Source Of Ischemia Research Articles

Coronary venous therapy to improve microvascular dysfunction

The coronary circulation is a complex system in which vascular resistances are determined by an interplay of forces in at least three compartments: the epicardial, the microvascular, and the venous district. Cardiologists, and particularly interventional cardiologists, normallly place the focus of their attention on diseases of the epicardial coronary circulation as possible causes of coronary syndromes and neglect the importance of the other two compartments of coronary circulation. The study of the coronary microcirculation, an increasingly recognized source of ischemia, has long been disregarded, but is witnessing a revival since the (re-)introduction of diagnostic tools in the better equipped catheterization laboratories. Unfortunately, to date our understanding of coronary microvascular disease remains incomplete and the numerous proposed classifications fail to reflect its complexity. Further, no specific therapy for these disorders is available. The coronary venous circulation is an even more neglected third vascular district. Its role in regulating coronary resistances is almost completely unexplored, but inital evidence suggests that the modulation of venous pressure might help improve coronary perfusion. Coronary sinus interventions are a group of invasive techniques (both surgical and catheter-based) that are designed to treat ischaemic heart disease by increasing coronary venous pressure and therefore redistributing coronary blood flow towards the endocardium. In this review paper, we revise the role of these interventions with particular focus on acute and chronic coronary microvascular disease.

1530 Colo Low Flow: A Case of Exercise-Induced Colon Ischemia

INTRODUCTION: Colon ischemia is the most common type of mesenteric ischemia and is responsible for 15% of hospitalizations for acute lower gastrointestinal bleeding.1 While it predominately affects the elderly, colonic ischemia can occur in younger individuals during periods of intense exercise, typically long-distance or marathon runners.2,3 CASE DESCRIPTION/METHODS: A 28 year-old male with a past medical history of type 2 diabetes mellitus and obesity presented to the hospital with two days of generalized abdominal pain associated with fevers, fatigue, and general malaise. The patient denied any diarrhea, blood in his stool, or vomiting. The patient did report an intentional 60 lb weight loss in the last 6 weeks through a diet and exercise regimen including up to 60 minutes of exercise per day. Physical examination demonstrated mild right sided abdominal tenderness but was otherwise unremarkable. Initial imaging with CT abdomen showed thickening and inflammation in the cecum and terminal ileum (Figure 1). Laboratory studies were normal apart from mild elevations of lactic acid 1.0, CRP 14.4, and ESR 31. Subsequently, a colonoscopy was performed which showed mild to moderate colon ischemia at the ileocecal valve and in the proximal right colon (Figures 2a and b). Sources of potential ischemia were further investigated with a CT angiography of the abdomen and echocardiography, both of which were normal. Given that no source of ischemia could be identified, the patient was diagnosed with colon ischemia secondary to exercise and managed with supportive care and close follow-up. DISCUSSION: Our case highlights an episode of nonocclusive colon ischemia triggered by shunting of blood away from the colon during periods of exercise. Importantly, our patient's presentation was non-specific and not characteristic for colon ischemia, which is classically a disease of elderly patients with risk factors for atherosclerotic disease; furthermore, when colon ischemia is induced by physical activity, most case reports have shown it is due to prolong intense exercise in long-distance and marathon runners.2,3 The occurrence of colon ischemia with only a moderate level of activity may be a reflection of the significant increase in our patient's activity from baseline without complete physiological adaptation. As such, it is important that clinicians are cognizant of the possibility for colon ischemia in any patient with regular exercise patterns, in particular if this represents a recent behavior change.

Matters of life and breath: A role for hypoxia in determining cell state

Mammalian cells require oxygen for essentially all aspects of metabolism during both embryonic development and adult life [1]. Yet, in vivo, mammalian cells experience a wide range of oxygen concentrations, depending on the tissue type, proximity of cells to major arterioles and capillaries, and pathological conditions such as blood vessel occlusions, other sources of ischemia and neoplasia. Cells have therefore evolved programmed responses to very low oxygen concentrations, or hypoxia, which helps them withstand hypoxic environments. Hypoxic responses have traditionally been view as survival mechanisms that are essential for the proper function of cells that reside in naturally low oxygen tissue environments -- and for the survival of cells challenged by pathological ischemia. Now, new findings by the Blagosklonny laboratory [2] uncover a novel, non-canonical role for hypoxia in determining whether cells enter a state of quiescence or senescence. These findings have particular importance for certain stem cells, such as those in the relatively hypoxic niches of the bone marrow or tumor masses, and hence for a variety of diseases [3], especially those associated with aging.

Identification of Early Markers for Symptomatic Vasospasm in Human Cerebral Microdialysate after Subarachnoid Hemorrhage: Preliminary Results of a Proteome-Wide Screening

A major complication of aneurysmal subarachnoid hemorrhage (SAH) is symptomatic vasospasm, a complex syndrome consisting of neurological deterioration and exclusion of other sources of ischemia. Approximately 30% of SAH patients are affected. Although symptomatic vasospasm is associated with high mortality and poor clinical outcome, it is not possible to identify the individual risk on a molecular level for patients before symptoms have developed. In this study, we hypothesize that protein changes occur in the cerebral microdialysate of patients who later develop symptomatic vasospasm which are not found in matched-pairs control subjects. We searched for changes in protein concentrations in microdialysate sampled from the fronto-temporal brain tissue of five vasospastic and five nonvasospastic SAH patients using proteomics technology based on two-dimensional gel electrophoresis and mass spectrometry. Microdialysate samples were taken at least 1.5 days before the onset of symptomatic vasospasm. Comparing protein expression profiles, we found that the protein concentrations of several isoforms of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were 1.79-fold+/-1.29 (N=5, P<0.05) higher in the group which later developed symptomatic vasospasm, whereas heat-shock cognate 71 kDa protein (HSP7C) isoforms were decreased to 0.50-fold+/-0.19 (N=5, P<0.05; all expression data means+/-s.d.). The changes in protein concentrations were detected 3.8+/-1.7 days (N=5, P<0.05) before symptomatic vasospasm developed. We conclude that GAPDH and HSP7C may be used as early markers indicating the later development of symptomatic vasospasm after SAH, enabling selective early therapeutic intervention in this high-risk group of patients.

Retinal vascular alterations associated with dome-shaped and mushroom-shaped choroidal melanomas.

Retinal vascular abnormalities are associated with choroidal melanoma. Although tumor ischemia, resulting in soluble angiogenic factor production, is a proposed etiology of these abnormalities, other sources of ischemia may also contribute. Mushroom-shaped choroidal melanomas have increased loss of the overlying choriocapillaris and increased subretinal fluid when compared to dome-shaped tumors; factors that may result in outer retinal ischemia, angiogenic factor production and resultant retinal vascular abnormalities. The differing amounts of retinal vascular abnormalities overlying dome-shaped compared to mushroom-shaped melanomas were determined to evaluate this hypothesis. Retinal vascular abnormalities observed on fluorescein angiograms of eyes with choroidal melanoma were compared to the tumor configuration and presence of subretinal fluid. 23 eyes of 22 patients were included in the study. Retinal vascular abnormalities observed included dilated capillaries, telangiectatic capillaries, capillary nonperfusion, microaneurysms, neovascularization, lipid exudation and late staining of dye within the retina. Retinal vascular abnormalities were present in 4 of 14 eyes with dome-shaped tumors (29%) and in 8 of 9 eyes with mushroom-shaped tumors (89%). (Fisher's Exact Test, p = 0.009). Retinal vascular abnormalities were present in 2 of 10 eyes without subretinal fluid (20%) and in 10 of 13 eyes with subretinal fluid (77%). (Fisher's Exact Test, p = 0.012). Retinal vascular abnormalities are associated with mushroom-shaped choroidal melanomas more commonly than dome-shaped tumors. Outer retinal ischemia may result from choriocapillaris loss or the presence of subretinal fluid, contributing to soluble angiogenic factor production and resultant retinal vascular abnormalities in these eyes. Retinal vascular abnormalities are associated with mushroom-shaped choroidal melanomas more commonly than dome-shaped tumors. These retinal vascular abnormalities may be related to an increase in outer retinal ischemia associated with mushroom-shaped tumors.

Clinically Significant Nondominant Right Coronary Artery Disease

The literature is scarce regarding the management of ischemia due to disease of the nondominant right coronary artery (NDRCA). We describe two patients who suffered from myocardial ischemia due to significant disease of the NDRCA. Both were managed with balloon angioplasty. Disease of the NDRCA can be a source of ischemia and should be dealt with like other coronary vessels. (J Interven Cardiol 1996;9:59–64)