Optical Imaging of Tumor Response to Hyperbaric Oxygen Treatment and Irradiation in an Orthotopic Mouse Model of Head and Neck Squamous Cell Carcinoma

PURPOSE: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. PROCEDURES: Orthotopic FaDu tumors were established in mice, and the response of the (irradiated) tumors to HBOT was monitored by bioluminescence imaging. Near infrared fluorescence imaging using AngioSense750 and Hypoxisense680 was applied to detect tumor vascular permeability and hypoxia. RESULTS: HBOT treatment resulted in accelerated growth of non-irradiated tumors, but mouse survival was improved. Tumor vascular leakiness and hypoxia were enhanced after HBOT, whereas histological characteristics, epithelial-to-mesenchymal transition markers, and metastatic incidence were not influenced. CONCLUSIONS: Squamous cell carcinoma responds to HBOT with respect to tumor growth, vascular permeability, and hypoxia, which may have implications for its use in cancer patients. The ability to longitudinally analyze tumor characteristics highlights the versatility and potential of optical imaging methods in oncological research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-015-0834-8) contains supplementary material, which is available to authorized users

The interplay between sympathetic overactivity, hypertension and heart rate variability (Review, invited)

The control of arterial pressure is a complex interaction of the long- and short-term influences of hormones, local vascular factors, and neural mechanisms. The autonomic nervous system and its sympathetic arm play important roles in the regulation of blood pressure, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. The baroreceptor system opposes either increases or decreases in arterial pressure, and the primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The ability of the baroreflex to powerfully buffer acute changes in arterial pressure is well established, but the role of the arterial baroreceptor reflex in long-term control of arterial pressure has been a topic of many debate and controversy for decades. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure. The aim of this paper has been to review the postulated role of sympathetic activation

Coronary Microcirculatory Dysfunction in Human Cardiomyopathies: A Pathologic and Pathophysiologic Review

Cardiomyopathies are a heterogeneous group of diseases of the myocardium. The term cardiomyopathy involves a wide range of pathogenic mechanisms that affect the structural and functional states of cardiomyocytes, extravascular tissues, and coronary vasculature, including both epicardial coronary arteries and the microcirculation. In the developed phase, cardiomyopathies present with various clinical symptoms: dyspnea, chest pain, palpitations, swelling of the extremities, arrhythmias, and sudden cardiac death. Due to the heterogeneity of cardiomyopathic patterns and symptoms, their diagnosis and therapies are great challenges. Despite extensive research, the relation between the structural and functional abnormalities of the myocardium and the coronary circulation are still not well understood in the various forms of cardiomyopathy. The main pathological characteristics of cardiomyopathies and the coronary microcirculation develop in a progressive manner due to (1) genetic-immunologic-systemic factors; (2) comorbidities with endothelial, myogenic, metabolic, and inflammatory changes; (3) aging-induced arteriosclerosis; and (4) myocardial fibrosis. The aim of this review is to summarize the most important common pathological features and/or adaptations of the coronary microcirculation in various types of cardiomyopathies and to integrate the present understanding of the underlying pathophysiological mechanisms responsible for the development of various types of cardiomyopathies. Although microvascular dysfunction is present and contributes to cardiac dysfunction and the potential outcome of disease, the current therapeutic approaches are not specific for the given types of cardiomyopathy