A ventricular-vascular coupling model in presence of aortic stenosis

In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V(3)) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V(3) model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99x - 2.36 with a coefficient of determination r(2) = 0.98. There was also very good agreement between estimated and measured stroke volumes (y = 1.03x + 2.2, r(2) = 0.96, SEE = 2.8 ml). Hence, this mathematical V(3) model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.     

Evidence for the presence of GPRC6A receptors in rat mesenteric arteries

In this study, the presence of GPRC6A receptors in rat mesenteric artery was investigated. In artery homogenates, GPRC6A mRNA was detected and Western blotting showed the presence of GPRC6A protein. Immunohistochemical studies revealed GPRC6A in both endothelial cells and myocytes. In whole vessel segments, the GPRC6A activators, 300 microM l-ornithine and 100 microM Al(3+), induced endothelium-dependent myocyte hyperpolarizations sensitive to 10 microM TRAM-34, a blocker of intermediate conductance, Ca(2+)-sensitive K(+) channels (IK(Ca)). Activation of IK(Ca) with calindol (300 nM; a positive allosteric Ca(2+)-sensing receptor - CaR - modulator) was inhibited by 500 nM ouabain (inhibition of rat type 2 and type 3 Na(+)/K(+)-ATPases) but unaffected by 30 microM Ba(2+) (blockade of inwardly rectifying K(+) channels). Neither l-ornithine nor Al(3+) activated CaRs heterologously expressed in CHO or HEK293 cells. In the presence of 300 microM l-ornithine or 100 microM Al(3+), myocyte hyperpolarizations to calindol were potentiated whereas this potentiation and hyperpolarizations to l-ornithine were lost following incubation with an anti-GPRC6A antibody. It is concluded that GPRC6A receptors are present on mesenteric artery endothelial cells and myocytes and that their activation selectively opens IK(Ca) channels. This triggers a ouabain-sensitive myocyte hyperpolarization suggesting a close functional relationship between GPRC6A, the IK(Ca) channel and type 2 and/or type 3 Na(+)/K(+)-ATPases.     

Innervation of the human internal carotid arteries under normal conditions and in stenosis]

The neurohistological investigation of a portion of the internal carotid artery removed in operation on the occasion of occlusion revealed afferent, cholinergic and adrenergic nerve elements randomly located in the examined area. The histochemical and electronmicroscopic investigation of the superior cervical sympathetic ganglion removed from 42 patient operated on the occasion of occlusion of the carotid artery revealed a depletion in the ganglia of synaptic active zones, focal absence of catecholamines and neurohistological materials suggests that a substantial role in the process of stenosing of vascular walls is played by sophisticated effects of innervation connections upon the vessel sheaths.     

Flow in a catheterized curved artery with stenosis

The fluid mechanics of blood flow in a catheterized curved artery with stenosis is studied through a mathematical analysis. Blood is modelled as an incompressible Newtonian fluid and the flow is assumed to be steady and laminar. An approximate analytic solution to the problem is obtained through a double series perturbation analysis for the case of small curvature and mild stenosis. The effect of catheterization on various physiologically important flow characteristics (i.e. the pressure drop, impedance and the wall shear stress) is studied for different values of the catheter size and Reynolds number of the flow. It is found that all these flow characteristics vary markedly across a stenotic lesion. Also, increase in the catheter size leads to a considerable increase in their magnitudes. These results are used to obtain the estimates of increased pressure drop across an arterial stenosis when a catheter is inserted into it. Our calculations, based on the geometry and flow conditions existing in coronary arteries, suggest that, in the presence of curvature and stenosis, and depending on the value of k (ratio of catheter size to vessel size) ranging from 0.1 to 0.4, the pressure drop increases by a factor ranging from 1.60 to 5.16. But, in the absence of curvature and stenosis, with the same range of catheter size, this increased factor is about 1.74-4.89. These estimates for the increased pressure drop can be used to correct the error involved in the measured pressure gradients using catheters. The combined effects of stenosis and curvature on flow characteristics are also studied in detail. It is found that the effect of stenosis is more dominant than that of the curvature. Due to the combined effect of stenosis, curvature and catheterization, the secondary streamlines are modified in a cross-sectional plane. The insertion of a catheter into the artery leads to the formation of increased number of secondary vortices.     

Response of isolated segments of hepatic arteries to serotonin in the presence of methergoline

The effect of metergoline (an anti 5-HT drug) on strips of calf hepatic arteries was investigated. Metergoline prevents or antagonizes the contraction induced by 5-Hydroxytryptamine. The inhibitory effect is dose-dependent.     

Numerical technique of blood flow through catheterized arteries with overlapping stenosis

This study is concerned with the surgical technique for the injection of a catheter through arteries with overlapping stenosis in the presence of externally applied magnetic field and Hall currents influences. The nature of blood is analyzed mathematically by considering it as a micropolar fluid. The analysis is carried out for an artery with a mild stenosis. The governing equations with the corresponding boundary conditions solved numerically using Crank–Nicolson implicit finite difference scheme. The numerical technique give excellent agreement for axial velocity of the fluid, the circumferential microrotation, the wall shear stress distribution and the contour plots of stream lines. The obtained results show that the value of axial velocity is higher for a Newtonian fluid than that for a micropolar fluid model, the effect of suitable moving magnetic field (Hall currents influences) accelerates the speed of blood, the size of trapped bolus for the stream lines decrease if the spinning movement of the fluid molecules have considerable value regardless of small or large size of the fluid molecules and the flow of fluid is better with increasing the Hall current effect and the size of trapping bolus increase clearly by increasing the maximum height of stenosis where the fluid moves as a bulk.     

Flow inhibits inward remodeling in cannulated porcine small coronary arteries

The mechanisms of flow-induced vascular remodeling are poorly understood, especially in the coronary microcirculation. We hypothesized that application of flow in small coronary arteries in organoid culture would cause a nitric oxide (NO)-mediated dilation and inhibit inward remodeling. We developed an organoid culture setup to drive a flow through cannulated arterioles at constant luminal pressure via a pressure gradient between the pipettes. Subepicardial porcine coronary arterioles with diameter at full dilation and 60 mmHg (D0) of 168 +/- 10 (SE) microm were cannulated. Vessels treated with Nomega-nitro-L-arginine (L-NNA) to block NO production and untreated vessels were pressurized at 60 mmHg for 3 days with and without flow. Endothelium-dependent dilation to 10(-7) M bradykinin was preserved in all groups. Tone was significantly less in vessels cultured under flow conditions in the last half of the culture period. Untreated and L-NNA-treated vessels regulated their diameter to yield shear stresses of 10.3 +/- 2.1 and 14.0 +/- 2.4 (SE) dyn/cm2, respectively (not significantly different). Without L-NNA, passive pressure-diameter curves at the end of the culture period revealed inward remodeling in the control group [to 92.3 +/- 1.3% of D0 (SE)] and no remodeling in the vessels cultured under flow conditions (100.2 +/- 1.3% of D0); with L-NNA, the group subjected to flow showed inward remodeling (92.1 +/- 2.5% of D0). We conclude that pressurized coronary resistance arteries could be maintained in culture for several days with flow. Vessels cultured under flow conditions remained more dilated when NO synthesis was blocked. Inward remodeling occurred in vessels cultured under no-flow conditions and was inhibited by flow-dependent NO synthesis.     

Flow visualization studies in a mold of the normal human aorta and renal arteries

To study the flow behavior in regions where hemodynamic effects have been suggested to participate in atherogenesis, we evaluated flow in a mold of the aorta and renal arteries of a previously healthy 27-year-old woman who died of trauma. A birefringent solution (vanadium-pentoxide) was used. When diluted, this material behaves like a Newtonian fluid. This method gives a complete picture of the entire flow field. Zones of flow separation and disturbed flow can be seen and the location and size of disturbed areas observed. Unseparated flow regions downstream from disturbed zones can be properly visualized and the method can be used for pulsatile flow as well as steady flow. During steady flow (only at branch to-trunk flow ratios greater than 0.20), zones of flow separation were observed in the aorta distal to the renal arteries. During pulsatile flow, disturbances were found at nearly all branch-to-trunk flow ratios.     

Comparison of the results of stenting ans balloon angioplasty of coronary arteries in relation to the type of stenosis

Based on the comparison of the immediate and late results of stenting and balloon angioplasty (BA), the authors consider whether it is expedient to perform stenting of coronary arteries (CA) in all cases of BA in patients with coronary heart disease (CHD) and different types of CA stenosis. The study included 410 patients: a group of stenting (n = 197) and a group of traditional BA (n = 213). All the patients in both groups were divided into four subgroups in relation to the type of detected stenosis according to the classification of the American Association of Cardiologists (ACC/AHA). The positive angiographic and clinical results were observed in all 197 patients after stenting. This was associated neither with the type of dilated stenosis nor with the design of an implanted stent. In dilation of types A and B1 stenoses, a stent-like result was significantly more frequently observed than in dilation of types B2 and C stenoses. There was no significant difference in the development of restenosis in patients after routine BA and stenting of types A and B1 stenoses. At the same time, after BA of types B2 and C stenoses, restenosis developed significantly more frequently than in stenting. Thus, on the basis of this study, it may be stated that the traditional BA yields the so-called stent-like result significantly more frequently in patients with uncomplicated forms of CA stenoses than in those with complicated ones. Once the stent-like result is achieved in patients with type A stenoses, stenting should not be performed since the latter fails to improve the immediate and late results of angioplasty. Despite that the stent-like result is achieved in patients with complicated forms of CA stenoses, it is expedient to make stenting. Our findings indicate that the obtained good immediate result reduces the incidence of restenosis.     

Influence of desoxycorticosterone on the reaction of isolated segments of coronary arteries to noradrenaline in the presence of pyrogallol

The effect of the desoxycorticosterone on the noradrenaline-induced relaxation of coronary arteries waw studied in vitro, after a known inhibitor of COMT, pyrogallol. Relaxation induced by noradrenaline was enhanced by desoxycorticosterone. Relaxation in response to noradrenaline was increased by desoxycorticosterone. Pyrogallol potentiated the responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of desoxycorticosterone. It is concluded that desoxycorticosterone enhances the reponse of coronary smooth muscle to noradrenaline by inhibiting and enzymatic pathway for the inactivation of catecolamines.     

Flow field and mass transport analysis in arteries with longitudinal ridges.

Recent observations have indicated that the earliest lesions of atherosclerosis frequently take the form of longitudinal and helical ridges in arteries of man. Since longitudinal vortices are expected to be present in the troughs between the longitudinal ridges, an analysis was carried out to investigate the three-dimensional flow field and the trasport of lipoproteins and oxygen molecules to arterial walls in the presence of such vortices. The calculations revealed that local hypoxia and lipoprotein accumulation may occur at the ridges, leading to subsequent intimal thickening and ridge growth. Higher shear stresses, calculated in the troughs between ridges, may also partially damage the endothelium and lead to intimal thickening and subsequent merging of the ridges. Meaningful measurements are needed in vivo to determine the strength of the vortices, their time-varying behavior, and the actual transverse variations in shear stress, oxygen transport, and lipoprotein accumulation from trough to ridge regions, in order to appraise the present findings and to learn more about the observed progressive thickening and widening of ridges with increasing degrees of intimal thickening and atherosclerosis.     

Influence of pyridoxal-5'-phosphate on responses of isolated coronary arteries to noradrenaline, in the presence of pyrogallol

The effect of PLP on the noradrenaline-induced relaxation of coronary arteries was studied in vitro, after known inhibitor of COMT, Pyrogallol. Relaxation of response to noradrenaline were increased by PLP. Pyrogallol potentiated responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of PLP. It is concluded that PLP enhances the response of coronary smooth muscle to noradrenaline by inhibiting a enzymatic pathway for the inactivation of catecolamines.     

Tying with thread of the rat coronary arteries, a method for the production of experimental coronary stenosis]

A method is described for producing a localized coronary artery stenosis by tieing two threads around the Ramus descendens of the left coronary artery, which produces progressive cell proliferation of the vascular wall. Studies on 102 male Wistar rats (70 experimental and 32 sham-operated control animals) have shown coronary artery stenosis narrowing the lumen by more than 50% (up to and exceeding 90%) to develop after 7 days in 30% of the animals, after 14 days in 75%, and after 21 days (postoperatively) in 100%. In about one-third of the cases subtotal infarction in the supply area of the left coronary artery occured as a result of post-operative damage to the coronary artery with obturating thrombosis. The induction of effective coronary stenosis limiting the coronary reserve offers possibilities for further experimental studies on the role of relative coronary insufficiency in the pathogenesis of myocardial infarction.