Foraging strategies and physiological status of a marine top predator differ during breeding stages.

Habitat characteristics determine the presence and distribution of trophic resources shaping seabirds' behavioural responses which may result in physiological consequences. Such physiological consequences in relation to foraging strategies of different life-history stages have been little studied in the wild. Thus, we aim to assess differences in oxidative status, condition (fat stores, i.e. triglyceride levels, TRI), stress (Heterophil/Lymphocyte (H/L) ratio), and leukocyte profiles between incubation and chick rearing highlighting the role of foraging strategies in a seabird (Calonectris diomedea). Chick rearing was more energetically demanding and stressful than incubation as demonstrated by high stress levels (H/L ratio and leukocytes) and lower body stores (assessed by TRI and the increment of weight) due to the high energy requirements of rearing chicks. Also, our results make reconsider the simplistic trade-off model where reproduction increases metabolism and consequently the rate of oxidative stress. In fact, high energy expenditure (VeDBA) during chick rearing was correlated with low levels of oxidative damage likely due to mechanisms at the level of mitochondrial inner membranes (uncoupling proteins or low levels of oxygen partial pressure). Further (more distant) and longer (more days) foraging trips were performed during incubation, when antioxidants showed low levels compared to chick rearing due to incubation fasting, a change in diet, or a combination of these factors; but unlikely because of oxidative shielding since no relation was found between oxidative damage and antioxidant capacity. Males showed higher numbers of monocytes which were positively correlated with antioxidant capacity compared to females, suggesting sexual differences in immune profiles. Species-specific costs and energetic demands of different breeding phases trigger behavioural and physiological adjustments.

Migrating birds avoid flying through fog and low clouds.

Different weather conditions are known to affect bird migration, yet the influence of fog and low clouds on migrating birds has been rarely examined so far, and hence, their impact on bird movement is not well understood. Fog avoidance could be a consequence of visual limitations within the fog or may be the outcome of deteriorated soaring conditions due to the obstruction of the sun. We carried out a radar study at the Strait of Messina, which is a bottleneck for migrating birds traversing the Central Mediterranean Sea, to determine if the intensity of diurnal soaring bird migration was influenced by fog and other weather variables. We recorded bird movements using an X-band radar, which can detect birds flying within the fog, and recorded weather conditions using local meteorological observations. We examined if bird passage rate (number of tracks/hour) at the radar site was influenced by fog, wind speed and direction, air temperature and the time of day. Our findings suggest that fog was the most important factor affecting bird migration intensity as recorded by the radar, indicating that birds actively avoided flying into fog. In addition, wind direction affected bird migration intensity, with lower numbers recorded with southerly tailwinds and higher numbers recorded with westerly crosswinds. Our findings highlight a consequence of widespread meteorological conditions, and of fog in particular, on migrating birds, with implications for bird migration navigation, path length and flight energetics.

Interactions between commercial fishing vessels and a pelagic seabird in the southern Mediterranean Sea.

BACKGROUND: Fishing activities can influence foraging behaviour of many seabird species worldwide. Seabirds are attracted by fishing vessels which can facilitate access to demersal fish as a novel food resource that otherwise would be unavailable. On the other hand, intense fishing activities cause depletion of fish stocks with a reduction of natural prey available for seabirds. Moreover, fisheries discards can have lower nutritional value than natural prey. However, the importance of fisheries discard for seabirds and the possible implications on their foraging ecology is still poorly understood. In this study, we analysed the interactions of Scopoli's shearwaters (Calonectris diomedea) during their foraging trips with fishing vessels. We combined the GPS and accelerometer data of shearwaters with the GPS data gathered during the same period from fishing vessels. Accelerometers allowed us to identify the main behaviours of birds. RESULTS: The presence of fishing vessels significantly affected the individual behaviour of Scopoli's shearwaters. Birds increased the time spent sitting on the water within 1.28 ± 0.13 km of fishing vessels likely feeding or waiting for discards. Approaches towards vessels within the interaction distance were therefore classified as an interaction and were recorded in about 40% of individuals. Birds interacting with fisheries had longer flight time during their foraging trips and covered longer distances to reach more distant foraging areas compared with individuals not approaching vessels. CONCLUSIONS: Our results suggested that fisheries discard consumption might not be a profitable source of food for Scopoli's shearwaters. Despite the high density of fishing vessels in the home range of Scopoli's shearwater, most individuals did not interact with them. Accordingly, scavenging individuals showed a lower foraging efficiency than their conspecifics. Intraspecific competition for foraging areas might play an important role for the foraging decision of birds to consume fisheries discards.

Testing cognitive navigation in unknown territories: homing pigeons choose different targets.

Homing pigeons (Columba livia) are believed to adopt a map-and-compass strategy to find their way home. Surprisingly, to date a clear demonstration of the use of a cognitive map in free-flight experiments is missing. In this study, we investigated whether homing pigeons use a mental map in which - at an unknown release site - their own position, the home loft and a food loft are represented simultaneously. In order to test this, homing pigeons were trained to fly to a 25-30 km distant food loft. A total of 131 hungry and satiated pigeons were then released from an unfamiliar site equidistant from the food loft and the home loft. Their vanishing bearings and homing times were assessed conventionally at four sites, and also their flight tracks from one release site by means of GPS loggers. The vanishing bearings of fed and hungry birds differed significantly at all release sites and a highly significant proportion of hungry birds flew to the food loft, while the fed birds headed home. The GPS experiment revealed a number of pigeons flying very precisely to the food loft, others correcting their flight direction after topography-induced detours. This implies that the pigeons knew their geographical position in relation to the targets, and chose a flight direction according to their locally manipulated needs - clearly the essence of a cognitive navigational map.

Variation of a carotenoid-based trait in relation to oxidative stress and endocrine status during the breeding season in the Eurasian kestrel: a multi-factorial study.

Carotenoid-based skin colorations vary seasonally in many bird species and are thought to be honest sexually selected signals. In order to provide more insight in the potential signal function and underlying mechanisms of such colorations we here quantified patterns of variation of leg coloration in adult male and female Eurasian kestrels (Falco tinnunculus tinnunculus) over the breeding season, and evaluated the relationship between coloration and levels of carotenoids, androgens and estrogens, oxidative damage and plasma non-enzymatic antioxidant capacity. We studied both reproducing wild and non-reproducing captive birds to test for the effect of diet and breeding effort. Males were more colored than females only during mating, and independently of diet, suggesting that leg-color is a sexually selected trait. Seasonal variation in leg color was associated with circulating carotenoids, but concentrations of these molecules were not related to antioxidant capacity, body condition or oxidative damage. These results indicate that carotenoid-based colorations may not be an honest signal of health status in this species. Production of carotenoid rich eggs coincided with low levels of circulating carotenoids in females, indicating that carotenoids might be a limited resource for laying female kestrels. Finally, young rearing males had higher levels of oxidative damage than females, and wild birds of both sexes had higher levels of these parameters than captive birds. These results may indicate that parental effort and physical activity are costly, independently from hormonal status. Since androgens did not explain carotenoid variation we suggest that multiple interacting factors can regulate carotenoid levels along the season.

Secondary prevention of coronary heart disease. A survey in an Italian primary care practice.

AIM: Management of patients with pre-existing coronary heart disease (CHD) relies for the most part on primary care physicians, an endeavour whose success is dependent upon acceptance and day-to-day application of guideline recommendations for secondary CHD prevention. The aim of this study is to analyze the status of secondary CHD prevention in an Italian primary care practice consisting of five partnered general practitioners attending 7006 subjects aged 15 years or more (3137 males, 3869 females) in Pontedera, Tuscany. METHODS: Retrieval of patients with history of CHD (previous myocardial infarction, [MI], and stable angina) from computerized records of the 5987 (2735 men, 3252 women) subjects aged 35-85 years enlisted in the practice. Patients with myocardial infarction <3 months at the time of the query were excluded. RESULTS: Search retrieved 153 (2.6%) subjects with history of CHD, 93 (3.4%) males and 60 (1.8%) females. Females were older and smoked more frequently than men. Antiplatelet drugs, beta-blockers, renin-angiotensin system blockers and statins were prescribed in 84%, 56%, 66% and 68% of the ischemic patients. LDL cholesterol targets of 100 and 70 mg/dL were achieved in only 60 (45%) and 11 (9%) respectively. Systolic blood pressure was above 140 mmHg in 25 out of 146 patients with available data. CONCLUSION: The surveys shows satisfactory uptake of guideline recommendations but also pitfalls in the implementation of secondary CHD prevention requirements. Targeted interventions on primary care physicians are critically needed to enhance further provider adherence to consensus guidelines for CHD risk reduction.

Long-term clinical outcomes in critical limb ischemia--A retrospective study of 181 patients.

OBJECTIVE: Critical limb ischemia (CLI) is the most severe manifestation of the peripheral arterial disease. To date, several prognostic factors have been identified but the data of long-term follow-up in real life setting are scarce. The aim of our study is to describe a large group of CLI patients and identify possible prognostic factors, in a long-term follow-up. PATIENTS AND METHODS: Case-control, retrospective study. 181 consecutive CLI patients with a minimum follow-up of 5 years were included in the study. RESULTS: Overall mortality was 15%, 24%, and 43% at 1, 2, and 5 years, respectively. Among known risk factors, only arterial hypertension was significantly correlated with survival rate; no differences were found between diabetics and non-diabetics. Patients treated with intravenous iloprost (46%), compared to untreated patients, showed a better (p < 0.0001) long-term outcome in terms of major amputation (6% vs. 21%), subsequent vascular surgery (4% vs. 32%) and survival rates (69% vs. 47%), at 5-year follow-up. Major amputations were significantly correlated with lower median forefoot transcutaneous values of O2 (0/3 mmHg, p < 0.001) and higher median values of CO2 (83/53 mmHg, p < 0.0001) in supine/dependent position, respectively. CONCLUSIONS: Our results confirm the poor prognosis of CLI patients in a very long-term follow-up and the severe metabolic damage caused by ischemia. A favourable role of iloprost was observed, in agreement with previous evidence in the literature.

Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients.

OBJECTIVE: Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ. PATIENTS AND METHODS: A retrospective study enrolling 102 consecutive patients between 2004-2008, with clinical and instrumental (ultrasound, angiography, transcutaneous tensiometry of oxygen TcpO2 and carbon dioxide TcpCO2 in the affected and contralateral limbs) diagnosis of critical ischemia. All patients received the best medical therapy. Iloprost was administered (0.5-2 ng/kg/min 6 hours/day for 2-4 weeks) in all patients initially considered unsuitable for revascularization, repeating it regularly in time every six-twelve months in the case of positive response. The minimum expected follow-up was 4 years. RESULTS: 71.5% of patients were treated with iloprost and the responder rate was 71.2%. Most of the patients were regularly retreated with repeated cycles. Initial median supine TcpCO2 in symptomatic limb was higher in untreated patients than those treated (58 vs. 49 mmHg; p < 0.05) and in non-responders compared to responders (60 vs. 49 mmHg; p < 0.05). TcpCO2 directly and significantly correlated with the highest risk of mortality and seems to represent a new accurate prognostic criterion of unfavourable short and long-term response to prostanoid. In iloprost group, major amputations were significantly reduced. Revascularization was significantly higher in non-responders (57.1% vs. 11.5%; p < 0.05). There was a significantly higher prevalence of subsequent myocardial infarction in the non-iloprost group (27.6% vs. 9.6%; p < 0.05). The survival rate of non-responders was higher than untreated up until the second year (76.2% vs. 62%; p < 0.05). At 4 years we found higher survival in patients treated with iloprost (64.3% vs. 41% in untreated; p < 0.05) and in responders (75% vs. 38.1% in non-responders; p < 0.05). CONCLUSIONS: Our results confirm the favourable role of iloprost on the long-term outcome in patients with CLI. In particular, the maximum benefit is obtained in responder patients treated with multiple cycles of infusion.

Orientation in the wandering albatross: interfering with magnetic perception does not affect orientation performance.

After making foraging flights of several thousands of kilometers, wandering albatrosses (Diomedea exulans) are able to pinpoint a specific remote island where their nests are located. This impressive navigation ability is highly precise but its nature is mysterious. Here we examined whether albatrosses rely on the perception of the Earth's magnetic field to accomplish this task. We disturbed the perception of the magnetic field using mobile magnets glued to the head of nine albatrosses and compared their performances with those of 11 control birds. We then used satellite telemetry to monitor their behavior. We found that the ability of birds to home specific nest sites was unimpaired by this manipulation. In particular, experimental and control birds did not show significant differences with respect to either foraging trip duration, or length, or with respect to homing straightness index. Our data suggest that wandering albatrosses do not require magnetic cues to navigate back to their nesting birds.

A large outdoor radial maze for comparative studies in birds and mammals.

For a comparative neurobiological analysis of spatial learning and memory, a large outdoor eight-arm radial maze was constructed which permits behavioral assessment of many avian and mammalian species both from the laboratory or the wild, using the same metric space and session schedules. It consists of a central part of 250cm diameter, and has arms of 650cm length, 170cm height and 80cm width. In order to determine appropriate training schedules for comparison of different species, we tested four mammalian and two avian species during 9-15 sessions: 18 albino rats (Rattus norvegicus), nine outdoors and nine in a conventional small indoor maze; six guinea pigs (Cavia porcellus); six rabbits (Oryctolagus cuniculus); five hedgehogs (Erinaceus europaeus); seven hooded crows (Corvus corone cornix) and six chickens (Gallus domesticus). Rats learned fast in both mazes yet significantly better in the large one. Good-to-excellent learning was also observed in juvenile rabbits and wild-caught crows, although the latter tended to avoid arms in the vicinity of the observer. Hedgehogs and chickens did not show significant learning as a group, but some individuals appeared to learn the task. Guinea pigs remained continuously passive and could not be trained. Thus, in spite of species-specific demands for reward, adaptation and pre-training, this type of radial maze permits to directly compare a wide variety of species. Such comparability is essential for an analysis of underlying neurobiological mechanisms.

Calcium channel blockers blunt postural cutaneous vasoconstriction in hypertensive patients.

The aim of this work was to test whether calcium channel blockers interfere with skin vasoconstrictor reflexes that minimize postural increases in capillary pressure and avoid fluid extravasation and eventually subcutaneous edema. Studies were conducted in 23 untreated mild to moderate essential hypertensives; drugs, either calcium channel blockers or not, were given for 2 weeks according to a crossover, sequence-randomized design. Skin blood flow was measured by laser Doppler flowmetry in two skin areas: (1) the dorsum of the foot, where arteriovenous anastomoses are poorly represented, and (2) the plantar surface of the great toe, where those anastomoses are predominant. Determinations were obtained both with the foot at heart level and with it placed passively 50 cm below the heart level; percent flow changes from the horizontal to the dependent position were the measure of postural vasoconstriction. Two dihydropyridine derivatives, amlodipine (10 mg UID) and nifedipine (60 mg UID), and verapamil (240 mg BID), a chemically unrelated compound, diminished to similar extents the postural fall in skin blood flow at the dorsum of the foot. Blockade of alpha1-adrenergic and AT-1 subtype angiotensin II receptors by doxazosin (4 mg UID) and losartan (50 mg UID), respectively, exerted no effect. Postural skin blood flow responses at the plantar surface of the great toe were unmodified during the pharmacological trials. Thus, calcium channel blockers of different chemical origins antagonized postural skin vasoconstriction at the dorsum of the foot. The data indicate altered postural capillary blood flow regulation, since arteriovenous anastomoses are anatomically absent at this site; the effect was independent of either alpha1-adrenoceptor or angiotensin II receptor antagonism. Interference with skin postural vasoconstrictor mechanisms may result in net filtration of fluid to the extravascular compartment. This mechanism might explain the as yet unknown pathogenesis of ankle edema during treatment with calcium antagonists.

Microalbuminuria and pulse pressure in hypertensive and atherosclerotic men.

To identify the biological covariates of microalbuminuria (albuminuria >/=15 microg/min) in nondiabetic subjects, brachial blood pressure, echocardiographic left ventricular mass, and other cardiovascular and metabolic parameters were evaluated in 211 untreated males (38 normal controls, 109 uncomplicated stage 1 to 3 essential hypertensives, and 64 patients with clinically stable atherosclerotic peripheral vascular disease either with [n=44] or without [n=20] essential hypertension) with normal cardiac and renal function. Compared with normoalbuminuric subjects, microalbuminuric subjects (n=67) were characterized by higher systolic blood pressure, comparable diastolic blood pressure, and, therefore, wider pulse pressure. Greater prevalence of hypertension, peripheral vascular disease, left ventricular hypertrophy, and reduced HDL cholesterol values further distinguished microalbuminuric from normoalbuminuric subjects in univariate comparisons. The risk of microalbuminuria increased by ascending pulse pressure quintiles in age-corrected logistic regression models, in which pulse pressure was more predictive than systolic pressure and was independent of mean pressure. When microalbuminuric status was regressed against a series of dichotomous (vascular and active smoker status) and continuous (age, pulse and mean pressure, left ventricular mass index, and HDL and LDL cholesterol) variables, only pulse pressure, left ventricular mass index, and smoking status were independent predictors. The association of increased albuminuria with wider pulse pressure, a correlate of the pulsatile hemodynamic load and conduit vessel stiffness as well as an important cardiovascular risk factor, may explain why microalbuminuria predicts cardiovascular events in nondiabetic subjects. The independence from concomitant vascular disease also suggests that wider pulse pressure, rather than representing a simple marker for atherosclerotic disease, influences albuminuria directly.

Forearm blood flow reserve and cardiac and renal indexes of pressure load in normotensive and hypertensive individuals.

In response to hypertension, arterioles remodel their structure, the heart develops myocardial hypertrophy, and the kidney reduces creatinine clearance and increases albuminuria. To better understand the interrelations among the target organs involved in hypertension, we evaluated minimal forearm vascular resistances--a hemodynamic index of arteriolar structure derived from mean blood pressure and maximal postischemic forearm blood flow--the echocardiographic indexes of cardiac structure, and urinary albumin excretion and creatinine clearance in 29 male mild to moderate non-macroalbuminuric essential hypertensive patients on no drugs and 11 age- and sex-matched normotensive control subjects. Minimal forearm resistances were elevated in hypertensive patients and correlated with left ventricular mass, wall thickness, and mean arterial pressure. Patients with abnormal minimal forearm resistances (2 SD above normal) were characterized by higher pressure, greater wall thickness, lower creatinine clearance, and higher albumin excretion, suggesting that maximal forearm flow capacity does relate to the hemodynamic load exerted on both the kidney and heart. However, the correlation with cardiac structure and mean arterial pressure explained only part of the variability of minimal forearm resistances. Furthermore, no correlation among these parameters was found when hypertensive patients were evaluated separately from normotensive subjects, possibly because of heterogeneous factors active on arteriolar structure and unrelated to the pressor load. Overall, the data suggest that the development of abnormal minimal forearm resistances in the course of the hypertensive process is related to the pressor load, but its details need further understanding.

Ultrasonic videodensitometric analysis of two different models of left ventricular hypertrophy. Athlete's heart and hypertension.

Absolute or relative increases in intramyocardial fibrosis accompany hypertrophy development in human hypertension. Myocardial texture analysis of two-dimensional echocardiographic gray-level distribution has been shown to identify alterations attributed to abnormal collagen content in several conditions. Therefore, this echocardiographic tool might help to identify those hypertensive individuals with abnormal interstitial collagen deposition, a condition that may promote and/or aggravate morbidity in this group of people who are at high risk for cardiovascular events. We compared male essential hypertensive subjects who had marked cardiac hypertrophy (left ventricular mass index adjusted for height > 2 SD of mean of control group) (group 1) with normotensive elite veteran athletes who had comparable cardiac hypertrophy (group 2) and sedentary normotensive subjects as controls (group 3). The groups (n = 14 each) were matched for age (+/- 2 years) and sex. We analyzed echocardiographic digitized data quantitatively by means of a calibrated 256 gray level digitization system to calculate midseptal and midposterior end-diastolic and end-systolic mean gray levels and to derive the so-called cyclic variation index, ie, the percent mean gray level variation during the cardiac cycle. Echocardiographic parietal and septal thicknesses and masses were evaluated according to the Penn convention. Left ventricular mass index (adjusted for height) overlapped between groups 1 and 2 (187.1 +/- 17.5 and 181.3 +/- 19.3 g/m, respectively; P = NS), whereas it was obviously smaller in control subjects (93.1 +/- 18.6 g/m; P < .001 for both). According to inclusion criteria, both septal and posterior wall thicknesses were comparable in athletes and hypertensive subjects, and they were higher than in the control group (P < .0001). The hypertensive subjects showed a significantly lower cyclic variation index than the control and athlete groups for both the septum (P < .001) and posterior wall (P < .001); no statistical difference was found between athletes and control subjects for this parameter. In conclusion, abnormalities of two-dimensional echocardiographic gray-level distribution are present in hypertensive hypertrophied individuals but seem unrelated to the degree of echocardiographic hypertrophy as such. An altered collagen network distribution or a decrease in capillary distribution in severe myocardial hypertrophy, secondary to pressure-volume overload in hypertension with other yet unknown mechanisms, could help to explain our findings. Further work is needed to establish the prognostic, clinical, and therapeutic implications of these findings.

Microalbuminuria and erythrocyte sodium-hydrogen exchange in essential hypertension.

Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min) and abnormalities of red blood cell sodium-hydrogen exchange coexist in essential hypertensive patients. To evaluate how the two phenomena relate, we recruited 10 untreated microalbuminuric male essential hypertensive patients without diabetes to be compared with an equal number of matched essential hypertensive patients excreting albumin in normal amounts as well as 10 healthy control subjects. Sodium-hydrogen exchange values were increased to a comparable extent in microalbuminuric and normoalbuminuric hypertensive patients. Systolic and mean blood pressures were higher in microalbuminuric patients. Fasting insulin was greater and high-density lipoprotein cholesterol lower in patients than control subjects. Urinary albumin excretion correlated positively with both mean blood pressure and left ventricular mass values in the absence of a relationship with circulating lipid and insulin levels. In contrast with microalbuminuria, sodium-hydrogen exchange covaried only with high-density lipoprotein cholesterol and insulin levels. Thus, microalbuminuria and an abnormal sodium-hydrogen exchange are unrelated phenomena in essential hypertensive patients. Microalbuminuria appears to be a hemodynamically driven biological variable, while an accelerated sodium-hydrogen exchange seems primarily conditioned by the metabolic abnormalities of hypertension, possibly in the context of an insulin-resistant syndrome.

Transvascular and urinary leakage of albumin in atherosclerotic and hypertensive men.

Increased urine albumin is associated with atherosclerotic disease and predicts cardiovascular morbidity and mortality in nondiabetic populations. This finding is frequently postulated to reflect the impact of atherosclerotic damage on glomerular and systemic capillary permeability, an interesting but as yet untested hypothesis. The transcapillary escape rate of albumin (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of capillary macromolecular permeability), albuminuria, lipid levels, echocardiographic wall thickness, and insulin responses to oral glucose were measured in 30 untreated dipstick-negative lean men and clinically stable atherosclerotic peripheral vascular disease; tolerance to oral glucose was a requirement for inclusion in the study. Because hypertension per se might influence TERalb, the sample included either normotensive (n=18, 118+/-6/72+/-7 mm Hg) or hypertensive (n=12, 141+/-7/84+/-6 mmHg by 24-hour blood pressure monitoring) arteriopathic patients; 11 normal age- and gender-matched subjects (121+/-7/76+/-5 mmHg) were used as control subjects. TERalb was higher in patients (10.7+/-3.2 versus 7.4+/-1.7%/h, P<0.013), a difference that persisted after postload glucose, insulin, and lipid levels were accounted for by covariance analysis; atherosclerosis and hypertension together did not further impair vascular permeation to albumin. In contrast with TERalb, albuminuria was elevated only in the hypertensive subgroup; the 2 variables showed no relationship, even when the data were analyzed separately in normotensive and hypertensive subgroups. Urine albumin correlated positively with 24-hour blood pressure and wall thickness. Thus, systemic capillary permeability is altered in nondiabetic atherosclerotic patients independently from blood pressure levels, but this abnormality is not reflected by proportionate changes in albuminuria.

Microalbuminuria and transcapillary albumin leakage in essential hypertension.

Microalbuminuria (an increased urinary albumin excretion that is not detectable by the usual dipstick methods for macroproteinuria) predicts cardiovascular events in essential hypertensive patients. A possible reason for this behavior is that albumin leaks through exaggeratedly permeant glomeruli exposed to the damaging impact of subclinical atherogenesis. To evaluate this possibility, the transcapillary escape rate of albumin (TER(alb), the 1-hour decline rate of intravenous (125)I-albumin), a parameter that estimates the integrity of systemic capillary permeability, albuminuria, blood pressure, echocardiographic left ventricular mass, lipids, and body mass index were measured in 73 uncomplicated, glucose-tolerant men with essential hypertension and normal renal function; 53 were normoalbuminuric, and 20 were microalbuminuric. Twenty-one normotensive age-matched male subjects were the controls. TER(alb) was higher in hypertensives, a behavior explained in part by a positive correlation with blood pressure values, although body mass index, lipids, and left ventricular mass showed no association. Transcapillary albumin leakage values did not differ between normoalbuminuric and microalbuminuric patients and were unrelated to albuminuria. Blood pressure, particularly systolic, and cardiac mass were higher in microalbuminuric patients in whom albuminuria correlated with both cardiovascular variables and indicated the influence of the hemodynamic load on urinary albumin levels. Thus, TER(alb), a parameter influenced by the permeability surface area product for macromolecules and the filtration power across the vascular wall, is altered in essential hypertensives. However, this abnormality is dissociated from the amount of albuminuria, which is contrary to the hypothesis that a higher albumin excretion reflects a greater degree of systemic microvascular damage in essential hypertension.

Ultrasonic myocardial texture versus Doppler analysis in hypertensive heart: a preliminary study.

-Doppler-derived parameters of transmitral flow are useful indices of diastolic dysfunction in the hypertensive heart. Different degrees of myocardial involvement in hypertensive heart can be detected by videodensitometric myocardial textural analysis. The aim of this study was to compare Doppler-derived and ultrasonic videodensitometric parameters in the differentiation of healthy hearts from hypertensive hearts. We compared a group of age-matched (59+/-9 years) male essential hypertensive patients (n=53) with normotensive healthy subjects as controls (n=32). All subjects provided ambulatory blood pressure measurements for the evaluation of 24-hour mean systolic and diastolic blood pressure. A transmitral flow Doppler analysis was performed on all subjects. A quantitative analysis of the echocardiographic digitized imaging was performed with the help of a calibrated digitization system to calculate the septum and the posterior wall textural parameters. The myocardial mean gray level (MGL) was calculated to derive the cyclic variation index (CVI): (MGLend-diastolic-MGLend-systolic)/MGLend-diastolic x100. When compared with controls, the hypertensive patients showed a significantly lower CVI for both septum (-11.1+/-26.8% versus 34. 7+/-16.3%; P<0.001) and posterior wall (-11.2+/-27.6% versus 38. 2+/-15.4%; P<0.001). Individual analyses for the ratio of peak transmitral flow velocity in early diastole to the peak transmitral flow velocity in late diastole showed that only 24% of the patients (13/53) were discriminated from normal subjects by this parameter. Individual analyses for CVI, however, at both septum and posterior wall levels, showed that 74% of the patients (39/53) were discriminated from normal subjects by this second parameter. In comparison with Doppler-derived indices of diastolic filling, the videodensitometric parameters showed a significantly higher ability to discriminate between hypertensive subjects and normal controls.

Simvastatin, capillary permeability, and acetylcholine-mediated vasomotion in atherosclerotic, hypercholesterolemic men.

OBJECTIVES: The aim of this study was to test the effect of high-dose simvastatin therapy on vascular permeability, a key variable in the atherogenic process, and endothelial-mediated vasodilator responses in patients with hypercholesterolemic atherosclerosis. METHODS: The transcapillary albumin escape rate (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of macromolecular permeability of capillary endothelium) and forearm vasodilatation (venous plethysmography) to intraarterial acetylcholine and sodium nitroprusside (7.5, 15, 30 microg/min and 0.8, 1.6, and 3.2 microg/min respectively, 5 minutes at each rate) to account for endothelium-dependent and independent mechanisms, were measured at baseline and after 1-month simvastatin (40 mg once daily) in 16 hypercholesterolemic (low-density lipoprotein cholesterol >130 mg/dL), atherosclerotic men. Thirteen healthy, untreated subjects were the controls. RESULTS: Baseline TERalb was higher and responsiveness to both acetylcholine and sodium nitroprusside was depressed in patients compared with controls. One-month high-dose simvastatin reduced low-density lipoprotein cholesterol by 39%, normalized TERalb, and improved local vasomotor responses to acetylcholine, without modifying those to sodium nitroprusside. Changes in TERalb and acetylcholine-mediated vasodilatation were dissociated and unrelated to lipid modifications. CONCLUSIONS: Low-density lipoprotein cholesterol reduction through 1 month of high-dose simvastatin normalized the exaggerated transvascular albumin leakage of patients with hypercholesterolemic atherosclerosis, perhaps by restoring an exaggerated endothelial permeability, apparently through mechanisms independent of circulating lipids. Improvements in acetylcholine-mediated vasomotion were also evident, but were dissociated from TERalb, demonstrating a heterogeneous behavior of the 2 indices of endothelial function in response to high-dose statin treatment.

Local insulin infusion stimulates expression of plasminogen activator inhibitor-1 and tissue-type plasminogen activator in normal subjects.

PURPOSE: Plasma levels of plasminogen activator inhibitor-1 are increased in obesity, hypertension, and diabetes. Their correlation with insulin levels supports the hypothesis that hypofibrinolysis may affect the development of atherosclerotic complications in patients with insulin resistance. To investigate the effect of insulin on fibrinolysis, we evaluated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) antigens during insulin infusion in the forearm vascular beds of 8 healthy subjects. MATERIALS AND METHODS: Insulin was infused in the brachial artery of each subject to raise local venous concentrations to approximately 100 microU/mL. Blood samples were obtained from the brachial artery and vein at baseline, after 30, 60, 90, and 120 minutes of infusion, and 30 minutes after the end of the infusion. RESULTS: Following intra-arterial infusion of insulin, forearm blood flow (mean +/- SD) increased progressively from 2.7 +/- 0.6 to 4.0 +/- 0.6 mL/dL/min (P <0.01) and did not return to baseline after the end of the infusion. Plasminogen activator inhibitor-1 balance increased (345 +/- 160 versus 8 +/- 152 fmol/dL/min, P <0.02) at 60 minutes, reaching baseline levels after the end of the infusion. After 90 minutes, tPA balance increased (40 +/- 26 versus 7 +/- 29 fmol/dL/min, P <0.01) with a profile similar to forearm blood flow. CONCLUSIONS: Local hyperinsulinemia induces regional vasodilation and expression of PAI-1 and tPA antigens. An alteration of this physiological process could be involved in the development of hypofibrinolysis and atherosclerosis in states of insulin resistance.