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Biomedical subjects

R Pedrinelli

Publications and source records attributed to R Pedrinelli.

At least 55 records · Page 3Linked to original sources
PubMed1997

Myocardial and forearm blood flow reserve in mild-moderate essential hypertensive patients.

BACKGROUND: Structural readaptation of systemic resistance-sized arterioles in response to an elevated blood pressure reduces the forearm vasodilator reserve in patients with essential hypertension. The development of a similar process at the coronary microvascular level has frequently been hypothesized, but little information about coronary remodeling during the uncomplicated stage of hypertension has been obtained, and the relationship with concomitant changes in forearm blood flow reserve is not known. OBJECTIVE: To assess the minimal myocardial resistance and its relationship with the minimal forearm resistance in a group of male patients with mild-to-moderate uncomplicated hypertension and carefully matched controls. MATERIAL AND METHODS: The minimal myocardial resistance (Rmin(myocardia), the mean arterial pressure: hyperemic myocardial flow ratio after administration of 0.84 mg/kg dipyridamole, measured by using positron emission tomography and [3N]-ammonia), minimal forearm vascular resistance (Rmin(forearm), a hemodynamic index of arteriolar structure derived from the mean blood pressure and maximal postischemic forearm blood flow by venous plethysmography), echocardiographic cardiac mass and wall thickness were measured in 25 male patients with mild-to-moderate uncomplicated essential hypertension, most of whom had previously been treated, and in seven sex- and age-matched normotensive controls. RESULTS: Rmin(myocardial) (and hyperemia: baseline myocardial flow ratios) did not differ significantly between the two groups, whereas Rmin(forearm) was significantly higher in hypertensives. There was no significant intra-individual correlation between the two parameters. The left ventricular mass index was greater in patients and was related previously to Rmin(forearm) but not to Rmin(myocardial) for the overall sample. In a subgroup analysis, Rmin(forearm) values were 2SD above control values in nine patients and within the normal range in the remaining 16. The myocardial reserve was very similar in the two subgroups. CONCLUSIONS: The myocardial vasodilator reserve appeared to be preserved in these mild-to-moderate uncomplicated hypertensive patients, whereas the forearm vasodilator capacity was reduced, suggesting that the hypertensive readaptation process was not distributed homogeneously over the two vascular beds.

Adaptation, Physiological↗
PubMed1997

Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis.

Vascular cell adhesion molecule-1 (VCAM-1) is a protein expressed on the surface of activated endothelial cells and expressed in early atherosclerosis. Because part of the protein is shed in the circulation and can be detected in peripheral plasma [soluble (s) VCAM-1], we hypothesized that sVCAM-1 may be a circulating marker of the presence and severity of atherosclerosis in humans. We selected 11 patients with essential hypertension plus peripheral vascular disease (PVD) and matched them for age, gender, body mass index, and smoking habits with 11 patients with uncomplicated essential hypertension (UH) and 11 healthy controls. We evaluated plasma concentrations of sVCAM-1 along with those of the soluble form of two other endothelial leukocyte adhesion molecules [sE-selectin and s-intercellular adhesion molecule-1 (sICAM-1)] and other markers of endothelial dysfunction/ damage [s-thrombomodulin, plasminogen activator inhibitor type I, and von Willebrand factor (vWF)]. We also measured insulin, glucose, fibrinogen, total and HDL cholesterol, and the urinary albumin excretion (UAE), which may also be related to atherosclerosis. Results of these assays were related to the echographic assessment of the maximum intima-media thickness (IMTmax) at the carotid bifurcation, as an index of atherosclerosis in the carotids. PVD patients had a clearly elevated IMTmax [2.7 (1.1-3.1) mm, median (range)] compared with both UH patients [1.2 (0.8-2.4) mm] and controls [1 (0.6-2) mm]. sVCAM-1 was clearly higher in PVD patients [990 (273-1808) ng/mL, median (range)] versus 340 (236-975) ng/mL in UH and 386 (204-835) ng/mL in controls, and it separated clinical categories better than sICAM-1, vWF, glucose, insulin, UAE, triglycerides, or total, LDL or HDL cholesterol, sVCAM-1 was also the best biohumoral correlate of IMTmax (R = .59; P < .001) in univariate analysis. Because many of the biohumoral variables assessed were mutually intercorrelated, they were entered in a multivariate analysis to assess their contribution in explaining IMTmax variability. sVCAM-1 remained the only independent predictor of IMTmax and totally abolished the contribution of other variables to IMTmax variability. Thus, sVCAM-1 is a good biohumoral correlate of overt atherosclerosis, independent of underlying hypertension, and may be an in vivo marker of endothelial activation. Its potential value as a surrogate for global risk assessment and its behavior in intervention studies remain to be determined.

Aged↗
PubMed1997

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.

Adult↗
PubMed1997

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.

Analysis of Variance↗
PubMed1996

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries.

BACKGROUND: To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. METHODS AND RESULTS: Specimens were mounted on a myograph and relaxes through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A(2)-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. CONCLUSIONS: Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A(2) adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3' 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

Journal Article↗
PubMed1996

Erythrocyte sodium-hydrogen exchange and microalbuminuria in type I diabetes.

OBJECTIVE: To evaluate the relationship between sodium-hydrogen (Na+/H+) exchange and microalbuminuria (an abnormal urinary albumin/creatinine ratio in morning collections) in IDDM patients. RESEARCH DESIGN AND METHODS: Amiloride-sensitive H+ efflux from cells acid loaded at pH 6.5 (defined as erythrocyte Na+/H+ exchange) was measured in normotensive IDDM patients with microalbuminuria and normal renal function (n = 16, serum creatinine < 106.1 mumol/l) and compared with both matched uncomplicated normoalbuminuric diabetic subjects and normal subjects (n = 16 each). RESULTS: Erythrocyte Na+/H+ exchange was elevated to a similar extent in diabetic patients with and without microalbuminuria. Blood pressure and lipids were normal in both diabetic groups. Daily insulin requirement, blood glucose, and glycated hemoglobin were higher and retinopathy more frequent in microalbuminuric patients. CONCLUSIONS: The abnormal erythrocyte Na+/H+ exchange of type I diabetic patients was unrelated to microalbuminuria and could not be ascribed to hypertension or dyslipidemia. Furthermore, the degree of metabolic control seemed to influence the progression of diabetic nephropathy, but not the abnormal antiport activity. The data imply that Na+/H+ exchange is an unlikely marker of nephropathy in type I diabetic patients.

Adult↗
PubMed1995

Pressor, renal and endocrine effects of L-arginine in essential hypertensives.

The pressor, renal and endocrine effect of the physiological precursor of endothelial derived nitric oxide, L-arginine was compared, with a substrate inactive on nitric oxide, hypertonic D-glucose, in hypertensive patients. Ten mild-moderate essential hypertensives were assigned to either L-arginine (n = 5) or D-glucose (n = 5). Substances were infused over 25 min at equiosmolal rates preceded and followed by saline infusion for 25 min. Blood pressure and heart rate were monitored at 3-min intervals, while hormonal and humoral variables, inulin and paraaminohippurate clearance and electrolyte excretion were measured at the end of each period under conditions of maximal diuresis. L-arginine and D-glucose increased serum osmolality comparably and caused similar haemodilution to that with control saline. During L-arginine infusion, systolic and diastolic blood pressure decreased by 16.6% and 11%, respectively, and recovered in the postinfusion period. Heart rate, plasma renin activity, and plasma noradrenaline did not change significantly. The percent blood pressure decrement induced by L-arginine was significantly greater than that by D-glucose. Glomerular filtration rate was stable and renal plasma flow was increased by both substances. However, natriuresis, kaliuresis and chloruresis were markedly stimulated only by L-arginine, which also promoted the development of systemic acidosis, possibly as a consequence of hydrochloridric acid generated during its metabolism. Circulating insulin, atrial natriuretic peptide, growth hormone and glucagon levels were increased and plasma aldosterone was unchanged during infusion of L-arginine. Insulin was stimulated and the other hormones inhibited during infusion of D-glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1995

The value of dipyridamole echocardiography in risk stratification before vascular surgery. A multicenter study. The EPIC (Echo Persantine International Study) Group--Subproject: Risk Stratification Before Major Vascular Surgery.

PURPOSE: Patients undergoing major vascular surgery are at relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for peri-operative risk stratification. PATIENTS AND METHODS: One hundred and twenty-one patients undergoing vascular surgery (age 65 +/- 7 years) were studied by dipyridamole echocardiography testing in six different centres. Of the total 136 patients, 15 were subsequently excluded because surgery was either cancelled (n = 8) or postponed pending cardiac revascularization (n = 7) because of the presence of a 'high-risk' stress echo response (identified 'a priori' as a positive dipyridamole echocardiography testing with a dipyridamole-time < 5 min and/or a peak wall motion score index > 2, upon scoring each segment from 1 = normal to 4 = dyskinetic in an 11-segment model). RESULTS: No major complications occurred during dipyridamole echocardiography testing. Technically adequate images were obtained in all patients; however, in one patient only the low dipyridamole dose (56 mg.kg-1 over 4 min) was given to limit side effects. Of the 121 patients undergoing surgery 28 (23%) had a positive test. Peri-operative events occurred in nine patients (8%): two deaths, two myocardial infarctions, five cases of unstable angina. Sensitivity and specificity of dipyridamole echocardiography testing for predicting cardiac events were 78% and 81%, respectively, with a positive predictive value of 25% and a negative predictive value of 98%. Dipyridamole echocardiography testing effectively singled out patients with, from those without, events, but neither clinical parameters, such as Detsky score, nor baseline echo parameters, such as resting wall motion score index or ejection fraction were able to distinguish between such patients. CONCLUSION: In conclusion, dipyridamole echocardiography testing is safe and well tolerated in patients undergoing major vascular surgery, and provides an effective pre-operative screening test for risk stratification of these patients mainly due to the extremely high negative predictive value. Stress echocardiography is a better discriminator than clinical and rest echocardiographic variables.

Aged↗
PubMed1995

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.

Aged↗
PubMed1995

Relationship between carotid wall thickness and forearm blood flow reserve in hypertension.

BACKGROUND: The development of a reduced forearm blood flow reserve and an increased carotid intima media thickness is a well known consequence of the structural adaptation of arterioles and large arteries in response to hypertension. It is unknown, however, how those two processes relate to each other in the individual hypertensive patient. METHODS: Minimal forearm vascular resistances (Rmin, the ratio of mean blood pressure to postischemic plethysmographic peak forearm blood flow), common carotid intima media thickness (IMT, high-resolution ultrasonography), blood pressure (indirect method), left ventricular mass, posterior wall and septum thickness (by echocardiography) and lipids were measured in 15 men with mild-to-moderate essential hypertension without evidence of atherosclerotic involvement of the carotid arteries, and in 14 normotensive controls with a similar age range. RESULTS: Rmin and IMT were greater in hypertensives, and a statistically significant positive correlation existed between the two variables. Both Rmin and IMT correlated with left ventricular structure indices and blood pressure. Age showed a positive correlation with IMT, while lipids were unrelated to either parameter. CONCLUSIONS: The micro- and macrovascular segments of the hypertensive circulation readapt in parallel in response to elevated blood pressure, possibly through the commensurate development of medial hypertrophy.

Arterioles↗
PubMed1994

Microalbuminuria and endothelial dysfunction in essential hypertension.

Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min) and endothelial dysfunction coexist in patients with essential hypertension. To evaluate whether the two phenomena are related and the determinants of that association, we recruited 10 untreated males with essential hypertension and microalbuminuria without diabetes to be compared with an equal number of matched patients with essential hypertension excreting albumin in normal amounts and 10 normal controls. The status of endothelial function was inferred from circulating von Willebrand Factor antigen (vWF), a glycoprotein secreted in greater amounts when the vascular endothelium is damaged. vWF concentrations were higher in hypertensive patients with microalbuminuria than in hypertensive patients without and controls. Individual vWF and urine albumin-excretion values were correlated (r = 0.55, p < 0.002). Blood pressure correlated with both urinary albumin excretion and vWF. Left ventricular mass index and minimal forearm vascular resistances were comparable in patients with hypertension and higher than in controls; total and low-density lipoprotein cholesterol, triglycerides, lipoprotein-a, Factor VII, and plasminogen activator inhibitor-1 did not differ. Fibrinogen was higher and creatinine clearance lower in microalbuminurics. Albuminuria in essential hypertension may reflect systemic dysfunction of the vascular endothelium, a structure intimately involved in permeability, haemostasis, fibrinolysis, and blood pressure control. This abnormality may have important physiopathological implications and expose these patients to increased cardiovascular risk.

Albuminuria↗
PubMed1994

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.

Adult↗
PubMed1994

Transcutaneous oxygen tension measurement in patients with chronic arterial obstructive disease: reliability and long-term variability of the method.

Although transcutaneous oxygen tension (TcpO2) measurement may be useful for assessing changes in regional perfusion induced over time by drug or surgical treatment in patients with chronic arterial obstructive disease (CAOD), the reliability of the method over a long-term period is not know. To approach this problem, the authors evaluated retrospectively the behavior of TcpO2 measurement over time in patients with CAOD. To eliminate confounding influences due to the concomitant vascular disease at the limb level, data analysis was performed on TcpO2 measured at the right infraclavicular position. The median length of follow-up ranged from twenty days in 34 patients to 832 days in 3 patients (n = 2 and n = 10 individual sequential replications respectively). Initial and final TcpO2 values did not differ significantly even at the longest follow-up term, which indicates that the parameter is constant over time. The intrapatient variation coefficient of TcpO2 (calculated over at least three individual replications) ranged between an average of 11% to 16.2%. The corresponding interpatient variation fluctuated between 15.5% and 33.4%, a variability explained to some extent by sex-related influences, but, at least in the range of this sample, not by age, arterial oxygen levels, or disease status. Thus TcpO2 levels per se are stable, implying that TcpO2 measurement has the potential to record consistent changes caused by specific therapeutic interventions or the clinical evolution of patients with CAOD. However, the intrapatient and interpatient variability of the method has to be taken into account when TcpO2 is used for the follow-up and the physiopathologic study of patients with CAOD.

Aged↗
PubMed1993

The interference by nicardipine and diltiazem on alpha-adrenergic receptor-mediated vasoconstriction in isolated human subcutaneous arterioles.

The effects of nicardipine and diltiazem on alpha-adrenergic receptor-mediated vasoconstriction in isolated human subcutaneous arterioles was studied. Arterioles were mounted in a myograph and stimulated at 50% of maximal contraction with norepinephrine. The vasoconstrictor responses to an unrelated agonist, endothelin, was used for comparison. The percentage of decrement in tension produced by nicardipine or diltiazem was the parameter evaluated. Both calcium channel blockers caused an equipotent and dose-dependent relaxation of the vasoconstrictor responses to norepinephrine and endothelin I. The equipotent alpha-adrenolytic effect exerted by nicardipine and diltiazem in subcutaneous arterioles contrasts with the preferential antagonism by local nicardipine in the forearm. This suggests that the interaction between alpha-adrenergic receptor activation and structurally unrelated calcium channel blockers is affected by the regional and functional characteristics of the vessels under study.

Adult↗