Simultaneous measurements of arterial diameter and blood pressure to determine the arterial compliance, wall mechanics and stresses in vivo.

BACKGROUND: to develop a periarterial dimensional clip-probe which, associated with endovascular pressure measurement, real-time digital signal processing/data treatment systems, enables characterisation of the basic wall mechanics in given arterial sites. DESIGN: experimental study. MATERIAL: a facing pair of ultrasonic crystals was incorporated in periarterial highlight probes, made of sterilisable silicone and manufactured from computer-designed stainless steel casts. The A/D converted diameter and pressure (from an endovascular micro-tip probe) signals, triggered by the ECG, were on-line processed to provide their respective profiles during an averaged cardiac cycle, and subsequently the arterial wall physics. The technique was tested in the iliac and renal arteries in eight pigs. RESULTS: the technique was found to indicate adequately that arterial responses to distending blood pressure, as given by Petersons modulus and relative pulsatility, were identical in renals and iliacs. In contrast, the compliance, circumferential incremental elastic modulus and midwall circumferential stress were higher in iliacs than in renals, whereas arterial stiffness of the renals surpassed that of the iliacs. DISCUSSION: the technique with sterilisable probes produces in vivo pressure-diameter relationships, arterial compliance, and wall mechanics and stresses, whatever the arterial size. The porcine iliacs and renals are elastic and viscorigid arteries, respectively.

Hemodynamics and wall mechanics after stent placement in swine iliac arteries: comparative results from six stent designs.

PURPOSE: To compare the hemodynamics and wall mechanics of swine iliac arteries after placement of six types of stent. MATERIALS AND METHODS: Stents were placed in the iliac artery of 18 pigs (three pigs each underwent placement with one of six types of stent); 16 untreated pigs served as control animals. Iliac arterial hemodynamics and wall mechanics were measured 4 days after placement. RESULTS: Four stents (Palmaz-Schatz, Cordis, Warren, NJ; and Strecker, Cragg, and Symphony, Boston Scientific/Vascular, Natick, Mass) caused decreased pulsatile flow rate in the treated and contralateral iliac arteries; one (Memotherm; Bard, Covington, Ga) caused increased flow pulsatility; and one (Wallstent; Schneider, Plymouth, Minn) had no effect. No compliance mismatching was noted for the Cragg, Symphony, and Memotherm stents, whereas a decrease in compliance was noted for the Palmaz-Schatz, Strecker, and Wallstent designs. The Palmaz-Schatz and Strecker stents caused increased arterial wall rigidity, the Symphony and Wallstent designs had no effect, and the Memotherm and Cragg stents caused decreased wall rigidity. Stents made of stiff metal yielded different early results than did stents made of the less rigid nitinol. CONCLUSION: Soon after implantation, the six stent designs elicited varying changes in blood flow, arterial compliance, and arterial wall mechanics. Contralateral arterial flow also was affected.

Effects of folate supplementation in hyperhomocysteinemic pigs.

OBJECTIVES: The aim of this study was to evaluate the therapeutic effects of folic acid in the pig model of hyperhomocysteinemia. BACKGROUND: We have previously shown that pigs fed a methionine-rich diet develop hyperhomocysteinemia, arterial lesions and thrombotic events. Elevated homocysteine level is an independent risk factor for atherosclerosis that can be markedly lowered with daily folic acid administration. However, it is not known whether this treatment can prevent arterial lesions. METHODS: Three groups of pigs were studied: 8 control subjects received a standard diet; 8 received a methionine-rich diet for four months; 8 received a methionine-rich diet for 1 month and then the methionine-rich diet + 5 mg/day folic acid for 3 months. At month 4 after hemodynamic investigation, all the pigs were sacrificed. RESULTS: Control animals developed few usual vascular streaks. All the pigs fed a methionine-rich diet without folic acid treatment developed hyperhomocysteinemia (10.3+/-1.3 micromol/liter at basal state, 18.2+/-2.5 micromol/liter at one month and 14.6+/-3.8 micromol/liter at four months), hemodynamic abnormalities and diffuse arterial lesions with smooth muscle cell hyperplasia, endothelial alterations and elastic lamina dislocation. In this group, one pig died of venous thromboembolism and one of myocardial infarction. The pigs fed a methionine-rich diet + folic acid displayed similar arterial lesions and two had thrombotic events (one myocardial infarction and one pulmonary embolism), despite normalization of homocysteine levels (10.9+/-1.3 micromol/liter at basal state, 19.5+/-2.5 micromol/liter at one month and 11.4+/-3.8 micromol/liter at four months). CONCLUSIONS: In the pig model of hyperhomocysteinemia, 5 mg/day folic acid did not prevent arterial lesions or thrombotic events.

Effects of cryopreservation on the viscoelastic properties of human arteries.

The purpose of this study was to use our newly developed mock circulation loop to determine the effects of cryopreservation on the common carotid artery (CCA) and the superficial femoral artery (SFA). Fourteen healthy arteries (7 CCA and 7 SFA) harvested from multiple organ donors between the ages of 18 and 35 years were tested before and after cryopreservation at -140 degrees C using dimethyl sulfoxide and the vapor phase of liquid nitrogen. Mean storage time was 4.2 months. The mock pulse rate was 60 beats/min and the following four systolic/diastolic pressures settings were used: 50/110, 80/140, 110/170, and 140/200 mm Hg. Simultaneous measurements of intra-arterial pressure and external arterial diameter were made using an intra-arterial pressure sensor and external piezoelectric sensors. Measured data were used to calculate pulsatility, volumetric compliance, stiffness, midwall radial arterial stress, Young's modulus, and the incremental modulus. After SFA cryopreservation, no significant changes were observed. Conversely, CCA cryopreservation led to a significant decrease in compliance and pulsatility and a significant increase in stiffness. Young's modulus, the incremental modulus, and midwall radial arterial stress did not change significantly. A clearcut decrease in hysteresis was observed after cryopreservation in the CCA. No evidence of structural changes was detected on light and scanning electron microscopy. Baseline findings in this study were consistent with classification of the CCA as an elastic artery and the SFA as a muscular artery. Cryopreservation had no effect on the viscoelastic properties of muscular arteries (SFA). Cryopreservation affected only values related to the cylindrical shape of the elastic arteries (CCA). It had no effect on values related to wall structure.

Therapeutic effects of nitric oxide-donor isosorbide dinitrate on atherosclerosis-induced alterations in hemodynamics and arterial viscoelasticity are independent of the wall elastic component.

Whether the arterial elastic structures are involved in the beneficial effects of long-term treatment with organic nitrates on atherosclerosis-induced changes in hemodynamics and arterial wall viscoelastic properties, are case for angiotensin-converting enzyme (ACE) inhibitors, is not known. In the present study, atherogenic (A) diet, and isosorbide dinitrate (ISDN) (I) (60 mg Risordan LP, daily dose) were given concomitantly for 4 months to adult Pitman-Moore minipigs (A + I animals, n = 8), which were compared with A (n = 8) or control (C, n = 8) animals. Blood flow was investigated by hemodynamics in the hindlimb arterial bed; and wall rheology, histomorphometry and elastin; and desmosine (DES) and isodesmosine (IDE) contents in the abdominal aorta. Atherosclerosis prominently impaired the function of capacitance and resistance arteries, altered blood pressure contours, increased aortic stiffness and wall tension, and reduced parietal viscoelasticity through viscous component blunting. The treatment with ISDN significantly improved aortic pulsatility, arteriolar opposition to blood flow, and blood pressure (BP) contours by restoring, at least in part, the wall viscoelastic properties. However, there was no significant change in the area of the pressure-diameter curve hysteresis between the three animal groups. In contrast, ISDN reduced neither the cross-sectional area of lesions nor the losses in wall elastin content and had no influence on lipid accumulations in vessels and in the blood. The present results demonstrate that the beneficial hemodynamic and wall viscoelastic effects elicited by ISDN in atherosclerotic minipigs are not accounted for by therapeutic properties of the nitric oxide (NO) donor against alterations of elastic structures, but by the viscoelastic properties in the arterial wall.

Viscoelastic properties of human arteries. Methodology and preliminary results.

In order to study the biomechanical properties of the arterial wall and to compare arteries with different histologic structures, we designed a device that allows testing of arterial segments under near-physiologic conditions. A hydrodynamic generator simulates systolo-diastolic pressures in an open loop. An intraarterial pressure sensor and a sonomicrometer connected to two piezoelectric crystals placed in diametric opposition on the arterial wall allow computer calculation of compliance, stiffness, midwall radial arterial stress, Young modulus, and incremental modulus for a given arterial segment at a given pressure setting. Seven healthy common carotid artery (CCA) segments and seven healthy (superficial) femoral artery (FA) segments were studied immediately after removal from brain-dead donors between the ages of 18 and 35 years. Histologic examination was performed to determine the density of elastic fibers in the arterial wall. Hysteresis was observed in all segments regardless of pressure settings. Compliance was greater and modulus values and stiffness were lower in CCA than in FA. No evidence of structural change was noted after testing in the circulation loop. These preliminary results open the way to a wide variety of applications for our hydrodynamic circulation loop. Experiments will be undertaken to compare the mechanical properties of arteries before and after cryopreservation.

[Mechanical properties of the arteries. Effects of cryopreservation]. / Propriétés mécaniques des artères. Effets de la cryopréservation.

The viscoelastic properties of the arterial wall are responsible for the blood pressure wave propagation throughout the arterial system. Arterial diseases may cause disorders in this propagation. We have developed a mock circulation system that allows assessment of viscoelastic properties in fresh or cryopreserved human arteries. It includes the following components:--a hydrodynamic generator that can simulate physiological pressure variations in fresh segments of human arteries;--a lightweight miniature flexible probe that can be placed around the artery to measure changes in the external diameter during systolo-diastolic cycles;--a computer program to analyse pressure and diameter data measured during a cardiac cycle. Using this system, it is possible to evaluate the main viscoelastic properties of the arterial wall (arterial compliance, arterial stiffness, midwall aortic stress, Young elastic modulus, incremental modulus). Human arterial samples were collected during organ harvesting in subjects from 18 to 35 years of age. Correlation between viscoelastic properties, arterial wall status, and histological aspect in nitrogen vapor (-140 degree C) were established. No statistically significant difference was observed in femoral arteries characteristics. Compliance decreased, while stiffness increased with statistically significant difference after cryopreservation in carotid arteries. No histological difference was observed in both arteries before and after cryopreservation.

Hyperhomocysteinemia-induced vascular damage in the minipig. Captopril-hydrochlorothiazide combination prevents elastic alterations.

BACKGROUND: Previous attempts in animals failed to reproduce the metabolic, pathological, and clinical situations encountered in homocystinuric patients. Minipigs on a methionine-rich caseinate-based diet, however, have a special long-lasting postprandial plasma accumulation of methionine, the metabolic precursor of homocysteine. We hypothesized that these minipigs develop hyperhomocysteinemia in the long term. Angiotensin-converting enzyme (ACE) inhibition prevents atherogenic alteration of viscoelastic functions of arterial pulsatility and compliance and reduces fragmentation of vascular elastic laminae in the minipigs. We consequently analyzed the therapeutic effects of the captopril-hydrochlorothiazide combination against the typical hyperhomocysteinemia-induced alterations of vascular elastic features. METHODS AND RESULTS: Thirty-two Götingen minipigs were randomized as control diet-fed (C), captopril (25 mg/d)/hydrochlorothiazide (12.5 mg/d)-treated C (C+Cp), caseinate-based diet-fed (M), and M+Cp minipigs. After 4 months, M and M+Cp animals had hyperhomocysteinemia (9.64 +/- 4.10 mumol/L, n = 16) compared with C and C+Cp minipigs (5.67 +/- 1.14 mumol/L, n = 16) (P < .05). In the M group, one minipig died from thromboembolic syndrome, and one had pulmonary infarction. M minipigs presented with systolic-diastolic hypertension and extended reactive hyperemia, as well as a mega-artery syndrome in hyperpulsatile arteries due to expanded volumetric compliance, curtailed stiffness, strengthened vascular tension, and prevalence of the viscous wall component. In their arterial tree, hypertrophic endothelial cells covered a thickened subendothelial space. Major elastic lamina dislocations were observed, as well as hypertrophy and reorientation of smooth muscle cells, resulting in the settlement of spreading pathways for medial cells between muscular laminae. In C+Cp and M+Cp animals, serum and lung ACE activity were inhibited by 74% and 40%, respectively. Although the treatment with captopril-hydrochlorothiazide did not modify the hyperhomocysteinemia per se, the therapeutic effects of the drug combination are made evident by the absence of death and ischemic diseases in the M+Cp group. Specifically, the drug combination prevented diastolic hypertension and improved aortic blood flow by normalizing peripheral resistances, abolished the vascular hyperpulsatile characters, and restrained the fragmentation and the splitting of elastic fibers in capacitance arteries. In contrast, the drugs slightly prevented systolic and mean hypertension. In addition, the aortic stiffness and stress response remained altered and vascular smooth muscle cell hypertrophy was still observed in the M+Cp group. CONCLUSIONS: In minipigs, the present methionine-rich caseinate-based diet induced hyperhomocysteinemia, which reproduces the metabolic and histopathological situation found in homocysteic patients. Our results show that hyperhomocysteinemia-induced vascular alterations favor the viscous component of the wall rheology to the detriment of the elastic component. Furthermore, they extend to hyperhomocysteinemia the therapeutic effects characteristically shared by ACE inhibitors in association with hydrochlorothiazide against the atherogenic activation of elastinolytic processes.

ACE inhibition with perindopril and atherogenesis-induced structural and functional changes in minipig arteries.

The effects of angiotensin-converting-enzyme (ACE) inhibition on atherosclerosis-induced changes in arterial function are unknown, as well as whether they are coupled to improvements of structural alterations in the arterial wall. An atherogenic (A) diet and the ACE inhibitor perindopril (P) were given concomitantly for 4 months to seven adult Pitman-Moore minipigs (7 months of age; A+P animals), which were compared with seven A and seven control (C) animals. Perindopril, at a daily dose of 4 mg PO that is commonly used in the clinical setting, induced a continuous 70% inhibition of serum ACE activity. At the end of the study, the atherosclerosis-induced impairment of arterial flow was investigated via the hemodynamics and vascular rheology of hindlimb arteries in non-barbiturate-anesthetized pigs. Structural alterations were evaluated from the histopathology of lesions in the arterial tree (abdominal aorta, left interventricular coronary artery [LIVCA], and brachiocephalic trunk [BCT]), with particular attention given to the analysis of the structure and composition of aortic elastic fibers. Atherosclerosis impaired the function of both capacitance and resistance arteries. Blood pressure (BP) rose significantly because of increased hindlimb peripheral resistance (HPR) and aortic input impedance (Zc), although blood flow was not affected. Altered aortic stress and elastic responses revealed that the stiffness of the aorta was markedly increased because of increased wall tension and reduced viscoelasticity, the viscous component being blunted in the arterial wall. Perindopril significantly opposed these alterations by reducing BP, HPR, and Zc and by returning parietal stiffness values to C values by increasing aortic compliance. ACE inhibition prevented the alteration of both stress and elastic responses. Major fibroproliferative fatty lesions were observed in the aorta and LIVCA, while moderate fibrosclerotic lesions were found in the BCT. Computerized densitometric analysis of orcein-stained elastin showed that elastic laminae fragmentation was prominent in the abdominal aorta, less in the LIVCA, and moderate in the BCT. Furthermore, the elastin content was reduced in the atherosclerotic aorta, although this loss of elastin was not associated with changes in the biochemical nature of alkali-insoluble elastin. Perindopril significantly prevented the development of atherosclerosis in the abdominal aorta, LIVCA, and BCT by decreasing the cross-sectional area of lesions as well as the number of lipid-laden cells in the abdominal aorta and LIVCA. In the abdominal aorta, ACE inhibition significantly prevented the alteration of elastic laminae by specifically preventing elastolytic fragmentation of dense elastic laminae, but it didn ot modify elastin content.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of angiotensin-converting enzyme inhibition with perindopril on hemodynamics, arterial structure, and wall rheology in the hindquarters of atherosclerotic mini-pigs.

The effects of ACE inhibition with perindopril on the atherosclerosis-induced impairment of arterial flow were investigated via histopathologic studies, hemodynamics, and vascular rheology of hindlimb arteries in 7 adult Pitman-Moore mini-pigs (7 months of age) fed for 4 months with an atherogenic diet and perindopril (at the daily oral dose of 4 mg, which induced a continuous 70% inhibition of serum ACE activity), versus 7 atherogenic and 7 control animals. Major fibroproliferative fatty lesions with medial intimalization were observed in the abdominal aorta. Atherosclerosis impaired the function of both capacitance and resistance hindlimb arteries. In atherogenic mini-pigs, blood pressure (BP) increased significantly due to increased hindlimb peripheral resistance (HPR) and aortic input impedance, although aortic blood flow was not affected. Altered aortic wall rheology revealed that the stiffness of the aorta was markedly increased due to increased wall tension and reduced viscoelasticity, the viscous component being reduced in the arterial wall. Perindopril significantly opposed these alterations by reducing BP, HPR and input impedance and by returning parietal stiffness to control values by increasing aortic compliance. Angiotensin converting enzyme (ACE) inhibition significantly prevented the development of atherosclerosis in the abdominal aorta by decreasing the cross-sectional area of lesions and the presence of lipid-laden cells, as well as by preventing alteration and fragmentation of elastic laminae. In conclusion, ACE inhibition with perindopril showed a significant preventive action on atherosclerosis-induced deleterious effects on vascular wall function and structure in mini-pig arteries.

[Inhibitors of angiotensin-converting enzyme and processus of intima proliferation in atherosclerosis]. / Les inhibiteurs de l'enzyme de conversion de l'angiotensine et les processus de prolifération intimale dans l'athérosclérose.

The renin angiotensin system is a negative feed-back system of blood pressure control. A number of concordant experimental and clinical results indicate that the angiotensin family has a trophic effect on the vessel wall. These properties of the angiotensins favorise the proliferation of the cells which make up the vessel wall and also amplify the vascular dysfunction in the absence of the inhibitory regulations. Angiotensin converting enzyme inhibitors could be a valuable therapeutic method of counteracting these deleterious effects on the composition and function of the vessel wall.

[Effects of isosorbide dinitrate and diltiazem used alone or combined on arterial hemodynamic and viscoelastic parameters. Experimental data in the rabbit]. / Effets du dinitrate d'isosorbide et du diltiazem, utilisés seuls ou en association, sur les paramètres hémodynamiques et viscoélastiques artériels. Données expérimentales chez le lapin.

An experimental model of simultaneous recording of aortic pressure and flow and vascular diameter at the entrance to a limited territory of systemic circulation has been developed in the rabbit. A system of data acquisitions and treatment has also been perfected to evaluate the different parietal viscoelastic parameters of arterial flow in capacitance and resistance arteries. This model was used to study the pharmacodynamic effects of two vasodilator drugs, isosorbide dinitrate (ISDN) and diltiazem (DILT), administered alone or in association (ISDN + DILT) by slow intravenous infusion over 30 minutes at dosages chosen to induce comparable hypotension of about 10%. Under these conditions, the effects of ISDN, DILT and ISDN + DILT on resistance parameters were slightly different. The ISDN had no marked effect on mean aortic flow (Qm) apart from a slight decrease after 10 minutes infusion (-10.4 +/- 3.8%, p less than 0.05). On the other hand, DILT alone or in association with IDN was associated with a significant increase in Qm (DILT: +8.5 +/- 0.8%, p less than 0.001; ISDN + DILT: +9.7 +/- 2.1%, p less than 0.01). This explains the absence of a significant effect of ISDN on peripheral resistance (PR) or entrance impedance (Zc) of the vascular bed. Conversely, the effects of DILT and ISDN + DILT on these parameters were very marked (DILT:RP = -17.2 +/- 0.9%, p less than 0.001; Zc = -8.2 +/- 0.5%, p less than 0.001; ISDN + DILT: RP = -16 +/- 1.4%, p less than 0.001; Zc = -8.0 +/- 0.4%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of uraemic hyperphosphatemia with calcium acetate: a safe alternative to calcium carbonate.

Clinical usefulness of calcium acetate (CAA) as phosphorus binder was assessed in 19 stable hemodialysis patients with persistent hyperphosphatemia. All were dialysed thrice weekly with a constant dialytic schedule and a dialysate calcium of 3.5 mEq/l. One month prior the study beginning all patients stopped assumption of Ca and vitamin D supplements. In the first period of the study CAA (mean daily doses 2.2 g) was administered for one month followed by 15 days of withdrawal. The mean serum phosphorus decreased from 7.6 +/- 1.4 to 5.8 +/- 0.8 mg% (p < 0.005). After 15 days of withdrawal mean serum phosphorus reached the pretreatment value. Then the patients entered a long term study with personalized doses of CAA (between 1 and 4 g/day) and administration in 8 of them of alpha-calcidol. After a mean follow-up period of 5.4 +/- 1.5 months serum phosphorus was reduced from 7.5 +/- 1.1 to 5.6 +/- 1.1 mg% (p < 0.0005) while calcemia increased from 9.0 +/- 0.7 to 9.6 +/- 0.6 mg% (p < 0.005). Only one patient developed mild hypercalcemia. We concluded that CAA is a safe alternative to calcium carbonate for the control of hyperphosphatemia of uraemic patients for the most efficient phosphorus binding and the lesser absorption of calcium.

[The homocysteinemia vascular risk factor. Methodologies and application to a clinical case]. / L'homocystéinémie facteur de risque vasculaire. Méthode de mise en évidence, application à un cas clinique.

Early onset vascular disease unexplained until today by usual risk factors (hyperlipidemia, hypertension, tobacco, stress), can now find an explanation in sulfur amino acid metabolism defect. By transsulfuration, alimentary methionine leads to homocysteine, which is itself turn into cysteine, or remethylated into methionine. Several abnormalities of these different pathways lead to plasma accumulation of homocysteine, which will be responsible of arterial or venous occlusive lesions, concerning peripheral or deep vessels. Homocysteine stays in plasma upon several forms: 75% being linked by disulfide bounds to proteins, 22% as disulfide, homocystine (homocysteine-homocysteine) or mixed-disulfide (homocysteine-cysteine), and less than 3% as free reduced homocysteine. Plasma reduction allows total homocysteine evaluation with amino acid autoanalyzer. The basal plasma homocysteine level is less than 14 microMl. However, levels near this basal value can be found in patients with latent abnormality, which needs to be revealed by a methionine loading test. This study concerns two methodologies and their application to the exploration of a patient with unidentified neurologic disorders. The first one describes a new galenic oral form of methionine. Other authors use the methionine load of 100 mg/kg dissolving it in a fruit juice glass. In order to obtain a complete dissolution of this weakly soluble substance and to ensure its total absorbtion by the patient, we prepare a granular form aimed to give in water a perfect flavoured suspension. The second methodology concerns methionine loading test and amino acid analysis. After 10 hours fasting, a 100 mg/kg peroral methionine load is realized performing 5 EDTA blood samples before and 4, 8, 12 and 24 hours after loading.(ABSTRACT TRUNCATED AT 250 WORDS)

[Application of ultrasono-micrometric technic to study vasomotility]. / Application des techniques ultrasonomicrométriques à l'étude de la vasomotricité.

An experimental model of simultaneous recording of pressure and flow (instantaneous and mean values) and of the vascular diameter (by ultrasonomicrometry) at the entry of a clearly limited territory of the systemic circulation has been developed in the animal together with a programme of data aquisition and analysis. This programme allows quantification of the different viscoelastic properties of the vessel wall which characterise arterial flow in the arteries of distribution (capacitance vessels) and irrigation (resistance vessels). The model was applied to the study of the pharmacological effects of two antianginal agents, a nitrate derivative (ND) administered acutely by slow intravenous infusion at a dose of 25 micrograms/Kg/mn over 20 minutes (total dose: 500 micrograms/Kg) and a substitute sydronimous substance (SYD) administered in the same manner at a dose of 15 g/Kg/mn over 20 minutes (total dose: 300 micrograms/Kg). The hypotensive effects obtained were comparable and significant (p less than 0.001) in both cases. The ND led to a fall in mean blood pressure of 9.7 +/- 1.3% and SYD of 10.0 +/- 2.1%. However, SYD led to an increase in aortic blood flow (11.7 +/- 3.6%, p less than 0.01) whilst the ND had no significant effect on this parameter (+ 6.07 +/- 5.7%). As a result, there was a much greater decrease of peripheral resistances after administration of SYD (-22.8 +/- 3.1%) than with the ND (-12.7 +/- 4.2%). This difference was also observed when the input impedence of the vascular bed was studied (-31.2 +/- 6.9% after SYD and -12.0 +/- 2.5% after the ND).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of SIN-1 on peripheral hemodynamics and viscoelastic properties of aorta in anesthetized rabbits.

In closed-chest, non-barbiturate-anesthetized rabbits, we have used a computer-based parameter estimation method to evaluate the effects of a slow intravenous infusion of SIN-1 (15 micrograms/kg/min for 20 minutes) upon hemodynamic, geometric, viscoelastic, and energetic characteristics of the hindlimb arterial bed from the measurement of abdominal aortic diameter, blood flow, and blood pressure. To evaluate intrinsic effects of SIN-1 upon arterial wall characteristics, a moderate arterial bleeding (3 ml/kg) was performed to achieve a -10% lowering of arterial pressure, i.e., to reach an equivalent blood pressure reference threshold in the absence of the drug. The SIN-1 IV infusion induced a marked blood pressure lowering (-10.0 +/- 2.1%), resulting from a relaxing action on smooth muscle vasculature both in capacitive and resistive components of the hindlimb vascular tree, thereby eliciting a lowering in peripheral resistance (-22.8 +/- 3.1%) and an increased blood flow (+11.7 +/- 3.6%). SIN-1 enhanced vascular compliance (+28.0 +/- 2.2%) and lowered vascular input impedance (-31.2 +/- 8.9%), as confirmed by modulus and phase spectra. SIN-1 IV infusion contrasted bleeding effects by increasing blood flow and maintaining constant or increasing aortic diameter, both of them being lowered by bleeding. The relaxing effect elicited by SIN-1 was further demonstrated by changes in viscoelastic characteristics, and it was further associated with a decreasing energetic demand as well. The present results demonstrated that SIN-1, administered as a slow IV infusion, exhibits vasodilating properties by acting both on capacitive and resistive vessels of the systemic circulation.

Control of the anti-thrombogenic endothelial cell defense by short- and long-term exposure of cultured endothelial cells to isosorbide nitrates.

Anti-thrombogenic endothelial cell defense (ATECD) refers to the overall properties that enable the endothelium to prevent circulating blood platelets adhering to, or aggregating on the vascular wall. The basic characteristics of ATECD have been further investigated in cultured arterial endothelial cells (EC). Freshly obtained endothelium cells (ECs) and confluent, quiescent Passage 0 ECs, similarly expressed ATECD, whereas subconfluent dividing ECs and senescent ECs both elicited a markedly lowered ATECD. When ECs were successively exposed to fresh platelets, ATECD was progressively exhausted until a plateau (50% of control ATECD) was reached after the third exposure of ECs to platelets. Similarly, platelet response to the aggregating agent was markedly lowered after the first exposure of ECs to platelets, whereas such an inhibition of platelet activity by ECs was much less pronounced in subsequent exposure of ECs to fresh platelets. Under acute pharmacological circumstances, isosorbide dinitrate (ISDN) antiplatelet activities were found to be profoundly magnified by ECs, thus revealing an EC-mediated antiplatelet activity for ISDN, but not for its mononitrate metabolites, 2-ISMN and 5-ISMN. Long-term exposure of ECs to isosorbide nitrates (ISNs) revealed that ISDN, as well as 2-ISMN elicited an ATECD-stimulation priming effect on ECs, although in the presence of 5-ISMN (a poor antiplatelet agent) the ISN overall effect upon ATECD was less than 50% of what would have been expected by cumulating individual ISN effects. It is concluded that ATECD provides a highly differentiated function for ECs; the ATECD mechanisms involve antiaggregating factors that may be trapped by platelets; and, finally, ATECD may be stimulated by ISDN both under acute and under chronic pharmacological circumstances.

[In vitro determination of the pressure-diameter relationship and velocity profiles by ultrasonic technics. In vivo application]. / Détermination in vitro de la relation pression-diamètre et des profils de vitesse par des techniques ultrasonores. Application in vivo.

A good knowledge of arterial flow mechanics and of the phenomena associated with fluid-boundary interactions is necessary for the determination of some fundamental parameters such as velocity, pressure and pressure-diameter relationship during a cardiac cycle. Ultrasonic techniques were developed on a test bench and directly applied to animals without major modification. On such a test bench allowing a good simulation of physiological type flows, velocity field and pressure-diameter relationship were determined. In vivo application of these techniques allowed a systematic analysis of velocity profiles in the rabbit abdominal aorta and a precise approach of rheological properties of the vascular wall.