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Biomedical subjects

M Intaglietta

Publications and source records attributed to M Intaglietta.

At least 109 records · Page 6Linked to original sources

Dynamic fluid redistribution in hyperosmotic resuscitation of hypovolemic hemorrhage.

A mathematical description of blood volume restoration after hemorrhage with resuscitative fluids, particularly hyperosmotic solutions, is presented. It is based on irreversible thermodynamic transport equations and known physiological data. The model shows that after a 20% hemorrhage, the rapid addition of a hypertonic (7.5% NaCl)-hyperoncotic (6% Dextran 70) solution amounting to one-seventh of the shed blood volume reestablishes blood volume within 1 min. Measurements of systemic hematocrit, hemoglobin concentration, and plasma osmolality taken from 13 experiments on anesthetized rabbits verify this prediction. The model shows that immediately after hyperosmotic infusion, water shifts into the plasma first from red blood cells and endothelium and then from the interstitium and tissue cells. The increase in blood volume is transitory; however, it occurs in a fraction of the time compared with isoosmotic fluids at the same infusion rate and is partially sustained by Dextran 70. We theorize that the concurrent hemodilution and endothelial cell shrinkage during hyperosmotic infusion lead to a decreased capillary hydraulic resistance, an effect that is even more significant in capillaries with swollen endothelium. Our results support the significant role of an osmotic mechanism during hyperosmotic resuscitation in quickly restoring blood volume with the added benefit of improved tissue perfusion.

Animals↗

Regulatory role of vasoactive peptides in subcutaneous skin microcirculation of the hamster.

The microcirculatory effects of vasoactive peptides on arteriolar diameter were determined in the dorsal skin-fold preparation of conscious Syrian hamsters and related to arterial blood pressure (MABP). (5 Ile)-angiotensin II (ANG II), (8 Arg)-vasopressin (AVP), vasoactive intestinal polypeptide (VIP), atrial natriuretic factor (ANF), and substance P (SP) were administered intravenously as bolus injections in picomolar concentrations. The diameters of subcutaneous A3 arterioles (15-40 microns) at bifurcation sites were determined via a microscope video system and stored in a digital memory. When spontaneous rhythmic vasoconstrictions and dilations (vasomotion) were present, the diameter oscillations were analyzed by means of the Prony Spectral Line Estimator. ANG II caused sustained arteriolar contraction at increased MABP, but did neither induce nor modulate vasomotion. Both ANF and VIP slightly reduced MABP and had no effect on microcirculatory parameters. SP led to a significant dilation of subcutaneous arterioles in the hamster skin with concomitant drop in MABP, but did not influence arteriolar vasomotion. Physiological concentrations of AVP, as determined in the plasma by radioimmunoassay, caused a marked contraction of the arterioles and evoked a mild pressor response. In addition, AVP induced or greatly enhanced vasomotoric activity. This study therefore provides evidence that endogenous vasoactive peptides play an important role in regulation of skin peripheral resistance by altering arteriolar diameter in a tonic or even dynamic way.

Angiotensin II↗

Contrast enhancement amplifier for television microscopy.

A video amplifier is described for the purpose of enhancing the contrast of televised scene features. The system operates by amplifying the video signals bracketed by selectable gray levels, in such a fashion that the features of interest take up the whole dynamic range of the video display. The system operates and can be used directly in conjunction with on line video processors such as automated microvessel diameter measuring systems and video blood cell velocimeters.

Amplifiers, Electronic↗

Model analysis of the enhancement of tissue oxygenation by hemodilution due to increased microvascular flow velocity.

The effect of hemodilution on oxygen delivery to the tissue was investigated analytically by taking into consideration the oxygen loss that occurs along the arterial microvasculature due to diffusion into the tissue and shunting to parallel running venules. The theoretical findings were related to experimental data on microvascular oxygen distribution and the blood flow weighted by the oxygen-carrying capacity of plasma and red blood cells (Q) during hemodilution. It was found that at 30-33% hematocrit, the amount of oxygen brought to the tissues is increased by 5% when diffusion is the only mechanism of oxygen loss, and by 15% when the loss is due to arteriole-venule (A-V) shunting. These increases are relative to the conditions of normal hematocrit, and are in addition to the 10% increase due to the enhancement of Q caused by hemodilution. The analysis was extended to conditions of low oxygen tension and flow condition, characteristic of ischemia. In the case of severe ischemia the total increase in oxygen delivery at hematocrit 30-33% was 38% for tissues with diffusion losses only, and 66% when shunting losses are predominant. These results suggest that hemodilution is particularly effective in increasing oxygenation in ischemic tissue, while it has a comparatively small effect in normal conditions.

Arterioles↗

Capillary video red blood cell velocimetry by cross-correlation and spatial filtering.

A spatial filter capillary red blood cell velocimeter was implemented in video format by means of a linear array of video photometric windows whose number could be varied from two to eight. Two windows of the same video linear window array were used to measure velocity by means of the conventional cross-correlation method. The two methods, spatial filtering and cross-correlation, were compared by means of a computer-controlled video test pattern generator designed to simulate red blood cell flow of variable hematocrit and velocity. It was found that at normal microvascular hematocrits, both methods provide essentially identical data. At low hematocrit, if the simulated red blood cell distribution is such that a cell is always present within the array, spatial filtering data processing provides a more stable measurement than does cross-correlation; however, under the same conditions spatial filtering yields measurement directly related to flux (red blood cells per unit time) rather than to velocity.

Blood Flow Velocity↗

Coordinated diameter oscillations at arteriolar bifurcations in skeletal muscle.

The spontaneous rhythmical luminal changes (vasomotion) at bifurcations in the microvasculature of the rabbit tenuissimus muscle were investigated by means of a microscope video photometric system. Video scenes, containing two terminal arterioles originating from one transverse arteriole, showed that adjacent terminal arterioles constricted synchronously in 26 out of 31 contraction cycles. The onset of 60 constrictions in the parent transverse vessels was synchronized with the activity in terminal arterioles in 75% of the cycles and delayed in 25%. Vasomotion in the parent transverse vessels was notably smaller than in the terminal vessels. All the terminal arterioles in the different animals oscillated at the fundamental frequency of 18.9 +/- 3.5 cycles/min. We conclude that in the skeletal muscle microcirculation 1) coordinated spontaneous diameter oscillations occur in arterioles that are in proximity, 2) diameter changes are most pronounced in the terminal arterioles, and 3) coordinated vasomotion in this tissue exhibits a characteristic narrow band frequency. The presence of a microvascular pacemaker is hypothesized.

Animals↗

Microcirculatory effects of normovolemic hemodilution in skeletal muscle.

The effect of successive normovolemic hemodilution was studied in the microcirculation of the skeletal muscle (tenuissimus) of the rabbit. Normovolemic hemodilution was obtained by the progressive equal replacement of blood with a 6% solution of dextran 70 (MW = 70,000). Systemic parameters (mean arterial pressure, heart rate, and systemic hematocrit) were monitored throughout the procedure to ensure that normovolemia was maintained, and that the animal did not have adverse responses to the procedure. Microcirculatory hemodynamics were characterized by the measurements of capillary red blood cell (RBC) flux, RBC velocity, capillary hematocrit (Hcap), and flowmotion (the effect of arteriolar vasomotion on capillary flow velocity). The same capillaries were chosen throughout a given experiment and the measurements in the hemodiluted states were normalized to the control value. The changes of RBC flux up to 50% hemodilution were not statistically significant and flux remained essentially constant. Capillary RBC velocity increased significantly, where it was 45% higher than control at 50% hemodilution. Hcap was maintained at the control level up to 25% hemodilution.

Animals↗

Tissue perfusion during normovolemic hemodilution investigated by a hydraulic model of the cardiovascular system.

Normovolemic hemodilution on a whole body basis is studied by means of a steady flow, hydraulic analogue simulation of the cardiovascular system, based on the Casson's model and current hemodynamic and rheological data. The vasculature is divided into serially connected compartments whose hydraulic resistance is characterized by the average diameter, length, number of vessels, and the corresponding rheological properties of blood formulated by Dintenfass (1971) and Lipowsky et al. (1980). This model computes the pressure distributions in all compartments, where the calculated venous pressure modulates the cardiac function according to the Starling mechanism for cardiac performance. The alterations of flow induced by the action of the heart are added to the effects due to changes in peripheral vascular resistance as a result of hematocrit variation. This model shows that when the response of heart to the changes of venous pressure is impaired, the maximum oxygen carrying capacity occurs at 40% hematocrit (H) where it is 1% higher than normal hematocrit (H = 44%). The normal cardiac response to the changes of venous pressure, causes the maximum oxygen carrying capacity to occur at 32% H where it is 12% greater than that at normal hematocrit. Mean arteriolar pressure and capillary pressure increase while venular pressure is slightly reduced during normovolemic hemodilution.

Blood Pressure↗

Measurement of the dynamics of arteriolar diameter.

The diameter of the arteriolar vessels of the microcirculation undergoes a continuous variation as a consequence of vasomotion. The quantification of this process requires the implementation of spectral analysis techniques that model short data records of a finite number of superposed sinusoidal waveforms. The following techniques were tested with artificially synthetized records and actual data: the fast Fourier transform, the high-resolution autoregressive method, the maximum entropy method, and the Prony Spectral Line Estimator (PSLE). It was found that the PSLE provides the most accurate estimation of the spectral components of the dynamics of diameter changes because it does not require any assumption on the nature of the data outside the interval under analysis.

Animals↗

Present state of intentional hemodilution.

Preoperative intentional hemodilution is induced by isovolemic exchange of whole blood with colloid solutions in order to gain autologous blood while maintaining normovolemia. The basic mechanism that compensates for the fall of oxygen capacity of the diluted blood is the rise in cardiac output, and organ blood flow, factors that result from the improved fluidity of blood at lower hematocrits. Normal tissues maintain adequate oxygenation during hemodilution through the enhanced redistribution of blood. In ischemic tissues this effect is enhanced, and causes an increase in the oxygenation of ischemic tissues. Limited preoperative and intraoperative hemodilution are alternatives to donor blood transfusion in patients undergoing elective surgery. In shock patients the hemodilution achieved with red cell free primary volume substitutes is an effective treatment for shock-induced microcirculatory disorders; furthermore, intentional hemodilution is the most effectual hemorheological therapy for the treatment of ischemic disease.

Animals↗

Variations of rhythmic diameter changes at the arterial microvascular bifurcations.

The variation of the pattern of the rhythmic diameter changes, in the hamster skin fold window preparation, was studied sequentially along the branching network of the arterial vessels, from A1 small arteries (70-100 micron diameter) to A4 terminal arterioles (less than 15 micron diameter). Contraction and dilation waveforms were characterized at all subsequent levels of bifurcation. The frequency of vasomotion was determined by a specialized spectral method called PRONY, which approximates the spectral composition of complex waveforms by the least square criteria and estimates the coefficient of correlation between reconstructed and original data. It was found that the frequency of vasomotion changes abruptly at the branching points, systematically increasing in the downstream direction. The power spectrum showed that the frequencies, which appear to originate at the bifurcations and have maximum amplitude at these points, are also found in the upstream waveforms. The downstream propagation of contractions and dilations causes superposition of waves. Thus the pattern of vasomotion is the composite effect of signals that originate at various branching points and spread downstream and upstream in the microvasculature. It seems likely to suggest that single unit smooth muscle cells, located at the branchings (local pacemakers), control the arterial rhythmic diameter changes. This time dependent phenomenon affects deeply the microvascular blood flow.

Animals↗

Microvessel diameter changes during hemorrhagic shock in unanesthetized hamsters.

The effects of hypovolemic shock on the time-dependent diameter changes of small arteries and arterioles were studied in the hamster skin fold window preparation. This experimental model permits the visualization of the microvasculature without the effects of acute surgery, anesthesia, and exposure. In these conditions, all the arterial microvessels showed vasomotion, while the venules and small veins, that were also studied, did not show rhythmic diameter changes. Hemorrhage was induced by the withdrawal of blood through a chronically implanted arterial catheter. The mean arterial blood pressure was reduced to 40 mm Hg in 20 min, and was maintained at this value for an additional 30-min period. Reinfusion of the withdrawn blood was made at 50 min. During the shock period, vasomotion disappeared in all arterial vessels. The small arteries and arterioles, A1 (70-100 micron, mean diameter), A2 (40-70 micron, md), and A3 (15-40 micron, md), contracted by 20 +/- 7, 33 +/- 10, and 34 +/- 11% of the control mean diameter, respectively. A4 terminal arterioles (less than 15 micron, md) dilated after the onset of bleeding; their rhythmic diameter changes subsequently stopped and their mean diameter increased by 75 +/- 7% of the original value. V1 small veins (150-200 micron, md) contracted during shock, while V2 (35-55 micron, md), V3 (25-35 micron, md), and V4 (15-25 micron, md) venous vessels did not show any significant change. Reinfusion of shed blood caused the reappearance of vasomotion; control vasomotion patterns recovered after reinfusion. Our results indicate that the microcirculatory responses to hypovolemic shock are dependent on the vessel type; this inhomogeneous reactivity may be due to the different responsiveness of microvessels to the mechanisms elicited by hemorrhage.

Animals↗

Automated diameter measurement of vasomotion by cross-correlation.

A method to measure automatically and continuously blood vessel diameters in the microcirculation is proposed. After imaging by video microscopy, the window of a video photometric analyzer scans the vessel of interest providing a continuous readout of the optical density along a selected direction in the video scene. The signal is differentiated to find the locations of the vessel walls and is cross-correlated to give their positions in relation to each other, thus mimicking electronically what the eye does in the image-shearing technique. Accuracy is limited to widths between twelve and sixty pixels on the video screen because of restrictions in the precision possible in tracking the peak of maximum cross-correlation. The scanning frequency was 1.2 Hz. Therefore, the method is suitable for quantifying the patterns of vasomotion.

Computers↗

The effects of alpha- or beta-adrenergic receptor agonists and antagonists and calcium entry blockers on the spontaneous vasomotion.

The effects of systemic injections of vasoactive substances were studied in the micro-circulation of the hamster skin fold window preparation, which can be observed without anesthesia, exposure, and acute surgical procedures. The effects were characterized by the continuous measurement of the diameter of the arterial microvessels ranging from 100 to 8 micron. Power spectrum analysis was utilized to determine the frequency and the amplitude of the fundamental component of spontaneous diameter changes. Epinephrine and norepinephrine increased the frequency of vasomotion and reduced mean diameter at low dosages. Phentolamine reduced the frequency of vasomotion and increased mean diameter. Propranolol increased the frequency of vasomotion and did not significantly change mean diameter. Adenosine and verapamil suppressed vasomotion and increased mean diameter. These results are explained by postulating that low-dosage alpha-adrenergic receptor stimulation facilitates the spontaneous discharge of smooth muscle cells; beta-adrenergic receptor stimulation has the opposite effect, whereas beta-adrenergic receptor inhibition also enhances the vasomotor effect. Calcium entry blockers abolish the rhythmic discharge. This explanation of the activity of the various substances supports the hypothesis that the spontaneous vasomotion of the arterial microvessels is related to the intrinsic property of smooth muscle cells.

Adrenergic alpha-Agonists↗

Quantitation of rhythmic diameter changes in arterial microcirculation.

The diameter of the arterial and arteriolar blood vessels was measured as a function of time in the hamster skin fold window preparation. When the animals recovered from the surgical implantation, the diameters of the arterial microvessels exhibited a continuous rhythmic activity throughout the preparation for a period of 2 wk while the chamber was intact. The amplitude of the diameter changes was directly proportional to the mean vessel size. The frequency of this phenomenon was determined by power spectrum analysis implemented with a Fourier transform method and was found to decrease from a maximum of 9-15 cycles/min in 8- to 15-micron A4 arterioles to 1-3 cycles/min in 70- to 100-micron A1 small arteries. A1 and A4 vessels had relatively well-defined characteristic fundamental frequencies, whereas A2 and A3 vessels showed a power spectrum that included the frequencies present in A1 and A4 vessels. The activity was not synchronized throughout the microvasculature, and frequencies and amplitudes of diameter variations changed at branching points. Anesthesia induced by the intravenous injections of pentobarbital and chloralose-urethan invariably stopped this activity throughout the preparation. The distribution of this time-dependent activity and the nature of the effect of the anesthetics suggests that this phenomenon is due to local pacemaker activity of groups of unitary smooth muscle cells.

Animals↗

Effects of anesthesia on the spontaneous activity of the microvasculature.

The effects of pentobarbital, alpha-chloralose, alphaxalone-alphadolone, diethyl ether and chloralose-urethane anesthesia on microvascular vasomotion were studied in the hamster skin fold window preparation. All these agents paralyzed vasomotion in the arterioles causing an initial vasodilation, where diameters were above the control-unanesthetized mean values (UMD) for a period of 5-60 min and returned to UMD, and lower, after periods up to 90 min depending on the type of anesthetic. During chloralose-urethane anesthesia vasodilation lasted until the end of observation (90 min). The responses were quantitatively different as a function of vessel type, being more pronounced in the smaller terminal arterioles. Vasomotion did not recover at the end of anesthesia, when the animals awoke, and the vessels tended to remain inert for periods up to 10-20 min, at which time the activity was reestablished with the same control fundamental frequency. Small veins and venules did not exhibit vasomotion and showed various reactions that were characteristic for each anesthetic and vessel type, where vasodilation was the prevalent feature during pentobarbital anesthesia while diethyl ether had the opposite effect. Venular microvessels recovered control diameters 10-20 min after awakening.

Anesthetics↗