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Biomedical subjects

M Intaglietta

Publications and source records attributed to M Intaglietta.

At least 19 recordsLinked to original sources
PubMed1992

Local tissue oxygenation by statistically distributed sources.

The effect of red blood cell separation on tissue oxygenation was analyzed using a previously developed model which accounts for the particulate nature of blood at the capillary level. Results show that an empirically based RBC pattern yields the same levels of oxygenation at 20% hematocrit as an even spacing pattern. Introduction of an empirically based RBC spacing pattern during hemodilution, where capillary hematocrit is reduced by half with concomitant doubling of velocity, results in a reduction of average tissue pO2 by 23% and volume of oxygenated tissue by 28%, whereas axial delivery of oxygen along the length of the capillary was unchanged. Tissue oxygenation levels are optimized with even RBC spacing pattern but not with an empirical pattern because the tissue does not effectively use the oxygen delivered by unevenly spaced RBCs despite an equivalent time-averaged flux. Model predictions for tissue oxygenation for statistically distributed spacing under normal and hemodilution conditions show trends consistent with previously obtained results using even spacing, namely, increased axial distance and volume oxygenated, with decreased average tissue pO2. During hemodilution, the volume of tissue oxygenated above 2 mm Hg decreased to 84%, while the volume above 1 mm Hg increased to 131% relative to control. This finding suggests a redistribution of oxygen within tissue during hemodilution, causing a greater amount of tissue to be exposed, but at a lower pO2.

Animals↗
PubMed1992

Periodic hemodynamics in skeletal muscle during local arterial pressure reduction.

The time-dependent features of red blood cell flow were evaluated with laser-Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New Zealand White rabbits during stepwise arterial occlusion. During the control period with a median femoral pressure of 72 mmHg, 29 animals showed minor irregular fluctuations in LDF blood flow, and only two animals displayed periodic variations of blood flow. Lowering femoral arterial pressure induced maximal periodic blood flow variations at a median pressure of 35 mmHg in all animals with a median frequency of 1.5 cycles/min (termed "slow-wave flow motion"). The median amplitude was 48% of the corresponding average flow. These slow waves disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow-wave flow motion. When slow-wave flow motion was seen at several pressure levels, their frequency was identical, which supports the local pacemaker concept. This study promotes a novel concept for the role and physiological significance of periodic hemodynamics in that it is a condition not characteristic for normal control situations but is activated below a specific local arterial blood pressure and flow threshold, which is known to be the lower end of autoregulation in the microcirculation of rabbit skeletal muscle. This also suggests that slow-wave flow motion is primarily under local control mechanisms.

Animals↗
PubMed1992

Amiloride-sensitive Na+ pathways in capillary endothelial cell swelling during hemorrhagic shock.

We recently discovered that the endothelium of skeletal muscle capillaries swells in the low-flow ischemia induced by hemorrhagic shock. The present study was undertaken to determine the Na+ transmembrane pathways involved in this swelling, since hypoxic cell swelling is attributed to an influx of Na+ and water. In an initial series of experiments, amiloride (5 mg/kg body wt), which blocks multiple Na+ pathways, was infused intravenously into anesthetized rabbits 30 min prior to shock (40% single-withdrawal hemorrhage). Intravital microscopy of treated capillaries in the rabbit tenuissimus muscle showed that after a 1-h shock period, there was no endothelial cell swelling, as evidenced by no measurable change in the width of red blood cells traversing the capillary. In contrast, the swollen endothelium of untreated capillaries reduced the luminal diameter by 20-25% with a preserved stationary abluminal membrane. The specific effects of amiloride on Na+ transport were investigated with amiloride analogues. Animal pretreatment with 5-(N,N-hexamethylene)amiloride, a selective inhibitor of Na(+)-H+ activity, in a dose of 0.5 mg/kg did not significantly mitigate shock-induced swelling; however, a dose of 1 mg/kg completely prevented it. Phenamil, a selective inhibitor of Na+ channel conductance, even at a potent dosage of 0.5 mg/kg, did not affect swelling. These results suggest a primary role for Na(+)-H+ exchange in endothelial cell swelling during hemorrhagic shock, possibly as a means to regulate cellular pH, which may become acidic during ischemia. Narrowed capillaries with elevated hydraulic resistances could delay and diminish resumption of microcirculatory flow on shock resuscitation.

Amiloride↗
PubMed1992

Effect of oxymetazoline nose drops on vascular permeability of the nasal mucosa in the rabbit after provocation with leukotriene B4.

The effects of oxymetazoline nose drops on the vascular permeability of the nasal mucosa in a provoked inflammatory reaction was studied in anesthetized rabbits. Vascular permeability (125I-albumin) was 53% higher in the leukotriene B4-provoked nostril (LTB4) compared with the vehicle-treated contralateral nostril (p < 0.05). The amount of secretions was, however, not different from the vehicle-treated side. The LTB4-induced increase in permeability was decreased by 22% when oxymetazoline was introduced (p < 0.05), and the amount of secretions was reduced by 22% (p < 0.01). The effect of oxymetazoline on the vascular permeability of the nasal mucosa can be attributed to a vascular constriction (decrease in blood flow) and/or a change in the permeability characteristics. The LTB4-induced increase in vascular permeability was not attenuated by the monoclonal antibody IB4 directed against the neutrophil adhesion complex CD11/CD18. The latter suggests that LTB4-induced vascular permeability does not require CD18-mediated neutrophil adherence in the nasal mucosa.

Administration, Intranasal↗
PubMed1992

Laser-Doppler flowmetry compared to intravital microscopy for assessment of blood flow in the nasal mucosa of the rabbit.

Laser-Doppler flowmeter (LDF) studies of the rabbit nasal mucosal microcirculation were compared with intravital videomicroscopy and with flow measured in single blood vessels in order to evaluate the applicability of the LDF technique. Access to the nasal mucosa for a microscope objective was gained surgically through the maxilla. Transillumination for microscopy was achieved through a prism inserted on the contralateral side of the septal cartilage. Blood flow changes were induced by the inhalation of N2, CO2 and O2 and by topically applying the vasoconstricting alpha-adrenoceptor agonist oxymetazoline. The effects were registered by LDF and direct visual observation. Flow in veins and capillaries was calculated using on-line cross-correlation, and off-line a computerized video-analysis system. LDF did not correlate to flow in single veins or capillaries but agreed well with the visual impression. LDF is considered a valuable method for the assessment of over-all blood flow changes in the nasal mucosa.

Animals↗
PubMed1992

Slow-wave flowmotion in rabbit skeletal muscle after acute fixed-volume hemorrhage.

Laser Doppler flux (LDF) was used to detect flowmotion (regular cyclic alterations in red blood cell flux) in the left gastrocnemius muscle of 14 rabbits that were bled 30% of their blood volume and let to recover spontaneously for 30 min. Only rabbits that met stated inclusion criteria during control conditions were used in the study. During control conditions when femoral artery pressure averaged 68 mm Hg (range 60-80), no animal displayed regular flowmotion. After the end of the acute hemorrhage, arterial pressure was 35 mm Hg (20-51) and slow wave flowmotion appeared instantaneously in 13 of the 14 animals. The maximum relative amplitude of the induced flowmotion was 31% (7-100) and the frequency was 1.8 cycles per minute (cpm) (1.4-4.0). Flowmotion persisted throughout the 30 min observation period in 11 animals, during which time arterial pressure recovered to 46 mm Hg (42-50). Fast-wave flowmotion was not detected in the present study. These results suggest that slow-wave flowmotion as measured with LDF is not a phenomenon characteristic of normal regulation of blood flow in skeletal muscle. After a 30% fixed-volume hemorrhage, slow-wave flowmotion is induced as arterial pressure drops below a certain threshold.

Acute Disease↗
PubMed1991

Hypoxia- or hyperoxia-induced changes in arteriolar vasomotion in skeletal muscle microcirculation.

Arteriolar vasomotion was characterized in the skin muscle of the unanesthetized hamster skinfold window preparation and related to the specific arterioles that give rise to the different types of activity. The arterioles were classified according to the Strahler method: order 0 was assigned to capillaries and order 4 to the largest arterioles. The arterioles showed vasomotion with a specific range of frequencies that varied according to the vessel order; the highest fundamental frequency (9.1 +/- 3.9 cycles/min) was detected in the smallest order 1 arterioles and the lowest frequency (2.1 +/- 0.9 cycles/min) in order 4 vessels. Hypoxia (8, 11, and 15% O2 gas mixture inspiration) increased the frequency of vasomotion, decreased mean and effective diameters, and reduced capillary blood flow. The effects were more pronounced with an 8 and 11% O2 gas mixture. Hypoxia caused high-frequency vasomotion to shift from order 1 and 2 arterioles to the beginning of order 3 arterioles, which in this condition dominated the daughter vessels and generated the prominent activity (24 +/- 4 cycles/min, 11% O2 gas mixture). Hypertoxia (100% O2) induced differentiated arteriolar responses. The smallest vessels showed prolonged constriction, decreased mean and effective diameters, and reduced frequency of vasomotion. Capillary blood flow was restricted. Order 3 vessels did not constrict or dilate.

Animals↗
PubMed1991

Arteriolar vasomotion: implications for tissue ischemia.

Vasomotion, the rhythmical contraction and relaxation of the arterioles, is a natural property of the arteriolar microcirculation. It is observed clinically through related flow variations (flux motion) which are detected by laser Doppler flowmetry. It presents two distinct regimens: slow and fast waves, with frequencies of 1-2 and 10-20 cpm, respectively. Both activities are found in normal tissues, and their rate of incidence as well as their magnitude become significantly enhanced during abnormal conditions associated with low blood pressure and hypoperfusion. The institution of this activity by abnormal tissue conditions suggests that vasomotion is a reaction of the microcirculation aimed at improving microvascular function.

Animals↗
PubMed1991

Spatial distribution of red blood cells in individual skeletal muscle capillaries during extreme hemodilution.

The effect of extreme hemodilution on single capillary red blood cell (RBC) distribution and microcirculatory hemodynamic parameters was studied in the resting rabbit tenuissimus muscle. Systematic hematocrit was progressively reduced to 26 +/- 3% of control by isovolemic hemodilution with a 6% dextran solution (70,000 MW). Heart rate and mean arterial pressure were monitored and noted to be constant throughout the procedure to ensure isovolemic exchange. Hemodilution induced an increase in the median spatial distance between RBCs within a capillary segment and a broadening of the range. Comparison of histograms constructed from normalized RBC spacing data relative to the median at each dilution level showed no statistical deviation from control, suggesting that spatial RBC distribution during capillary transit is independent of hematocrit reduction. Thus progressive hemodilution, while reducing capillary hematocrit and increasing the median spacing, did not alter the relative spatial distribution of RBCs within a vessel. The hemodynamic parameters analyzed were capillary hematocrit (HCTc), RBC flux (RBCf), and RBC velocity (VRBC). The reduction of the systemic hematocrit (HCTs) was not followed by a proportional fall in HCTc, implying a Hctc regulation. RBCf was maintained by an overall increase in VRBC which reached 101 +/- 61% of the control level at an average HCTs of 11 +/- 1.4%. The relative pattern of RBC spacing remained fixed, despite the change in cell number and modification of velocity. During extreme hemodilution, the potential supply of oxygen to the tissue remained constant and the pattern of RBC delivery pass the tissue was unchanged.

Animals↗
PubMed1990

Four window differential capillary velocimetry.

A video red blood cell velocimeter was implemented with four photometric windows in such a fashion that the upstream and downstream signals are the difference between spatially separated window pairs. The performance of this system was compared with that of a conventional dual window photometric video velocimeter. Tests were made with artificial patterns of red blood cells that simulated long trains of contiguous cells, or large plasma gaps. It was found that the four window system produces a correlogram that is better suited for delay to maximum cross-correlation detection. Similarly, when the responses of the two methods were compared in terms of ability to detect changes of velocity, the time constant for a test step velocity change was found to be 1.2 +/- 0.7 sec for the four window system vs 2.3 +/- 0.6 sec for the two window system. It is concluded that this modification of the capillary red blood cell velocimetry methodology is better suited for detecting the spontaneous flow variations due to vasomotion.

Blood Flow Velocity↗
PubMed1990

The efficacy of iso- and hyperosmotic fluids as volume expanders in fixed-volume and uncontrolled hemorrhage.

Rapid blood volume expansion is the goal in prehospital hemorrhage resuscitation. A comparison was made for fixed volume and uncontrolled hemorrhage between three fluid regimes: Ringer's lactate (RL), Macrodex (MD), or a small volume of a hyperosmotic solution (HSD, 7.5% NaCl/6% dextran 70) followed by RL. A mathematical model was developed to simulate blood volume restoration for these given hemorrhage and resuscitation situations. Model predictions for a fixed hemorrhage (35%) and reinfusion of each fluid regime (1 mL.min-1.kg-1) were found to agree with hematocrit and osmolality changes from experiments on anesthetized rabbits. HSD gave the quickest volume expansion after the controlled hemorrhage, which is a useful experimental model; however, it is not realistic of many trauma injuries. The model suggests for severe uncontrolled hemorrhage that HSD/RL initially hastens the bleed, yet the blood volume expansion is still more effective than RL alone for the first 20 minutes, making it an effective prehospital expander for most urban trauma situations.

Animals↗
PubMed1990

Microvascular responses in rabbit skeletal muscle after fixed volume hemorrhage.

The effect of hemorrhage on the microvascular responses in the tenuissimus muscle was studied by means of intravital microscopy in rabbits anesthetized with urethan. The rabbits were bled 30% of their calculated blood volume within 3 min. Hemorrhage initially caused mean arterial pressure to drop from 70 +/- 7 to 26 +/- 5 mmHg. During the subsequent 30-min observation period it increased to 43 +/- 8 mmHg. The transverse arterioles (TRs), supplying both muscle tissue proper and adjacent connective tissue, gradually constricted to 75% of control over the 30-min period. Terminal arterioles (TEs) branching from the TR in the muscle tissue constricted to 65% in 10 min and then gradually relaxed, eventually reaching 80% of control diameter. The constriction of the TEs was confined to a short sphincterlike structure (10-20 microns) at the origin of the bifurcation. Upon constriction, the diameter of the sphincterlike structure was less than the critical diameter for erythrocyte passage. Given that the effective blood viscosity in the narrow TE is strongly dependent on luminal diameter, the overall effect on blood flow and its distribution in the tenuissimus muscle was a dramatic reduction of volume flow to 20-30% of the control value. During the early phase, the reduced flow was diverted to the connective tissue at the expense of nutrient flow to the muscle tissue. This early blood flow pattern gradually reversed, partially restoring nutrient flow to the muscle fibers.

Animals↗
PubMed1990

Capillary narrowing in hemorrhagic shock is rectified by hyperosmotic saline-dextran reinfusion.

Previously, we showed that skeletal muscle capillaries narrow during hemorrhagic shock due to swelling of endothelial cells. The present study investigated if these narrowed capillaries affected reflow and compared the effects of fluid reinfusion with iso- and hyperosmotic solutions, in particular 7.5% NaCl/6% dextran 70 (HSD) and Ringer's lactate (RL). Intravital microscopy was used to visualize capillaries in the rabbit tenuissimus muscle during 1 h of shock (40% hemorrhage) and subsequent reinfusion period. Changes in capillary lumenal diameter were inferred by changes in the width of red blood cells traversing the capillary. At the end of the shock period, the capillary diameter was reduced by 20.4 +/- 8.0% (N = 24). With infusion of HSD (dose equal to one-seventh of the shed blood volume; N = 7), there was a sustained flow resurgence and complete return of the capillary diameter to control values after 30 min. The response appears to result from both the hypertonic saline and dextran components. Reinfusion with RL (dose equal to the shed blood volume; N = 7) caused only a transient increase in flow and no change in the lumenal narrowing. We conclude that HSD surpasses conventional RL treatment in reestablishing capillary hemodynamics owing to a decreased hydraulic resistance from osmotically induced endothelium shrinkage.

Animals↗
PubMed1990

Hemodynamic responses in rabbit tenuissimus muscle arterioles during local reduction in perfusion pressure.

Transverse (TR) and terminal (TE) arteriolar diameters and TR pressure were measured in the rabbit tenuissimus muscle during steady state reductions in perfusion pressure. An inflatable occluder was positioned on the abdominal aorta proximal to the bifurcation to alter perfusion pressure. In the control conditions, TEs exhibited highly regular cyclic activity (20 +/- 4 cpm). In contrast, TRs seldom exhibited regular vasomotor activity. Pressure reductions from 76 +/- 1 to 40-50 mm Hg caused no significant change in the observed hemodynamic variables. Reductions below this level caused proportional dilations of TRs and a change in vasomotion pattern of TEs; i.e. the fundamental frequency was unaltered, but periods without vasomotion increased in duration. At an arterial pressure of 30-40 mm Hg, vasomotion in the TEs completely disappeared. Pressure in the distal TR was autoregulated at 40 +/- 4 mm Hg until a threshold (40-50 mm Hg) was reached; thereafter TR pressure decreased in proportion to the arterial pressure decrements. These results suggest that the TRs are the last generation of arterioles involved in the autoregulation of microvascular pressure. Furthermore, the basic frequency and maximal amplitude of vasomotion in TEs are not affected by pressure reductions.

Animals↗
PubMed1989

Confocal laser tomographic analysis of the retina in eyes with macular hole formation and other focal macular diseases.

To study the retinal surface in the human eye in normal and diseased states we used laser scanning tomography. The confocal arrangement of the laser tomographic scanner permits examination of retinal topography in the axis perpendicular to the retinal surface. The eyes examined with the laser tomographic scanner included normal eyes, eyes with macular holes, impending macular holes, radiation retinopathy, macular edema, photocoagulation scars, subfoveal scars, and serous detachment of the fovea associated with subretinal neovascularization. The laser tomographic scanner is a new method that allows measurements of the topography of the internal limiting membrane in the macular area and may improve our understanding of the pathophysiologic characteristics and treatment of a variety of disorders of the macula.

Adult↗