Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Phase interference for probing topological fractional charge in a BiSbTeSe₂-based Josephson junction array

Abstract Fractional charges can be induced by magnetic fluxes at the interface between a topological insulator (TI) and a type-II superconductor due to axion electrodynamics. In a Josephson junction array with a hole in the middle, these electronic states can have phase interference in an applied magnetic field with 4 × 2 π period, in addition to the 2π interference of the Cooper pairs. Here, we test an experimental configuration for probing the fractional charge and report the observation of phase interference effect in superconducting arrays with a hole in the middle in both Au- and TI-based devices. Our numerical simulations based on resistive shunted capacitive junction model are in good agreement with the experimental results. However, no clear sign of an axion charge-related interference effect was observed. We will discuss possible reasons and perspectives for future experiments.</jats:p

Cerebral oxygenation during changes in vascular resistance and flow in patients on cardiopulmonary bypass - a physiological proof of concept study

Despite a rise in blood pressure, cerebral oxygenation decreases following phenylephrine administration, and we hypothesised that phenylephrine reduces cerebral oxygenation by activating cerebral alpha 1 receptors. We studied patients on cardiopulmonary bypass during constant flow. Phenylephrine raised mean arterial pressure (alpha(1)-mediated) from mean (SD) 69 (8) mmHg to 79 (8) mmHg; p = 0.001, and vasopressin raised mean arterial pressure (V-1 mediated) from 69 (8) mmHg to 83 (6) mmHg; p = 0.001. Both drugs elicited a comparable decrease in cerebral oxygenation from 61 (7)% to 60 (7)%; p = 0.023 and 61 (8)% to 59 (8)%; p = 0.022, respectively. This implies that after phenylephrine or vasopressin administration, cerebral oxygenation declines as a result of cerebral vasoconstriction, due to either both cerebral a(1) and V-1 receptors being equipotentially activated or to an intrinsic myogenic mechanism of cerebral vasculature in reaction to blood pressure elevatio