Search PubMedSearch

Biomedical subjects

B W Zweifach

Publications and source records attributed to B W Zweifach.

At least 19 recordsLinked to original sources

Penetration of the systemic blood pressure into the microvasculature of rat skeletal muscle.

A series of arterial micropressure measurements in different skeletal muscles of the Wistar-Kyoto and spontaneously hypertensive rat is presented. The micropunctures were carried out with minimal surgical intervention through small skin incisions and the micropressures were recorded simultaneously with femoral artery pressures. The measurement sites were located at the entry points into the muscles for the proximal and distal supply arteries and at the midpoint of the arteriolar arcade bridge which directly connects these two supply arteries in the center of the muscle parenchyma. In contrast to feed artery pressure values from exteriorized muscles, which in the past have been reported to be as low as 40 mm Hg, the current mean pressure values are substantially higher and in the range between 70 and 100 mm Hg, equivalent to 70 to 90% of the mean systemic pressure. Systolic and diastolic values exhibit comparable trends to the mean pressures and they are similar in muscles at different locations in the body. Although in spontaneously hypertensive rats the absolute pressures were significantly higher compared with their controls, the normalized pressures were virtually identical at the locations used in this study. These data indicate that the absolute pressure in the central arteries of spontaneously hypertensive animals is reduced to a greater degree than in Wistar-Kyoto rats, while in both strains the major pressure reduction in skeletal muscle still occurs in the microcirculation.

Animals

Leukocyte counts and activation in spontaneously hypertensive and normotensive rats.

The etiology for the progressive organ injury in hypertension is largely speculative. Recent studies have shown that leukocytes play a key role in several cardiovascular diseases. As an initial step toward investigating the role of leukocytes in hypertension, we measured leukocyte counts and spontaneous activation of granulocytes of freshly drawn unseparated blood samples in spontaneously hypertensive rats and in their normotensive counterpart, Wistar-Kyoto rats. The animals were derived from one breeder in the United States and from two breeders in Europe. Total leukocyte counts in young, mature, and old hypertensive rats were 50-100% above the controls. The number of granulocytes in mature and old spontaneously hypertensive rats in more than 100% elevated compared with control rats. In young hypertensive rats the mean granulocyte count was only slightly elevated. The number of spontaneously activated granulocytes, as detected by the nitroblue tetrazolium reduction, increases with age in both species; in mature spontaneously hypertensive rats, it is more than 300% above the values in the controls. Furthermore, in mature hypertensive rats the number of monocytes, activated monocytes, and the lymphocyte count are also significantly elevated over the values in the normotensive controls. It is proposed that these elevated leukocyte counts may constitute an enhanced risk for organ injury in the spontaneously hypertensive rat.

Animals

Polymorphonuclear neutrophil contribution to induced tolerance to bacterial lipopolysaccharide.

The objective of this study was to investigate mechanisms by which polymorphonuclear neutrophils (PMNs) contribute to the tolerance induced by repeated lipopolysaccharide (LPS) injections. Tolerance was developed by daily intraperitoneal injections of sublethal doses of LPS for 4 days (LPS-tolerant group); controls were not pretreated (LPS-control group). Both groups were challenged with 9 mg/kg i.v. Escherichia coli LPS, a dose that resulted in 25% survival in LPS-control rats compared with 100% survival in LPS-tolerant rats. LPS injection caused an initial neutropenia in both groups. The neutropenia persisted throughout the experiment in LPS-control rats, whereas in LPS-tolerant rats the circulating PMN count increased dramatically; after 6 hours, the PMN count was 16-fold higher than that in LPS-control rats. Activation of circulating PMNs, PMN adhesion to nylon fibers, and tumor necrosis factor/cachectin activity were all increased in control rats given LPS. In contrast, LPS-tolerant rats had low activation of circulating PMNs, no trend for PMN adhesion to nylon fibers, and markedly reduced tumor necrosis factor activity. To determine whether neutropenia was associated with a trapping of PMNs in the microcirculation, we used a carbon perfusion technique 6 hours after LPS injection and examined histological sections of the myocardium. All of the arterioles and venules in both groups contained carbon; only capillaries showed evidence of obstruction. A significantly higher percentage of obstructed capillaries was observed in LPS-control rats than in LPS-tolerant rats. Obstruction of capillaries was consistently associated with trapped leukocytes. We conclude that PMN cytotoxicity induced by LPS involves microcirculatory entrapment and activation of PMNs. Repeated LPS pretreatment reduces dramatically circulating PMN activation and adhesion and is associated with an elevated circulating PMN count, a low degree of microvascular plugging, and survival after a normally lethal dose of LPS.

Animals

Wall structure of arteries and arterioles feeding the spinotrapezius muscle of normotensive and spontaneously hypertensive rats.

Vessel wall structure in feed arteries and their hierarchical ramifications were investigated in a rat skeletal muscle. Emphasis was placed on the transition of wall structure elements from the axillary and thoracodorsal arteries to the feeder arteries and the arcade and transverse arterioles forming the microcirculation of the spinotrapezius muscle. Semi-thin sections, prepared for light microscopy, and ultra-thin sections for electron microscopy were used to compare mature (15-20 week old) normotensive and hypertensive animals. The results demonstrate a gradual transition of the elastica intima and the smooth muscle from the central arteries towards the arterioles, accompanied by an attenuation of the adventitia. The elastica intima in 60-40 microns arcade arterioles is reduced from a continuous sheet in the central arteries to single fibers oriented parallel to the vessel axis. The multiple layers of smooth muscle cells at the level of the feeder arteries are reduced in the majority of arcade arterioles and in transverse arterioles to a single smooth muscle coat. Comparisons of the smooth muscle mass per unit length of vessel at selected sites of normotensive and spontaneously hypertensive rats show evidence for some degree of wall hypertrophy in the axillary artery, but no evidence for wall hypertrophy in arterioles of the microcirculation. There is no evidence of a pressure-mediated structural medial wall hypertrophy along this peripheral vascular pathway.

Animals

Granulocytes and no-reflow phenomenon in irreversible hemorrhagic shock.

Recent evidence shows that circulating granulocytes play an important role in capillary stasis and tissue injury. We investigated two aspects of the problem in a Wiggers hemorrhagic shock model of the rat: the survival rate and the microvascular no-reflow phenomenon. A conventional group of rats with normal blood cells and a neutropenic group of rats pretreated with intraperitoneal antigranulocyte antibody were used to evaluate the effects of granulocytes. Two hemorrhagic shock protocols (HSP) were carried out. In HSP-1, the rats were subjected to 40 mm Hg mean arterial pressure for 3 hours. The conventional group (n = 11) showed a 36% survival rate compared with 100% in the neutropenic group (n = 6). In HSP-2, the hypotension was more severe, 30 mm Hg mean arterial pressure for 7 hours. There were no survivors in the conventional group (n = 8), compared with a 100% survival rate in the neutropenic group (n = 6). The extent, location, and mechanism of the no-reflow phenomenon was investigated by examining histological sections from several organs after infusion of a contrast medium to mark vessels with flow in a control group without shock and in the HSP-2 model 2 hours after blood replacement. The arterioles and venules uniformly contained contrast medium in all three groups; only capillaries showed no-reflow. A significantly higher percentage of no-reflow was observed in the capillaries of the conventional shock group than in the neutropenic shock group. We concluded that the obstruction of capillaries was largely due to trapped granulocytes, suggesting that these leukocytes play a key role in the capillary no-reflow phenomenon and survival from hemorrhagic shock.

Animals

Microvascular tone in a skeletal muscle of spontaneously hypertensive rats.

We studied the degree of arteriolar smooth muscle constriction in the spinotrapezius muscle microcirculation of spontaneously hypertensive rats and their normotensive controls, Wistar-Kyoto rats. The constriction was expressed in the form of a nondimensional tone as the difference between steady state and dilated diameter (after papaverine treatment) divided by the dilated diameter. Both animal strains showed on average a progressive increase of tone toward the more distal arterioles, with a peak tone being reached in the transverse arterioles. Tone values in the hypertensive animals were consistently elevated. The number of arterioles that had more than 5% tone (so-called responder arterioles) was higher in the hypertensive animals. These studies suggest that, besides the anatomical adjustments documented earlier in our laboratory in the arteriolar network of this muscle, functional adjustments in the form of an elevated microvascular tone are associated with the elevated resistance in spontaneously hypertensive rats.

Animals

Analysis of microvascular network in bulbar conjunctiva by image processing.

A digital image processing procedure has been developed for obtaining quantitative morphometric data on the microcirculatory network in the human bulbar conjunctiva. Highlights of this semi-automated approach include: 1. extraction of morphometric information that cannot be readily obtained by manual methods--length, diameter, and diffusion distributions; 2. speed and consistency in data generation--only 10 minutes are required to scan and to analyze 6.7 mm2 of conjunctiva microvasculature. The variation was less than 5% when images of the same area in the same eye were subjected to analysis at different times; 3. avoid the human bias factor--the data obtained by repeated analysis of the same negative varied by less than 0.02%.

Conjunctiva

The microvasculature in skeletal muscle. II. Arteriolar network anatomy in normotensive and spontaneously hypertensive rats.

A quantitative comparison of the anatomical arrangement of arterioles in the skeletal muscle of mature (16 to 20-week-old) Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) is provided. In both species several feeding arterioles supply blood to a network of arterioles covering the entire muscle, designated as arcade arterioles. The connections from the arcade arterioles to the capillary network are provided by the transverse arterioles. Comparison of the spinotrapezius muscle of the WKY and the SHR shows several types of rearrangement of the network. In both species there is a wide distribution of vessel size in the arcade and transverse arterioles. The length of the arcade arterioles per unit muscle volume is higher in the SHR, forming a denser network. There are almost twice as many transverse arteriolar trees per unit tissue volume in hypertensive animals although on the average each transverse tree has shorter branches. No evidence for significant anatomical rarefaction was found among arcade and transverse arterioles. Arcade arterioles following maximal dilation were found to be 25% narrower in the SHR, whereas for transverse arterioles no differences in diameter could be detected under these vasodilated conditions.

Animals

Network anatomy of arteries feeding the spinotrapezius muscle in normotensive and hypertensive rats.

An understanding of blood flow requires a detailed picture of vascular and microvascular anatomy. To this end an investigation of the arteries feeding the spinotrapezius muscle in normotensive and spontaneously hypertensive rats was performed. Arteries were dilated and filled with resin materials and analyzed quantitatively for their network pattern and vessel geometry. The results show that there exists extensive meshworks of interconnected arteries forming an interogan plexus. The spinotrapezius muscle has multiple inflows from the thoracodorsal and intercostal arteries which interconnect in an arcade network in the muscle. Some but not all arteries of hypertensive rats are narrower in the dilated state at 100 mm Hg inflation pressure than their controls. Arterioles within the muscle proper, however, are not significantly different, suggesting that lumen narrowing of structural origin is progressively reduced towards the microcirculation.

Animals

Microvascular adjustments during irreversible hemorrhagic shock in rat skeletal muscle.

A study was made of microvessel response to hemorrhagic hypotension and the subsequent restoration of blood volume. The experiments were conducted on anesthetized rats in which the cremaster muscle was exteriorized for intravital microscopy. Variables measured during hypotension (40 mm Hg for 60 min) and after blood restoration (120 min observation) included systemic blood pressure, heart rate, arteriolar and venular diameter, sensitivity to epinephrine, velocity and volumetric flow rate. These findings were correlated with 24-hr survival statistics. The response to hemorrhagic hypotension is a reflection of two separate adjustments, cardiac output and peripheral vascular behavior. In survivors, the microvascular sequelae following blood replacement was one of continuous improvement of muscle perfusion, whereas in nonsurvivors the picture was one of progressive deterioration. The consistent hallmark of irreversibility, arteriolar hyposensitivity, was associated with a continuous falling off in mean arterial pressure despite restoration of normal blood volume.

Abdominal Muscles

The microvasculature in skeletal muscle. III. Venous network anatomy in normotensive and spontaneously hypertensive rats.

A quantitative description of the anatomical arrangement of venules in the spinotrapezius muscle of mature (12-15 week old) Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) is provided. In both strains, asymmetric, dichotomous collecting venule trees route blood from the capillaries to a network of interconnected or arcade venules which spans the entire muscle. The arcade network is drained of blood through several draining venules which exit the muscle. A new branching scheme is proposed for the venular microvascular network. Comparison of WKY and SHR values shows that the arcade venules in the WKY are, on the average, narrower. Conversely, SHR postcapillary vessels are narrower than those in the WKY. Aside from these differences, however, the venular microvasculature and network pattern in the two strains is similar.

Animals

Endoneurial pressure in hexachlorophene neuropathy.

Increased endoneurial pressure of up to 17.0 cm H2O was recorded in the peripheral nerves of rats fed hexachlorophene in their laboratory diet. The pressure was measured using a micropressure transducer developed for recording pressure in the microcirculation. The results were correlated with morphologic findings. Teased nerve fibers and araldite-embedded specimens of hexachlorophene damaged sciatic nerve revealed the characteristic severe intramyelinic edema due to splits in the minor dense lines of compact myelin giving rise to wide interlamellar spaces as shown in previous studies. The endoneurial pressure of rats exposed to hexachlorophene for 11 days and subsequently fed a normal diet returned to normal (0.2-3.0 cm H2O) after 12 days, and morphologic examination showed few residual abnormalities. Prolonged exposure to hexachlorophene for up to 4 weeks caused widespread axonal degeneration in addition to intramyelinic edema. Animals treated with hexachlorophene for 21 days followed by a normal diet for 14 days showed degenerated axons, phagocytosis of myelin as well as interstitial edema and elevated endoneurial pressure. It is suggested that axonal degeneration in hexachlorophene neuropathy is caused by increased endoneurial pressure.

Animals