Vascular Disease Prevention - Current Issue

Acute alveolar hypoxia often causes pulmonary edema which is associated with pulmonary inflammation and later on, with transition into fibrosis. Strong sympathetic activation and elevated plasma levels of catecholamines (CAs) induce similar changes in the lung. Adrenergic mechanisms are involved in circulatory changes, in formation and resolution of pulmonary edema, in the activation of proinflammatory cytokines as well as in the regulation of the extracellular matrix. As hypoxia is associated with sympathetic activation, the question arises for the role of CAs in the pathogenesis of hypoxia-induced pulmonary injury. In this review, the pathogenesis of pulmonary injury in conditions with elevated CA levels is compared with the development of hypoxia-induced lung injury. In both conditions, elevated pulmonary capillary pressure is considered to play a pivotal role in the formation of pulmonary edema. This edema is accompanied by activation of proinflammatory cytokines and inflammation, and is followed by development of fibrosis. Pathogenic mechanisms of CA- and hypoxia-induced pulmonary injuries are characterized. Similar time courses and pathogenic features of the two models of lung injury might be explained by hypoxia-induced sympathetic activation and norepinephrine release as well as by stimulation and upregulation of pulmonary α1-adrenoceptors.

The trigemino-cardiac reflex (TCR) is defined as a sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea or gastric hypermotility during the stimulation of any of the sensory branches of the trigeminal nerve. The sensory nerve endings of the trigeminal nerve transmit neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. Through this physiological response, adjustments of the systemic and cerebral circulations are initiated to change cerebral blood flow in a manner that is not yet understood. It appears that the cerebrovascular response to hypoxemia is, to a large extent, due to this reflex and generated by the activation of neurons of the rostral ventrolateral reticular nucleus. TCR is therefore an “oxygen-conserving-reflex” in human as it produces cross-tolerance to oxygen deprivation, thus reinforcing cerebral adaptation to oxygen demand/ supply mismatching via energy-sparing pathways. The existence of such endogenous neuroprotective strategies may extend beyond the actually known clinical appearance of the TCR and include the prevention of other potential brain injury states as well. Thus, we show that the beneficial effects of TCR extend beyond providing neuroprotection during the acute phase after ischemia. Induction of growth factor expression and neurogenesis by TCR might be a positive adaptation for an efficient repair and plasticity in the event of an ischemic insult.

Acute kidney injury is a serious complication following cardiovascular surgery, resulting in significant inhospital and long-term morbidity and mortality. The mortality rate is distressingly high despite improvements in intensive care and dialytic technology, but survivors experience an acceptable quality of life. Fenoldopam mesylate is a dopamine A-1 receptor agonist that decreases systemic vascular resistance while increasing renal blood flow. Fenoldopam, used as an antihypertensive drug, has recently demonstrated nephroprotective properties in critically ill patients or during major surgery. Two recent meta-analyses suggested that fenoldopam reduces the need for renal replacement therapy and mortality in critical ill patients and particularly in those undergoing cardiovascular surgery. In the first meta-analysis of 16 randomised clinical trials for a total of 1290 patients, fenoldopam usage reduced all-cause mortality (81/537 [15.1%] vs 110/581 [18.9%], OR=0.64 [0.45-0.91], p=0.01). Another meta-analysis was performed in the specific setting of cardiovascular surgery and included 1059 patients (4 trials were performed in vascular surgery and 9 in cardiac surgery). Fenoldopam dosage varied across studies, being always >0.03 μg/kg/min and most often 0.1 μg/kg/min, reaching 0.3 μg/kg/min. Fenoldopam usage reduced the risk of death and the risk of renal replacement therapy (30/528 [5.7%] in the fenoldopam group vs 71/531 [13.4%] in the control arm (OR=0.37 [0.23-0.59], p<0.001). In this article we review the evidence based medicine to support the use of fenoldopam in patients with or at risk for acute kidney injury and underline the need for a large randomized controlled study to confirm these promising results.

Background: Soluble fibrin (SF) is considered to be useful for the diagnosis of thrombosis, however, evidence for the diagnosis of pre-thrombosis by SF is still not well established. Objective: The present study was designed to evaluate the usefulness of new SF assay (New SF) in the diagnosis of thrombosis and a pre-thrombotic state. Patients/Methods: The plasma concentrations of New SF were measured in 748 inpatients suspected to have thrombosis and they correlated with thrombosis. Results and Conclusions: The plasma concentrations of New SF were significantly higher in patients with disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and cerebral thrombosis, in comparison to those of patients without thrombosis, but there was no significant difference of the New SF assay between patients with thrombosis and those after an operation. The New SF assay was moderately correlated with the other two SF assays. The New SF levels were significantly higher in patients before the onset of thrombosis than in those without thrombosis but other hemostatic molecular markers were not significantly elevated. Our findings suggest that the New SF assay is useful for the diagnosis of not only thrombosis but also of a pre-thrombotic state.

Atherosclerotic disease is a major cause of morbidity and mortality. The early detection of preclinical atherosclerosis with non-invasive tools has become paramount in order to identify the vulnerable patient and provide aggressive prevention measures. A valid surrogate marker should not only be proven to correlate with underlying atherosclerosis but also needs to be accurate, reproducible and inexpensive. There are currently a number of methods that are widely used for the detection of preclinical atherosclerosis. In this review, we chose 4 methods for discussion namely, (1) Flow-mediated dilatation, (2) Carotid intima media thickness, (3) Pulse wave velocity, and, (4) Ankle brachial index. Clinical evidence concerning their detection of underlying atherosclerosis and their predictive value of cardiovascular events together with their individual drawbacks is discussed.

Most cardiovascular functions exhibit circadian changes. On one hand, predictable-in-time differences in the physiological status of the cardiovascular system give rise to rhythmic variations in the susceptibility to morbid and mortal events. On the other, the pathological mechanisms of cardiovascular disease exhibit temporal changes in both their manifestation and severity, leading to predictable-in-time differences in the ability to precipitate the overt expression of disease. It is known that the occurrence of cardiovascular events shows temporal patterns that vary with time. The incidence of potentially life-threatening cardiovascular events, e.g. acute myocardial ischemia and infarction, sudden cardiac death, ischemic and hemorrhagic stroke, and rupture or dissection of aortic aneurysms, displays a diurnal pattern, tending to be higher in the morning. On arousal and the start of daily activities, blood pressure (BP) shows a surge that may last 4- 6 h. Morning BP surge, together with circadian variations in biochemical and physiological parameters, may be potential triggers for acute cardiovascular events. This may open up potential for applications in medical therapy. It is possible that antihypertensive medication given once daily in the morning may not protect against this surge if its duration of action is too short. Thus, the timing of drug administration or specific drug delivery systems that lead to a greater effect at night and/or mitigate the early morning BP surge may provide protection against cardiovascular events.

Acute ischemic stroke remains one of the main causes of death and disability in the world. The only approved therapy for stroke is the intravenous thrombolysis with recombinant tissue plasminogen activator within 3 h from symptom onset. The European, American and Canadian guidelines define unenhanced brain CT as the only imaging technique mandatory before thrombolysis. Its only goal is the exclusion of hemorrhage and not the diagnosis of ischemia, although the identification of early ischemic changes, involving more than one third of middle cerebral artery territory, was soon used in the therapeutic decision. At the moment the need of vascular imaging in the acute phase of stroke is sustained by several researchers and the practical directions actually in progress are the diagnosis of presence and site of vessel occlusion, whose prognostic role is demonstrated, and the perfusional evaluation for the quantification of core/penumbra mismatch and the overcoming of the time window concept. The ideal tool for identify reliably, easily, reproducibly and cheaply the vascular pattern in each patient is the ultrasound technique, particularly Transcranial Colour-Coded Duplex Sonography. It allows also the real-time monitoring of recanalization process, i.e. the timing of vessel patency restoration.