C. Corbellini

Effect of Treatment on Flow-Dependent Vasodilation of the Brachial Artery in Essential Hypertension

off aim of our study was to evaluate the effect of antihypertensive treatment on flow-mediated dilation (FMD)of a large artery, a noninvasive estimate of endothelial function, in hypertensive patients. In 78 consecutive hypertensive patients (40%men; age range, 42 to 67 years) we measured by a high-resolution ultrasound system the changes of brachial artery diameter during reactive hyperemia and after sublingual glyceryl trinitrate (400 microg); brachial artery flow velocity was measured by pulsed Doppler. The results of 2 studies are reported. In the first study, this procedure was repeated in 58 patients after 6 and 12 months of treatment with a combination of antihypertensive drugs; in a second study, the FMD was assessed in 20 patients after 2 months of monotherapy with either nifedipine or hydrochlorothiazide. In the first study, FMD was significantly increased after treatment compared with baseline (from 3.1+/-3% at baseline to 6.5+/-4.5% at 6 months and to 8.12+/-4. 6% at 12 months; P<0.001 by ANOVA), concomitant with blood pressure reduction (from 162+/-24/102+/-13 mm Hg to 141+/-12/89+/-6 mm Hg and to 141+/-9/89+/-6 mm Hg; P<0.001 by ANOVA); significant changes of endothelium-independent dilation were also observed, but only after 12 months of treatment (from 14.2+/-4.8 at baseline to 15.5+/-4.7 at 6 months and 16.8+/-5.9% at 12 months; P=0.03 by ANOVA). In the second study, FMD was significantly increased during nifedipine treatment as compared with baseline (from 5+/-6.18% at baseline to 9. 45+/-3.94%, P<0.001), while it did not change in patients receiving hydrochlorothiazide (from 5.15+/-5.28% at baseline to 4.69+/-4.34%, NS). No significant changes of endothelium-independent dilation were observed with both drugs (from 17.10+/-2.4% to 18.14+/-3.76% and from 18.73+/-4.07% to 17.46+/-4.27% during nifedipine and hydrochlorothiazide, respectively, NS). Thus, in essential hypertensive patients an improvement of the impaired FMD of the brachial artery, evaluated by noninvasive ultrasound, may be observed after long-term, effective blood pressure reduction, suggesting a beneficial effect of antihypertensive treatment on endothelial function. It seems that beyond blood pressure control, a calcium antagonist may be more effective than a diuretic in this respect.

The smoothness index, but not the trough-to-peak ratio predicts changes in carotid artery wall thickness during antihypertensive treatment.

Background It has recently been demonstrated that the smoothness index (SI) (the ratio between the average of the blood pressure changes computed for each hour of the recording and its standard deviation), a new and reproducible measure of the homogeneity of blood pressure reduction by antihypertensive treatment, has evident advantages over trough-to-peak ratio (T/P) in the prediction of the regression of left ventricular hypertrophy. Therefore we considered it to be worthwhile to compare the ability of SI and T/P to predict changes of the carotid artery intima–media thickness (IMT) during pharmacological treatment in patients with essential hypertension. Methods In 100 patients with essential hypertension, 24 h ambulatory blood pressure and carotid artery IMT were measured after 3 weeks of therapeutic wash-out and after 12 months of antihypertensive treatment (calcium antagonists, diuretics, angiotensin converting enzyme (ACE) inhibitors or β-blockers). The homogeneity of the effect of treatment over blood pressure was evaluated by computing T/P and SI. Results Twenty-four hour blood pressure was significantly reduced by therapy, while, on average, a small but significant increase in indices of carotid artery wall thickness was observed. However, IMT was clearly reduced in patients with high SI. Statistically significant correlations were observed between changes in indices of carotid artery IMT during therapy and SI. No significant correlation was observed between indices of carotid artery morphology and T/P, basal 24 h blood pressure or changes in blood pressure during therapy. Conclusions SI, but not T/P is the predictor of changes in carotid artery wall thickness. The information provided by SI is independent from basal blood pressure values. For carotid artery morphology, the smoothness of blood pressure reduction is even more important than its absolute change.

Effects of Weight Loss on Structural and Functional Alterations of Subcutaneous Small Arteries in Obese Patients

Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media:lumen ratio, are frequently present in hypertensive and/or diabetic patients and may represent the earliest alteration observed. In addition, media:lumen ratios of small arteries have a strong prognostic significance. However, no data are available about the structure of small resistance arteries of obese patients, particularly after weight loss. We have investigated 27 patients with severe obesity. Twelve of them were normotensive, and 15 were hypertensive. All of the obese patients underwent bariatric surgery. We compared results obtained with those observed in 13 normotensive lean controls and in 13 hypertensive lean patients. All of the subjects and patients underwent a biopsy of subcutaneous fat during surgical intervention. In 8 obese patients, a second biopsy was obtained after consistent weight loss, during a surgical intervention for abdominoplasty. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and structural parameters were measured. A concentration-response curve to acetylcholine was performed to evaluate endothelial function. Obese patients, independent from the presence of hypertension, show the presence of an increased media:lumen ratio and media cross-sectional area, together with an impaired endothelial-dependent vasodilatation. After surgical correction of obesity and consistent weight loss, a significant improvement of microvascular structure and of some oxidative stress/inflammation markers were observed. In conclusion, our data suggest that the presence of obesity is associated with structural alterations of subcutaneous small resistance arteries, mainly characterized by hypertrophic remodeling. Weight loss may improve microvascular structure.

Flow-mediated dilatation of the brachial artery and left ventricular geometry in hypertensive patients

Objectives In arterial hypertension, the spectrum of geometric patterns in the left ventricle may parallel the structural alterations detected in the carotid arteries and in subcutaneous small arteries. It has been also reported that hypertensive left ventricular hypertrophy (LVH) may be associated with endothelial dysfunction, as evaluated by the response of coronary or forearm vasculature to acetylcholine infusion. The aim of this study was to evaluate the flow-mediated vasodilatation (FMD) of the brachial artery, non-invasive estimate of endothelium-dependent vasodilatation according to left ventricular geometric adaptations in hypertensive patients. Methods and results In 16 normotensive (nine males, seven females, aged 40–68 years) and in 78 hypertensive subjects (50 males, 28 females, aged 42–67 years), we performed an echocardiographic study for the measurement of left ventricular mass index (LVMI) and relative wall thickness (RWT); we measured to a high resolution the brachial artery diameter at rest, during reactive hyperaemia (5 min of brachial artery occlusion) and after sublingual glyceril trinitrate (GTN); brachial artery flow velocity was measured by pulsed Doppler. Twenty-six hypertensive patients had a normal LVMI (LVMI < 51 g/m2.7) and geometry (RWT < 0.44), five had concentric remodelling (RWT ⩾ 0.44), and concentric and eccentric LVH were observed in 19 and 28 patients, respectively. FMD was reduced in hypertensive patients as compared with normotensive subjects (P < 0.01). No correlation was found between FMD and LVMI (r =− 0.078) or RWT (r = 0.049); in addition, no difference in FMD was found among the left ventricular geometric patterns in hypertensive patients. Conclusions In hypertensives, the presence of endothelial dysfunction is not associated with the LVH or with different left ventricular geometric patterns, suggesting that different and independent mechanisms may be responsible for the presence of LVH and of endothelial dysfunction.

Circulating endothelial progenitor cells, microvascular density and fibrosis in obesity before and after bariatric surgery.

Abstract It is not known whether, in obesity, the capillary density or the number of circulating endothelial progenitor cells (EPCs) are reduced, or whether fibrosis of small vessels is also present. In addition, possible effects of weight reduction on these parameters have never been evaluated. Therefore, we investigated EPCs and capillary density in 25 patients with severe obesity, all submitted to bariatric surgery, and in 18 normotensive lean subjects and 12 hypertensive lean patients as controls. All patients underwent a biopsy of subcutaneous fat during bariatric surgery. In five patients, a second biopsy was obtained after consistent weight loss, about 1 year later, during a surgical intervention for abdominoplasty. EPCs and capillary density were reduced in obesity, and EPCs were significantly increased after weight reduction. Vascular collagen content was clearly increased in obese patients. No significant difference in vascular collagen was observed between normotensive obese patients and hypertensive obese patients. After pronounced weight reduction, collagen content was nearly normalized. No difference in stress–strain relation was observed among groups or before and after weight loss. In conclusion, our data suggest that microvascular rarefaction occurs in obesity. EPCs were significantly reduced in obese patients. Pronounced weight loss induced by bariatric surgery seems to induce a significant improvement of EPC number, but not of capillary rarefaction. A pronounced fibrosis of subcutaneous small resistance arteries is present in obese patients, regardless of the presence of increased blood pressure values. Consistent weight loss induced by bariatric surgery may induce an almost complete regression of microvascular fibrosis.

Changes in midwall systolic performance and cardiac hypertrophy reduction in hypertensive patients.

Objective To investigate changes in left ventricular (LV) performance, as evaluated by measurement of midwall LV fractional shortening (FS), after reduction of cardiac hypertrophy. Design and methods Echocardiographic evaluation of LV anatomy and function was performed by M-mode echocardiography at baseline, after long-term antihypertensive therapy, and after treatment withdrawal in 68 asymptomatic hypertensive patients (50 males, 18 females, age range 22–62 years). Patients were divided according to the presence of LV hypertrophy (LVH) at baseline (LV mass index, LVMI ≥ 51 g/m2.7). Results At baseline patients with concentric (relative wall thickness >0.44) LV hypertrophy (n = 38) or remodelling (n = 7) had reduced midwall shortening with respect to patients with normal LV geometry (n = 4) or eccentric LVH (n = 19); no differences were observed for endocardial FS. After long-term treatment (average 15 months), in 11 patients LV mass remained within normal limits, in 45 patients LVH reduction was obtained, while in 12 patients LV mass remained persistently elevated. Midwall FS was significantly increased in patients with reduction of LVH both during treatment and after withdrawal of treatment, while it remained significantly lower in patients with persistently elevated LV mass. Changes in midwall fractional shortening were independently associated with modifications in relative wall thickness (P < 0.00001), with changes in end-diastolic dimensions (P < 0.0001) and those of LVMI (P < 0.02) as shown by multivariate analysis. Conclusion LV midwall systolic performance significantly improved after reduction of LVH, even in the presence of high blood pressure values. Modifications in relative wall thickness are more independently associated with changes, in LV diastolic dimensions and mass, to midwall improvement.

Calliphora vicina human myiasis: a case report

A 30-year-old man with a history of cocaine and alcohol abuse attempted suicide by jumping into a canyon in the afternoon of a warm day of summer 2011. He was found alive after 24 h, with a contused and lacerated scalp wound, several hematomas and bruises all over the body. At admission in the emergency department (ED), the patient was conscious and complained of headache and of pain throughout his entire body. Head, thorax and abdominal CT scans did not show any internal injuries or fractures. White blood cell count (18.680 mm), serum creatinine (3 mg/100 ml), serum muscle enzymes (creatine phosphokinase 10,200 mU/ml), creatine kinase isoenzyme MB (26 mU/ml) and troponin I were elevated (0.61 ng/ml). Electrolytes were normal and on the venous blood gases measurement, venous CO2 was slightly reduced and bicarbonate gap was slightly negative, possibly secondary to respiratory alkalosis compensation. The electrocardiogram showed ST segment elevation with normal concavity in the inferior leads and no other signs of cardiac injury, including dysrhythmia or significant conduction delays. The echocardiogram was normal; in particular, the LV ejection fraction was normal (68%) and no regional contractility abnormalities were observed. A diagnosis of acute renal failure secondary to volume depletion and rhabdomyolysis was made, and the patient was then admitted to the internal medicine intensive care unit for vital parameters and ECG monitoring. The head wound was cleaned, medicated and sutured immediately after admission, in the late evening. The patient was treated by fluid infusion (saline 100 ml/h and sodium carbonate 40 ml/h) and antibiotic therapy for possible bacterial infection (amoxicillin–clavulanic acid 3 g/day). The next morning, the patient was quiet and had fewer complaints of pain, but still declaring suicidal ideation. The ECG ST-segment abnormalities had regressed. Serum creatinine was decreased, as well as CPK MB and troponin I, and white cell count regressed to normal after 48 h. While dressing the head wound (about 12 h after the previous medication), a large amount of overgrowing maggots were seen (video and Figs. 1, 2 and 3). A sample of maggots was taken for microscopic examination, and a wound specimen for bacterial culture was also performed. At the microscopic examination, larvae of Calliphora vicina were identified, while the bacterial culture was negative. No change to the current treatment was made. The patient was discharged with close psychiatric follow-up. Electronic supplementary material The online version of this article (doi:10.1007/s11739-011-0720-6) contains supplementary material, which is available to authorized users.