S. Pecchi

Strain Gauge Plethysmography in the Study of Circulation of the Limbs

Plethysmography means registration of spontaneous or provoked volume changes in a segment of the body, with which it is possible to obtain information on the circulation of blood in that segment. This method has been known for a long time and has been applied by physiologists to several circulatory problems. However, the first plethysmographic instruments, water plethysmographs, presented such difficult technical problems that their use was restricted to sophisticated research in animals and only rarely in man. The water-filled plethysmograph was then replaced by the air-filled types, but these instruments also had grave technical problems. The principle of the so-called impedance plethysmography or rheography is based on electric impedance changes when a high-frequency and low-power alternating electric current passes through the body segment under investigation. This method, developed in the 1950s and designed to detect pulse waves in the limb, does not really reflect volume changes, but changes in the electrolyte content of the segment; so it cannot be compared with methods developed to measure blood flow.

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.

In Vivo and in Vitro Evidence of an Adenosine-Mediated Mechanism of Calcium Entry Blocker Activities

Drugs such as dipyridamole (200 μg/kg/min), an adenosine uptake in hibitor, and theophylline (300 μg/kg/min), an adenosine receptor antagonist, respectively increased and decreased postischemic hypere mia in normal subjects, as well as in POAD patients. Moreover, dipyrida mole pretreatment was able to antag onize the reduction of peak flow in duced by nifedipine, and the potenti ating effect of flunarizine on postis chemic hyperemia was affected sig nificantly by theophylline, thus sug gesting a possible interference of calcium entry blocker drugs with the endogenous adenosine system. In a cellular model (polymorphonuclear leukocytes — PMN) the inhibitory ef fect of calcium entry blockers on stimulated functions (degranulation and free radical production) was highly antagonized by theophylline. Finally, a 1H-NMR spectroscopy study showed a binding interaction between adenosine and flunarizine on the cell membrane. An adenosine-re ceptor coupling to the calcium entry blocker channels is suggested.

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.

EVIDENCE OF AN ADENOSINE‐DEPENDENT MECHANISM IN THE HYPOTENSIVE EFFECT OF l‐ARGININE IN MAN

1. The hypothesis that endogenous adenosine could play a role in the haemodynamic response to l‐arginine is investigated.

Plethysmographic Evaluation of the Vascular Effects of Human Calcitonin Gene-Related Peptide in Man

Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardio vascular effects that include positive inotropic and chronotropic actions systemic vasodilation, and hypotension in animals and in man. The mechanism of action of CGRP is still, however, not clear, and in particular it is not known whether vasodilation by CGRP occurs by changes in cutaneous or in muscular blood flow, or both. The aim of the study was, therefore, to evaluate the cutaneous and muscular blood flow, at rest and after ischemic test, induced by an IV bolus 25 μg human CGRP infusion in 5 healthy normotensive volunteers, using a strain gauge plethysmographic procedure with venous occlusion. Human CGRP pro voked a transient but significant decrease in sistolic and diastolic blood pressure, associated with tachycardia, marked flushing, a significant increase in plasma noradrenaline, adrenaline, and cyclic AMP levels, and a slight, but significant, decrease in serum total calcium. Moreover, a significant increase in the carpal cutaneous blood flow at rest was observed, with no significant change in the lower extremity muscular blood flow at rest and after ischemic test. Finally human CGRP produced a significant increase in the venous partial 02 pressure and in the hematocrit and a significant decrease in the venous partial CO2 pressure. The results of the present study confirm the acute cardiovascular and meta bolic effects of CGRP. In fact, hypotension, tachycardia, flushing, and the increased cutaneous blood flow indicate a systemic vasodilation by the neuropep tide, with a secondary sympathetic response, as documented by the augmented catecholamine and cyclic AMP plasma levels. Moreover, the plethysmographic study suggests a blood flow redistribution, from the muscular tissues to the cutaneous surface, with a relative lower oxygen uptake and CO2 release and a partial hemoconcentration phenomenon. In conclusion, these results are in agreement with the hypothesis that the vasodilative action of human CGRP is stronger on the skin than on the muscles of the lower extremities, even if a concomitant involvement of other vascular beds such as the splanchnic territory, by CGRP, cannot be excluded.

Hemodynamic and hemorheologic effects of iv dilevalol in hypertensive patients

The authors evaluated the effect of Dilevalol infusion on blood pressure, heart rate, central hemodynamics, and rheologic parameters in hospitalized inpatients affected with mild or moderate hypertension. After a dose-finding phase and a washout period of one week, 10 patients aged fifty to seventy-two-years (median 61.5) were given either a single dose of Dilevalol 60 mg or placebo, and seven days later they underwent the other treatment, according to a single-blind, crossover design. Central hemodynamic measurements were performed by means of M-mode echocardiography, and hemorheologic parameters were evaluated by means of strain-gauge plethysmography. The maximal increase in lower extremity flow at rest had been obtained with the infusion of 60 mg Dilevalol during dose-finding, and so this dose was chosen for the second part of the study. The infusion of Dilevalol significantly increased rest flow and decreased blood viscosity, but the changes in central, parameters were not considered clinically relevant, although statistically significant. Blood pressure decreased without significant changes in heart rate. Thus, the acute administration of Dilevalol reduced blood pressure, without affecting heart rate and central hemodynamics, confirming the vasodilating effect of the drug. A significant improvement was also shown on blood viscosity in these hypertensive patients.

Pharmacological Basis and Therapeutic Efficacy of Flunarizine in Peripheral Artery Disease

In the last few years we have accumulated some evidence that calcium entry blockers could interfere with an endogenous purinergic mechanism, namely, with membrane adenosine receptors.’” This property seemed to be shared by different groups of such drugs, independently from their chemical structure, thus opening new questions on the molecular mechanism of action.24 Among these substances, first flunarizine and then dihydropyridines claimed our attention, and now we want to summarize the findings of our studies, not following the logical development of the adenosine hypothesis in our mind, but assembling our data according to the type of experimental design. In this paper the thread of the argument implies a continuous hypothetical comparison with the adenosine system. Our studies dealt with clinical pharmacological investigations on the circulatory activity of flunarizine either in control subjects or in peripheral obliterative arterial disease (POAD) patients. The design of the study included the plethysmographic investigation of the leg hemodynamics after flunarizine infusion and after treatment with drugs that either block adenosine receptors, such as theophylline, or inhibit adenosine uptake, such as dipyridamole. Finally a cellular model was approached to clarify a possible interference of calcium entry blocker with adenosine a t the membrane receptor level.

Effects of a Single I.V. Dose of Nicergoline on Haemorrheological and Haemodynamic Parameters in Peripheral Vascular Disease. A Double-Blind, Cross-over Study

Peripheral obliterative arterial disease (POAD) is a clinical condition characterized from a pathophysiological point of view by a reduction of nutritional blood flow due to atherosclerotic stenosis or occlusion of great or medium-sized arteries of the legs. In this condition, blood flow supply to the tissue can be insufficient to meet the metabolic needs and ischaemia can occur. The blood flow reduction usually develops slowly and a compensatory mechanism can be activated to antagonize ischaemia.

Wirkungen einer einmaligen intravenösen Dosis von Nicergolin auf hämorheologische und hämodynamische Parameter bei peripheren Gefäßerkrankungen

Periphere obliterierende arterielle Erkrankungen (im weiteren Text als POAD—peripheral obliterative disease —abgekurzt) sind pathophysiologisch durch eine Reduktion der nutritiven Durchblutung gekennzeichnet, die durch arteriosklerotische Stenosen oder Verschlusse der grosen oder mittleren Beinarterien hervorgerufen wird.