Objective: To compare anesthetic, analgesic, and cardiorespiratory effects in dogs after IM administration of dexmedetomidine (7.5 μg/kg)–butorphanol (0.15 mg/kg)–tiletamine-zolazepam (3.0 mg/kg; DBTZ) or dexmedetomidine (15.0 μg/kg)-tramadol (3.0 mg/kg)-ketamine (3.0 mg/kg; DTrK) combinations. Animals: 6 healthy adult mixed-breed dogs. Procedures: Each dog received DBTZ and DTrK in a randomized, crossover-design study with a 5-day interval between treatments. Cardiorespiratory variables and duration and quality of sedation-anesthesia (assessed via auditory stimulation and sedation-anesthesia scoring) and analgesia (assessed via algometry and electrical nerve stimulation) were evaluated at predetermined intervals. Results: DBTZ or DTrK induced general anesthesia sufficient for endotracheal intubation ≤ 7 minutes after injection. Anesthetic quality and time from drug administration to standing recovery (131.5 vs 109.5 minutes after injection of DBTZ and DTrK, respectively) were similar between treatments. Duration of analgesia was significantly longer with DBTZ treatment, compared with DTrK treatment. Analgesic effects were significantly greater with DBTZ treatment than with DTrK treatment at several time points. Transient hypertension (mean arterial blood pressure > 135 mm Hg), bradycardia (heart rate < 60 beats/min), and hypoxemia (oxygen saturation < 90% via pulse oximetry) were detected during both treatments. Tidal volume decreased significantly from baseline with both treatments and was significantly lower after DBTZ administration, compared with DTrK, at several time points. Conclusions and Clinical Relevance: DBTZ or DTrK rapidly induced short-term anesthesia and analgesia in healthy dogs. Further research is needed to assess efficacy of these drug combinations for surgical anesthesia. Supplemental 100% oxygen should be provided when DBTZ or DTrK are used.

Large increases in systemic and pulmonary arterial pressures of exercising healthy ponies have been observed. Because exercise causes a considerable increase in PCV of ponies, we examined the effect of splenectomy on exercise-induced changes in systemic and pulmonary pressures. These pressures (taken with catheter-tip micromanometers) and indicator dilution cardiac output were determined on 9 healthy ponies that had undergone splenectomy 4 to 9 weeks before the study. Data obtained at rest and during submaximal (10.5 to 11.0 mph) and maximal (14 to 15 mph) exercise from these ponies were compared with similar data from clinically normal ponies. Following splenectomy, PCV increased by only 4 vol% during maximal exercise, but cardiac output of splenectomized ponies reached values similar to those of clinically normal ponies. Despite this similarity in cardiac output, the systemic and pulmonary arterial pressures of exercising splenectomized ponies increased to significantly lower levels than those in clinically normal ponies (P less than 0.01); total pulmonary vascular resistance and total peripheral resistance decreased to values significantly less than those in clinically normal ponies (P less than 0.01). Thus, it appears that increases in blood viscosity induced by increases in PCV may contribute substantially to the pulmonary and systemic hypertension of exercise in clinically normal ponies.

OBJECTIVE To investigate cardiac structural and functional changes by tissue Doppler imaging (TDI) and strain imaging in dogs with spontaneous type 1 diabetes mellitus. ANIMALS 30 client-owned dogs, of which 10 had normotensive type 1 diabetes mellitus and 20 were healthy. PROCEDURES All dogs underwent physical examination, laboratory analyses, standard echocardiography, and TDI. RESULTS On TDI and strain imaging, transmitral peak early diastolic velocity (E)-to-tissue Doppler–derived peak early diastolic velocity at basal segment (E') of septum ratio, E:lateral E’ ratio, and septal tissue Doppler–derived peak late diastolic velocity at basal segment (A') were significantly higher and the septal E':A’ ratio and lateral longitudinal strain were significantly lower for diabetic dogs than for control dogs. Furthermore, in diabetic dogs, serum glucose and fructosamine concentrations after a 12-hour period of food withholding were positively correlated with regional systolic functional variables (septal and lateral longitudinal strain) and left ventricular filling pressure indices (E:septal E’ and E:lateral E’ ratios) but were negatively correlated with diastolic functional variables (E:transmitral peak late diastolic velocity and septal and lateral E':A’ ratios). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that myocardial function in diabetic dogs may be altered before the development of clinical heart-associated signs and that the change may be more readily detected by TDI and strain imaging than by conventional echocardiography. In addition, findings indicated that hyperglycemia could have detrimental effects on myocardial function, independent of hypertension, other cardiac diseases, and left ventricular hypertrophy, in dogs with type 1 diabetes.

OBJECTIVE To investigate systemic changes following low-dosage prednisolone administration in dogs. ANIMALS 4 healthy purpose-bred adult male Beagles. PROCEDURES Dogs were administered prednisolone PO at a dosage of 2 mg/kg/d for 2 weeks, 1 mg/kg/d for 4 weeks, and 0.5 mg/kg/d for 3 weeks. Body weight, blood pressure, hepatic size and echogenicity, percentage of vacuolated hepatocytes, serum hepatic enzyme activities and glucose concentration, adrenal gland size, and pancreatic echogenicity were evaluated weekly for 9 weeks. RESULTS The only significant change identified was an increase in hepatic echogenicity, assessed by measuring liver-kidney contrast on ultrasonographic images. Increases in hepatic size and percentage of vacuolated hepatocytes were identified, but values did not differ from baseline values. Similarly, serum hepatic enzyme activities increased, but changes were mild and not significantly different from baseline values. Body weight, pancreatic echogenicity, and serum glucose concentration did not show noticeable changes. Mild systemic hypertension was seen, but blood pressure was not significantly different from the baseline value. Similarly, adrenal gland size steadily decreased during the first 6 weeks and increased again after the prednisolone dosage was decreased to 0.5 mg/kg/d. However, mean adrenal gland size was not significantly different from the baseline value at any time. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in dogs, administration of prednisolone at a low dosage was associated with minimal systemic effects.

OBJECTIVE To assess the possible impact of medetomidine on concentrations of alfaxalone in plasma, when coadministered as a constant rate infusion (CRI) to dogs, and to determine the possible impact of medetomidine on the cardiopulmonary effects of alfaxalone during CRI. ANIMALS 8 healthy adult Beagles. PROCEDURES 3 treatments were administered in a randomized crossover design as follows: 1 = saline (0.9% NaCl) solution injection, followed in 10 minutes by induction of anesthesia with alfaxalone (loading dose, 2.4 mg/kg; CRI, 3.6 mg/kg/h, for 60 minutes); 2 = medetomidine premedication (loading dose, 4.0 μg/kg; CRI, 4.0 μg/kg/h), followed by alfaxalone (as in treatment 1); and, 3 = medetomidine (as in treatment 2) and MK-467 (loading dose, 150 μg/kg; CRI, 120 μg/kg/h), followed by alfaxalone (as in treatment 1). The peripherally acting α2-adrenoceptor antagonist MK-467 was used to distinguish between the peripheral and central effects of medetomidine. Drugs were administered IV via cephalic catheters, and there was a minimum of 14 days between treatments. Cardiopulmonary parameters were measured for 70 minutes, and jugular venous blood samples were collected until 130 minutes after premedication. Drug concentrations in plasma were analyzed with liquid chromatography–tandem mass spectrometry. RESULTS The characteristic cardiovascular effects of medetomidine, such as bradycardia, hypertension, and reduction in cardiac index, were obtunded by MK-467. The concentrations of alfaxalone in plasma were significantly increased in the presence of medetomidine, indicative of impaired drug distribution and clearance. This was counteracted by MK-467. CONCLUSIONS AND CLINICAL RELEVANCE The alteration in alfaxalone clearance when coadministered with medetomidine may be attributed to the systemic vasoconstrictive and bradycardic effects of the α2-adrenoceptor agonist. This could be clinically important because the use of α2-adrenoceptor agonists may increase the risk of adverse effects if standard doses of alfaxalone are used.

This study investigated the effects of onion juice on the serum lipid components and blood pressure in obese rats fed high fat diets. Thirty-nine of Sprague-Dawley rats were divided into six groups, and were treated for 8 weeks: (1) normal diet (ND); (2) high fat diet (HFD); (3) HFD for first 4 weeks and high fat diet with 40% onion juice for the last 4weeks (H-H+O); (4) HFD with 40% onion juice for 8 weeks (H+O); (5) HFD for first 4 weeks and ND for the last 4 weeks (H-N); (6) HFD for first 4 weeks and ND with 40% onion juice for the last 4 weeks (H-N+O). The rates of increasing body weight were reduced in H+O and H-H+O groups compared with HFD group. The levels of triglyceride, low density lipoprotein-cholesterol and total cholesterol in blood serum were significantly decreased in the H+O and H-H+O groups compared with the HFD group. Administration of onion reduced the size of adipocyte, steatosis, and serum hyperlipidemia in obese rats fed HFD. Moreover, the antihypertensive effects of onion were observed in obesity rat fed HFD. Overall results suggest that onion reduces the serum lipid components and improves hypertension in obese rat fed HFD.

Objective-To characterize structural changes in pulmonary vessels of dogs with dirofilariosis. Animals-8 dogs with dirofilariosis and 2 unaffected control dogs. Procedure-Pulmonary artery pressure was measured in affected dogs, and dogs then were euthanatized. Scanning electron microscopy was used to examine vascular corrosion casts of pulmonary vasculature. Tissue sections of pulmonary vasculature were evaluated by use of histologic examination. Results-Pulmonary artery pressure was higher in dogs with severely affected pulmonary vessels. In tissue sections, dilatation, as well as lesions in the tunica intima and proliferative lesions resulting in constriction or obstruction, were frequently observed in branches of the pulmonary artery. Numerous dilated bronchial arteries were observed around affected pulmonary arteries. Hyperplastic venous sphincters were observed in small pulmonary veins and venules. In corrosion casts, affected pulmonary lobar arteries had dilatation, pruning, abnormal tapering, constriction, and obstruction. In small arteries and arterioles, surface structures representing aneurisms and edema were seen. Bronchial arteries were well developed and extremely dilated, and they formed numerous anastomoses with pulmonary arteries at all levels, from the pulmonary trunk to peripheral vessels. Capillaries in the lungs were dilated with little structural change. Small pulmonary veins and venules had irregular annular constrictions that were caused by hyperplastic smooth muscle cells of venous sphincters. Conclusions and Clinical Relevance-Scanning electron microscopy of microvascular casts delineated links between the bronchial and pulmonary circulations in dogs with dirofilariosis. Results of scanning electron microscopy provided a structural explanation for the development of pulmonary circulatory disturbances and pulmonary hypertension in dogs affected by dirofilariosis.

The severity of pulmonary thromboembolism and pulmonary hypertension induced by heartworms dying after administration of 2 adulticides was evaluated. Because melarsomine dihydrochloride (RM340) has been shown to be more effective in killing Dirofilaria immitis (heartworms) than the traditional approved adulticide, thiacetarsamide, an attempt was made to determine whether this new adulticide induced more severe lung disease. Before adulticide treatment, 32 dogs with naturally acquired heartworm infections received physical examinations, semiquantitative antigen concentration tests, CBC, platelet counts, serum biochemistry analyses, arterial blood gas determinations, thoracic radiography, pulmonary arteriography, and pulmonary hemodynamic tests. Eight dogs with a low burden and 9 dogs with a high burden of heartworms were treated with thiacetarsamide, and 7 dogs with a low burden and 8 dogs with a high burden were treated with RM340. Except for the heartworm-burden test, tests were repeated at regular intervals during the first 7 weeks after treatment. None of the dogs coughed or had dyspnea after treatment. Six of 9 dogs with high worm burdens and 4 of 8 dogs with low worm burdens had surviving heartworms after thiacetarsamide treatment, in contrast to only 3 of 15 RM340-treated dogs. Differences between the 2 adulticide treatments were minimal as determined by thoracic radiography, pulmonary hemodynamic tests, clinical laboratory analyses, pulmonary arteriography, or necropsy. The RM340 treatment was a more effective adulticide, but it did not increase the severity of hypertension and thromboembolism.

Vascular medial thickening is a prominent finding in people and animals with refractory neonatal pulmonary hypertension. Smooth muscle cells are capable of 2 distinct growth responses in vivo: hypertrophy or hyperplasia. Hypertrophic smooth muscle cells may undergo DNA synthesis without cell division, leading to a polyploid state. To better understand the nature of smooth muscle cell growth in healthy and pulmonary hypertensive neonatal calves, we measured incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) and total DNA content in medial cells from control (pulmonary arterial pressure = 32 +/- 2 mm of Hg) and hypobaric hypoxia-exposed (pulmonary arterial pressure = 120 +/- 7 mm of Hg) calves. Labeling of medial cells with BrdUrd measured by flow cytometry was increased (P < 0.02) in pulmonary arteries of hypoxia-exposed calves (n = 5), compared with control calves (n = 5). Immunohistochemical localization of BrdUrd indicated that BrdUrd labeling of large elastic pulmonary arteries from hypoxia-exposed calves was increased almost exclusively in the outer half of the medial wall. Increased BrdUrd labeling of muscular pulmonary arteries from hypoxia exposed calves was observed in the arterial media and adventitia, and tended to exit in clusters. Analysis of DNA content by flow cytometry indicated a decrease (P < 0.05) in percentage of tetraploid medial cells in pulmonary arteries from hypoxia-exposed calves, compared with control calves. Bivariate analysis for BrdUrd labeling and DNA content of cells from the pulmonary arteries of hypoxia-exposed calves indicated a subpopulation of diploid cells with positive BrdUrd labeling, suggestive of DNA synthesis and subsequent cell division. Results are suggestive of smooth muscle cell hyperplasia in the vascular media of hypoxia-exposed calves.

To investigate the potential role of sympathetic nerves in preventing pronounced increases in cerebral blood flow, we evaluated the effects of abrupt hypertension on the cerebral circulation of newborn pigs with intact cerebral sympathetic innervation and after cerebral sympathetic denervation. Epinephrine infusion was used to induce abrupt increases in mean (+/- SEM) arterial pressure (innervated pigs, 62 +/- 3 mm of Hg to 115 +/- 3 mm of Hg; denervated pigs, 71 +/- 4 mm of Hg to 132 +/- 4 mm of Hg) that remained increased for the 3 minutes of the study. Abrupt hypertension increased blood flow to all brain regions. In denervated pigs, the increased flow to the cerebrum was prolonged, compared with that in pigs with intact sympathetic innervation. Differences between pigs of the innervated and denervated groups were not apparent, with respect to blood flow to any other region (caudate region, brain stem, cerebellum). In newborn pigs, sympathetic nerves may attenuate hypertension-induced increases in blood flow to the cerebrum, but do not appear to affect flow to the rest of the brain.