Computed tomographic (CT) coronary angiography is a well-established, noninvasive imaging modality for detection of coronary stenosis, but it has limited accuracy in demonstrating whether a coronary stenosis is hemodynamically significant. An additional functional test is often required because both anatomic and functional information is needed for guiding patient care. Recent developments in CT technology allow CT evaluation of myocardial perfusion during vasodilator stress, thereby providing information about myocardial ischemia. Investigators in several single-center studies have established the feasibility of performing stress myocardial perfusion CT imaging in small groups of patients and have shown that stress myocardial perfusion CT in combination with CT coronary angiography improved the diagnostic accuracy in comparison with CT coronary angiography alone. However, CT perfusion acquisition protocols must be optimized in terms of acquisition and reconstruction parameters, contrast material protocol injections, and radiation dose. Further research is needed to establish the clinical usefulness of this novel technique. The purpose of this review is to (a) provide an overview of the physiology of coronary circulation and myocardial perfusion; (b) describe the technical prerequisites, challenges, and mathematic modeling related to CT perfusion imaging; (c) note recent advances in CT scanners and CT perfusion protocols; and (d) discuss the interpretation of CT perfusion images. Finally, a review and summary of the current literature are provided, and future directions for research are discussed.

Ever since the discovery of free radicals, many hypotheses on the deleterious actions of reactive oxygen species (ROS) have been proposed. However, increasing evidence advocates the necessity of ROS for cellular homeostasis. ROS are generated as inherent by-products of aerobic metabolism and are tightly controlled by antioxidants. Conversely, when produced in excess or when antioxidants are depleted, ROS can inflict damage to lipids, proteins, and DNA. Such a state of oxidative stress is associated with many pathological conditions and closely correlated to oxygen consumption. Although the deleterious effects of ROS can potentially be reduced by restoring the imbalance between production and clearance of ROS through administration of antioxidants (AOs), the dosage and type of AOs should be tailored to the location and nature of oxidative stress. This paper describes several pathways of ROS signaling in cellular homeostasis. Further, we review the function of ROS in cardiovascular pathology and the effects of AOs on cardiovascular outcomes with emphasis on the so-called oxidative paradox.

It is increasingly recognized that obesity is a risk factor for microvascular disease, involving both structural and functional changes in the microvasculature. This review aims to describe how obesity impacts the microvasculature of a variety of tissues, including visceral adipose tissue, skeletal muscle, heart, brain, kidneys, and lungs. These changes involve endothelial dysfunction, which in turn (i) impacts control of vascular tone, (ii) contributes to development of microvascular insulin resistance, (iii) alters secretion of paracrine factors like nitric oxide and endothelin, but (iv) also influences vascular structure and perivascular inflammation. In concert, these changes impair organ perfusion and organ function thereby contributing to altered release and clearance of neurohumoral factors, such as adipokines and inflammatory cytokines. Global microvascular dysfunction in obese subjects is therefore a common pathway that not only explains exercise-intolerance but also predisposes to development of chronic kidney disease, microvascular dementia, coronary microvascular angina, heart failure with preserved ejection fraction, chronic obstructive pulmonary disease, and pulmonary hypertension.

Sarcomeric dysfunction plays a central role in reduced cardiac pump function in heart failure. This review focuses on the alterations in sarcomeric proteins in diseased myocardium that range from altered isoform expression to post-translational protein changes such as proteolysis and phosphorylation. Recent studies in animal models of heart failure and human failing myocardium converge and indicate that sarcomeric dysfunction, including altered maximum force development, Ca²⁺ sensitivity, and increased passive stiffness, largely originates from altered protein phosphorylation, caused by neurohumoral-induced alterations in the kinase–phosphatase balance inside the cardiomyocytes. Novel therapies, which specifically target phosphorylation sites within sarcomeric proteins or the kinases and phosphatases involved, might improve cardiac function in heart failure.