A. Acciavatti

Experimental Model of Short-Time Exercise-Induced Preconditioning in POAD Patients:

Regular physical exercise improves walking performance in patients affected with periph eral obliterative arterial disease (POAD). The mechanisms underlying the phenomenon are still controversial. In order to verify the hypothesis that physical conditioning of lower limbs on a treadmill and ischemic preconditioning of the heart could share some biolog ical aspects, 14 POAD subjects underwent a training program on the treadmill consisting of five repeated submaximal exercises at five-minute and two-hour intervals preceding the maximal tolerance test. Moreover, a protocol with two daily submaximal walking exercises over one week was also performed. Pain-free and total walking distance were measured before and after they performed the program. Moreover, plasma levels of adenosine and adenosine triphosphate (ATP) were measured and polymorphonuclear (PMN) leukocyte activity was studied together with rheologic parameters. Pain-free distance was prolonged by 15.4% and 14.3%, and total distance was prolonged by 23.1% and 26.9%, in the exercises with five-minute and two-hour intervals, respectively. After one week of daily exercises, the onset of pain and the end of the test were delayed by 24% and 43.7%, respectively. An improvement in blood rheology and a reduced PMN reactivity were also observed with the three protocols, associated with an increase in plasma levels of adenosine and ATP. Similarly to ischemic preconditioning in the heart, the possibility is suggested that an adenosine-mediated mechanism may contribute to the development of physical condi tioning in treadmill-trained POAD patients.

Pharmacodynamic Effects of Sulodexide on Profibrinolytic and Haemorrheological Patterns

SummaryTwenty-four patients with vascular disorders, randomly divided into 3 dosage groups of 8 patients, were treated with a single oral dose of sulodexide (50, 100 or 200mg) and placebo. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) activity and antigen, euglobulin lysis time, α2-antiplasmin, plasminogen, fibrinogen, blood and plasma viscosity, and whole blood filtration rate were determined before administration and over the following 24 hours. Sulodexide significantly increased t-PA activity linearly with the dose over the range of 50 to 200mg. At the same time, it also significantly decreased the concentration of PAI-1 linearly and proportionally with the dose. No clear effects were observed on the other monitored parameters, although euglobulin lysis time and plasma viscosity showed a tendency to decrease after the administration of sulodexide. These results justify the clinical activity of sulodexide. Indeed, the concomitant increase of t-PA and decrease of PAI-1 activity and antigen might increase the natural fibrinolytic activity with a physiological potentiation, without other adverse effects. The known activity of sulodexide in decreasing plasma viscosity during long term treatment is, however, not immediately explicable by the single-dose effects.

Allopurinol prevents ischaemia-dependent haemorheological changes

SummaryPre-treatment with allopurinol is able markedly to attenuate the deterioration in blood viscosity (BV) and whole blood filterability (WBF) that occurs after ischaemia during exercise. It also reduces the exercise-induced increase in serum oxidase activity, although this action is slightly less effective in peripheral obliterative arterial disease (POAD) patients.Conversely, allopurinol is completely ineffective in modifying haemorheological parameters in vitro, and it does not affect superoxide anion generation or enzyme release from neutrophils stimulated in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP).It is suggested that allopurinol may attenuate changes in BV and WBF by affecting xanthine-oxidase-dependent free radical formation in tissues.

Effect on rheological and some peripheral haemodynamic parameters of defibrotide in POAD patients

Received 1.12.1986; Accepted 19.1.1987 by Editor T. DiPerri) In ten POAD patients, 800 mg. of Defibrotide (polideoxynucleotide extracted from mammalian lung, with antitrombotic and fibrinolytic activity) were infused i.v. Blood and plasma viscosity, haematocrit, blood filterability and fibrinogen concentration were controlled, in basal conditions and after one hour from the end of infusion. Haemodynamic parameters: rest flow, peak flow, time to peak flow, half time and total time of reactive hyperemia by means of strain gauge pletismography, were controlled at lower limbs before infusion and after 1 h., 2 h., 6 h., from the end of infusion. The present investigation showed an improvement of rheological parameters and a decrease of total time and half time of reactive hyperemia. These data demonstrate a rheological activity of Defibrotide as well as the fibrinolytic one.

Paraneoplastic necrotizing myopathy associated with adenocarcinoma of the lung – a rare entity with atypical onset: a case report

IntroductionInflammatory myopathies (such as dermatomyositis and polymyositis) are well-recognized paraneoplastic syndromes. However, paraneoplastic necrotizing myopathy is a more recently defined clinical entity, characterized by rapidly progressive, symmetrical, predominantly proximal muscle weakness with severe disability, and associated with a marked increase in serum muscle enzyme levels. Paraneoplastic necrotizing myopathy requires muscle biopsy for diagnosis, which typically shows massive necrosis of muscle fibers with limited or absent inflammatory infiltrates.Case presentationWe report the case of an 82-year-old Italian-born Caucasian man who was admitted to hospital because of heart failure and two drop attacks. Over the following days, he developed progressive severe weakness, dysphagia, and dysphonia. Testing showed increasing serum muscle enzyme levels. Electromyography showed irritative myopathy of the proximal muscles and sensorimotor polyneuropathy. Muscle biopsy (left vastus lateralis) showed massive necrosis of muscle fibers with negligible inflammatory infiltrates, complement membrane attack complex deposition on endomysial capillaries, and moderate upregulation of major histocompatibility complex-I. Computed tomography of the thorax showed a nodular mass in the apex of the right lung. The patient was diagnosed with paraneoplastic necrotizing myopathy. In spite of high-dose corticoid therapy, he died 1 month later because of his aggressive cancer. Subsequent electron microscopic examination of a muscle biopsy specimen showed thickened walls and typical pipestem changes of the endomysial capillaries, with swollen endothelial cells. Poorly differentiated adenocarcinoma of the lung was confirmed on post-mortem histological examination.ConclusionsParaneoplastic necrotizing myopathy is a rare syndrome with outcomes ranging from fast progression to complete recovery. Treatment with corticosteroids is often ineffective, and prognosis depends mainly on the characteristics of the underlying cancer. This case shows that paraneoplastic necrotizing myopathy may have an atypical appearance, and should be considered in elderly patients with neoplastic disease. In this case, the diagnosis was delayed by the unusual clinical picture that suggested heart disease rather than muscle disease.

Influence of Non-Selective and Selective Beta Adrenoceptor Blockade on Isoxsuprine-Dependent Hemodynamic and Rheologic Changes

The infusion of isoxsuprine was followed by an increase of heart rate and calf blood flow and by a decrease of arterial diastolic pressure and blood viscosity both in normal controls and patients with peripheral obstructive arterial disease. The pre-treatment with a non-selective beta adrenoceptor blocker (propranolol) canceled all the isoxsuprine-dependent changes, while the pre-treatment with a selective beta adrenoceptor blocker (metoprolol) abolished only tachycardia and did not influence the increase of calf blood flow and the decrease of blood viscosity. These findings indicate the different role of vascular beta receptors in the regulation of muscular blood flow and suggest the pharmacologic possibility to unmask the beta2-dependent vaso dilation.

Buflomedil prevents ischaemia-dependent changes in blood rheology and neutrophil reactivity. A possible adenosine-mediated mechanism

In patients affected with peripheral obliterative arterial disease, the intravenous infusion of 50 mg buflomedil prevented ischaemia-dependent impairment of whole blood viscosity (WBV) and filterability (WBF) in the course of isotonic ischaemic exercise of an upper limb. The drug was also able to reduce the effects of ischaemia on some functional parameters of polymorphonuclear leukocytes (PMNs), such as superoxide anion generation induced by the formylated oligopeptide fMLP, and cytosolic free calcium level modifications in resting and fMLP-stimulated cells. An enhancement of ischaemia-dependent increase in adenosine plasma levels was also observed as associated with the effects of buflomedil. Treatment with the adenosine receptor antagonist theophylline was able to partially remove the effects of buflomedil. Thus, the possibility is suggested that some pharmacological properties of buflomedil could depend, at least in part, on an interference with the adenosine system.

CIRCADIAN VARIATION OF PLATELET AGGREGATION AND BLOOD RHEOLOGY

Many vascular pathologies have been reported to follow a diurnal rhythm (AMI, angina, stroke, sudden cardiac death, pulmonary thromboembolism) with a peak in the early morning. Aim of the study was to evaluate the existence of a diurnal rhythm of platelet aggregability and blood rheology. The study was carried out in 12 subjects; blood withdrawings were performed every 3 hour for 24 hours and in each blood sample platelet aggregation (on PRP and on washed platelets) and haemorheological parameters (blood viscosity, blood filterability, haematocrit and fibrinogen) were measured. Moreover systolic and diastolic blood pressure was recorded by dynamiC monitoring. The results show that a circadian rhythm of the above mentioned parameters does exists. Even if our data do not prove a strict correlation between these parameters and the incidence of the vascular pathology, it could be interesting to keep in mind the existence of a temporal parallelism when starting preventive therapy.

Genetic influence in liver steatosis prevalence and proatherothrombotic/inflammatory profile in familial combined hyperlipoproteinemia

presentation data could potentially have affected our results. Our results were also limited to in-hospital outcomes, but benefits of reduced DTB may emerge later, with a reduction in heart failure and a later mortality. In conclusion, our study found no correlation between short DTB or time to presentation and in-hospital mortality. Further investigation is needed to prove that short DTB does not have an impact onmortality in Japanese STEMI patients.

Haemorheological changes after thrombolytic treatment with Streptokinase in acute myocardial infarction

Ischaemic heart disease and its various clinical manifestations, whether acute or chronic, are shown to be characterized by hyperviscosity syndrome, more evident in the acute than in the chronic phase. In the present study the effect of i.v. Streptokinase (SK) treatment in 13 patients affected by AMI was evaluted; the haemorheological parameters (blood and plasma viscosity, blood filterability, fibrinogen and haematocrit) were measured in basal conditions, at the end of the infusion and 24 hours later. The patients showed high blood and plasma viscosity and low blood filterability in basal conditions. A decrease of blood and plasma viscosity with reduction of fibrinogen was observed at the end of the infusion, associated with an improvement in blood filterability. After 24 hours the haemorheological parameters showed a trend towards basal values without reaching them. On the contrary, 13 patients with AMI who could not undertake SK treatment showed an increase of blood and plasma viscosity and a reduction of blood filterability at the 8th hour lasting until the 24th hour. The haemorheological improvement observed in. patients treated with SK may be correlated to the fibrinogenolytic activity of the drug; the results of the present study support the hypothesis that SK may be a useful tool in AMI manegement.