Attenuation of histamine-induced endothelial permeability responses after pacing-induced heart failure: role for endogenous catecholamines.

OBJECTIVE: After congestive heart failure (CHF), lung endothelial permeability responses to a number of perturbations, including acute barotrauma, angiotensin II, and thapsigargin are blunted. Our hypothesis was that similar attenuation of permeability responses occurs in peripheral vascular beds after CHF. We compared peripheral microvascular permeability responses to the autacoid histamine in control dogs and in dogs paced to heart failure (245 bpm for approximately 36 days). Since catecholamines attenuate autacoid-induced increases in microvascular permeability in skin and muscle in normal animals, we also tested whether the known elevation in catecholamines in CHF was involved in any downregulation of permeability responses in this group. METHODS: Control and paced dogs were anesthetized, intubated, and ventilated, and a hindpaw lymphatic cannulated. The reflection coefficient for total proteins (sigma) was measured at baseline and during one-hour, local intra-arterial histamine infusion. RESULTS: In controls, sigma fell from 0.83 +/- 0.02 to 0.73 +/- 0.04 after histamine (p < 0.05), while in the paced group sigma was no different from that at baseline (0.77 +/- 0.02). To test whether this difference was due to endogenous catecholamines, dogs were pretreated with propranolol (controls only) or the specific beta 2-antagonist ICI 118,551 prior to histamine infusion. After beta-blockade, histamine significantly reduced sigma in both control (0.83 +/- 0.01 to 0.55 +/- 0.05) and paced (0.83 +/- 0.01 to 0.57 +/- 0.07) groups (p < 0.05). CONCLUSION: We conclude that endogenous catecholamines, acting via beta 2-adrenergic receptors, attenuate the permeability response to histamine in pacing-induced heart failure.

Modulation of microvascular permeability by 21-aminosteroids after burn injuries.

Burn injuries initiate lipid peroxidation in capillary endothelial cells and cause alterations in microvascular permeability, with subsequent leakage of fluid and protein from the plasma into the interstitium. We evaluated the effects of two lazaroid compounds (U74389F and U75412E) on alterations in microvascular permeability that resulted from burn injuries. A canine model was used for the evaluation of microvascular permeability at the site of the burn injury with the use of a measure of the reflection coefficient (sigma(d)). Hindpaw lymph flow, lymph and plasma total protein concentrations, and arterial, venous, and capillary pressures were measured before burn injuries and for 6 hours in 6 different groups. Footpaw weight gain was then calculated as the percentage of increase of experimental hindpaw relative to the contralateral paw. The damage was attenuated by 20 mg/kg of lazaroid U75412E given before the injuries, but a lower dose was not effective. This agent was also effective in limiting edema formation, as evidenced by changes in footpaw weight gain. However, the administration of either lazaroid compound produced no significant effect on the burn-induced changes in capillary permeability. We conclude that these lazaroids do not prevent burn-induced changes in permeability at the site of injury when administered after an injury. U75412E administered before the injury was effective in limiting the alterations in microvascular permeability.

Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries.

Little information is available regarding the vasoactive effects of epoxyeicosatrienoic acids (EETs) in the lung. We demonstrate that 5, 6-, 8,9-, 11,12-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a concentration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-EET is blocked by indomethacin or ibuprofen (10(-5) M), SQ-29548, endothelial denuding, or submaximal preconstriction with the thromboxane mimetic U-46619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabolize arachidonate to products that comigrate on reverse-phrase HPLC with authentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-EETs, but no cyclooxygenase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E, CYP2J, CYP1A, and CYP2C subfamilies are present in pulmonary artery and peripheral lung microsomes. Constriction of isolated rabbit pulmonary arteries to EETs is nonregioselective and depends on intact endothelium and cyclooxygenase, consistent with the formation of a pressor prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone.

Remodeling of lung interstitium but not resistance vessels in canine pacing-induced heart failure.

We previously showed that pacing-induced heart failure in dogs results in an enhancement of pulmonary vascular reactivity. In the present study we hypothesized that enhanced matrix deposition and structural remodeling of lung resistance microvessels would underlie these functional changes. Using biochemical measures, we found no difference in the normalized lung content of hyaluronan, uronic acid, and collagen between control dogs and dogs paced for 1 mo, although lung dry weight and noncollagen protein content increased significantly in the paced group (P < 0.05). From separate Formalin-fixed lung lobes, 5-microm frozen sections were prepared and stained with Masson's trichrome, and vascular structure was evaluated using standard morphometric techniques. When perivascular fluid cuffs were excluded from the measure of wall thickness, collagen and media volume fractions in any size range did not differ between paced and control groups. Similarly, in the paced group, medial thickness in <400-microm arterial or venular microvessels did not vary significantly from that in the controls. In contrast, the relationship of interstitial fluid pressure to lung water was significantly shifted to the right in the paced group, such that normal tissue pressures were observed, despite the increased water content. We conclude that although 1 mo of pacing-induced heart failure results in altered interstitial function, the attendant pulmonary hypertension and/or hormonal responses are insufficient to induce medial hypertrophy or other remodeling of the extra-alveolar microvasculature.

Alpha-adrenergic vasoreactivity of canine intrapulmonary bronchial arteries in pacing-induced heart failure.

We hypothesized that pacing-induced congestive heart failure alters alpha-adrenergic constriction in intrapulmonary bronchial arteries. Cumulative dose responses to norepinephrine (NE), phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) were determined in pressurized vessel segments. ED(50) values for NE and PE were higher for control (-5.34 +/- 0.09 and -4.27 +/- 0.08 M, respectively) vs. paced (-5.73 +/- 0.10 and -5.06 +/- 0.28 M, respectively) groups. Prazosin increased the ED(50) values for NE and PE in both control and paced groups. Yohimbine decreased NE ED(50) in the control group only. Endothelium removal or nitric oxide synthase (NOS) inhibition decreased control but not paced NE ED(50). Maximum vasodilation and sensitivity (i.e., -ED(50) values) were decreased for ACh but were similar for SNP in paced vs. control groups. Secondary segments were more reactive than paired primary segments in both groups, although pacing effects on ED(50) were unrelated to branching order. In conclusion, adrenergic constriction of canine intrapulmonary bronchial arteries is predominantly mediated via alpha(1)-adrenoreceptors and is enhanced after pacing. Endothelium-derived relaxing factor(s) normally opposes alpha-adrenergic vasoconstriction but not after pacing in this vasculature.

Involvement of cytochrome P-450 enzyme activity in the control of microvascular permeability in canine lung.

Products of cytochrome P-450 enzymes may play a role in capacitative Ca2+ entry in endothelial cells, which can promote a rise in vascular permeability. Thapsigargin (150 nM) stimulated capacitative Ca2+ entry and increased the capillary filtration coefficient (Kf,c) in isolated normal canine lung lobes. Pretreatment of the lobes with cytochrome P-450 inhibitors clotrimazole (10 microM) or 17-octadecynoic acid (5 microM) abolished the thapsigargin-induced increases in Kf,c. Because clotrimazole also blocks Ca2+-activated K+ channels, the K+-channel blocker tetraethylammonium (10 mM) was used to ensure that permeability was not influenced by this mechanism. Tetraethylammonium did not affect thapsigargin-induced permeability. The effects of the cytochrome P-450 arachidonic acid metabolite 5,6-epoxyeicosatrienoic acid (EET) were also investigated in lobes taken from control dogs and dogs with pacing-induced heart failure (paced at 245 beats/min for 4 wk). 5,6-EET (10 microM) significantly increased Kf,c in lobes from the control but not from the paced animals. We conclude that cytochrome P-450 metabolites are involved in mediating microvascular permeability in normal canine lungs, but an absence of 5,6-EET after heart failure does not explain the resistance of lungs from these animals to permeability changes.

Ablation of lung endothelial injury after pacing-induced heart failure is related to alterations in Ca2+ signaling.

We have previously shown that ANG II increases microvascular permeability in normal dog lungs but not after pacing-induced heart failure. This study investigated how ANG II induces permeability in isolated blood-perfused canine lung lobes and what alterations occur during heart failure. In normal lobes, the protein kinase C (PKC) inhibitors staurosporine (500 nM) or chelerythrine (10 microM) did not modify ANG II-induced increases in the capillary filtration coefficient (Kf,c, ml . min-1 . cmH2O-1 . 100 g-1; an index of microvascular permeability), suggesting that PKC is not involved. Thapsigargin (150 nM) was used to stimulate capacitative Ca2+ entry in lobes from control dogs and dogs paced at 245 beats/min for 4 wk to induce heart failure. In control lobes, Kf,c rose after thapsigargin, from 0.06 +/- 0.01 to 0.17 +/- 0.03 ml . min-1 . cmH2O-1 . 100 g-1 (mean +/- SE, P < 0.05) but did not change in the paced group. A Ca2+ ionophore, A-23187, increased Kf,c in both control (10 microM; 0.05 +/- 0.01 to 0.17 +/- 0.05 ml . min-1 . cmH2O-1 . 100 g-1, P < 0.05) and pace (5 microM; 0.06 +/- 0.01 to 0. 21 +/- 0.07 ml . min-1 . cmH2O-1 . 100 g-1, P < 0.05) lobes, indicating that increasing intracellular Ca2+ is sufficient to induce pulmonary microvascular permeability after pacing. We conclude that during heart failure, Ca2+ signaling within the pulmonary microvascular endothelium is altered.

Enterostatin efflux in cat intestinal lymph: relation to lymph flow, hyaluronan, and fat absorption.

The question addressed in this study was whether enterostatin, the pancreatic procolipase activation peptide, modulates intestinal hyaluronan turnover via lymph. In anesthetized cats, segments of ileum were surgically isolated from the proximal and distal gut, the draining lymphatic was cannulated, and the segment was autoperfused in situ. In several groups, concentrations of immunoreactive enterostatin in lymph were compared with that in plasma at baseline and elevated lymph flow and in the absence and presence of fat absorption. The baseline ratio of lymph enterostatin to that in plasma (L/P) in the absence of fat absorption was 1.44 +/- 0.29 compared with 4.93 +/- 0.42 after cream feeding (P < 0.05). In a separate group, when the intestinal lumen was perfused for 2 h with a mixture of oleic acid and taurocholate, enterostatin L/P doubled compared with baseline. At high lymph flows, enterostatin concentrations fell in all groups, resulting in an L/P of 0.47 +/- 0.09 (P < 0.05) in the absence of fat absorption, 0.77 +/- 0.35 after oleic acid, and 1.26 +/- 0.13 in the cream-fed group. These changes correlate with the pattern of hyaluronan efflux from the ileum into lymph after fat absorption [R.K. Reed, M.I Townsley, V.H. Pitts, T.C. Laurent, and A.E. Taylor. Am. J. Physiol, 263 (Gastrointest. Liver Physiol. 26): G6-G11, 1992] However, in separate groups when enterostatin was introduced into ileum, either as a close intra-arterial bolus or via the intestinal lumen, there were no resultant changes in efflux of hyaluronan from the intestine into lymph. In conclusion, despite the fact that delivery of pancreatic exocrine secretions to the ileal lumen was blocked in this model, enterostatin concentration in lymph increased after fat absorption. Nonetheless, it seems clear that enterostatin does not modify intestinal hyaluronan turnover.

Pulmonary vascular response to angiotensin II in canine pacing-induced heart failure.

The effects of angiotensin II(ANG II) on pulmonary vascular resistance and microvascular permeability were studied in isolated, blood-perfused, ventilated canine lung lobes from control animals (n = 40) and animals with pacing-induced heart failure (n = 15). Conditioned dogs were paced (245 beats/min) for 30.6 +/- 0.9 (SE) days until left ventricular shortening fraction decreased by 56% (P < 0.05). Baseline pulmonary arterial resistance (Ra) (19.1 +/- 1.6 vs. 8.0 +/- 1.1 cmH2O.1(-1).min.100g) and venous resistance (Rv) (17.1 +/- 2.3 vs. 7.8 +/- 1.0 cmH2O.1(-1).min.100 g) were greater (P < 0.05) in the paced group compared with controls, respectively. Increments in Ra (delta Ra) and Rv(delta Rv) were measured after intra-arterial boluses of ANG II (1-10 micrograms). ANG II produced a dose-dependent response in delta Ra that was enhanced after pacing (P < 0.05). There was no effect on delta Rv in either group. At increased venous pressure (Pv = 20 cmH2O), the increments in delta Ra were significantly attenuated in both groups. In control lobes at low Pv, delta Ra and delta Rv both tended to decrease with increased lobar blood flow, suggesting that blood flow affects the pulmonary vascular response of ANG II. The baseline capillary filtration coefficient (Kf,c) was not different in the paced group compared with control, nor was there any effect of ANG II on Kf,c in the paced group. However, Kf,c did increase after ANG II in the control groups evaluated at either low or high Pv (P < 0.05). This difference in Kf,c was not seen if the experiment was done at increased Pv but without ANG II administration. We conclude that the pulmonary vasoconstrictor activity of ANG II is modestly enhanced in canine pacing-induced heart failure. Nonetheless, ANG II does not likely contribute to increased pulmonary vascular resistance in vivo in heart failure, since this effect was abolished at increased Pv. Finally, the absence of any effect of ANG II on pulmonary microvascular permeability in the paced group is suggestive of some adaptive remodeling of the capillary endothelial barrier.

Pulmonary microvascular permeability. Responses to high vascular pressure after induction of pacing-induced heart failure in dogs.

The pressure threshold for injury of pulmonary capillaries is approximately 50 to 55 cm H2O in the canine lung, as measured by changes in the filtration coefficient (Kf,c). Since the pulmonary endothelial basement membrane has been observed to thicken in patients with heart failure and pulmonary venous hypertension, we hypothesized that both baseline permeability and the threshold for high-vascular-pressure injury would be altered as a result. Dogs (n = 12) were chronically paced at 245 beats per minute for approximately 4 weeks, then were paced at 225 beats per minute for an additional 3 weeks. Lung lobes from anesthetized paced dogs and additional control dogs (n = 14) were then isolated, ventilated, and perfused with blood. Although vascular resistance was increased nearly threefold and vascular compliance reduced by 50% in the paced group, Kf,c referenced to 1 g blood-free dry weight was no different from control. Despite this lack of difference at normal pulmonary vascular pressures, several significant results were obtained. First, in the paced group there was a significant increase in the threshold for high-vascular-pressure injury: Kf,c measured at pulmonary vascular pressures commonly seen in heart failure (20 to 50 cm H2O) were significantly less in this group compared with control. Model predictions showed that in vivo, this difference in Kf,c would result in a 50% reduction in the amount of water and protein cleared across the pulmonary capillary endothelial barrier in the paced group.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-activating factor increases vascular resistance in rat hindquarters by thromboxane A2.

The effects of platelet-activating factor (PAF) on vascular resistance and capillary permeability were studied in the isolated rat hindquarter. Six groups were studied (n = 30): control; PAF alone (1.4 microM); and PAF (1.4 microM) pretreated with ibuprofen (30 mg/kg), thromboxane A2 (TxA2)-receptor antagonist (BM-13505, 2 mg/kg), PAF-receptor antagonist (WEB-2086, 5 mg/kg), or dexamethasone (5 mg/kg). The vascular resistance was calculated, and the reflection coefficient (sigma) was determined as an index of capillary permeability. Exogenous PAF caused a threefold increase in vascular resistance peaking at 5 min and a 2.5-fold increase in capillary permeability. The increased vascular resistance caused by PAF alone was significantly attenuated by ibuprofen, BM-13505, and dexamethasone. The PAF-induced permeability was neither attenuated by ibuprofen nor BM-13505. However, both the increased vascular resistance and permeability were blocked and attenuated by WEB-2086 and dexamethasone, respectively. We conclude that TxA2 mediates the PAF-induced increased vascular resistance; however, the increased vascular permeability is independent of the formation of TxA2 in the isolated hindquarter.

Hyaluronan efflux from canine lung with increased hydrostatic pressure and saline loading.

Although lymphatic washout of hyaluronan during lung hydration has been postulated to deplete lung interstitial hyaluronan content and thereby contribute to the decreased interstitial exclusion of albumin observed under these conditions, this hypothesis has not been directly tested. In anesthetized, ventilated mongrel dogs, a prenodal lung lymphatic was cannulated for measurement of lymph flow and hyaluronan concentration. Following baseline measurements, Pla was increased in four steps of 5 cm H2O in Group 1 or set to one pressure ranging between 6 and 32 cm H2O in Group 2. In Group 3, saline (15% body weight) was infused over 30 min and then Pla increased as in Group 2. Invariably, as lymph flow increased in Groups 1 through 3, lymph hyaluronan concentration and hyaluronan flux increased significantly (p < 0.05). In a separate control group, there were no changes in lymph flow, hyaluronan concentration, or hyaluronan flux. In Group 3, lung hyaluronan content at 5 h (0.76 +/- 0.08 mg/g dry weight) was not significantly less than that during baseline (0.88 +/- 0.05 mg/g dry weight), although total uronic acid content actually increased by 38% over the same time course. In contrast, in the control group, both lung hyaluronan and uronic acid content remained stable over the experimental period. From these data, approximately 2 to 3% of lung hyaluronan is predicted to leave the interstitium via lymphatic flux per day under baseline conditions. The daily turnover of interstitial hyaluronan by this route increased to 15 to 18% of total content when Pla was elevated and to 54% following saline infusion. Thus, lung hyaluronan can be rapidly mobilized with increased lymph flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of graded thermal injury on microvascular permeability at the site of injury.

To define whether capillary permeability traits at the site of a burn differ according to injury severity, a canine hind leg lymphatic was cannulated to measure macromolecular permeability in response to three different scalding solutions. Leg venous pressure was raised to approximately 40 mm Hg and maintained until a minimal lymph-to-plasma total protein ratio (CL/CP)min and steady-state lymph flow (QL; microliter/min/100 g) was attained. The protein reflection coefficient (1-CL/CP), fluid filtration coefficient (Kf; microliter/min/mm Hg/100 g), and QL were determined before and for 6 hr after a 5-sec hind paw immersion in either 100 degrees C (n = 7), 80 degrees C (n = 7), or 70 degrees C (n = 7) water. A group of five animals served as controls. In the absence of any systemic hemodynamic alterations, the 100 and 80 degrees C scald groups experienced significant (P < 0.05, ANOVA) increases in QL, CL/CP, and Kf as compared to respective preburn values and time-matched unburned control values. Most monitored parameters were significantly higher following 100 degrees C injury vs 80 degrees C injury. Parameters in the 70 degrees C group did change after scald, but were not significantly different from preburn values or from the control group. Alterations in capillary permeability to protein and fluid flux measured at the burn site are graded, not all or none phenomena, being dependent upon the severity of injury.

Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure.

Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.

Increased hyaluronan flux in canine paw lymph is induced by histamine and the histamine-releasing agent compound 48/80.

The present experiments investigated hyaluronan (HYA) flux from skin of pentobarbital anesthetized mongrel dogs when transcapillary fluid flux was increased by local intraarterial injection of histamine (50 micrograms) or Compound 48/80 (C48/80) (100 micrograms) inducing mast cell degranulation. A prenodal lymphatic draining the hindpaw was cannulated and the paw flexed passively at 50 times/min. Grand mean (n = 18) of control lymph flow and HYA concentration was 16 +/- (SD) 14 microliters/min and 8.8 +/- 2.3 micrograms/ml, respectively. Lymph flow increased 11- and 15-fold within 10 min after histamine and C48/80 injection, respectively, and returned to control values after 3 h for histamine while it did not return fully in the C48/80 group. HYA concentration decreased by 30 and 40% during the first hour after histamine and C48/80, respectively, while HYA flux increased 11-15 times control. Control experiments (saline vehicle) showed an unexpected and gradual increase in HYA concentration during the 8-hour experimental period, regardless of unchanged lymph flow. This increase became statistically significant at the end of the experimental period, suggesting either an increased synthesis or increased rate of release of bound HYA from the paw. The present data show that HYA is loosely bound and easily mobilized from the interstitial matrix and that histamine and C48/80 cause a release of bound HYA from the interstitium. An increase in HYA concentration towards the end of the 8-hour experimental period most likely represents an increased synthesis of HYA.

Permeability of parietal pleura to liquid and proteins.

The permselectivity of the parietal pleura was determined in spontaneously breathing anesthetized rabbits and dogs. In rabbits, we injected intrapleurally 5 ml of 1-g/dl albumin solution containing 100 microCi of 131I-labeled albumin plus 100 microCi of either lactate dehydrogenase (LDH) or alpha 2-125I-macroglobulin. Dogs received 100 ml of 1-g/dl albumin solution containing 100 microCi of 131I-albumin plus 100 microCi of alpha 2-125I-macroglobulin. A transpleural pressure gradient was set, lowering the intracapsular pressure to -30 cmH2O. The solvent drag reflection coefficients (sigma f) were calculated as the ratio between tracer concentrations in capsular and pleural liquid collected at 60-180 min. In rabbits sigma f was 0.44 +/- 0.2 (SD) for albumin, 0.84 +/- 0.1 for LDH, and 0.93 +/- 0.05 for alpha 2-macroglobulin. In dogs sigma f was 0.30 +/- 0.19 for albumin and 0.53 +/- 0.15 for alpha 2-macroglobulin. The hydraulic conductivity of the parietal pleura was 2.18 +/- 1.54 microliters.h-1.cmH2O-1.cm-2 in rabbits and 1.22 +/- 1.13 microliters.h-1.cmH2O-1.cm-2 in dogs. The parietal pleura could be modeled by two pore populations with radii of 83-89 and 156-222 A. The permeability coefficient averaged 0.08-0.21 x 10(-6) cm/s for albumin, 0.06-0.09 x 10(-6) cm/s for LDH, and 0.01-0.03 x 10(-6) cm/s for alpha 2-macroglobulin.

Effects of pentafraction administration on microvascular permeability alterations induced by graded thermal injury.

BACKGROUND: Pentafraction is a pentastarch derivative hypothesized to limit burn edema by "sealing" damaged capillaries, restoring a barrier to fluid translocation and macromolecular (protein) flux. METHODS: Canine hind paw lymph flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured before and for 6 hours after (1) 5-second 100 degrees C (n = 6) or 80 degrees C (n = 6) foot paw scald, (2) 100 degrees C (n = 5) or 80 degrees C (n = 5) foot paw scald followed 30 minutes later by a 4 cc/kg bolus of 6% pentafraction, or (3) pentafraction infusion without scald (n = 5). Before scald or pentafraction infusion, hind paw venous pressure was elevated and maintained by outflow restriction until a steady state, minimal CL/CP was reached. The reflection coefficient, sigma d, was determined as 1-CL/CP, and the (fluid) filtration coefficient (Kf) was calculated. RESULTS: Scalding uniformly produced statistical (p < 0.05, ANOVA) increases in QL, CL/CP, sigma d, Kf, and paw weight gain. Postburn pentafraction infusion produced no enduring alterations in any measured parameter as compared with those of animals who received a matched severity scald without pentafraction. CONCLUSIONS: Pentafraction does not appreciably ameliorate the adverse microcirculatory consequences observed at the site of burn injury.

Lymphatic hyaluronan flux from skin increases during increased lymph flow induced by intravenous saline loading.

Hyaluronan is a structural component of the interstitial matrix in skin and is catabolized locally in skin as well as by lymphatic removal and subsequent degradation in lymph nodes and liver. The present experiments were designed to evaluate the role of interstitial fluid flux in turnover of hyaluronan in skin by measuring the maximal lymphatic flux of hyaluronan. Lymph flow, total protein concentration, hyaluronan concentration, and flux were measured every 15 min in prenodal lymph from the hind paw in 12 pentobarbital-anesthetized mongrel dogs at normal and increased interstitial fluid flux. An intravenous saline load (15% of body weight during the course of 30 min) was followed by a one-step increase in local venous pressure 30 min later (to a maximum of 50 mm Hg) and maintained at this level for the next 240 min. Lymph flow and hyaluronan concentration during the control period averaged 25.6 +/- (SD) 23.2 (range 4.7-61.9) microliters/min and 8.6 +/- 2.8 (range 2.0-11.6) micrograms/ml, respectively. The hyaluronan concentration fell by 30% during the experimental period, while the lymph flow increased up to ten times above control. Total tissue water increased from 1.73 +/- 0.11 ml/g dry weight during the control period to 1.91 +/- 0.12 ml/g dry weight at the end of the experiment (p < 0.01). The corresponding tissue contents of hyaluronan averaged 3.5 +/- 0.9 and 3.6 +/- 0.6 mg/g dry weight, respectively (p > 0.05). The average lymphatic hyaluronan flux was 8.4 +/- 5.4 micrograms/h during the control period, peaked at about 60 micrograms/h, and averaged 33.6 +/- 13.9 micrograms/h during the last hour of the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of albumin administration on microvascular permeability at the site of burn injury.

In a canine hind leg model, lymph flow (QL), lymph (CL), and plasma (CP) total protein concentrations, the reflection coefficient for total proteins (sigma d), and the filtration coefficient (Kf) were determined before and for 6 hours after a 5-second 100 degrees C hind paw scald (3% total body surface area, TBSA). Before injury, hind leg venous pressure was elevated and maintained by outflow restriction until a minimal, steady-state CL/CP ratio was achieved. Albumin (5%) was infused 30 minutes after the scald at low (0.4 mL/kg/% TBSA) or high (2 mL/kg/% TBSA) doses. Scald uniformly increased QL, CL/CP, Kf, and paw weight gain (PWG). Whereas postburn infusion of low-dose albumin mildly attenuated increases in CL/CP and PWG noted in scald-alone animals, no differences were noted between the scald and scald/high-dose albumin groups.