Cat Skeletal Muscle Research Articles

Extramedullary Plasmacytoma of the Third Eyelid in a Cat

Background: Extramedullary plasmacytoma is a neoplasm originating from plasmacytes with benign behavior, although it can present malignant characteristics such as local invasion and metastases in some cases. Primary extramedullary plasmacytoma in the third eyelid is rare in humans and animals and has not yet been described in cats. Thus, the goal of the present study is to describe the cytological and histopathological findings of an extramedullary plasmacytoma in a cat's third eyelid.Case: A 5-year-old female feline patient with a history of ocular alteration for approximately 30 days was referred to the ophthalmology service. Upon ophthalmic examination of the left eye, an increase in volume with tissue proliferation was identified in the third eyelid's conjunctiva. A collection of material for cytopathological examination was performed. Numerous plasmocytes and atypical lymphocytes with anisocytosis and anisokaryosis were observed, with a possible neoplastic injury being suggested and referred to the patient for surgical removal of the third eyelid. In the histopathological analysis, it was possible to observe several plasma cells and vascular neoformation along the entire conjunctive margin below the epithelium. The glands, serous and mucous, present in the fragment, revealed areas of intervening plasmacytic infiltrate and a large area close to the hyaline cartilage containing intense plasmacytic inflammatory infiltrate with rare neutrophils and macrophages. There was also a structural breakdown of glandular components and lymphocyte cells with mitosis figures and discrete cellular pleomorphism.Discussion: Plasmacytoma is a rare neoplasm in both dogs and cats. The anatomical regions most frequently affected are the digits, lips, and pinna. Concerning the 3rd eyelid tumor involvement, numerous types of neoplasms have been reported in dogs in the veterinary literature, including transmissible venereal tumor, squamous cell carcinoma, and melanocytoma melanoma, lymphoma, plasmacytoma, hemangioma, hemangiosarcoma, mastocytoma, and myoepithelioma. In cats, the third eyelid is the third site most affected by primary tumors. Adult and elderly animals are the most affected; however, an extramedullary plasmacytoma (PEM) has been reported in an eight-month-old male cat's skeletal muscle. Plasmacytoma aspirates, like other round cells, tend to be highly cellular, the cell morphology has a plasmacytoid aspect, resembling mature cells, the cytoplasm is intensely basophilic, and the round nucleus with an eccentric disposition has thin chromatin and indistinct nucleolus. Binucleate and multinucleate cells are common, and the absence of lymphoglandular corpuscles helps differentiate extramedullary plasmacytoma from lymphomas. Histologically, PEM is similar in dogs, humans, and felines, and variations in mature and immature plasma cells can be seen. The diagnosis of extramedullary plasmacytoma is fundamentally histological, and immunohistochemical analysis can also be performed. Surgical excision with safety margins is the primary type of treatment for neoplasms in the 3rd eyelid, being considered an effective method, as seen in this report, during the patient's follow-up for 13 months, no recurrence or metastasis of the neoplasm was seen. When signs of malignant neoplasms are found, it is recommended to evaluate the indication for chemotherapy before surgery and monitor the case after treatment due to recurrence risk.

PPADS does not block contraction-induced prostaglandin E2synthesis in cat skeletal muscle

Pyridoxal-phosphate-6-azophenyl-2'-4-disulfonate (PPADS), a purinergic 2 (P2) receptor antagonist, has been shown to attenuate the exercise pressor reflex in cats. In vitro, however, PPADS has been shown to block the production of prostaglandins, some of which play a role in evoking the exercise pressor reflex. Thus the possibility exists that PPADS blocks the exercise pressor reflex through a reduction in prostaglandin synthesis rather than through the blockade of P2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E2 (PGE2) concentrations during the intermittent contraction of the triceps surae muscle before and after a popliteal arterial injection of PPADS (10 mg/kg). We found that the PGE2 concentration increased in response to the intermittent contraction before and after the injection of PPADS (both, P < 0.05). PPADS reduced the pressor response to exercise (P < 0.05) but had no effect on the magnitude of PGE2 production during contraction (P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex.

Counterpoint: There is not capillary recruitment in active skeletal muscle during exercise

The notion that a substantial proportion of capillaries do not contain moving red blood cells (RBCs) in muscle at rest but are “recruited,” i.e., begin flowing with RBCs during contractions, is one basis for our present understanding of blood-muscle exchange during exercise ([20][1], [28][2]).

The permeability-reducing effects of prostacyclin and inhibition of Rho kinase do not counteract endotoxin-induced increase in permeability in cat skeletal muscle

cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular permeability during noninflammatory conditions, most likely by decreasing contractility of actomyosin filaments in the endothelial cell, but their effects on permeability during inflammatory conditions are not clarified. The objective of this in vivo study, performed on the autoperfused and denervated calf muscle of the cat, was therefore to evaluate to what extent cAMP stimulation and inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic reflection coefficient for albumin was used as a measure of altered protein permeability and change in capillary filtration coefficient (CFC) as a measure of altered fluid permeability. After inducing a significant increase in protein and fluid permeability by infusion of lipopolysaccharide (LPS), we determined to what extent the increased permeability was decreased by the cAMP stimulator prostacyclin [1.0 ng/kg/min intravenously (iv)] or the Rho kinase inhibitor Y-27632 [1.05 μg/ml plasma/h intraarterially (ia)]. These doses are known to decrease permeability under noninflammatory conditions. The reflection coefficient for albumin and CFC were determined before and during LPS, and during LPS plus prostacyclin ( n = 6) or LPS plus Y-27632 ( n = 6). The reflection coefficient was reduced by about 30% ( P < 0.05) and CFC was increased by about 25% ( P < 0.05) by LPS, and these permeability parameters were not affected by prostacyclin or Y-27632. We conclude that cAMP stimulation and Rho kinase inhibition reduce permeability by other pathways and mechanisms than those by which permeability is increased during endotoxemia.

Vasopeptidase inhibition with omapatrilat increases fluid and protein microvascular permeability in cat skeletal muscle.

BACKGROUND Vasopeptidase inhibition is a new antihypertensive approach combining inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), but severe oedema, mainly angio-oedema, has been reported. As ACE and NEP catalyse degradation of the permeability-increasing peptide bradykinin, and NEP also catalyses degradation of permeability-increasing peptides such as atrial natriuretic peptide, substance P, endothelin-1 and angiotensin II, vasopeptidase inhibition may increase microvascular permeability. OBJECTIVE To analyse the effects of vasopeptidase inhibition on permeability. DESIGN The study was performed on the autoperfused cat calf skeletal muscle, evaluating the effects on fluid and protein permeability of a clinically relevant dose of the vasopeptidase inhibitor, omapatrilat. The effects were compared with those of the vehicle, of selective ACE and NEP inhibition, and of omapatrilat during bradykinin receptor blockade. METHODS Effects on fluid permeability were determined with a capillary filtration coefficient (CFC) technique, and effects on protein permeability were assessed from changes in the osmotic reflection coefficient for albumin. RESULTS After 1.5 h of intravenous infusion of omapatrilat (0.35 mg/kg per hour), mean arterial pressure was reduced from 114 mmHg to 86 mmHg (P < 0.01) and skeletal muscle vascular resistance was reduced from 14.5 peripheral resistance units (PRU) to 11.5 PRU (P < 0.05). CFC was increased by 22% (P < 0.01) and the reflection coefficient was decreased by 17% (P < 0.01). Infusion of vehicle had no effects. Inhibition of NEP increased permeability without affecting blood pressure, whereas ACE inhibition decreased blood pressure without affecting permeability. The increase in permeability associated with omapatrilat was reduced by bradykinin blockade. CONCLUSIONS A clinically relevant antihypertensive dose of omapatrilat reduces vascular resistance and increases fluid and protein permeability, the permeability effect more by inhibition of NEP than by inhibition of ACE, by a mechanism involving bradykinin.

Vasopeptidase inhibition with omapatrilat increases fluid and protein microvascular permeability in cat skeletal muscle.

Vasopeptidase inhibition is a new antihypertensive approach combining inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), but severe oedema, mainly angio-oedema, has been reported. As ACE and NEP catalyse degradation of the permeability-increasing peptide bradykinin, and NEP also catalyses degradation of permeability-increasing peptides such as atrial natriuretic peptide, substance P, endothelin-1 and angiotensin II, vasopeptidase inhibition may increase microvascular permeability. To analyse the effects of vasopeptidase inhibition on permeability. The study was performed on the autoperfused cat calf skeletal muscle, evaluating the effects on fluid and protein permeability of a clinically relevant dose of the vasopeptidase inhibitor, omapatrilat. The effects were compared with those of the vehicle, of selective ACE and NEP inhibition, and of omapatrilat during bradykinin receptor blockade. Effects on fluid permeability were determined with a capillary filtration coefficient (CFC) technique, and effects on protein permeability were assessed from changes in the osmotic reflection coefficient for albumin. After 1.5 h of intravenous infusion of omapatrilat (0.35 mg/kg per hour), mean arterial pressure was reduced from 114 mmHg to 86 mmHg (P < 0.01) and skeletal muscle vascular resistance was reduced from 14.5 peripheral resistance units (PRU) to 11.5 PRU (P < 0.05). CFC was increased by 22% (P < 0.01) and the reflection coefficient was decreased by 17% (P < 0.01). Infusion of vehicle had no effects. Inhibition of NEP increased permeability without affecting blood pressure, whereas ACE inhibition decreased blood pressure without affecting permeability. The increase in permeability associated with omapatrilat was reduced by bradykinin blockade. A clinically relevant antihypertensive dose of omapatrilat reduces vascular resistance and increases fluid and protein permeability, the permeability effect more by inhibition of NEP than by inhibition of ACE, by a mechanism involving bradykinin.

Low-dose prostacyclin restores an increased protein permeability after trauma in cat skeletal muscle.

Increased microvascular permeability inducing leakage of plasma from the intravascular to the extravascular space after trauma is a pathophysiologic event of great clinical significance. A substance reducing an increased microvascular permeability, and especially an increased protein permeability, therefore could be of value to maintain normovolemia and to reduce the need for plasma substitution. Prostacyclin is suggested to have permeability-reducing properties as shown for fluid permeability, but its effects on protein permeability, which may be controlled by partly different mechanisms, are unclear. The present study evaluates whether prostacyclin at a low, clinically relevant, nonvasodilating dose can reestablish an increased protein permeability after trauma. The study was randomized, blinded, and performed on surgically traumatized, autoperfused, and denervated cat calf muscle. Relative changes in the osmotic reflection coefficient for albumin after 1.5 hours of prostacyclin (1 ng/min/kg) (n = 7) or vehicle (n = 7) treatment were used as a measure of altered protein permeability from a state of increased permeability after trauma. We found that the osmotic reflection coefficient for albumin was increased by about 35% in the prostacyclin group compared with the vehicle-treated group (p < 0.001). If applicable to humans, prostacyclin is a potential therapy for reducing plasma leakage in the critically ill trauma patient by restoring permeability from an increased level.

Endogenous Nitric Oxide Reduces Microvascular Permeability and Tissue Oedema during Exercise in Cat Skeletal Muscle

Based on a proposed increase in the release of the vasodilators nitric oxide (NO) and prostacyclin during exercise, and the fact that these substances have vascular permeability-reducing properties, this study was designed to evaluate (1) possible effects of exercise on hydraulic permeability, (2) whether permeability and muscle swelling are reduced by an increased release of NO and prostacyclin during exercise and (3) whether NO and prostacyclin are involved in exercise hyperaemia. The study was performed on an autoperfused cat calf muscle preparation with ligated lymph vessels, and exercise was induced by somatomotor nerve stimulation. Change in microvascular hydraulic permeability was estimated by a capillary filtration coefficient (CFC) technique. We found that the marked muscle volume increase after the start of the exercise gradually decreased, reaching an isovolumetric state within 25 min where CFC had decreased by about 25% (p < 0.05). CFC recovered completely after exercise was stopped. The decrease in CFC was abolished during blockade of endogenous NO by the NO synthase inhibitor L-NAME, but was preserved during blockade of endogenous prostacyclin by tranylcypromine. The muscle volume increase during exercise was about 60% greater with L-NAME than during vehicle or tranylcypromine (p < 0.01). Neither L-NAME nor tranylcypromine had any effect on exercise hyperaemia. We conclude that microvascular hydraulic permeability is reduced during exercise, that this effect reduces exercise-induced muscle swelling, and that the effects are mediated via release of NO. NO and prostacyclin are not involved in exercise hyperaemia.

Inhibition of Rho kinase decreases hydraulic and protein microvascular permeability in cat skeletal muscle

Rho-associated kinases are involved in regulation of actin–myosin contractility and the organization of the actin cytoskeleton in both endothelial and smooth muscle cells. By influencing the contraction of the intraendothelial filaments, Rho kinases may affect the size of the interendothelial gaps and thereby influence microvascular permeability. The aim of the study was therefore to investigate whether Rho kinases influence hydraulic and protein microvascular permeability. The study was performed on the autoperfused cat skeletal muscle. A capillary filtration coefficient (CFC) technique was used to evaluate changes in hydraulic permeability, and protein permeability was evaluated by estimation of the change in the reflection coefficient for albumin. In the first part of each experiment, the effects on CFC of three doses of the Rho kinase inhibitor Y-27632 of about 0.35, 0.70, and 1.05 μg/h per ml plasma flow were determined. There was a reduction in CFC at the lowest dose, and a tendency to further reduction at the higher doses used, reaching a decrease in CFC of 20%. The effects on CFC of the high and the middle dose did not differ. The reflection coefficient for albumin was increased by 31% following infusion of the highest dose of Y-27632. We conclude that hydraulic and protein microvascular permeability increase by Rho kinase activation, and that Rho kinase is involved in regulation of microvascular permeability.

Nitric Oxide and Prostacyclin Play a Role in the Regulation of Microvascular Protein and Hydraulic Permeability in Cat Skeletal Muscle

Nitric Oxide and Prostacyclin Play a Role in the Regulation of Microvascular Protein and Hydraulic Permeability in Cat Skeletal Muscle

Nitric oxide and prostacyclin play a role in the regulation of microvascular protein and hydraulic permeability in cat skeletal muscle.

To evaluate a possible role of nitric oxide (NO) and prostacyclin in the regulation of basal microvascular protein and hydraulic permeability. The study was performed on the autoperfused cat calf muscle. Changes in the osmotic reflection coefficient for albumin, calculated from the extended Starling equation, were used as a measure of altered protein permeability, whereas changes in capillary filtration coefficient (CFC) were used as a measure of altered hydraulic permeability. Inhibition of the endogenous NO production with L-nitro-arginine methyl ester given intra-arterially to the muscle decreased the reflection coefficient to 70% of the control (p < 0.05) and increased the CFC by 17% (p < 0.05). The addition of a simultaneous intra-arterial infusion of the NO precursor L-arginine restored both the reflection coefficient and the CFC back to control level. Blockade of the endogenous prostacyclin production with tranylcypromine given intra-arterially decreased the reflection coefficient to 72% of the control (p < 0.05) and increased the CFC by 24% (p < 0.05), and they were both restored to control levels by a simultaneous intravenous infusion of a nonvasodilating dose of prostacyclin (1.0 ng/kg per minute). The results support the view that endogenous NO and prostacyclin decrease both protein and hydraulic permeability. Assuming a dynamic endogenous release of these substances, they may act as bidirectional regulators of protein and hydraulic permeability.

Endotoxin increases both protein and fluid microvascular permeability in cat skeletal muscle.

To evaluate effects of lipopolysaccharide (endotoxin) on protein and fluid permeability in a whole organ skeletal muscle preparation. Controlled, prospective laboratory study. University research laboratory. Eleven adult male cats. The study was performed on the autoperfused and denervated calf muscles of the cat hindlimb placed in a fluid-filled plethysmograph. The endotoxin-induced change in the osmotic reflection coefficient for albumin was used as a measure of alteration in protein permeability of the microvascular wall, and the simultaneous change in capillary filtration coefficient was used as a measure of alteration in fluid permeability. Endotoxin as a bolus infusion (1 mg/kg iv) was given to six cats, and another five cats given only the vehicle (NaCl) were used as control. Arterial blood flow, arterial and venous blood pressures, total vascular resistance, and tissue volume changes were measured continuously. The ratio between the osmotic reflection coefficients for albumin on two occasions (before and about 1.5 hr after endotoxin infusion) was calculated from the Starling fluid equilibrium equation. This was performed by measurement of the maximum absorption rate from an isovolumetric state by an intravenous bolus infusion of 20% human albumin (0.6 g/kg) and the capillary filtration coefficient. Albumin concentrations were measured before and after the albumin infusion to correct for effects of difference in plasma volume on the induced increase in colloid osmotic pressure. We found that the osmotic reflection coefficient for albumin was reduced by 30% (p <.05), and the capillary filtration coefficient was increased by 31% (p <.05) by endotoxin. No changes were seen in the vehicle experiments. Endotoxin causes a significant increase in both protein and fluid microvascular wall permeability. These effects may explain the marked leakage of plasma to the interstitium that is often seen in critically ill patients with sepsis and systemic inflammatory response syndrome.

Nitric Oxide and Prostacyclin Play a Role in the Regulation of Microvascular Protein and Hydraulic Permeability in Cat Skeletal Muscle

Nitric Oxide and Prostacyclin Play a Role in the Regulation of Microvascular Protein and Hydraulic Permeability in Cat Skeletal Muscle

Oxygen transport and intracellular bioenergetics on stimulated cat skeletal muscle.

A unique multiparameter recording of skeletal muscle bioenergetics, biochemistry and biomechanics has permitted determination of novel relationships among hemodynamics, cellular high-energy metabolites and mitochondrial bioenergetics in feline skeletal muscle. The study utilizes 31P NMR, NIR, and NADH fluorescence spectrophotometry, biochemical assays and muscle performance. Seven cats were anesthetized and mechanically ventilated. Calf muscles were stimulated through sciatic nerve electrical stimulation and tension was monitored by a strain gauge connected to the Achilles tendon. We stimulated the muscle to produce several workloads up to Vmax. We also changed FiO2 from normoxia to hypoxia for each %Vmax. From these results, the most sensitive indicators of cellular hypoxia leading to a reduction in muscle performance can be determined. Hemoglobin deoxygenation generally does not correlate with cellular hypoxia, although when the HbO2 drops below 30% saturation there is an increased incidence of cellular hypoxia. The [ADP], which is known to regulate mitochondrial function, has a close relation to the work, not to the hypoxia. On the other hand, the mitochondrial NADH does respond to cellular PO2. The degree of oxidation (NADH decrease) due to the ATP flux shifts with oxygen availability in mild to moderate hypoxia (at FiO2 down to 9%). As cellular hypoxia causes decreases in muscle performance (moderate to severe hypoxia), NADH is being reduced rather than oxidized with increasing workloads.

Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle

The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ETB receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20–40 ng/min/100 g) induced filtration despite further vasoconstriction. Low-dose endothelin-1 had no significant effect on CFC, while CFC was reduced to at most 55% of baseline at higher doses (P < 0.01). Simultaneous local intraarterial infusion of the prostacyclin synthesis inhibitor tranylcypromine restored CFC to 114% of baseline (P < 0.01) and further increased vascular resistance. A low, nonvasodilator dose of prostacyclin given intravenously counteracted the tranylcypromine effect on CFC. The decreased CFC induced by a high dose of endothelin-1 was counteracted by the ETB receptor antagonist BQ-788 with no change in vascular resistance (P < 0.05). We conclude that the decreased CFC following high doses of endothelin-1 can be attributed to a decrease in microvascular hydraulic conductivity, mediated by secondary release of prostacylin via stimulation of the ETB receptor. Endothelin-1 may induce edema through postcapillary vasoconstriction.

Effects of hypertonic saline, mannitol, and urea with regard to absorption and rebound filtration in cat skeletal muscle.

To study the effects of the hypertonic solutions 15% mannitol, 3% and 7.5% saline, and 30% urea at clinically relevant plasma concentrations with regard to absorption and rebound effects on tissue volume in skeletal muscle. A prospective, experimental study. University laboratory. Twenty-eight anesthetized cats. The study was performed on an autoperfused and denervated cat calf muscle placed in a fluid-filled plethysmograph. Muscle volume changes and capillary filtration coefficient (reflecting capillary fluid conductivity) were measured before, during, and after intra-arterial infusion (4 mL/hr) of the hypertonic solutions. Mannitol and 3% saline have the same osmolality and were compared specifically in an attempt to distinguish osmotic effects from those specific to the compound. All solutions reduced muscle volume during the infusion (p < .05). The maximum volume reduction persisted after 2 hrs of infusion for 3% and 7.5% saline, whereas there was a tendency for volume recovery during the urea infusion and a complete recovery back to control for mannitol. After discontinuation of the infusions, the muscle volume increased for all four solutions, stabilizing at the initial control for 3% and 7.5% saline, whereas it increased to levels above control for mannitol and urea (p < .05). Capillary filtration coefficient was increased by hypertonic saline (p < .05) but was unaffected by mannitol and urea. The effectiveness of a hypertonic solution in reducing tissue volume and its tendency to cause a rebound volume increase depends not only on the osmolality of the solution. Hypertonic saline may in the long run be superior to mannitol and urea to increase plasma volume or decrease tissue volume of an organ, because it lacks rebound effects. Alterations in capillary filtration coefficient (fluid conductivity) may reflect volume changes of the capillary endothelial cell and thereby differences in cell membrane permeability for the hypertonic solutions, also consistent with the obtained differences in tissue volume effects.

Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle.

The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine (n = 7) or angiotensin II (n = 6), causing a blood flow reduction from 7.2 +/- 0.8 to at most 2.7 +/- 0.2 ml x min(-1) x 100 g(-1) (P < 0.05). The decrease in arterial pressure reduced blood flow from 4.8 +/- 0.4 to 1.40 +/- 0.1 ml x min(-1) x 100 g(-1) (n = 6). Vascular resistance increased to 990 +/- 260% of control after the infusion of microspheres (n = 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.

Dextran, gelatin, and hydroxyethyl starch do not affect permeability for albumin in cat skeletal muscle.

To evaluate the effects of the three commercially available colloid solutions, 6% dextran 70, 6% hydroxyethyl starch (HES) 200/0.5, and 3.5% urea-linked gelatin on permeability for human albumin in a skeletal muscle in vivo model by evaluating their effects on the reflection coefficient for albumin. Controlled laboratory study. University research laboratory. Eighteen adult cats. The autoperfused and denervated calf muscles of the cat hindlimb were placed in a plethysmograph. The transvascular fluid absorption induced by an increase in the colloid osmotic pressure following a fixed intravenous bolus of human albumin was analyzed, first before start of, and then during an intra-arterial infusion to, the muscle preparation of the synthetic colloid to be analyzed. Capillary filtration coefficient as a measure of microvascular fluid permeability (conductance) was analyzed before and after start of the synthetic colloid. Arterial blood flow, arterial and venous blood pressures, total vascular resistance, tissue volume changes, capillary filtration coefficient, and plasma volume were measured before and during the colloid infusion. According to the Starling fluid equilibrium, the ratio between the reflection coefficients for albumin on two occasions (before and after infusion of the synthetic colloid) can be calculated from the maximum osmotic absorption rates induced by a fixed intravenous bolus infusion of albumin and from the capillary filtration coefficients. Obtained data were adjusted for different plasma volume at the two occasions. We found that none of the three synthetic colloids analyzed had any significant effect on the reflection coefficient for albumin. An effect on albumin microvascular permeability of the synthetic colloids dextran 70, HES 200/0.5, and urea-linked gelatin could not be shown by a method analyzing their effect on the reflection coefficient for albumin.

Effect of erythrocyte aggregation on velocity profiles in venules.

A recent whole organ study in cat skeletal muscle showed that the increase in venous resistance seen at reduced arterial pressures is nearly abolished when the muscle is perfused with a nonaggregating red blood cell suspension. To explore a possible underlying mechanism, we tested the hypothesis that red blood cell aggregation alters flow patterns in vivo and leads to blunted red blood cell velocity profiles at reduced shear rates. With the use of fluorescently labeled red blood cells in tracer quantities and a video system equipped with a gated image intensifier, we obtained velocity profiles in venous microvessels (45-75 microm) of rat spinotrapezius muscle at centerline velocities between 0.3 and 14 mm/s (pseudoshear rates 3-120 s(-1)) under normal (nonaggregating) conditions and after induction of red blood cell aggregation with Dextran 500. Profiles are nearly parabolic (Poiseuille flow) over this flow rate range in the absence of aggregation. When aggregation is present, profiles are parabolic at high shear rates and become significantly blunted at pseudoshear rates of 40 s(-1) and below. These results indicate a possible mechanism for increased venous resistance at reduced flows.

Effects on capillary fluid permeability and fluid exchange of albumin, dextran, gelatin, and hydroxyethyl starch in cat skeletal muscle

To evaluate the peripheral hemodynamic effects in a skeletal muscle in vivo model of the four commercially available colloid solutions, 20% human albumin, 6% dextran-70, 6% hydroxyethyl starch 200/0.5 (HES), and 3.5% urea-linked gelatin. Controlled laboratory study. University research laboratory. Fifteen adult cats. The isolated, autoperfused, and denervated calf muscles of the cat hindlimb were placed in a plethysmograph. The colloids tested were given intra-arterially to the muscles in increasing rates of clinically relevant doses. Arterial blood flow, arterial and venous blood pressures, total vascular resistance, tissue volume changes, and capillary filtration coefficient were measured before, during, and after the colloid infusions. The altered capillary filtration coefficient reflects a change in capillary fluid permeability. The capillary filtration coefficient was decreased by albumin and dextran, not affected by HES, and increased by urea-linked gelatin. Albumin induced transcapillary fluid absorption, gelatin induced transcapillary filtration, and no transcapillary fluid exchange was observed with dextran and HES. After discontinuation of the infusions, HES and gelatin induced a rebound transcapillary filtration. No such effect was seen after dextran and albumin. All colloids increased muscle blood flow. We conclude that capillary fluid permeability is decreased by albumin and dextran, unchanged by HES, and increased by gelatin. This and the differences in the rebound effect may contribute to the differences in the plasma volume expanding properties of the respective colloid. The increased blood flow induced by the colloids was more an effect of reduced vascular tone than of lowered blood viscosity.