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The goal of this study was to determine the degree of sympathetic postganglionic neuronal loss required to impair cardiovascular-related sympathetic activity. To produce neuronal loss separate groups of rats were treated daily with guanethidine for either 5days or 11days, followed by a recovery period. Sympathetic activity was measured by renal sympathetic nerve activity (RSNA). Stereology of thoracic (T13) ganglia was performed to determine neuronal loss. Despite loss of more than two thirds of neurons in T13 ganglia in both treated groups no effect on resting blood pressure (BP) or heart rate (HR) was detected. Basal RSNA in rats treated for 5days (0.61±0.10μV∗s) and 11days (0.37±0.08μV∗s) was significantly less than vehicle-treated rats (0.99±0.13μV∗s, p<0.05). Increases in RSNA by baroreceptor unloading were significantly lower in 5-day (1.09±0.19μV∗s) and 11-day treated rats (0.59±0.11μV∗s) compared with vehicle-treated rats (1.82±0.19μV∗s, p<0.05). Increases in RSNA to chemoreceptor stimulation were significantly lower in 5-day treated rats (1.54±0.25μV∗s) compared with vehicle-treated rats (2.69±0.23μV∗s, p<0.05). Increases in RSNA in 11-day treated rats were significantly lower (0.75±0.15μV∗s, p<0.05) compared with both vehicle-treated and 5-day treated rats. A positive correlation of neurons to sympathetic responsiveness but not basal activity was detected. These data suggest that diminished capacity for reflex sympathetic responsiveness rather than basal activity alone must be assessed for complete detection of neurophysiological cardiovascular impairment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Environmental exposures occurring early in life may have an important influence on cancer risk later in life. Here, we investigated carryover effects of dichloroacetic acid (DCA), a small molecule analog of pyruvate with metabolic programming properties, on age-related incidence of liver cancer. The study followed a stop-exposure/promotion design in which 4-week-old male and female B6C3F1 mice received the following treatments: deionized water alone (dH2O, control); dH2O with 0.06% phenobarbital (PB), a mouse liver tumor promoter; or DCA (1.0, 2.0 or 3.5g/l) for 10 weeks followed by dH2O or PB (n = 20-30/group/sex). Pathology and molecular assessments were performed at 98 weeks of age. In the absence of PB, early-life exposure to DCA increased the incidence and number of hepatocellular tumors in male and female mice compared with controls. Significant dose trends were observed in both sexes. At the high dose level, 10 weeks of prior DCA treatment induced comparable effects (≥85% tumor incidence and number) to those seen after continuous lifetime exposure. Prior DCA treatment did not enhance or inhibit the carcinogenic effects of PB, induce persistent liver cytotoxicity or preneoplastic changes on histopathology or alter DNA sequence variant profiles within liver tumors compared with controls. Distinct changes in liver messenger RNA and micro RNA profiles associated with prior DCA treatment were not apparent at 98 weeks. Our findings demonstrate that early-life exposure to DCA may be as carcinogenic as life-long exposures, potentially via epigenetic-mediated effects related to cellular metabolism., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The mineralocorticoid receptor (MR) antagonists PF-03882845 and eplerenone were evaluated for renal protection against aldosterone-mediated renal disease in uninephrectomized Sprague-Dawley (SD) rats maintained on a high salt diet and receiving aldosterone by osmotic mini-pump for 27 days. Serum K(+) and the urinary albumin to creatinine ratio (UACR) were assessed following 14 and 27 days of treatment. Aldosterone induced renal fibrosis as evidenced by increases in UACR, collagen IV staining in kidney cortex, and expression of pro-fibrotic genes relative to sham-operated controls not receiving aldosterone. While both PF-03882845 and eplerenone elevated serum K(+) levels with similar potencies, PF-03882845 was more potent than eplerenone in suppressing the rise in UACR. PF-03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID while eplerenone was effective only at the highest dose tested (450 mg/kg BID). All doses of PF-03882845 suppressed aldosterone-induced increases in collagen IV, transforming growth factor-β 1 (Tgf-β 1), interleukin-6 (Il-6), intermolecular adhesion molecule-1 (Icam-1) and osteopontin gene expression in kidney while eplerenone was only effective at the highest dose. The therapeutic index (TI), calculated as the ratio of the EC50 for increasing serum K(+) to the EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone. Thus, the TI of PF-03882845 against hyperkalemia was 57-fold superior to that of eplerenone indicating that PF-03882845 may present significantly less risk for hyperkalemia compared to eplerenone.

Fumonisinmycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B(1), the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice when fed at concentrations higher than 50 ppm (70 micromol/kg) in the diet for 2 years. We sought to determine the relative toxicities of several naturally occurring fumonisin derivatives when included in the diet of female B6C3F(1) mice. Mice were fed diets containing fumonisin B(1), fumonisin B(2), fumonisin B(3), fumonisin P1, hydrolyzed-fumonisin B(1), N-(acetyl)fumonisin B(1), or N-(carboxymethyl)fumonisin B(1) (approximately 0, 14, 70, and 140 micromol/kg diet) for 28 days. None of the doses used caused a decrease in body weight gain over the 28 days. Serum levels of total bile acids, cholesterol, and alkaline phosphatase were increased only in mice receiving 72 and 143 micromol/kg fumonisin B(1), suggesting that only fumonisin B(1) was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 micromol/kg fumonisin B(1). Consistent with fumonisin B(1) inhibition of ceramide synthase, the liver sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were decreased only in the mice receiving 72 and 143 micromol/kg fumonisin B(1). Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 micromol/kg fumonisin B(1). The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B(1) is the principal hepatotoxic derivative in the B6C3F(1) mouse.

alpha- and beta-Hydroxy acids have been used extensively in cosmetic and dermatological formulations. At present, there is an inadequate amount of information with which to assess the safety of topical applications of alpha- and beta-hydroxy acids in conjunction with exposure to ultraviolet light. In the present study, we examined changes in the epidermal basal cell proliferation and the edemal response using skin thickness measurements elicited in SKH-1 mice following exposure to simulated solar light (SSL) with or without topical treatment with creams containing alpha- (glycolic) and beta-hydroxy (salicylic) acids. The dose of SSL light required to induce measurable edema (MED(BIOL)) in nai;ve, free-moving SKH-1 mice was determined to be 90 mJ. CIE/cm(2). Pretreating the mice with daily (5 days/week) exposures of 14 mJ. CIE/cm(2) for 6 weeks resulted in a doubling of the MED(BIOL) to 180 mJ. CIE/cm(2). Topical application of control cream (pH 3.5), or creams containing glycolic acid (10%, pH 3.5) or salicylic acid (4%, pH 3.5) for 6 weeks (5 days/week) increased the MED(BIOL) to 137 mJ. CIE/cm(2). Daily treatments with SSL (14 mJ. CIE/cm(2)) and control cream (pH 3.5), glycolic (10%, pH 3.5) or salicylic (4%, pH 3.5) acid-containing creams for 6 weeks (5 days/week) resulted in an MED(BIOL) value of 180 mJ. CIE/cm(2), which was the same as treatment with light alone for 6 weeks. These data indicate that a 6-week treatment of mouse skin with a representative skin cream, with or without representative alpha- and beta-hydroxy acids (glycolic and salicylic acid, respectively), changes the UV light sensitivity; however, treatment with the cream, with or without the acids, does not contribute to the UV sensitivity of mice cotreated with low doses of UV light.

Alpha- and beta-hydroxy acids are compounds that have been used extensively in cosmetic and dermatological formulations. Clinical and qualitative effects of alpha- and beta-hydroxy acids have been well characterized, but little is known about their mechanism of action or acute and chronic biochemical effects. In the present study, we examined the acute proliferative effects of glycolic and salicylic acids on cell proliferation in the epidermis of SKH-1 female mice, using BrdU incorporation as a marker of epidermal proliferation. In preliminary experiments, we observed an increase in the rate of proliferation after 3 days of treatment with 10% glycolic acid-containing cream and this was sustained throughout a 6.5-week (treatment 5 days/week) time course compared with untreated control animals. After each treatment with cream containing glycolic acid there was a wave of proliferation that was maximal 12 to 16 h (significant at p < 0.05) after treatment, followed by a subsequent increase in epidermal thickness at 18 to 20 h (significant at p < 0.05). The effects of the concentration and pH level of glycolic acid- and salicylic acid-containing creams on the rate of proliferation and increases in skin thickness in SKH-1 epidermis were also investigated. We observed a dose-dependent increase in epidermal proliferation of animals treated with either glycolic or salicylic acid. A similar time-dependent response was observed in the epidermal thickness in animals treated with salicylic acid, but not with glycolic acid. Differences in pH (3.5 or 4.0) had no significant effect on either epidermal proliferation or skin thickness. The data that we present here should be useful in characterizing not only the beneficial but also the adverse effects that occur following acute or chronic usage of alpha-hydroxy acids., (Copyright 2001 Academic Press.)

Background and Purpose: Soman, an organophosphorus, anticholinergic, chemical warfare nerve agent, is studied at few research facilities, and there have been few pathologic studies of soman-exposed primates. We describe the brain, heart, and skeletal muscle lesions, review lesions described in literature, and discuss possible pharmacologic mechanisms for soman-induced neuron necrosis., Methods: In this retrospective, histopathologic study, records were obtained for 36 rhesus macaques (Macaca mulatta) that were euthanized 10 days after soman exposure, from a larger group of 103 monkeys that were exposed to soman and used for pharmacologic and lethality studies., Results: Brain lesions were seen in 9 of 15 animals that convulsed and in only 1 of 21 that did not convulse. The brain lesions in our primates were limited to the hippocampus, amygdala, and thalamus (of one animal), and consisted of neuron necrosis and dropout, spongiosis, gliosis, astrocytosis, and vascularization. Heart lesions consisted of myocardial degeneration and necrosis. Three animals had brain and heart lesions, 7 had brain lesions only, and 3 had heart lesions only. Skeletal muscle lesions, although minimal to mild, were in most of the animals, whether they had convulsed, but most had muscular tremors. These lesions were in the biceps brachii (11 of 22 monkeys), anterior tibialis (8/22), biceps femoris (7/22), flexor carpi radialis (5/22), gastrocnemius (3/22), and diaphragm (1/22). The limited literature on soman lesions in primate brain and heart, and the limited information on skeletal muscle lesions, is reviewed., Conclusions: Brain lesions were not as wide-spread as reported in other studies of primates and rodents, and were significantly associated with convulsions. Unlike other studies using rodents, we observed poor correlation between heart and brain lesions; thus, a single hypothesis to explain the pathogenesis for the brain and heart lesions may be difficult to establish.

Although no animal is a perfect skin model for the study of toxicological and therapeutic agents, structurally the pig may be superior to even non-human primates. Because our work involves effects of toxicological and therapeutic agents on the skin, we wanted to identify stains which may prove useful as well as determine cross-reactivity of some newer antihuman antibodies. We performed a battery of formalin-fixed skin from weanling pigs and minipigs. The battery of antibodies included LCA, CD3, OPD-4, CD34, UCHL-1, L-26, KP-1, MAC-387, Factor XIIIa, Leu-7, S-100 protein, HMB-45, GFAP, synaptophysin, neurofilament protein, ubiquitin, vimentin, type IV collagen, laminin, fibronectin, Factor VIII related antigen, Desmin-M, smooth muscle actin, cytokeratin 7, cytokeratin 20, AEI/AE3, CAM 5.2, EMA, GCDFP, Ki-67, and PCNA. Immunohistochemical stains for CD3, Leu-7, S-100 protein, type IV collagen, laminin, Factor VIII related antigen, GFAP, synaptophysin, neurofilament protein, ubiquitin, smooth muscle actin, vimentin, Desmin-M, cytokeratin 7, cytokeratin 20, AE1/AE3, CAM 5.2, Ki-67 and PCNA showed consistent cross-reactivity. In formalin-fixed tissue, only antibodies to lymphoreticular cells showed poor cross-reactivity. A high percentage of the remaining antibodies did show good cross-reactivity but with some interesting similarities and differences in specificity.

Animal models have an important role in cutaneous research. The guinea pig has proven to be a useful model in a wide spectrum of these cutaneous studies; however, its usefulness is often compromised by the need for depilation. A euthymic hairless guinea pig (HGP) model avoids the problems associated with depilation. Morphologically, as in human skin, these animals have a multi-cell-layer epidermis. Proliferation kinetic studies, as well as documentation of the degree of immunologic cross-reactivity between available antibodies to human cutaneous antigens, could extend the usefulness of this animal model. We performed a battery of anti-human antibodies on formalin fixed tissue, to a variety of antigens present within the skin and on inflammatory cells. These included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin, collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of antibodies is limited, the markedly increased staining of Ki-67 and PCNA within keratinocytes in the epidermis as compared to normal human skin reflects a high proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may be useful in studying effects on cell cycle kinetics and apoptosis.

Sulfur mustard (SM), a chemical warfare agent first used early in the 20th century, has re-emerged in the past decade as a major threat around the world. At present, there are no effective therapeutic measures for SM exposure. Because the skin as well as other interface epithelial surfaces are the first tissues effected as this agent is absorbed, reactions within the skin are an area of active research into the mechanism of action of this alkylating agent. The euthymic hairless guinea pig has been used as the animal model for the study of SM induced injuries because of morphologic similarity of its skin to human skin, with a multiple layer epidermis, and because this animal has a normal immune system. We reviewed 102 biopsy specimens from 51 animals exposed to three different dose times of saturated SM vapor. Histopathologic evidence exists for increased programmed cell death as well as cellular necrosis, subepidermal blister formation, and delayed re-epithelialization secondary to problems with adhesion. Information obtained from this study adds to the body of information important in the investigation of the mechanisms of action of SM.

Smoke inhalation is a significant comorbid factor in thermal trauma. The effect of inhaled nitric oxide (NO) on smoke inhalation injury was evaluated in an ovine model. Following smoke exposure, group 1 animals (n = 9) spontaneously breathed room air, and group 2 animals (n = 8) breathed 20 parts per million of NO in air for 48 hours. Cardiopulmonary variables and blood gases were serially measured; bronchoalveolar lavage (BAL) was performed and wet-to-dry lung weight ratios (W/D) determined at 48 hours. Pulmonary vasoconstriction following smoke inhalation was significantly attenuated by inhaled NO (p < 0.05), which exerted no apparent effect on the systemic circulation. In group 2, the serial decline in pulmonary oxygenation was less than in group 1, consistent with a smaller physiologic shunt (p < 0.05). There were no significant differences in W/D, lung compliance, BAL fluid analysis results, or histologic evaluation findings between the two groups. These results suggest that inhaled NO exerted beneficial effects on pulmonary arterial hypertension and oxygenation following smoke inhalation without apparent amelioration of airway inflammation.

Bronchopulmonary injury secondary to smoke inhalation is a significant comorbid factor following major thermal trauma. The present study evaluates the effects of pentoxifylline (PTX) on pulmonary function in an ovine model of inhalation injury. Following smoke exposure to produce a moderate inhalation injury, 16 animals were divided into two groups. Group 1 animals (n = 8) were untreated; Group 2 animals (n = 8) were treated continuously with pentoxifylline following smoke exposure. The animals were observed in the unintubated, awake state for 48 hr. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution (VA/Q), analyzed using the multiple inert gas elimination technique, and bronchoalveolar lavage (BAL) were performed at 48 hr. The wet to dry lung weight ratio was measured following necropsy. In Group 2, the progressive hypoxemia observed following smoke inhalation was attenuated with less VA/Q mismatching than in Group 1 (P < 0.05). Pulmonary hypertension secondary to increased vascular resistance was also attenuated in Group 2 (P < 0.05). In BAL fluid, polymorphonuclear leukocytes, total protein content, and conjugated dienes were less in Group 2 than in Group 1 (P < 0.05). Plasma-conjugated diene levels were also lower in Group 2 at 48 hr. Extravascular lung water and decrease in lung compliance were greater in Group 1. There was less morphologic evidence of airway injury in Group 2 compared to Group 1. The improvement of pulmonary function following treatment with PTX suggests that this agent may be useful in the management of smoke inhalation injury.

In the course of developing a model of inhalation injury, the relationship between the severity of pulmonary injury and specific techniques and doses of smoke exposure was examined in pairs of rabbits simultaneously exposed to smoke. In group I (5 pairs), one animal in each pair was exposed to smoke with a breath hold (BH) at the end of each exposure; the second animal received an exposure producing the same level of carboxyhemoglobin without BH. In group II (6 pairs), both animals were exposed to 25 units of smoke simultaneously, with BH. In group III (3 pairs), one animal received a 20-unit exposure and the other a 25-unit exposure, both with BH. In group IV, 9 animals received 25-unit exposures with BH and were observed for 4 days. Groups V and VI served as controls. Smoke exposure with BH regularly produced severe injury in terms of decreased PaO2 and histopathologic changes, while exposure without BH did not, despite high levels of carboxyhemoglobin after smoke inhalation. The mean differences in percent residual PaO2 (PaO2 at 48 hours x 100/pre-injury PaO2) and in extravascular lung water (EVLW) at 48 hours within pairs of animals receiving 25 units with BH were 12.3% +/- 5.33%, and 0.271 +/- 0.157 mL/g, respectively. Histologic findings such as necrotic tracheobronchitis with pseudomembrane were consistently present. No differences were observed between animals receiving exposure of 20 and 25 units. During the 4 days of observation, three animals in group IV died. PaO2 was lowest on the second day and rose thereafter in all surviving animals except in one that had massive pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

A 1.5-year-old male Belgian Malinosis Military Working Dog presented with a 1-month history of intermittent hematuria. Diagnostic ultrasound and contrast radiography demonstrated large blood clots in the urinary bladder and a filling defect in the right renal pelvis. At surgery, clotted blood was present in the right ureter and bladder. Following right nephrectomy, the dog returned to training. One month later, elevations in urea nitrogen and creatinine were noted. Hematuria recurred at 3 months and the dog was found dead in its kennel. Necropsy showed a blood-filled left renal pelvis and ureter.

Pulmonary injury resulting from inhalation of chemical and particulate products of incomplete combustion is one of the principal determinants of mortality following burn injury. In this study, the histopathology of inhalation injury was examined in sheep. Mild, moderate, or severe smoke injury was produced in anesthetized sheep by insufflation with various doses of ambient temperature smoke, generated by burning polyethylene, wood pulp, and nonwoven cellulose pads. A total of 64 sheep were exposed and evaluated at times ranging from 15 minutes to 4 weeks after exposure. Morphologic changes in the lungs were studied using light microscopy and both transmission and scanning electron microscopy. The primary, dose-responsive injury observed was acute cell membrane damage in the trachea and bronchi leading to edema, progressive necrotic tracheobronchitis with pseudomembrane formation, and airway obstruction. These inflammatory and occlusive effects were followed by congestion, alveolar space edema, atelectasis, and bronchopneumonia. Morphologic changes occurring in the alveolar epithelium following high smoke dosage included intracellular edema in type-I cells, changes in the membrane-bound vacuoles of type-II cells, and septal thickening caused by interstitial edema. No capillary endothelial changes were observed.

We have examined the effects of direct current (DC) conducted through silver-nylon dressings on the healing time and morphologic maturation of split-thickness grafts placed on tangentially excised deep partial-thickness burn wounds. Male guinea pigs (n = 120) were used as the experimental hosts. The DC-treated animals required 2 days for complete revascularization of their grafts; control animals required 7 days (p less than 0.01). The DC-treated animals had increased epithelial proliferation at the graft-wound interface as compared with controls (p less than 0.01). Grafts from DC-treated animals were firmly adherent within 4 days, whereas graft adherence in controls was weak before 7 days after grafting. At 3 months after grafting, control animal grafts had mild contraction with moderate hair loss and thick subepidermal fibrosis; the grafts in DC-treated animals expanded with the growth of the animals and had abundant hair growth and significantly reduced dermal fibrosis (p less than 0.01).

Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE-treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001).

The time required for wound healing, contraction, and hypertrophic scarring often limit the use of deep partial-thickness burn wounds as donor sites for split-thickness grafts. We have examined the effects of weak direct current and silver nylon dressings on the healing of partial-thickness scald burns, split-thickness grafts taken from these wounds when healed, and the resulting donor sites in a guinea pig model. Dorsal scald wounds treated with weak direct current reepithealized by 12 days postinjury. Split-thickness grafts taken from healed scald wounds showed more rapid revascularization with direct current treatment than did control grafts. Grafts and donor sites treated with direct current showed more rapid reepithelialization, decreased contraction, improved hair survival, and decreased dermal fibrosis when compared to controls not treated with direct current. Only donor wounds treated with weak direct current were reusable as donor sites.

The influence of early graft surface thromboreactivity on long-term arterial polyester (Dacron) graft patency was investigated with separate ex vivo and in vivo animal models. First, parallel, flow-regulated external aortocaval fistulae were created in five pigs with use of paired 8 mm X 35 cm crimped, warp-knitted, low-profile filamentous velour Dacron tubes: one tube preclotted with autologous blood, the other autoclaved after being soaked in human albumin. Autologous radiolabeled platelets, red cells, and radiolabeled human fibrinogen were injected at initiation of graft flow, with timed graft samples submitted for isotope gamma well-counting. Flow surface accumulation of radiolabeled blood elements was greater on the preclotted graft limb at-all time intervals studied, greatest after 5 minutes of flow initiation with RBC accumulation on the preclotted limb 5.19 +/- 0.84 (x +/- S.E.), platelet accumulation 5.57 +/- 1.00, and fibrinogen accumulation 1.82 +/- 0.14 times greater than that on the albumin-treated limb. Second, bilateral iliofemoral artery bypass grafts were placed in 12 mongrel dogs using 6 mm X 10 cm externally supported, noncrimped, warp-knitted, low-profile filamentous Dacron tubes. Before implant in each dog, one graft limb was clotted with autologous blood and the other was autoclaved after being soaked in 25% human albumin. Fresh autologous radiolabeled platelets were injected after wound closure in seven of these dogs. Postimplant graft imaging at 24 and 72 hours showed radiolabeled platelet accumulation to be 1.43 +/- 0.21 and 2.05 +/- 0.18 times greater on the preclotted graft limb. Six of 12 preclotted graft limbs and 7 of 12 albumin-treated graft limbs were patent when animals were killed 5 to 6 months after implant (not significant). Heat-denatured albumin-coated Dacron surfaces have a reduced early thromboreactivity but do not appear to greatly potentiate long-term arterial graft patency.

Dacron fabrics with a wide range of porosities were autoclaved for 3 minutes after being soaked in serum, 5% albumin, or 25% albumin. Porosity of compound Dacron grafts made with 25% albumin was less than 1 ml/min/cm2 regardless of the fabric base, whereas porosity of grafts made with serum or 5% albumin was proportional to the porosity of the base fabric. Porosity of the compound grafts remained stable for more than 48 hours and to pressure greater than 450 mm Hg, if the grafts were kept moist. Tubes of Marlex mesh coated with heat-denatured albumin, implanted as infrarenal aortic replacements in dogs, showed complete albumin absorption by 3 weeks. However, perigraft tissue reaction and graft incorporation were minimal and extensive false aneurysm formation resulted. Knitted filamentous Dacron 6 mm tubes coated with heat-denatured albumin were implanted as iliofemoral bypass grafts in 12 dogs, with blood-preclotted knitted filamentous Dacron grafts implanted as contralateral control grafts. Comparison of the albumin-coated grafts with the blood-preclotted control grafts showed no differences in healing or patency at 4 to 6 months. Heat-denatured 25% albumin forms a strong and hemostatic coating regardless of fabric base. Albumin-Dacron compound grafts are easily and rapidly made in the operating room, handle well, and are suitable for large and medium-sized arterial replacements without changes in healing or patency. Because of slow tissue incorporation, however, albumin-coated knitted Dacron grafts should be avoided in patients who require long-term anticoagulation therapy.

Fifty-two, 8-week-old, male White Pekin ducklings (Anas platyrhynchos domesticus) were allotted into control (n = 7) and isoproterenol-injected groups (n = 45). One control duck and 5 to 7 isoproterenol-injected (200 mg/kg of body weight) ducklings were euthanatized at postinjection hours (PIH) 1, 12, and 24 and at postinjection days (PID) 2, 4, 7, and 14. The left ventricular myocardium was examined, using electron microscopy. The earliest ultrastructural alteration in damaged myocytes was myofibrillar lysis at PIH 12. At PIH 24, affected myocytes had necrosis with mineralization of mitochondria. By PID 2, macrophages had invaded into areas of myocardial necrosis, mineralization was prominent in myocyte mitochondria, and dedifferentiated myocytes with reduced numbers of myofibrils, increased numbers of polysomes, large nuclei, and prominent nucleoli were first observed. The primary myocardial finding at PID 4, 7, and 14 was 2 populations of sublethally damaged myocytes. One population of injured myocytes had numerous polysomes in the sarcoplasm and large nuclei with prominent nucleoli, indicating attempts at repair of myofibrillar damage. The 2nd population of myocytes with myofibrillar lysis did not have morphologic evidence of myofibrillar repair. Therefore, the sequential ultrastructural alterations of damage and repair induced by isoproterenol in the duckling myocardium provided model for comparative studies of cardiotoxicity.