Passive aortic counterpulsation: Biomechanical rationale and bench validation

Aortic counterpulsation (IABP) consists in an ECG-controlled forced deflation and inflation of a balloon positioned in the aorta. The device is designed to decrease the ventricular afterload during systole and to increase the coronary driving pressure during diastole. In biomechanical terms, the IABP improves the mechanical matching between the pump and the load, facilitating the transfer of ventricular energy. This paper describes a completely passive aortic counterpulsation solution, with an intra-aortic balloon without a pumping system, designed to improve the mechanical matching between the ventricle and the artery at very low cost and complexity. The only requirement is an external reservoir to amplify the balloon pulsations due to physiologic arterial pressure pulse.     

Wave intensity analysis of para-aortic counterpulsation

Wave intensity analysis (WIA) was used to delineate and maximize the efficacy of a newly developed para-aortic blood pump (PABP). The intra-aortic balloon pump (IABP) was employed as the comparison benchmark. Acute porcine experiments using eight pigs, randomly divided into IABP (n = 4) and PABP (n = 4) groups, were conducted to compare the characteristics of intra- and para-aortic counterpulsation. We measured pressure and velocity with probes installed in the left anterior descending coronary artery and aorta, during and without PABP assistance. Wave intensity for aortic and left coronary waves were derived from pressure and flow measurements with synchronization correction applied. To achieve maximized support efficacy, deflation timings ranging from 25 ms ahead of to 35 ms after the R-wave were tested. Similar to those associated with IABP counterpulsation, the PABP-generated backward-traveling waves predominantly drove aortic and coronary blood flows. However, in contrast with IABP counterpulsation, the nonocclusive nature of the PABP allowed systolic unloading to be delayed into early systole, which resulted in near elimination of coronary blood steal without diminution of systolic left ventricular ejection wave intensities. WIA can elucidate subtleties among different counterpulsatile support means with high sensitivity. Total accelerating wave intensity (TAWI), which was defined as the sum of the time integration of accelerated parts of the positive and negative wave intensities, was used to quantify counterpulsation efficacy. In general, the larger the TAWI gain, the better the counter-pulsatile support efficacy. However, when PABP deflation timings were delayed to after the R-wave, the TAWI was found to be inversely correlated with coronary perfusion. In this delayed deflation timing setting, greater wave cancellation occurred, which led to decreased TAWI but increased coronary perfusion attributed to blood regurgitation reduction.     

Quantitative study of aortic wall permeability

Fluorescent microscopy with trypan blue was used to assay aortal wall permeability. The dye permeation to the vascular wall was assayed by photometry with graphic data recording. The technique described enabled exploring aortal wall permeability in rabbits with experimental hypertension associated with induced atherosclerosis.     

Numerical simulation of cardiovascular dynamics with different types of VAD assistance

A variety of methods by which mechanical circulatory support (MCS) can be provided have been described. However, the haemodynamic benefits of the different methods have not been adequately quantified. The aim of this paper is to compare the haemodynamic effects of six forms of MCS by numerical simulation. Three types of ventricular assist device (VAD) are studied: positive displacement; impeller and a novel reciprocating-valve design. Similarly, three pumping modes are modelled: constant flow; counterpulsation and copulsation. The cardiovascular system is modelled using an approach developed previously, using the concentrated parameter method by considering flow resistance, vessel elasticity and inertial effects of blood in individual conduit segments. The dynamic modelling of displacement and impeller pumps is represented by VAD inlet/outlet flow-rate changes. The dynamics of the reciprocating-valve pump is modelled with a specified displacement profile. Results show that in each simulation, the physiological variables of mean arterial pressure and systemic flow are adequately maintained. Modulation of the impeller pump flow profile produces a small (5 mmHg) oscillatory component to arterial pressure, whereas the displacement and reciprocating-valve pumps generate substantial arterial pressure and flow pulsatility. The impeller pump requires the least power input, the reciprocating valve pump slightly more, and the displacement pump the most. The in parallel configuration of the impeller and displacement pump designs with respect to the left ventricle provides near complete unloading and can cause the aortic valve to remain closed throughout the entire cardiac cycle with the attendant risk of aortic valve leaflet fusion following prolonged support. The in series configuration of the reciprocating-valve pump avoids this shortcoming but activation must be carefully synchronized to the cardiac cycle to allow adequate coronary perfusion. The reciprocating-valve pump is associated with haemodynamic advantages and a favourable power consumption.     

Quantifying division of aortal smooth muscle cells in culture stimulated by 1,25(OH)2D3

Inhibitory effect of 1,25dihydroxycholecalciferol (1,25D₃ = calcitriol) in different cell type is well recognized but its promoting effect on vascular smooth muscle cells (SMCs) is poor established. Therefore, the aim of this study was to determine stimulatory effect of calcitriol on aortal SMCs proliferation in culture. We used the cell division analysis procedure based on the quantitative sequential halving of the stably incorporating fluorescent dye carboxyfluorescein diacetate succinimidyl ester (CFSE). This technique allowed the visualization of cycles of SMCs division by flow cytometry. Rat aortal SMCs were labeled with CFSE and cultured for up to 10 days with defined concentration of calcitriol in medium. Proliferative activity as the percentage of SMCs in different phases of the cell cycle using propidium iodide was determined. Apoptosis was assessed using Annexin-V/CFDA method. The results suggest that low concentrations of an active form of vitamin D—1,25dihydroxycholecalciferol applied in supraphysiological concentration of 10 nmol/l is a mitogenic factor for aortal SMCs. None of the applied concentrations of calcitriol caused apoptosis. The findings well support our morphological (LM) and ultrastructural (TEM and SEM) observations.     

Quantifying division of aortal smooth muscle cells in culture stimulated by 1,25(OH)2D3

Inhibitory effect of 1α,25dihydroxycholecalciferol (1,25D₃ = calcitriol) in different cell type is well recognized but its promoting effect on vascular smooth muscle cells (SMCs) is poor established. Therefore, the aim of this study was to determine stimulatory effect of calcitriol on aortal SMCs proliferation in culture. We used the cell division analysis procedure based on the quantitative sequential halving of the stably incorporating fluorescent dye carboxyfluorescein diacetate succinimidyl ester (CFSE). This technique allowed the visualization of cycles of SMCs division by flow cytometry. Rat aortal SMCs were labeled with CFSE and cultured for up to 10 days with defined concentration of calcitriol in medium. Proliferative activity as the percentage of SMCs in different phases of the cell cycle using propidium iodide was determined. Apoptosis was assessed using Annexin-V/CFDA method. The results suggest that low concentrations of an active form of vitamin D—1α,25dihydroxycholecalciferol applied in supraphysiological concentration of 10 nmol/l is a mitogenic factor for aortal SMCs. None of the applied concentrations of calcitriol caused apoptosis. The findings well support our morphological (LM) and ultrastructural (TEM and SEM) observations.     

Exophiala dermatitidis de Hoog from a valvular aortal prothesis

A case of endocarditis originating from a valvular aortal prothesis contaminated with Exophiala dermatitidis de Hoog is described.     

Surgical anatomy of subaortic conus of the normal heart]

One hundred and fourty-three normal hearts have been studied. The conoid septum, supraventricular crest, bulboventricular fold, area of the fibrous tissue between the aortal and mitral valves and the anterior interventricular septum make the walls (frontal view, in the direction of the hour hand) of the left ventricular cone. In the normal heart there is no real contact between the fibrous rings of the aortal and mitral valves. They are connected by means of a strip of the fibrous tissue, its size varies. The subaortal cone and deferent part of the left ventricular axes make an obtuse angle; the axes of the subpulmonary and subaortal cones have a cross direction. The geometrically definitive left ventricular cone is seen as obliquely-sectioned overturned isosceles cone, with its big base directed upward, right and back, and the small one forward and left.     

Principles of organization of tissue mosaics of simple squamous epithelia

With the aim to study general principles on organization of tissue mosaics of various types of simple squamous epithelii, a quantitative topological analysis has been performed in the frog mesothelial mosaics, in the posterior epithelium of the rabbit cornea and in the rat aortal endothelium after Lewis method. To all the types of simple squamous epithelii studied the histological law of Lewis can be applied. As demonstrates the qualitative analysis of the mosaics, the mesothelium and the posterior epithelium of the cornea are typical isotropic mosaics, while the mosaic of the aortal endothelium is nearer to the polystichous one. The possibilities of qualitative and quantitative topological analysis of the biological mosaics after Lewis method for studying their organization, degree of regularity, histogenesis and proliferative properties are discussed.     

Arteriovenous difference in antithrombin III activity and the antiaggregation properties of the vessel wall

The paper is concerned with the data on the arteriovenous difference in antithrombin III activity and antiaggregation properties of the aortal and inferior vena cava walls in Wistar rats. A correlation between the changes identified and different thromboresistance of the arteries and veins is suggested.     

Current Status of Counterpulsation in Cardiac Assistance: A Summary of Experimental Experience in the Dog

Synchronized counterpulsation was applied to two groups of nine dogs using a new fluid-coupled pulse generator. Pump performance and synchronization were superior to earlier pneumatic systems. Improvement in cardiac function was evidenced by reduction in left ventricular pressure, work and oxygen consumption. Peripheral hemodynamics were adversely affected as evidenced by reduction in blood pressure, cardiac output, renal and carotid blood flows and decrease in central venous oxygen saturation. Evaluation of counterpulsation in acute left ventricular failure produced in 15 dogs by serial coronary ligations revealed that the elevated left atrial pressure was reduced, but neither cardiac output nor arterial pressure was improved by counterpulsation.     

Induction of endothelial cell migration by proline analogs and its relevance to angiogenesis

The proline analogs cis-4-hydroxy-L-proline, 3,4-dehydro-L-proline, and 2-azetidinecarboxylic acid induced increases in the migration rate of retinal capillary endothelial cells, aortal endothelial cells, corneal endothelial cells, aortal smooth muscle cells, and retinal pericytes. cis-4-hydroxy-D-proline did not. The optimal concentration for migration induction by any of the active agents was approximately 10(-5) M. At higher concentrations (5 x 10(-4) M) migration was not induced or was inhibited. When tested by subcutaneous implant assays in rabbits, cis-4-hydroxy-L-proline and 2-azetidinecarboxylic acid consistently elicited a marked angiogenic response. Whereas these compounds are known to modulate collagen synthesis and secretion, the concentrations at which they are effective inducers of migration suggest that they may have a more specific target than general collagen synthesis.     

Constitutional and age-related properties of the aortic isthmus

By means of micro- and macropreparation and morphometry methods in 200 corpses of children and adult persons, it has been stated that skeletotopy and syntopy of the aortal isthmus depends on the constitution of the person. Certain objective criteria have been elaborated for surgical approaches to the aortal isthmus. In little children, during early and first childhood, anterolateral thoracotomy should be performed in the III intercostal space; in persons with brachymorphose type of constitution--left-sided thoracotomy in the IV intercostal space; in persons with transitional and long-narrow thorax--left-sided thoracotomy in the V intercostal space with resection of the V rib.     

Impaired regulation of corticosterone levels during fasting in aging rats.

The concentration of corticosterone in aortal blood of 3-day fasted rats decreases approximately 75% between 2- and 24-months of age. The reduced level of hormone in aging rats is not attributable to an enhanced rate of corticosterone utilization from the blood or to a diminished steroidogenic capacity of the adrenal cortex, but apparently reflects a deficiency in extraadrenal regulatory mechanisms.     

Age and individual variability of aortic valve structure in man

In persons of both sex at the age beginning from birth up to 90 years. 275 aortal valves have been investigated. A morphological classification of the valves has been suggested depending on peculiarities of their structure and main dimentions: valves with the valvula surfaces looking as a part of a spheroid, ellipsoid, or having a stepwise, cochliowise form; according to the mode of the valvula closure when the valve is closed: with straight, arched and wavy lines of closure; according to the size: valves with predominant dimentions of one valvula when two others are equal, valves with two equal valvulae and both are larger than the third one, valves with equal valvulae, valves with three different valvulae. Distribution of various types of the valves in accordance with the given classification is determined, the most frequently occurring forms are demonstrated. The valvulae grow in different directions unevenly and asynchronously with the aortal ostium growth, therefore during certain age periods a probability on a nonhermetic valve increases, especially from 1 up to 3 and from 56 up to 70 years of age.     

Endothelial cell phagokinesis in response to specific metal ions

Salts of Cu^{I, II}, Ni^II, Sn^II, In^III and a sub-fraction of the cupoprotein ceruloplasmin induced phagokinesis of cultured aortal endothelial cells. A variant aortal endothelial cell line was highly sensitive; cells travelled up to 1000 μm in 24 h in response to 2× 10^?6 M SnCl₂. Other metal ions tested (Zn^II, Co^II, Mn^II, Cr^II, Fe^III, Al^III, Sb^III and Mo^II) were not active. The motility response of endothelial cells to Cu ions in vitro is proposed as a model system for studying early events in neovascularization and as a sensitive assay for detecting angiogenic activity in fractions from cells and tissues.     

State of the endothelium of the aorta during chronic stress

In 50 white male rats (18-control and 32-experimental) using morphometrical and stereological methods for film preparations of endothelium, the state of the internal aortal lining at various stages of chronic stress developing during muscular activity has been studied. The data obtained are statistically treated by the sliding averages method, reliability of the differences is estimated according to the value of nonparametrical criterion of Wilcoxon-Mann-Whitney. For objective periodization of the endothelial reaction to stress, centered moving averages curves are performed with subsequent calculation of the coefficient of variation for the aligned ordinates of the approximated values in every temporal point. The aortal endothelium reaction to the stress is of phasic character. During the alarm reaction, destructive changes predominate; they are accompanied with an increased mitotic activity of endotheliocytes up to 2.2%. The resistance stage increases compensatory-adaptive rearrangements, which are manifested not only as cellular hyperplasia, but as hyperthrophy of nuclei, increasing number of strangulated nuclei, nucleoli, as well as binuclear and trinucler cells. To the exhaustion period the increase of alternative and restorative transformations of the tissue corresponds.     

Effects of skim milk, skim milk yogurt, orotic acid, and uric acid on lipid metabolism in rats

The effects of feeding two milk products (skim milk and skim milk yogurt) and two proposed hypocholesterolemic factors (orotic acid and uric acid) on serum cholesterol (HDL, LDL, total, HDL/Total and HDL/LDL), liver lipids (total liver lipids and liver cholesterol), and aortal cholesterol were studied. Ten groups, of nine rats each, were fed isocaloric Chow-based diets containing water, 45% skim milk (SM), 45% skim milk yogurt (SMY), and 0.0025% orotic acid (OA) or 0.001% uric acid (UA), without or with cholesterol. The SM diet (with cholesterol) resulted not only in lower total cholesterol (P < 0.10), LDL cholesterol (P < 0.05), aortal cholesterol (P < 0.01), and liver cholesterol (P < 0.10), but also in increased HDL (P < 0.05) and HDL/LDL (P < 0.10) cholesterol ratio. The SMY diet, on the other hand, resulted in lowered total serum cholesterol (P < 0.05) and aortal cholesterol (P < 0.01) and in higher LDL (P < 0.05) cholesterol. The hypocholesterolemic effects were more marked for SM than for SMY. Addition of OA and UA to diets increased serum cholesterol, LDL cholesterol, and total liver lipids; the OA diet also increased liver cholesterol. Neither OA nor UA alone was the factor responsible for the hypocholesterolemic effects seen with SM and SMY feeding.     

Cholesterol in the plasmalemma of endotheliocytes in the normal aorta and in hypercholesterolemia (scanning electron microscopy research)

Using a specific latex marker (SLM) and scanning electron microscopy, distribution of cholesterin in plasmolemma of endotheliocytes of the thoracic part of the rabbit aorta has been studied under normal conditions and at experimental atherosclerosis, as well as on the surface of liposomes and flat bilayer films. SLM reacts with a high specificity directly with cholesterin of the membrane. When studying microtopography of cholesterin, it is possible to distinguish microdomains with various density of distribution of SLM particles. Amount of SLM per 1 mcm2 of the artificial membrane surfaces grows at increase of the cholesterin-phospholipid (Ch/Phl) index of the membrane; Ch/Phl can bind with the membranes beginning only with the threshold value of the Ch/Phl index equal to 0.5. At hypercholesterolemia amount of SLM on the luminal surface of plasmolemma of the aortal endotheliocytes increases by 78%. Hence, at hypercholesterolemia in the luminal part of plasmolemma of the aortal endotheliocytes the Ch/Phl index increases; this should be taken into consideration, when observing mechanisms of reorganization of the endothelial cells layer at atherosclerosis.     

Dissecting aneurysm of the ascending aorta as a late complication of the treatment of acquired defects of the aortic and mitral valves

A diffuse aneurysm of the ascending aorta was observed five months after prosthetic valve implantation in to mitral and aortic orifices because of the acquired valvular heart disease. The main factor predisposing to the formation of a false aneurysm was an infection of the endocardium and ascending aortal wall which were observed previously during cardiac surgery. The diagnosis, based on the clinical symptoms and non-invasive investigations, was later confirmed with aortography and intra-operatively.