Laboratory Animal Management Dogs (1994) / Chapter Skim
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6 SPECIAL CONSIDERATIONS
6 SPECIAL CONSIDERATIONS
Pages 76-130
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From page 76... ...
delineate the proposed study, including a description of each of the following: · the purpose of the study; · the rationale for selecting dogs as the research subjects; · the breed, age, and sex of the dogs to be used; · the numbers of dogs in various groups of the protocol and the total number to be used; · experimental methods and manipulations; · experimental manipulations that will be performed repeatedly on an individual dog; 76
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From page 77... ...
Many protocols are subjected to extensive, external scientific review as part of the funding process; in such instances, the IACUC can be relatively assured of appropriate scientific review.
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. SPECIAL CARE FOR ANIMAL MODELS The remainder of this chapter deals with some common uses of laboratory dogs in which aspects of care vary from the general guidelines provided in previous chapters.
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The committee recognizes that not every research procedure and circumstance can be anticipated, and it assumes that sound professional judgment, good veterinary practices, and adherence to the spirit of this guide will prevail in unusual situations. The final subsection of this chapter introduces the reader to the technique of somatic cell gene therapy.
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From page 80... ...
Frequent checking and recording of body weights can help in assessing whether food intake is adequate. Changes in diet are sometimes dictated by the clinical diagnosis of disease (e.g., a low-protein diet for chronic, progressive renal disease and a low-sodium diet for chronic heart failure)
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From page 81... ...
Cardiovascular Diseases Congenital Heart Defects Clinical Features Dogs with hereditary cardiovascular malformations have been used to investigate the role of genetic and embryologic factors in the cause and pathogenesis of congenital heart defects, including hereditary patent ductus arteriosus, conotruncal defects (e.g., ventricular septal defect, tetralogy of Fallot, and persistent truncus arteriosus) , discrete subaortic stenosis, and pulmonary valve dysplasia.
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From page 82... ...
Polycythemia occurs in If ductus is large and pulmonary cyanotic dogs with a large vascular resistance is high, put- patent ductus arteriosus lmonary arterial pressure can (PDA) , pulmonary hyper exceed aortic pressure, and blood tension, and right to left will flow from right to left, sending blood flow through the PDA.
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Subaortic stenosis in Newfoundlands also appears to be monogenic with variable expression (Patterson, 1984~. Patent ductus arteriosus and pulmonary valve dysplasia are inherited in a non-Mendelian pattern.
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Induced Heart Defects Clinical Features Many animal models of cardiac disease are surgically induced in physiologically normal animals. Aims of the research protocol and humane considerations must often be carefully balanced to ensure that the maximal amount of information is derived from each animal.
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Some dogs achieve a stable, compensated postoperative condition; others undergoing the same procedure develop signs of acute heart failure immediately after surgery. Careful monitoring on the days after surgery is critical.
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From page 86... ...
Similarly, a dog with induced right ventricular pressure overload requires frequent monitoring because decreased coronary blood flow can lead to acute right-side heart failure (Fixler et al., 1973; Vlahakes et al., 1981~. Conversely, a stable model of left ventricular hypertrophy can be produced in 8-week-old pups by aortic banding, which causes a systolic pressure gradient of 15-20 mm Hg (O'Kane et al., 1973~.
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From page 87... ...
Generally, hypertension in dogs is induced by constricting the renal artery. The resulting reduction in renal perfusion causes systemic arterial pressure and renal arterial pressure distal to the constriction to rise enough to maintain renal function.
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From page 88... ...
A colony of spontaneously hypertensive dogs has been described (Bovee et al., 1986~. Husbandry and Veterinary Care Proper care of hypertensive dogs involves the following: · careful design and establishment of the hypertensive model to produce stable hypertension; routine evaluation of renal function; · regular and frequent monitoring of blood pressure · regular monitoring of the retinas; · appropriate treatment with antihypertensives when required; and .
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From page 89... ...
Renal failure caused by lowering blood pressure to below the renal autoregulatory range should be corrected by reducing the dose of the antihypertensive drug to a point that allows blood pressure to remain high enough to maintain renal function. Malignant hypertension can be treated with antihypertensives and reduced salt intake (Ross, 1989; see below)
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From page 90... ...
That is done in recognition that indirect methods can lead to a deviation of up to 10 mm EIg from true arterial pressure. Normal systolic blood pressure ranges from 112 to 142 mm Hg; normal diastolic pressure from 56 to 110 mg Hg.
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From page 91... ...
Routine care of hypertensive dogs must include a consideration of diet because both salt intake and protein intake will affect blood pressure and renal function. A high salt intake will exacerbate hypertension, and a high protein intake might accelerate the loss of renal function.
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Husbandry and Veterinary Care The extreme fragility of the skin must be considered in managing dogs with this syndrome. Affected dogs should be housed singly in smoothsurfaced pens of glass, concrete, or sheet steel.
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. ypoaarenocort~c~sm Pheochromocytoma Diabetes mellitus Gastrinoma Hyperparathyroidism Hypoparathyroidism Acromegaly Diabetes insipidus Hypopituitarism Hyperthyroidism Hypothyroidism Hyperlipidemia Hypoglycemia
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Frequent monitoring is mandatory for the successful management of dogs with diabetes mellitus. Daily measurements, before the first meal of the day and 6-12 hours later, are required to stabilize and control blood glucose in diabetic dogs.
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From page 95... ...
Some dogs find the product unpalatable, but it is generally accepted if it is mixed with canned food. Diabetic dogs can be maintained for long periods, but sequelae of diabetes mellitus including neuropathy, immune system compromise, and delayed healing do occur, and a shorter than normal life span should be expected.
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From page 96... ...
Calcium derangements. Although disorders of the parathyroid glands are usually suspected when hypercalcemia or hypocalcemia is present, the calcium abnormality is more often associated with other conditions, including pseudohyperparathyroidism, the most common cause of hypercalcemia (Feldman and Nelson, 1987~; hypoadrenocorticism; renal failure; bone lesions; and hypervitaminosis D
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From page 97... ...
Low factor VIII coagulant activity but normal or increased von Willebrand factor antigen concentrations; spontaneous bleeding diathesis of varied severity, depending on factor VIII activity; severely affected dogs often exhibit spontaneous hemarthroses and large joints. The most common severe inherited bleeding disease.
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From page 98... ...
Autosomal Persistent compensated hemolytic anemia with episodes of intravascular hemolysis, hemoglobinuria, and fever associated with stress or exercise; hemolytic crises follow hyperventilation-induced alkalemia; red cells of affected dogs are extremely alkaline and fragile in vitro. Found in English springer spaniels.
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From page 99... ...
Severely affected dogs should be housed individually because the risk of injury in playing with other dogs is substantial. To provide socialization, it is advisable to construct pens that allow visual contact between dogs; this can be achieved by building pens across an aisle from or perpendicular to each other.
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From page 100... ...
For example, basenjis with pyruvate kinase deficiency and recurring anemia must be closely monitored because of their increased susceptibility to infection or stress (Hall and Giger, 1992; Harvey, 19891; beagles with hereditary nonspherocytic hemolytic anemia must be closely monitored for episodes of hemolytic crisis (MaggioPrice et al., 1988~; and English springer spaniels with erythrocyte phospho
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Immunologic Diseases Primary Immunodeficiency and Autoimmune Diseases Clinical Features Immunodeficiency is characterized by failure to manifest a normal immune response when challenged by infectious agents or other substances
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, and severe combined immunodeficiency disease (Jezyk et al., 1989; Patterson et al., 1982~. Dogs with particular autoimmune diseases also suffer from immunodeficiency.
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From page 103... ...
; corneal ulcers associated with dry eyes; excessive dental caries; inflamed gums; signs associated with hypothyroidism, including tendency to obesity, tendency to seek warm places, bilaterally symmetrical hair loss, and changes in skin thickness Signs associated with hypothyroidism, including tendency to obesity, tendency to seek warm places, bilaterally symmetrical hair loss, and changes in skin thickness Signs associated with hypothyroidism, inappetence, megaloblastic anemia, and atrophic gastritis Increased susceptibility to bacterial infections Familial Mediterranean fever, characterized by fever, synovitis, and renal failure Small body stature; generalized increase in susceptibility to infectious diseases
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From page 104... ...
The susceptibility of immunodeficient dogs to infectious diseases is handled in various ways. All immunodeficient dogs can benefit from an environment that minimizes contact with canine pathogens; however, for some of these conditions (e.g., severe combined immunodeficiency)
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From page 105... ...
They also develop a membranoproliferative glomerulonephritis, which can be detected histologically by the age of 1 year (Cork et al., 19911. Affected dogs are normally active and appear well; the only clinical sign of this renal disease is proteinuria.
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From page 106... ...
The presence of proteinuria can be detected by testing for total-protein excretion in the urine over a 24-hour period, and renal biopsies can be used to evaluate the progression of renal disease. As dogs age, periodic measurements of total serum protein, albumin, and serum urea nitrogen can be used to identify dogs whose renal disease is becoming severe or those in which a nephrotic syndrome might lead to fluid accumulation in body cavities.
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From page 107... ...
Dogs might need to be housed individually in intensive-care facilities during early convalescence. Dogs undergoing bone marrow transplantation are profoundly immunodeficient for 200-300 days after lethal total-body irradiation and successful marrow engraftment, and they require intensive supportive care (Ladiges et al., 1990~.
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Affected dogs exhibit mainly necrologic signs. By the age of 12 months, affected dogs show subtle behavioral changes and might have an overextended posture.
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As the clinical signs progress, affected dogs should be handled carefully to prevent injury. They should be fed, exercised, and housed separately from normal dogs.
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The teeth of dogs that are fed a diet composed mainly of canned food require periodic scaling of tartar. MPS I-affected dogs are rarely maintained until they die naturally.
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, ~ Dystrophic dogs require high-calorie food that is easy to prehend and swallow because of the weakness of their tongue, jaw, and esophageal muscles. Canned food mixed with moistened dry food seems to constitute an adequate diet, but careful monitoring of food intake and weight is necessary.
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A Valentine, Department of Pathology, New York State College of Veterinary Medicine, Cornell University, Ithaca, N.Y., unpublished)
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Food and water intake should be monitored. Dogs should be weighed regularly to ensure that body weight is maintained.
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In the research setting, ocular problems that require special management techniques are visual impairment, painful ocular conditions, untoward sequelae of interfering with the eye's external protective mechanisms, and combinations of these conditions. Blindness.
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Common causes include anesthesia, radiation, surgical procedures, and drugs. Husbandry and Veterinary Care It is recommended that all experimental protocols involving dogs with ophthalmologic problems whether the problems are "natural" (i.e., genetic)
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From page 116... ...
Personnel responsible for the care and handling of dogs used in ophthalmologic research should suspect that ocular pain is present when there is periocular soiling or when there are behavioral changes, such as decreased activity, decreased appetite, increased yawning, and changes in vocalization patterns. Conditions associated with failure of the eye's external protective mechanisms.
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From page 117... ...
At doses of 2-4 Gy, signs become progressively more severe. Doses greater than 4 Gy cause destruction of bone marrow, loss of circulating blood cells, immunosuppression, increased tendency to bleed, and moderate to severe gastrointestinal toxicity.
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From page 118... ...
The distinctions between those emissions are important for providing care for laboratory animals. Alpha emissions from radionuclides, such as plutonium or americium, are generally high-energy emissions, but they travel very short distances in tissue.
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From page 119... ...
Animal health is of immediate concern only when large quantities of radionuclides are given. Husbandry and Veterinary Care Dogs exposed to external radiation can be housed in the usual manner (see Chapter 3~; however, it is critical that immunosuppressed dogs be protected from other dogs that might harbor pathogens.
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From page 120... ...
A number of target tissues for gene therapy have been used; this section will cover three of them. Hematopoietic Stem Cells In preparation for gene transfer, marrow is aspirated while the dog is under general anesthesia.
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From page 121... ...
. Studies have demonstrated that vascular smooth muscle cells are easily obtained, cultured, and genetically modified and replaced and provide a good target tissue for gene therapy that involves both secreted and nonsecreted proteins (Lim et al., 1991~.
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1991. Effect of the dopamine p-hydroxylase inhibitor, SK&F 102698, on blood pressure in the 1-kidney, 1clip hypertensive dog.
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Pp. 279308 in The Clinical Chemistry of Laboratory Animals, W
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Pp. 74-113 in Experimental Surgery and Physiology: Induced Animal Models of Human Disease, M
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Animal models of inherited hematologic disease.
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From page 126... ...
1991. Telemetric monitoring of laboratory animals: An advanced technique that has come of age.
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From page 127... ...
, Institute of Laboratory Animal Resources, Committee on Care and Use of Laboratory Animals.
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From page 128... ...
1986. Public Health Service Policy on Humane Care and Use of Laboratory Animals.
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From page 129... ...
1978. Canine systemic lupus erythematosus: Phenotypic expression of autoimmunity in a closed colony.
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From page 130... ...
Pp. 197-264 in Spontaneous Animal Models of Human Disease, vol.
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