A model of left ventricular dysfunction caused by intracoronary adriamycin.

Experimental evaluation of new therapy for congestive heart failure has been hampered by the lack of a simple and reliable animal model of heart failure. This study was undertaken to develop a canine model of chronic left ventricular dysfunction. A left thoracotomy was performed in 9 adult mongrel dogs. A 1.5-mm Silastic (Dow Corning) catheter with an attached subcutaneous access port was positioned in the left main coronary artery. Six animals received five weekly infusions of Adriamycin (doxorubicin hydrochloride) (10 mg/wk), and 3 received saline solution. Hemodynamic studies were performed before insertion of the catheter and 2 weeks after completion of the infusions. In animals that received Adriamycin, rest ejection fraction declined from 0.54 +/- 0.03 to 0.35 +/- 0.03, cardiac output fell from 5.6 +/- 0.6 to 3.9 +/- 0.5 L/min, and left ventricular end-diastolic volume increased from 76 +/- 9 to 99 +/- 12 mL (p less than 0.05). There was a small increase in right atrial pressure (2.7 +/- 1 versus 5.7 +/- 1 mm Hg) but no change in right ventricular ejection fraction (0.31 +/- 0.04 versus 0.30 +/- 0.03). In no animal did alopecia, weight loss, neutropenia, or anemia develop. Histological changes consistent with Adriamycin-induced cardiac toxicity were found in each dog. No significant hemodynamic or histological changes occurred in the control animals. Administration of Adriamycin into the left main coronary artery causes left ventricular dysfunction without resulting in systemic side effects or compromising right ventricular function. This animal model could be used to evaluate the effects of new possible therapy, such as cardiomyoplasty, on left ventricular failure.

Small intestinal submucosa as a small-diameter arterial graft in the dog.

Autogenous saphenous vein, human umbilical vein, modified bovine collagen, Dacron, and PTFE have been used as small-diameter arterial grafts with moderate success. We tested autogenous small intestine submucosa as a small-diameter arterial graft in both a carotid and femoral artery (mean ID 4.3 mm) of 18 dogs (total of 36 grafts). All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by Doppler ultrasound techniques and angiography. Two grafts ruptured and 5 grafts occluded by 21 days after surgery. One graft became occluded at 14 weeks. Fifteen dogs were sacrificed at periodic intervals until 48 weeks after surgery. Patent grafts had no evidence of infection, propagating thrombus, or intimal hyperplasia. Graft aneurysmal dilation occurred in 4 grafts (11%). The grafts were composed of a dense organized collagenous connective tissue with no evidence of endothelial cell growth on the smooth luminal surface. Three dogs are alive at 76 to 82 weeks after surgery. Overall, graft patency was 75%. Graft patency after cessation of anticoagulation therapy was 92.3% (12 of 13 grafts). We conclude that autogenous small intestinal submucosa can be used as a small-diameter arterial graft in the dog and is worthy of further investigation.

Small intestinal submucosa as a vascular graft: a review.

Continuing investigations of vascular graft materials suggest that unacceptable graft complications continue and that the ideal graft material has not yet been found. We have developed and tested a biologic vascular graft material, small intestine submucosa (SIS), in normal dogs. This material, when used as an autograft, allograft, or xenograft has demonstrated biocompatibility and high patency rates in aorta, carotid and femoral arteries, and superior vena cava locations. The grafts are completely endothelialized at 28 days post-implantation. At 90 days, the grafts are histologically similar to normal arteries and veins and contain a smooth muscle media and a dense fibrous connective tissue adventitia. Follow-up periods of up to 5 years found no evidence of infection, intimal hyperplasia, or aneurysmal dilation. One infection-challenge study suggested that SIS may be infection resistant, possibly because of early capillary penetration of the SIS (2 to 4 days after implantation) and delivery of body defenses to the local site. We conclude that SIS is a suitable blood interface material and is worthy of continued investigation. It may serve as a structural framework for the application of tissue engineering technologies in the development of the elusive ideal vascular graft material.

Prevention of reperfusion injury in surgically induced gastric dilatation-volvulus in dogs.

Canine gastric dilatation-volvulus (GDV) is a naturally acquired condition of large-breed dogs primarily and is associated with high mortality. The clinical course suggests that reperfusion injury may be important in the pathogenesis of GDV. To evaluate the role of xanthine oxidase and iron-dependent lipid peroxidation (which are purported mechanisms of reperfusion injury) in the pathogenesis of GDV-related mortality, we created experimental GDV in 21 dogs. These dogs were then treated with either allopurinol (a xanthine oxidase inhibitor), U74006F (an experimental lipid peroxidation inhibitor), or saline solution (NaCl, 0.85%). Three of 8 dogs died in the allopurinol-treated group, none of 5 died in the U74006F-treated group, and 4 of 8 died in the saline solution-treated group. Tissue malondialdehyde concentration, a nonspecific indicator of lipid peroxidation, was significantly (P less than 0.05) greater in the duodenum, jejunum, colon, liver, and pancreas of the saline-solution treated and allopurinol-treated dogs than in the same tissues of the U74006F-treated dogs after surgical correction of the GDV (ie, during reperfusion), compared with malondialdehyde concentrations determined before inducing GDV. The results of this study support the concept that lipid peroxidation associated with reperfusion injury is important in the pathogenesis and high mortality of canine GDV. Furthermore, this lipid peroxidation and mortality may be preventable by appropriate and timely treatment.

Treatment of reperfusion injury in dogs with experimentally induced gastric dilatation-volvulus.

In dogs, gastric dilatation-volvulus (GDV) is characterized by cardiogenic shock, with resulting hypoperfusion. Treatment goals include reperfusion of transiently ischemic tissues, which indicates that reperfusion injury may be a factor in the physiopathogenesis of GDV. Recently, we obtained data that indicate that reperfusion injury may be involved in experimentally induced GDV. Using this GDV model, we evaluated mortality in 24 dogs of 4 equal groups, treated with deferoxamine (an iron chelator), dimethylsulfoxide (a free radical scavenger), a combination of the 2 drugs, or isotonic saline solution. All 6 dogs that were given deferoxamine survived; however, 3 dogs of the dimethylsulfoxide-treated group, 2 dogs of the combination-treated group, and 4 dogs of the saline-treated group died. Results of the study indicate that mortality associated with experimentally induced GDV is reduced by appropriate and timely pharmacologic intervention to prevent or attenuate reperfusion injury, and that deferoxamine may be more effective than dimethylsulfoxide.

Transsphenoidal hypophysectomy in the clinically normal dog.

Pituitary function and short-term clinical effects after transsphenoidal hypophysectomy were investigated in clinically normal dogs. In study I, 8 dogs were given polyionic fluids IV during the first 12 hours after surgery. In study II, 4 dogs were given polyionic fluids IV and glucocorticoid supplementation for 7 days. Pituitary function was assessed by evaluating basal ACTH concentrations and results of a growth hormone stimulation test before and 1 and 12 weeks after hypophysectomy, an ACTH stimulation test, a thyrotropin-releasing hormone-stimulation test, and a modified water deprivation/vasopressin response test before and 1, 4, 8, and 12 weeks after hypophysectomy. Gross and histologic evaluations of the surgery site, thyroid and adrenal glands, and skin were done at 12 weeks after surgery. Four dogs from study I died within 27 hours after hypophysectomy. Postmortem examinations of these dogs revealed liver and lung congestion compatible with circulatory collapse. None of the dogs in study II died. For the surviving dogs in both studies, diabetes insipidus developed immediately after hypophysectomy and resolved within 2 weeks. Hypernatremia also developed immediately after hypophysectomy and resolved by 1 week. Production of ACTH was evident at 1 and 12 weeks after hypophysectomy in all dogs, and results of ACTH stimulation tests after surgery were not notably different from results obtained before surgery. Results of thyrotropin-releasing hormone stimulation and growth hormone-stimulation tests supported the diagnosis of hypothyroidism and hyposomatotropism attributable to hypophysectomy. Histologic examination revealed thyroid atrophy, epidermal and dermal atrophy, and normal adrenal glands in all dogs and remnants of the hypophysis in 2 dogs from study I.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermittent open-mouth locking of the temporomandibular joint in a cat.

Impingement of a mandibular coronoid process on the ipsilateral zygomatic arch resulted in intermittent open-mouth locking of the temporomandibular joint in a 3-year-old male cat. Radiographic evaluation of the temporomandibular joints did not reveal abnormalities. Locking could not be recreated by manipulation of the mandible in the anesthetized cat, but the left coronoid process briefly contacted the left zygomatic arch. Excision of the rostroventral portion of the left zygomatic arch failed to stop the locking episodes; however, later excision of the rostroventral portion of the right zygomatic arch did prevent recurrence of locking.

Partial mandibulectomy for treatment of mandibular fractures in dogs: eight cases (1981-1984).

Partial mandibulectomy was performed in 8 dogs with open or infected mandibular fractures (3 second degree and 5 third degree) because of economic restriction, osteomyelitis, or severe bone and soft tissue injury. Six dogs ate voluntarily by the second day after surgery, and 2 dogs required pharyngostomy tube feeding for 2 to 6 days. Complications included oral wound dehiscence (3 dogs), shifting of the mandible toward the operated side (6 dogs), and drooping of the tongue (2 dogs). Slight malocclusion was of no consequence, and all dogs were eating normally at follow-up evaluations (10 days to 24 months; median, 13 months). Mandibular function was maintained in all dogs.

Intermittent open-mouth lower jaw locking in five dogs.

Intermittent open-mouth lower jaw locking was documented in 5 dogs. In contrast to what has been reported in other cases, pronounced radiographic abnormalities in the temporomandibular joints were not observed. In 4 of the dogs, locking episodes started at a later age (35 to 83.5 months) than had been reported by others (6 to 22 months). Duration and frequency of locking were variable. Lateral shifting of the jaw and lack of neurologic deficits indicated a temporomandibular joint abnormality. Excision of the rostroventral portion of the involved zygomatic arch prevented locking in all cases. This syndrome involves variable severity of temporomandibular joint dysplasia, which could account for the variable age of onset and random frequency of locking episodes.

Surgical excision of ectopic thyroid carcinoma involving the base of the tongue in dogs: three cases (1980-1987).

Localized thyroid carcinoma involving the base of the tongue was diagnosed in 3 dogs examined because of a midline cervical mass rostroventral to the larynx. These masses had been present for 4 to 12 months and were firm, nonsensitive, and fixed in position. One dog had progressive dysphagia and dyspnea. Masses were surgically excised together with the base of the tongue and portions of the hyoid apparatus. Severe dyspnea that developed immediately after surgery in 1 dog was managed by tracheostomy intubation for 4 days. Transient dysphagia developed in all dogs. Hydration was maintained by IV fluid administration until water and food of gruel consistency could be swallowed 1 to 6 days after surgery. Consistency of food was gradually thickened to normal, as swallowing improved 6 days to 2 months after surgery. One dog developed aspiration pneumonia that resolved after antimicrobial administration and improved swallowing that prevented further aspiration. After 9 months, 3 years, and 6 years, the dogs were clinically normal.

Acquired myasthenia gravis in a cat with thymoma.

A 4-year-old castrated Abyssinian cat was evaluated for profound neuromuscular weakness. Results of electromyography and repetitive nerve stimulation tests were normal. Thoracic radiography revealed a cranial mediastinal mass, which was excised and identified as a thymoma. Serum acetylcholine receptor antibodies were detected at high concentration, supporting a diagnosis of acquired myasthenia gravis. Clinical signs of disease responded to treatment with pyridostigmine and corticosteroids.

Acquired arteriovenous fistula secondary to castration in a dog.

A 6-year-old castrated male Basset Hound was examined because of a 1-year history of a pulsating mass in the right inguinal region. The pulsatile mass was diagnosed as an arteriovenous fistula by physical examination and angiography. Surgical exploration revealed that the right testicular artery and vein, the artery of the ductus deferens, and the cremasteric artery were involved in the fistula. The fistula was believed to have developed secondary to castration performed at 6 months of age. The mass and associated vessels were completely excised and signs of recurrence were not observed 13 months after surgery.

Comparison of survey radiography with ultrasonography and x-ray computed tomography for clinical staging of subcutaneous neoplasms in dogs.

A study of 26 dogs (examined consecutively) with infiltrative subcutaneous neoplasms (mastocytoma, n = 11; soft tissue sarcoma, n = 13; and adenocarcinoma, n = 2) was conducted. Dogs were evaluated by physical examination, survey radiography, ultrasonography (US), and x-ray computed tomography (CT) prior to surgical excision of the tumor. The purpose of the evaluation was to accurately define gross neoplastic margins before surgical excision and to determine whether a difference could be observed between routine clinical staging (physical examination and survey radiography) and more detailed clinical staging (US and CT imaging). The clinical stage of 5 of 26 neoplasms assessed by US and of 17 of 26 neoplasms assessed by CT was determined to be more advanced because of previously undetected neoplasia, greater neoplastic size, or greater tissue invasiveness. Preoperative imaging of infiltrative subcutaneous neoplasms, using US and CT, is highly recommended to accurately determine gross neoplastic margins.

Pancreatic abscess in dogs: six cases (1978-1986).

Pancreatic abscess was diagnosed by exploratory celiotomy in 6 dogs. The most common clinical signs included acute onset of lethargy (n = 5), anorexia (n = 6), vomiting (n = 5), and diarrhea (n = 2). Physical examination revealed pain response to abdominal palpation (n = 5), depression (n = 5), icterus (n = 3), fever (n = 3), and cranial abdominal mass (n = 2). Consistent preoperative clinicopathologic abnormalities included leukocytosis with left shift, observance of toxic neutrophils on the blood smear, hyperlipasemia, hyperamylasemia, hyperbilirubinemia, and increased serum alkaline phosphatase activity. In 5 of 6 dogs, abdominal radiography revealed increased soft tissue density in the cranial portion of the abdomen. Ultrasonography performed on 4 dogs confirmed pancreatic mass. In all dogs, exploratory celiotomy revealed a cavitary pancreatic mass that contained sterile, mucopurulent material. Histopathologic diagnoses included acute necrotizing or chronic-active pancreatitis and steatitis. Two dogs were euthanatized at the time of diagnosis, and the remaining 4 were treated by use of pancreatic debridement(s), open abdominal drainage, and intensive administration of fluids and antibiotics. One dog was euthanatized 4 days after surgery, because of progressive pancreatic abscessation. Three dogs recovered and were discharged.

Analysis of risk factors for gastric dilatation and dilatation-volvulus in dogs.

The Veterinary Medical Data Base was usd to conduct an epidemiologic study of gastric dilatation and dilatation-volvulus (GDV) to describe changes over time in frequency of canine hospital admissions, to identify risk factors, and to estimate their relative importance. Cases in this case-control study included 1,934 dogs with GDV that were admitted to 12 participating veterinary hospitals from 1980 to 1989. The controls were 3,868 dogs with other diagnoses that were randomly selected from the same hospitals. Frequency of GDV per 1,000 canine hospital admissions ranged from 2.9 to 6.8. The case fatality rate was 28.6 and 33.3% for gastric dilatation alone and for gastric dilatation with volvulus, respectively. Using logistic regression analysis, the odds ratio (OR) and its 95% confidence limits (95% CL) for GDV associated with purebred vs mixed-breed dogs were 2.5 and 2.1, 3.0, respectively. The risk of GDV was associated with increasing age (chi 2 = 305.6, P < 0.0001) and increasing weight (chi 2 = 627.8, P < 0.0001). Significant association of GDV risk with sex or neuter status was not found. The 5 breeds having at least 10 cases and 8 controls and with the highest risk of GDV were Great Dane (OR, 10.0; 95% CL, 6.4, 15.6), Weimaraner (OR, 4.6; 95% CL, 2.3, 9.2), Saint Bernard (OR, 4.2; 95% CL, 2.3, 7.4), Gordon Setter (OR, 4.1; 95% CL, 1.8, 9.3), and Irish Setter (OR, 3.5; 95% CL, 2.4, 5.0). The effect of increasing body weight on GDV risk was less than that of increasing ideal adult breed weight, determined by published breed standards.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical remodeling of small-intestine submucosa small-diameter vascular grafts--a preliminary report.

Small-intestine submucosa (SIS) is cell-free, 100-mu-thick collagen derived from the small intestine. It has been used as a vascular graft and has the highly desirable ability to be remodeled to become histologically indistinguishable from native adjacent artery. To date there has been limited reporting of its preimplantation and explant mechanical properties as a vascular graft. In this study, compliance, elastic modulus, and burst pressure were measured on preimplant-tested 5- and 8-mm SIS grafts and two 60-day remodeled grafts. Seven prefabricated grafts were implanted in the carotid (n = 7) in dogs, which were sacrificed after 55-63 days. The animals (n = 4) weighed from 22 to 27 kg. One dog received a unilateral carotid graft, and 3 dogs received bilateral carotid grafts. The fabrication technique employed hand-suturing with either nonresorbable or resorbable sutures. None of the grafts had a patency failure. Angiograms taken at 1 month and just before explantation showed uniform flow and no dilation. At the time of explantation, all carotid grafts were found to be encased in fibrous tissue. The grafts made with nonresorbable sutures showed thicker tissue growth at the suture line compared with those made with the resorbable sutures. Along the suture line, the grafts made with resorbable sutures exhibited a more natural color than those sutured with nonresorbable sutures. When the explanted carotid grafts were slit open, the lumen was white, shiny, and glistening. The grafts sutured with nonresorbable sutures exhibited small areas of fibrin and red blood cells when the suture was within the lumen. The resorbable-sutured grafts did not exhibit this response. The mean compliance (percent diameter increase for a pressure rise from 80 to 120 mm Hg) was on average 4.6% (range, 2.9%-8.6%) for the 5-mm preimplant-tested grafts. For the 8-mm preimplant-tested grafts, the increase in diameter for the same pressure rise was 8.7%, on average (range, 7.2% to 9.5%). For comparison, the small-diameter SIS graft at the time of implantation was about one half as compliant as the adjacent dog carotid artery, about 4 times more compliant than a typical vein graft, and more than 10 times more compliant than synthetic vascular grafts. The compliance measured on two 60-day carotid grafts was 10.5% and 7.2%, respectively. This is midway between the original compliance value and the compliance of a typical canine carotid artery (14%), indicating that mechanical remodeling occurred. The modulus of elasticity (E) increased exponentially with increasing pressure according to E = E0e alpha P, where E0 is the zero-pressure modulus and alpha is the exponent that describes the rate of increase in E with pressure; the unit of measure for variables E, E0, and P is g/cm2. The mean value for E0 was 4106 gm/cm2 (range, 1348-5601). The mean value for alpha was 0.0059 (range, 0.0028-0.0125). At 100 mm Hg, the mean value for E was 8.03 x 10(6) dynes/cm2 (range, 4.95-15.7 x 10(6)). For a 60-day SIS graft implant, the elastic modulus at 100 mm Hg decreased from a high value at implant time to twice that of a typical native canine carotid artery. The mean burst pressure for 5.5-mm grafts was 3517 mm Hg (range, 2069-4654). The burst pressure of the remodeled carotid grafts averaged 5660 mm Hg. The burst pressure for a typical carotid artery is about 5000 mm Hg. The results of this preliminary study complement those of previous SIS-vascular-graft studies and add a new factor, namely that the mechanical properties of the remodeled graft approach those of the vessel it replaces.

Post-anesthetic cortical blindness in cats: twenty cases.

The medical records of 20 cats with post-anesthetic cortical blindness were reviewed. Information collected included signalment and health status, reason for anesthesia, anesthetic protocols and adverse events, post-anesthetic visual and neurological abnormalities, clinical outcome, and risk factors. The vascular anatomy of the cat brain was reviewed by cadaver dissections. Thirteen cats were anaesthetised for dentistry, four for endoscopy, two for neutering procedures and one for urethral obstruction. A mouth gag was used in 16/20 cats. Three cats had had cardiac arrest, whereas in the remaining 17 cases, no specific cause of blindness was identified. Seventeen cats (85%) had neurological deficits in addition to blindness. Fourteen of 20 cats (70%) had documented recovery of vision, whereas four (20%) remained blind. Two cats (10%) were lost to follow up while still blind. Ten of 17 cats (59%) with neurological deficits had full recovery from neurological disease, two (12%) had mild persistent deficits and one (6%) was euthanased as it failed to recover. Four cats (23%) without documented resolution of neurological signs were lost to follow up. Mouth gags were identified as a potential risk factor for cerebral ischemia and blindness in cats.

Healing comparison of small intestine submucosa and ePTFE grafts in the canine carotid artery.

Continuing investigation of small-diameter vascular graft materials suggests that unacceptable graft complications continue and that the ideal material has not yet been found. We compared healing of xenogeneic small diameter grafts (3.5 to 5.0 mm diameter) made from porcine small intestine submucosa (SIS) implanted in the carotid artery to expanded polytetrafluorethylene (ePTFE) in the contralateral carotid in 8 dogs. Two dogs were sacrificed for graft evaluation at 7, 28, 90, and 180 days after surgery. Only one SIS graft was occluded at 28 days and the other 7 were patent. Six of 8 ePTFE grafts were occluded with thrombi. One was patent at 7 and one at 90 days. At 7 days post-implant, the luminal surface of the SIS graft was covered by a thick (30 microns), compact fibrin meshwork. By 28 days endothelial cells were seen completely covering the fibrin meshwork which stained for FVIII-related antigen. Smooth muscle cells were observed in the neo-intima. Most ePTFE grafts had fibrin on the luminal surface which formed fibrin thrombi with platelets and numerous red blood cells. Complete endothelial coverage of the ePTFE grafts was not observed by 180 days. There was not a pronounced neointima seen on the luminal surface of the graft. The vasa vasorum was present in the fibrous capsule surrounding the ePTFE graft, but it did not penetrate into the graft as seen in the SIS graft. At 90 days the SIS vascular graft had the histological appearance similar to a normal artery. The SIS graft potency and healing characteristics were superior to the synthetic ePTFE graft and warrant further investigation.

Surface modification with PEO-containing triblock copolymer for improved biocompatibility: in vitro and ex vivo studies.

Poly(ethylene oxide) (PEO) has been frequently used to modify biomaterial surfaces for improved biocompatibility. We have used PEO-polybutadiene-PEO triblock copolymer to graft PEO to biomaterials by gamma-irradiation for a total radiation dose of 1 Mrad. The molecular weight of PEO in the block copolymer was 5000. In vitro study showed that fibrinogen adsorption to Silastic, polyethylene, and glass was reduced by 70 to approximately 95% by PEO grafting. On the other hand, the reduction of fibrinogen adsorption was only 30% on expanded polytetrafluoroethylene (e-PTFE). In vitro platelet adhesion study showed that almost no platelets could adhere to PEO-coated Silastic, polyethylene, and glass, while numerous platelet aggregates were found on the ePTFE. The platelet adhesion in vitro corresponded to the fibrinogen adsorption. When the PEO-grafted surfaces were tested ex vivo using a series shunt in a canine model, the effect of the grafted PEO was not noticeable. Platelet deposition on ePTFE was reduced by PEO grafting from 8170 +/- 1030 to 5100 +/- 460 platelets 10(-3) microm2, but numerous thrombi were still present on the PEO-grafted surface. The numbers of platelets cumulated on Silastic, polyethylene, and glass were 100 +/- 80, 169 +/- 35, and 24 +/- 22 platelets 10(-3) microm2, respectively. This is about 35% reduction in platelet deposition by PEO grafting. While the numbers of deposited platelets were small, the decreases were not as large as those expected from the in vitro study. This may be due to a number of reasons which have to be clarified in future studies, but it appears that in vitro platelet adhesion and fibrinogen adsorption studies may not be a valuable predictor for the in vivo or ex vivo behavior of the PEO-grafted surfaces.