MRI and CT in the diagnosis of coronary artery disease: indications and applications

In recent years, technical advances and improvements in cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI) have provoked increasing interest in the potential clinical role of these techniques in the non-invasive work-up of patients with suspected coronary artery disease (CAD) and correct patient selection for these emerging imaging techniques. In the primary detection or exclusion of significant CAD, e.g. in the patient with unspecific thoracic complaints, and also in patients with known CAD or advanced stages of CAD, both CT and MRI yield specific advantages. In this review, the major aspects of non-invasive MR and CT imaging in the diagnosis of CAD will be discussed. The first part describes the clinical value of contrast-enhanced non-invasive CT coronary angiography (CTCA), including the diagnostic accuracy of CTCA for the exclusion or detection of significant CAD with coronary artery stenoses that may require angioplastic intervention, as well as potentially valuable information on the coronary artery vessel wall. In the second section, the potential of CT for the imaging of myocardial viability and perfusion will be highlighted. In the third and final part, the range of applications of cardiac MRI in CAD patients will be outlined

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 µm(3) vs. 1002.4±11.8 µm(3)) and in the dentate gyrus (525.9±27.2 µm(3) vs. 421.5±24.6 µm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 µm(3)) and the dentate gyrus (536.1±27.2 µm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended

Endothelium-dependent contractions and endothelial dysfunction in human hypertension

The endothelium is a crucial regulator of vascular physiology, producing in healthy conditions several substances with a potent antiatherosclerotic properties. Accordingly, the presence of endothelial dysfunction is associated with subclinical atherosclerosis and with an increased future risk of cardiovascular events. A large body of evidence supports the fundamental role of nitric oxide (NO) as the main endothelium-derived relaxing factor. However, in the presence of pathological conditions, such as hypertension, endothelial cells, in response to a number of agents and physical stimuli, become also a source of endothelium-derived contracting factors (EDCFs), including endothelins and angiotensin II and particularly cyclooxygenase-derived prostanoids and superoxide anions. These latter were at first identified as responsible for impaired endothelium-dependent vasodilation in patients with essential hypertension. However, cyclooxygenase-dependent EDCFs production is characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. It is worth noting that both in aging and hypertension EDCF production is associated with a parallel decrease in NO availability, suggesting that this substance could be oxygen free radicals themselves. Accordingly, in hypertension both indomethacin, a cyclooxygenase inhibitor, and vitamin C, an antioxidant, increase the vasodilation to acetylcholine by restoring NO availability. In conclusion, hypertension is characterized by a decline in endothelial function, associated with a progressive decrease in NO bioavailability and increase in the production of EDCF. The mechanisms that regulate the balance between NO and EDCF, and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators remain to be determined

Effect of verapamil, trandolapril and their combination on vascular function and structure in essential hypertensive patients.

AIM: The aim of the present study is to evaluate the effect of treatment with verapamil, trandolapril and their combination on peripheral microcirculation vasoreactivity. METHODS: Twenty hypertensive patients were randomized to receive oral trandolapril (4 mg oid; TRA) or verapamil (240 mg oid; VER) for 6 months and then the combination of the two drugs for additional 6 months. At baseline, 6 months and 12 months, peripheral microcirculation vasoreactivity was evaluated by forearm blood flow technique (venous plethysmography), as vasodilation to an endothelium-dependent (acetylcholine) and an endothelium-independent stimulus (sodium nitroprusside, SNP); minimal forearm vascular resistances (MFVR) were also evaluated. RESULTS: Blood pressure decreased similarly and progressively in both groups throughout the study period. In VER, 6-month verapamil treatment significantly increased vasodilation to acetylcholine, but not to SNP. The superimposition of trandolapril increased the response to SNP, and less to acetylcholine. In TRA group, 6-month treatment with trandolapril improved the response to SNP, but not to acetylcholine. In this group, the superimposition of verapamil caused a significant improvement in the response to acetylcholine, but not to SNP. At the end of the study, MFVR were significantly reduced in both groups, but to a greater extent in TRA. CONCLUSION: The present study demonstrates that chronic treatment with verapamil ameliorates endothelial function in the forearm microcirculation of essential hypertensive patients, while trandolapril protects microcirculation from structural alterations. The combination of the two drugs is potentially a powerful tool to counteract hypertension-related microvascular dysfunction and damage

Obesity in the childhood: a link to adult hypertension

The rapid increasing prevalence of obesity worldwide represents a serious health hazard. Obesity predisposes to increased risk for diabetes, hypertension, renal failure. Direct mechanisms link visceral adiposity and the atherosclerosis process through the action of adipose-derived proinflammatory cytokines. In particular, hypertension can be considered the most important cardiovascular risk factor linking obesity to the development of cardiovascular disease. Obesity among children and adolescents has also reaching epidemic proportions in the industrialized world. Childhood obesity strongly predisposes to cardiovascular adult mortality. Recent reports documented a tracking of blood pressure from childhood to adulthood and obesity occurring in young age plays a crucial pathogenic role. Indeed, fighting overweight and obesity in the pediatric and adolescent age may prevent the occurrence of adults with hypertension and cardiovascular disease. The main strategies for prevention and treatment of overweight and obesity in childhood, which need to involve community, school and family, are the promotion of lifestyle interventions, including as a correct dietary approach, rich in fruit and vegetables and low-fat dairy products, and physical activity