Inflammation and atrial remodeling after a mountain marathon.

Endurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long-distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic-determined signal-averaged P-wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow-up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P < 0.001). Left and right atrial volumes showed no significant differences over time, and there were no correlations of atrial volumes and SAPWD. Prolongation of the SAPWD was accompanied by a transient increase in levels of high-sensitivity C-reactive protein, proinflammatory cytokines, total leucocytes, neutrophil granulocytes, pro atrial natriuretic peptide and high-sensitivity troponin. In conclusion, marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise-induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias.

Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

INTRODUCTION: Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. PATIENTS AND METHODS: We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. RESULTS: Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p < 0.05). Post-ischemic peak flow with laser-Doppler flow increased after PLC. TcPO2 increased, while TcPCO2 decreased after PLC; CO2 production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. CONCLUSIONS: In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

Haemodynamic effects of AT1 inhibition and Ca2+-channel blockade in hypertensive patients during isometric stress.

To assess the effects of valsartan and amlodipine on the haemodynamics of forearm circulation in hypertensive patients undergoing isometric stress. A total of 24 patients with essential hypertension were subjected to a double blind-cross-over study. The artery left arm flow (strain gauge plethysmography), distensibility of digital arteries (piezoelectric plethysmography) and blood pressure were measured. District resistance was calculated as the ratio between mean arterial pressure and blood flow. The tests were performed at basal conditions (T0) and after 8 days (T8) of therapy with valsartan (160 mg) or amlodipine (10 mg), at rest and during handgrip (HG); treatments were inverted after 15 days of washout. Valsartan and amlodipine reduced blood pressure after 8 days (P<0.05), handgrip increased systolic and diastolic values and heart rate at T0 and only a slight raising in diastolic values at T8. The recovery time of pressure values was longer in hypertensives treated with amlodipine (P<0.05). The forearm flow increased after HG (at T0 an T8) and increased even further after valsartan (P<0.005). Valsartan increased arteriolar distensibility, expressed by the ratio between time to peak and total time (PT/TT) calculated on the sphygmic wave. Amlodipine did not affect PT/TT ratio, whereas it reduced local resistance (T8 vs T0, P<0.05). The reduction effect of valsartan on resistance was detectable also during handgrip, on the contrary amlodipine did not control the increase. Inhibition of AT1 is able to reduce haemodynamic modifications elicited by isometric stress in hypertensive patients.

Increased fibrinogen levels and hemostatic abnormalities in patients with arteriolar nephrosclerosis: association with cardiovascular events.

Increased plasma fibrinogen levels and hemostatic abnormalities suggestive of a prothrombotic state are present in patients with end-stage renal failure and could contribute to increased cardiovascular morbidity in these patients. We investigated the relationship between abnormalities of the hemostatic system and the degree of renal failure and whether these abnormalities are associated with increased prevalence of cardiovascular events in patients with arteriolar nephrosclerosis. In 425 patients recruited at a hypertension clinic we assessed the renal function by creatinine clearance, urinary protein excretion, and microalbuminuria, the prevalence of atherosclerotic disease, and measured prothrombin time, activated partial thromboplastin time. fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, and antithrombin. Early impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) caused by arteriolar nephrosclerosis was found in 172 patients. Patients with early renal failure were significantly older and had significantly greater values of blood pressure, plasma fibrinogen, F1+2, and D-dimer than patients with normal renal function. Elevated D-dimer and fibrinogen levels were independently associated with the presence of decreased creatinine clearance. Log fibrinogen, log F1+2, and log D-dimer were inversely correlated with creatinine clearance. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was significantly greater in patients with mild renal failure than in those with normal renal function. Elevated levels of fibrinogen and D-dimer were associated with the presence of atherosclerotic disease independent of renal function and other risk factors. In conclusion, changes in hemostatic parameters occur early in the course of renal failure in patients with arteriolar nephrosclerosis, suggesting a prothrombotic state that may contribute to the risk for atherosclerotic disease at all levels of renal function.

Effects of sustained-release isradipine on blood pressure and peripheral hemodynamics in hypertensive patients.

In a double-blind crossover study, 16 hypertensive patients (mean age, 41 years) were randomly assigned to receive placebo or 5 mg of an extended-release formulation of isradipine for 30 days. Blood pressure and heart rate were recorded by an automatic device and hemodynamics measured by a duplex scanner and plethysmography. After the first dose and after 30 days' treatment with isradipine, blood pressure was significantly reduced (mean arterial pressure 4 hours after the first dose, 106 +/- 3 vs 120 +/- 4 mmHg, P < 0.01; 22 hours after the last dose, 108 +/- 3 mmHg, P < 0.01) with no significant changes in heart rate. The compliance of the brachial artery was significantly increased (2.823 +/- 0.358 vs 1.204 +/- 0.156 dyn-1.cm4.10(-7), P < 0.002) and the characteristic impedence decreased (49 +/- 6 vs 91 +/- 12 dyn.s.cm-5.10(2), P < 0.05) as well as local resistances (71 +/- 5.6 vs 198 +/- 18 mmHg.ml-1.s, P < 0.001). After 30 days of isradipine treatment, 22 hours after the last dose, compliance was still increased (2.575 +/- 0.453 dyn-1.cm4.10(-7), P < 0.01) whereas impedance and forearm vascular resistances were reduced (59 +/- 8 dyn.s.cm-5.10(2), P < 0.05, and 97 +/- 14 mmHg.ml-1.s, P < 0.001, respectively). The results indicate that sustained-release isradipine ensures good blood pressure control up to the time of the following dose and restores the large artery dumping function against cyclic variations in intraluminal pressure.

Congenitally corrected transposition of the great arteries in an 80 year old woman.

Congenitally corrected transposition of the great arteries (CCTGA) is a rare form of congenital heart disease characterised by atrioventricular as well as ventriculoarterial discordance. It is usually associated with a variety of severe intracardiac defects. Few patients with this abnormality survive past 50 years. An 80 year old woman was admitted to the hospital because of mild congestive heart failure. Cardiac examination revealed a 4/6 holosystolic and a 2/6 decrescendo diastolic murmur at the left sternal border. Radiography, echocardiography, and computed tomography confirmed newly diagnosed CCTGA without associated intracardiac defects.

Glycosylated hemoglobin in chronic alcoholics.

Glycosylated hemoglobin (Hb AI) is commonly accepted as a parameter of the last 2-3 months metabolism of the glucides; therefore its growth must be proportionate to the metabolic unbalance [1]. We observed that chronic alcoholics often had significantly increased levels of Hb AI when compared with normal controls, although with a normal oral glucose tolerance test (OGTT); we therefore tried to correlate other metabolic factors with glycosylated hemoglobin: uricemia, triglyceridemia, cholesterolemia and high density lipoprotein (HDL)-cholesterol.

Correlation between peripheral hemodynamic changes and left ventricular diastolic function in hypertensive patients treated with urapidil.

We evaluated the modifications induced by chronic treatment with an alpha 1-adrenolytic hybrid drug, urapidil, on the hemodynamic parameters in peripheral artery and left ventricle diastolic function. Fifteen mild to moderate essential hypertensive patients (13 men, 2 women; mean age 42 years, range 32-54 years) received urapidil (60 mg b.i.d.) for 6 months. Peripheral hemodynamic and cardiac parameters were evaluated by duplex scanner, coupled with a plethysmographic method, basally (T0) and after 6 weeks' (T1) and 6 months' treatment (T2). Mean blood pressure (BP) showed a reduction after 6 weeks of -9.07 mm Hg (confidence intervals [CI] 95%: -9.21; -8.92; P < 0.01), which was maintained after 6 months (-8.21 mm Hg, CI 95%: -8.97; -7.43; P < 0.01), while no significant change was seen in heart rate. Compliance showed highly significant changes after both 6 weeks (+1.073 dyn-1.cm4.10(-7), 95% CI: +0.965; +1.181, P < 0.001) and 6 months (+0.933 dyn-1.cm4. 10(-7), 95% CI: +0.903; +0.963, P < 0.001), as well as characteristic impedance (T1:-16.689 dyn.s.cm-5/10(2), 95% CI: -16.914; -16.463 P < 0.001; T2: -15.98 dyn.s.cm-5. 10(2), 95% CI: -18.186; -13.784; P < 0.001) and forearm resistances (T1: -26.153 mm Hg.ml-1.s, 95% CI: -34.553; -17.753, P < 0.01; T2: -43.587 mm Hg.ml-1.s, 95% CI: -52.711; -34.464, P < 0.01). Similarly, we have recorded a similar change in left ventricular end-diastolic posterior wall thickness (T1: -1.067 mm, 95% CI: -1.099; -1.035, P < 0.01; T2: -2.866 mm, 95% CI: -3.044; -2.688, P < 0.01), end-diastolic interventricular septum thickness (T1: -0.921 mm, 95% CI: -1.511; -0.289, P < 0.05; T2: -2.711 mm, 95% CI: -3.211; -2.199, P < 0.01), end-diastolic volume (T1: +6.4 ml, 95% CI: +6.343; +6.456, P < 0.01; T2: +19.867 ml, 95% CI: +18.564; +21.170, P < 0.01), and mass/volume index (T1: -0.11, 95% CI: -0.118; -0.101, P < 0.01; T2: -0.218, 95% CI: -0.221; -0.217, P < 0.01). Changes in arterial compliance have shown a statistically significant correlation with changes in mass/volume index (r = -0.468; P < 0.03), end diastolic volume (r = 0.501; P < 0.02), as well as left ventricle rapid filling phase (r = 0.426; P < 0.05) and left ventricle end diastolic posterior wall thickness (r = -0.478, P < 0.03). Our results suggest that the antihypertensive efficacy of urapidil coupled with the restoration of the dumping function of the large arteries, and the reduced activation of reflex sympathetic activation, may play a considerable role among the mechanisms allowing the regression of the functional modifications affecting the left ventricular diastole.

Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.

Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function.

Increased endogenous nitric oxide production induced by physical exercise in peripheral arterial occlusive disease patients.

The effects of 14-day physical exercise or iloprost treatment (0.5-2 ng/Kg/min) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease (Fontaine Stage II). Peripheral venous blood samples and 4-h urine samples were collected before, immediately after 14 days of therapy and 7-10 days after therapy in order to evaluate neutrophil adhesion, nitrite/nitrate and cGMP excretion rates. A longer pain free walking distance was observed after exercise, compared to iloprost (>500 m in 3/10 subjects). Urinary nitrite/nitrate, as well as cGMP concentrations, significantly increased after exercise. Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion. No variations were observed in these parameters in iloprost treated patients. The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise. The results from the present and previous observations indicate that, besides pharmacological treatments, a regular aerobic exercise improves peripheral arterial occlusive disease.

Erythropoietin and the anemia of chronic diseases.

The red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin. Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubule in response to signals from a renal oxygen-sensing device, probably a heme protein (1). In the bone marrow, erythropoietin binds to and activates specific receptors on the erythroid progenitor cells (2). In the presence of this erythropoietin-receptor complex the progenitor cells continue their predestined development into mature erythrocytes. Erythropoietin was the first hemopoietic growth factor to be molecularly cloned in 1985 (3). Our understanding of the biology and physiology of erythropoietin has been considerably improved with the advent of recombinant human erythropoietin (rHuEpo). During the past 7 years, rHuEpo has undergone extensive testing in clinical trials. It has been approved for treatment of the anemia of chronic renal failure, both in progressive renal failure and endstage renal failure (ESRD). In these instances, the administration of rHuEpo has been used in effect as a substitutive therapy, since patients' erythropoietin levels are very low despite severe anemia, due to the failure of affected kidneys to produce adequate amounts of the hormone. However, the application of rHuEpo has now moved largely from the primitive indication of renal diseases, and the hormone is currently under study in a number of anemic states of different etiologies, even with relatively high serum erythropoietin levels. Among these, some of the best documented indications are the anemia associated with malignancies, either due to neoplastic bone marrow infiltration or to chemotherapy-related myelosuppression, the anemia of myelodysplastic syndromes and AIDS, the anemia of chronic inflammatory diseases, prematurity, and bone marrow transplantation (4). The purpose of this review is to provide a summary of our present knowledge regarding rHuEpo therapy for the anemia of renal failure. We provide some clues for the correct use of rHuEpo in the treatment of the anemia of chronic inflammatory diseases. In addition, we address a series of new issues in the attempt to better understand the relationship between erythropoietin and liver disease.

Changes induced by nicardipine slow release in forearm and myocardial hemodynamics of subjects with essential hypertension.

OBJECTIVE: To evaluate the modifications induced by chronic treatment with a new formulation of nicardipine (slow release) on the hemodynamic parameters in peripheral artery and left ventricle diastolic function. MATERIALS AND METHODS: Ten mild to moderate essential hypertensive male patients (mean age 42 years, range 32-54 years) received nicardipine slow release (40 mg b.i.d.) for six months. Peripheral hemodynamic and cardiac parameters were evaluated by duplex scanner, coupled with a plethysmographic method, basally (T0) and after 1 (T1) and 6 months' treatment (T2). RESULTS: Blood pressure showed a significant reduction after 1 month (mean blood pressure 109 +/- 2 vs 124 +/- 3 mmHg, M +/- SE, p < 0.001), which was maintained after 6 months (mean blood pressure 112 +/- 3 mmHg, p < 0.001), while heart rate showed only a slight, non-significant increase. There were highly significant changes in distensibility (0.29 +/- 0.02 vs 0.16 +/- 0.01 s2.cm-2, T2 vs T0, p < 0.001), characteristic impedance (55 +/- 3 vs 78 +/- 3 dyn.s.cm-5.10(2), T2 vs T0, p < 0.001) and local resistances (71 +/- 5 vs 118 +/- 4 mmHg.ml-1. s, T2 vs T0, p < 0.001) in the brachial artery, and also in left ventricle posterior wall diastolic thickness (10.2 +/- 0.4 vs 11.5 +/- 0.3 mm, T2 vs T0, p < 0.05), end diastolic volume (127 +/- 3 vs 109 +/- 3 ml, T2 vs T0, p < 0.01) and mass/volume index (1.21 +/- 0.03 vs 1.35 +/- 0.03, p < 0.05). CONCLUSIONS: The antihypertensive efficacy of nicardipine slow release, with only two daily administrations, allows the restoration of the dumping function of the large arteries, and the regression of the functional modifications affecting the left ventricular diastole.

Relationship of lipoprotein(a) to variables of coagulation in hypertensive subjects.

BACKGROUND: Coagulation factors are independent predictors of cardiovascular damage in the general population. The purpose of this study was to investigate the relationships between general cardiovascular risk factors, lipoprotein(a) (Lp(a)), and some hemostatic variables, and to characterize the isoforms of apolipoprotein(a) (apo(a)) in hypertensive subjects. METHODS: Plasma lipids, apolipoproteins, Lp(a), apo(a) isoforms, fibrinogen, and parameters that directly reflect the coagulation activation were measured in 389 untreated essential hypertensive patients recruited at a hypertension clinic. Hypertensive patients were compared with 323 normotensive controls. RESULTS: In normotensive subjects, Lp(a) concentrations were significantly correlated with fibrinogen (r = 0.138; P < 0.02) but not D-dimer (r = 0.074; not significant). In hypertensive subjects, log Lp(a) concentrations were significantly correlated with age (r = 0.127; P < 0.02), apo-B (r = 0.128; P < 0.02), plasma fibrinogen (r = 0.193; P < 0.001), and fibrin D-dimer (r = 0.200; P < 0.001) levels, but not with body mass index, blood pressure, cholesterol, triglycerides, apo-AI, prothrombin fragment 1 + 2, and antithrombin III. The relationship of Lp(a) with fibrinogen (male: r = 0.198, P < 0.002; female: r = 0.177, P < 0.01) and D-dimer (male: r = 0.211, P < 0.002; female: r = 0.188, P < 0.01) was significant in both sexes, whereas the relationship of Lp(a) with age and apo-B was found only in males. Multivariate analysis showed that both fibrinogen and D-dimer were independently related with Lp(a). Elevated fibrinogen, D-dimer, and Lp(a) levels were significantly and independently associated with clinical evidence of atherosclerotic disease. Apo(a) phenotypes were analyzed to investigate the genetic background of the relationships between Lp(a) and coagulation parameters. In both hypertensive and normotensive subjects, Lp(a) levels were inversely correlated with apo(a) isoform protein size, whereas fibrinogen and D-dimer concentrations were comparable in patients with apo(a) isoforms of different size. CONCLUSIONS: The relationship between Lp(a) and clotting variables is significantly stronger in hypertensive than in normotensive subjects, providing a compelling argument for accelerated progression of atherothrombosis in these patients.

Serum reverse T3 assay for predicting glucose intolerance in uremic patients on dialysis therapy.

Sixty patients with end stage chronic renal failure (CRF) enrolled in a dialysis program underwent studies of serum thyroid hormones and carbohydrate metabolic state. The aim of the study was: 1) to evaluate whether the glucose intolerance per se represents a factor for the alteration of circulating thyroid hormones; and 2) to explore the potential usefulness of specific thyroid hormones and particularly reverse T3 (RT3) as indicators for predicting glucose intolerance. Forty-two patients received hemodialysis and 18 were on intermittent peritoneal dialysis (IPD). CRF patients had reduced serum total T4 and T3 levels, slightly decreased RT3 and TBG concentrations and normal TSH values. There was no significant difference in serum thyroid hormone indices between HD and IPD patients. Glucose intolerance was found in 25 patients. Ten had fasting hyperglycemia and diabetic response to oral glucose tolerance test (OGTT), 15 had an impaired glucose tolerance according to the criteria of the National Diabetes Data Group. In CRF patients with glucose intolerance, serum T3 and T3/T4 molar ratio were significantly lower than in those with a normal OGTT response, whereas serum RT3 and RT3/T4 molar ratio were found to be higher. In the whole group of CRF patients these serum thyroid hormones closely correlated with glucose tolerance indices. To investigate the usefulness of serum RT3 assay in predicting glucose intolerance we compared the outcome of the OGTT and serum RT3 values. Using the results of the OGTT as the true diagnosis of glucose intolerance, serum RT3 assay showed a diagnostic specificity of 94.2% and a sensitivity of 100%. In conclusion these results suggest that: 1) the glucose intolerance, which frequently occurs in uremia, may influence circulating thyroid hormones probably leading to a shift in the peripheral tissue conversion of T4 from T3 to RT3; and 2) serum RT3 assay could assume a clinical interest in assessing carbohydrate metabolic state in treated end stage renal failure independently of the type of dialysis therapy.

Sympathetic stimulation using the cold pressor test increases coronary collateral flow.

BACKGROUND: Little is known about the vasomotor function of human coronary collateral vessels. The purpose of this study was to examine collateral flow under a strong sympathetic stimulus (cold pressor test, CPT). METHODS: In 30 patients (62 +/- 12 years) with coronary artery disease, two subsequent coronary artery occlusions were performed with random CPT during one of them. Two minutes before and during the 1 minute-occlusion, the patient's hand was immerged in ice water. For the calculation of a perfusion pressure-independent collateral flow index (CFI), the aortic (Pao), the central venous (CVP) and the coronary wedge pressure (Poccl) were measured: CFI = (Poccl - CVP)/(Pao - CVP). RESULTS: CPT lead to an increase in Pao from 98 +/- 14 to 105 +/- 15 mm Hg (p = 0.002). Without and with CPT, CFI increased during occlusion from 14% +/- 10% to 16% +/- 10% (p = 0.03) and from 17% +/- 9% to 19% +/- 9% (p = 0.006), respectively, relative to normal flow. During CPT, CFI was significantly higher at the beginning as well as at the end of the occlusion compared to identical instants without CPT. CFI at the end of the control occlusion did not differ significantly from the CFI at the beginning of occlusion with CPT. CONCLUSIONS: During balloon occlusion, collateral flow increased due to collateral recruitment independent of external sympathetic stimulation. Sympathetic stimulation using CPT additionally augmented collateral flow. The collateral-flow-increasing effect of CPT is comparable to the recruitment effect of the occlusion itself. This may reflect a coronary collateral vasodilation mediated by the sympathetic nervous system.

Clinical and circulatory effects of Iloprost either administered for 1 week or 4 weeks in patients with peripheral obstructive arterial disease at Leriche-Fontaine stage III.

BACKGROUND: Iloprost therapy for severe peripheral obstructive arterial disease (POAD) has demonstrated to be effective in reducing the need for amputation. However the feasibility of a 28-day infusion regimen in less severe stages of the disease is poor due to the length in hospital stay. A randomized, controlled, parallel-group pilot study was carried out with the aim to evaluate clinical and circulatory effects of Iloprost, a stable prostacyclin analogue, administered with two different infusion schedules to patients with POAD at Leriche Fontaine stage III. METHODS: Twenty patients 16 males and 4 females, mean age 66 +/- 6 years) with objective signs of POAD, rest pain for at least two weeks and posterior tibial artery pressure > 50 mmHg, were randomized to either Iloprost i.v. infusion up to 2 ng/Kg/min for 6/h/day for 28 days (Group A) or to Iloprost i.v. infusion up to 1.5 ng/Kg/min for 16/h/day for 7 days (Group B). At baseline (before starting first infusion) after 7 days (for group B only, end of therapy) and after 28 days (end of therapy for Group A, end of study for Group B) the following parameters were evaluated: walking distance, rest pain and analgesic consumption, plethysmographyc parameters (first flow, peak flow and peak flow time) and laser Doppler parameters (rest flow, post ischemic flow). RESULTS: After 28 days, both Iloprost infusion schedules increased walking capacity (maximum walking distance/pain free walking distance +119/+84% +199/+85% respectively, for Group A and B respectively) reduced ischemic pain (-45% and -48% respectively for Group A and B) and analgesic consumption and improved plethysmographyc and laser Doppler parameters. Tolerability seemed to be better in Group B, suggesting that the lower dose and the shorter duration of the therapy period might result in reduced incidence of headache thus, in principle, increasing patient acceptability. CONCLUSIONS: The results of this pilot study, if confirmed by larger trials, could have important positive implications in terms of costs, patient comfort and management.

Prevalence of morphological alterations in cervical vessels: a colour duplex ultrasonographic study in a series of 3300 subjects.

BACKGROUND: In order to define the morphological variants involved in carotid elongation in terms of their clinical implications, we have analysed the prevalence of morphological alterations in patients routinely subjected to carotid colour duplex ultrasonography evaluation. METHODS: From January 1, 1993 to June 30, 1996, 3300 subjects were examined for central nervous system symptoms (41% of cases) or for screening related to ischaemic heart disease, lower limb arterial disease, hypertension or major dyslipidaemia (59% of cases). The chi(2)-test was used for statistical analysis. RESULTS: Morphological alterations increased with age. While kinking was more prevalent in females (female:male ratio 58% vs 42%), sharp kinking was significantly more frequent in males (39% vs 15%, p<0.001). Atheromatous plaques predominated in males (79% vs 46%, p<0.001), as well as cases with haemodynamically significant involvement (16% vs 7%, p<0.001). In patients with kinking there was a prevalence of haemodynamically significant lesions (chi(2)=52.7, p<0.001). A possible link between conformational abnormalities and hypertension appeared highly significant owing to a very different prevalence of high blood pressure in the group of subjects with kinking (chi(2)=239, p<0.001). We did not find a significant association between major neurological symptoms and the presence of kinking (chi(2)=0.215, p=0.643), but we found an association with transient ischaemic attacks (chi(2)=6.9, p<0.01). CONCLUSIONS: Conformational abnormalities like kinking, seem much more prevalent in subjects suffering from arterial hypertension. Even though high blood pressure is an important risk factor for transient ischaemic attacks, it is possible that the prevalence of atheromatous lesions and the flow turbulence linked to kinking may also play a role in their pathophysiology.

Origin of glycosylated hemoglobin A1 in chronic renal failure.

In chronic renal failure both HbA1 and HbA1c levels have been reported to be elevated. In order to investigate the causes of such increase we measured HbA1 (cation-exchange chromatography), blood urea nitrogen, arterial blood pH, plasma bicarbonate, phosphatemia, serum iron and serum ferritin before dialysis in 60 uremic patients receiving long term hemodialysis. The increased levels of HbA1 do not correlate with glucose intolerance, phosphatemia, blood urea nitrogen, time averaged concentration of urea, serum iron and serum ferritin. On the contrary the presence of a highly significant correlation between HbA1 and arterial blood pH (p less than 0.001) and between HbA1 and plasma bicarbonate (p less than 0.001) seems to emphasize a major role for acidosis in increasing the HbA1 levels in uremic patients on long term hemodialysis.