burden that warrants attention. Complications of DM include nephropathy, retinopathy, neuropathy, and cardiomyopathy. DM-induced hyperglycemia causes oxidative stress, inflammation, endothelial and mitochondrial abnormality, and subsequently, cardiomyopathy. Hyperglycemia stimulates many signaling pathways including polyol, and hexokinase, resulting in the formation of vascular endothelial lesions, free radicals and carbonyl anions, transforming growth factor-β1, fibronectin, and nuclear factor kappa-B, which increase fibrosis and inflammation in the myocardium. All of these pathological processes lead to defective vascular permeability and hypoxia in cardiac tissue, ischemia, and eventually heart failure, and sudden cardiac death. The onset of diabetic cardiomyopathy could be delayed with a healthy lifestyle (balanced diet, physical activity, sleep, low stress, non-smoking). GLP-1 receptor agonists with or without SGLT2i are beneficial additions for the treatment of diabetic cardiomyopathy.

Part of the book: Etiology, Prevention and Management of Cardiomyopathy [Working title]