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Inotropic mechanisms of dopexamine hydrochloride in horses
1992
Muir, W.W. III.
Mechanisms responsible for the positive inotropic effects of dopexamine were investigated in 8 halothane-anesthetized horses. The hemodynamic effects of increasing infusions of dopexamine (5, 10, 15 microgram/kg of body weight/min) were determined before and after sequential administration of specific antagonists. Using glycopyrrolate and chlorisondamine, and atenolol and ICI 118,551, muscarinic and nicotinic ganglionic, and beta, and beta-adrenergic receptor blockade, respectively, was induced. Dopexamine infusions induced increase in heart rate, cardiac output, systolic and mean arterial blood pressure, and maximal rate of left ventricular pressure development (+dP/dt(max)). Right atrial pressure and systemic vascular resistance decreased. Parasympathetic and ganglionic blockade attenuated cardiac output, systolic and mean aortic blood pressures, and +dP/dt(max) responses to dopexamine infusion. Dopexamine-induced increase in heart rate was potentiated by parasympathetic and ganglionic blockade. beta-Adrenergic receptor blockade decreased heart rate, cardiac output, arterial blood pressure, and +dP/dt(max) from baseline values and markedly reduced the response to dopexamine infusion. beta-Adrenergic receptor blockade induced further decrease in hemodynamic variables from baseline values and completely abolished the cardiostimulatory effects of dopexamine on +dP/dt(max) These data indicate that baroreflex activity, beta- and beta 2-adrenergic receptor stimulation may be an important cause of dopexamine's positive inotropic effects in horses.
Mostrar más [+] Menos [-]Influence of furosemide on hemodynamic responses during exercise in horses
1992
Olsen, S.C. | Coyne, C.P. | Lowe, B.S. | Pelletier, N. | Raub, E.M. | Erickson, H.H.
Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced RAP and PAP during exercise in dose-dependent manner, but did not influence heart rate. Mean CAP was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only PAP was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence PCV or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in PCV and hemoglobin concentration were small in comparison with changes in RAP and PAP, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.
Mostrar más [+] Menos [-]Cardiopulmonary responses to experimentally induced gastric dilatation in isoflurane-anesthetized dogs
1992
Hodgson, D.S. | Dunlop, C.I. | Chapman, P.L. | Grandy, J.L.
Gastric dilatation was experimentally induced in 6 anesthetized dogs maintained with constant-dose isoflurane in oxygen. An intragastric balloon was used to distend the stomach with a constant 30 mm of Hg for 3.5 hours. The PaCO2, was maintained between 35 and 45 mm of Hg, using intermittent positive-pressure ventilation. Cardiopulmonary measurements prior to stomach distension (baseline) were compared with measurements taken during 0.1, 0.5, 1.0, 1.5, 2.5, and 3.5 hours of stomach distension by analyzing the change from baseline in a randomized-block analysis with each dog as a block. After distending the stomach, cardiac index increased (P < 0.01) from 1.5 to 3.5 hours. Stroke volume did not change, thus the increase in the, cardiac index was attributable to an increase in heart rate. During inflation, increases were observed in systemic arterial, pulmonary arterial, and right atrial pressure. Respiratory frequency was unchanged; however, to maintain PaCO2, constant, it was necessary to progressively increase peak airway pressure. Although PaO2, tended to decrease during gastric dilation, the dogs were never hypoxemic. These results indicate that when our methods are used to maintain a constant anesthetic dose of isoflurane in oxygen, an observed increase in cardiovascular performance is expected. This differs from other studies in anesthetized dogs that have shown reduction in cardiovascular performance following gastric dilatation.
Mostrar más [+] Menos [-]Effect of intravenous and aerosol administration of 5-hydroxytryptamine on pulmonary function values in healthy calves
1992
Desmecht, D.J.M. | Linden, A.S. | Rollin, F.A. | Amory, H. | Lekeux, P.M.
Effects of IV and aerosol administration of 5-hydroxytryptamine (5-HT) on ventilation, pulmonary mechanics values, pulmonary arterial pressure, and heart rate were investigated in healthy unsedated Friesian calves. Minute volume increased significantly, mainly because of an increase in respiratory rate. Except for total pulmonary resistance after bolus injection, continuous administration of 5-HT given by either route caused significant alterations of lung dynamic compliance and total pulmonary resistance, the former decreasing to one-fifth of its baseline value and the latter increasing twofold. Pulmonary arterial pressure increased significantly, whatever the speed or route of administration. Administration of a bolus did not affect heart rate, whereas continuous iv administration of 5-HT as well by perfusion or by aerosol resulted in sustained tachycardia. It was concluded that 5-HT induces reversible bronchoconstriction and pulmonary vasoconstriction in healthy unsedated calves, 5-HT-induced functional alterations depend on the speed of administration, and excess of 5-HT production or depression in uptake by the lungs during bovine respiratory tract diseases could contribute to pulmonary dysfunction.
Mostrar más [+] Menos [-]Effects of lactated Ringer solution and prednisolone sodium succinate on dogs with induced hemorrhagic shock
1992
Hankes, G.H. | Dillon, A.R. | Ravis, W.R.
Hemorrhagic shock was induced in nonsplenectomized dogs by removing 41% of their blood volume over a 15-minute period. Hemodynamic and metabolic variables were determined prior to and for 3 hours after completion of hemorrhage. One group of 5 dogs was not treated. After the 30-minute sample was collected, a second group of 5 dogs was given lactated Ringer solution (LRS) at 88 ml/kg of body weight, IV. A third group of 5 dogs was given LRS (88 ml/kg, IV) and prednisolone sodium succinate (11 mg/kg, IV) 30 minutes after hemorrhage. The IV administration of LRS was completed within 15 minutes. The glucocorticoid was administered as an IV bolus after 500 ml of LRS had been given. The large volume and administration of LRS significantly (P = 0.05) improved many of the hemodynamic and metabolic effects of acute hemorrhage and hemorrhagic shock. At one time or another during the 2.5-hour observation period after the initiation of treatment, mean arterial pressure, cardiac index, systemic vascular resistance, heart rate, respiratory rate, lactate, glucose, and arterial and venous blood gas values were significantly (P = 0.05) improved, compared with baseline values. The addition of prednisolone sodium succinate to the treatment regimen improved the effectiveness of LRS alone only in some dogs at random sampling times. Significant trends were not observed except, possibly, the improvement of venous pH and A-V pH and P(CO)2 differences.
Mostrar más [+] Menos [-]Analgesia and behavioral responses of dogs given oxymorphone-acepromazine and meperidine-acepromazine after methoxyflurane and halothane anesthesia
1992
Sawyer, D.C. | Rech, R.H. | Adams, T. | Durham, R.A. | Richter, M.A. | Striler, E.L.
This study was designed to test analgesia, duration, and cardiovascular changes induced by meperidine (MEP) and oxymorphone (OXY) following methoxyflurane (MOF) and halothane (HAL) anesthesia. Eight healthy dogs were given atropine and acepromazine, and anesthesia was induced with thiamylal and maintained with 1.5 minimal alveolar concentration of MOF or HAL for 1 hour during controlled ventilation. Eight treatments were given with each anesthetic: 3 with MEP (0.5, 1.0, and 2.0 mg/kg, IV), 3 with oxymorphone (OXY; 0.05, 0.1, and 0.2 mg/kg, IV), and 2 placebos with sterile water. Test drugs were given at the end of anesthesia when early signs of recovery were evident. Minimal threshold stimulus/response nociception was assessed by use of an inflatable soft plastic colonic balloon. Blood pressures and pulse rate were measured with a noninvasive monitor. Meperidine and OXY were found to be effective analgesics and could be reversed with naloxone. Intravenous administration of 2.0 mg of MEP/kg provided analgesia for 36 +/- 6 minutes and 39 +/- 15 minutes after MOF and HAL, respectively. In contrast, OXY was effective at all 3 doses with effects of IV administration of 0.2 mg of OXY/kg lasting 154 +/- 13 minutes and 152 +/- 12 minutes, after MOF and HAL, respectively. Analgesia could not be demonstrated after anesthesia for acepromazine, MOF, or HAL. Blood pressure was not changed by either anesthetic nor was it influenced by MEP or OXY. Pulse rate was significantly depressed by the higher doses of OXY following HAL, but was not changed by MEP following either anesthetic. This study demonstrated the longer duration of analgesia of OXY. In addition, we could not find that analgesia was provided by either MOF or HAL following recovery from anesthesia.
Mostrar más [+] Menos [-]Parasympathetic influence on the arrhythmogenicity of graded dobutamine infusions in halothane-anesthetized horses
1992
Light, G.S. | Hellyer, P.W. | Swanson, C.R.
We investigated the influence of parasympathetic tone on the arrhythmogenicity of graded dobutamine infusions in horses anesthetized under clinical conditions. Six horses were used in 9 trials. Two consecutive series of graded dobutamine infusions were given IV; each continuous graded dobutamine infusion was administered for 20 minutes. The dobutamine infusion dosage (5, 10, 15, and 20 microgram/kg of body weight/min) was increased at 5-minute intervals. Isovolumetric saline solution vehicle (v) or atropine (A; 0.04 mg(kg) was administered IV, or bilateral vagotomy (VG) was performed as a treatment before the second series of dobutamine infusions. Treatment was not administered prior to the first dobutamine infusion. Significant interaction between treatment and dosage of dobutamine infusion existed for differences from baseline for mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, heart rate, and cardiac index at dosages of 5 and 10 micrograms of dobutamine/kg/min, given IV and for heart rate at dosage of 15 micrograms of dobutamine/kg/min, given IV. Results for group-V horses were different from those for group-A and group-VG horses, but were not different between group-A and group-VG horses in all aforementioned cases, except for heart rate and cardiac index at dosage of 5 micrograms of dobutamine/kg/min, given IV. Normal sinus rhythm, second-degree atrioventricular block, and bradyarrhythmias predominated during low dobutamine infusion rates during the first infusion series (nontreated horses) and in group-V horses during the second infusion series. Only tachyarrhythmias were observed during the second infusion series in the horses of the A and VG groups. The modulating influence of parasympathetic nervous system activity on hemodynamics and development of arrhythmia was conspicuous during low dobutamine infusion rates. Significant differences were not observed in hemodynamic responses to dobutamine, with respect to parasympathetic influence at high dobutamine infusion rates.
Mostrar más [+] Menos [-]Plasma renin activity and aldosterone and vasopressin concentrations during incremental treadmill exercise in horses
1992
McKeever, K.H. | Hinchcliff, K.W. | Schmall, L.M. | Reed, S.M. | Lamb, D.R. | Muir, W.W. III.
Six untrained mares were subjected to incremental treadmill exercise to examine exercise-induced in plasma renin activity (PRA) and plasma aldosterone (ALDO) and plasma arginine vasopressin (AVP) concentrations. Plasma renin activity, ALDO and AVP concentrations, and heart rate (HR) were measured at each step of an incremental maximal exercise test. Mares ran up a 6 degrees slope on a treadmill set at an initial speed of 4 m/s. Speed was increased 1 m/s each minute until HR reached a plateau. Plasma obtained was stored at - 80 C and later was thawed, extracted, and assayed for PRA and ALDO and AVP values by use of radioimmunoassay. Exercise caused significant increase in HR from 40 +/- 2 beats/min (mean +/- SEM) at rest to 206 +/- 4 beats/min (HRmax) at speed of 9 m/s. Plasma renin activity increased from 1.9 + /- 1.0 ng/ml/h at rest to a peak of 5.2 +/- 1.0 ng/ml/h at 9 m/s, paralleling changes in HR. Up to treadmill speed of 9 m/s, strong linear correlations were obtained between exercise intensity (and duration) and HR (r = 0.87, P < 0.05) and PRA (r = 0.93, P < 0.05). Heart rate and PRA reached a plateau and did not increase when speed was increased from 9 to 10 m/s. Plasma ALDO concentration increased from 48 +/- 16 pg/ml at rest to 191 +/- 72 pg/ml at speed of 10 m/s. Linear relation was found between exercise intensity (and duration) and ALDO concentration (r = 0.97, P < 0.05). Plasma AVP concentration increased from 4.0 +/- 3.0 pg/ml at rest to 95 +/- 5.0 pg/ml at speed of 10 m/s. The relation between AVP concentration and exercise intensity (and duration) appeared to be curvilinear, and was described by an exponential function (r = 0.92, P < 0.05). These data indicate that PRA and ALDO and AVP concentrations increase in horses during progressive treadmill exercise.
Mostrar más [+] Menos [-]Effect of xylazine on the arrhythmogenic dose of epinephrine in thiamylal/halothane-anesthetized horses
1992
Gaynor, J.S. | Bednarski, R.M. | Muir, W.W. III.
The effect of xylazine on the arrhythmogenic dose of epinephrine (ADE) was studied in 9 horses. Anesthesia was induced by administration of guaifenesin (50 mg/kg of body weight, IV) followed by thiamylal (4 to 6 mg/kg, IV) and was maintained at 1 minimal alveolar concentration MAC) of halothane (0.89%). Base apex ECG and facial artery pressure were recorded. Epinephrine was infused in a sequence of arithmetically spaced increasing rates (initial rate 0.25 (Lg/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 microgram/kg/min at which at least 4 premature ventricular depolarizations occurred in a 15-second period. Xylazine (1.1 mg/kg, IV) was administered after the control ADE was determined. Xylazine did not significantly alter the ADE (control, 1.12 +/- 0.38 microgram/kg/min; xylazine, 1.21 +/- 0.46 microgram/kg/min). Blood pressure increased transiently for 8 minutes after xylazine administration. Baseline systolic and diastolic arterial pressures and heart rate were not significantly different from control baseline pressures and heart rate 15 minutes after xylazine administration. Blood pressure and heart rate increased significantly during control and xylazine ADE determinations. Significant differences in pH, PaO2, PaCO2, or base excess were not observed between baseline and ADE in the control or xylazine groups. One horse developed atrial fibrillation, and 2 horses developed ventricular fibrillation during ADE determinations.
Mostrar más [+] Menos [-]Potential use of simple manganese salts as antioxidant drugs in horses
1992
Singh, R.K. | Kooreman, K.M. | Babbs, C.F. | Fessler, J.F. | Salaris, S.C. | Pharm, J.
The scavenging of superoxide radicals by endogenous and therapeutically administered superoxide dismutases may prevent superoxide-mediated oxidative stress leading to lipid peroxidation, membrane lysis, and cell death in a wide variety of normal and pathologic states. Simple inorganic manganous salts such as MnCl2 also have superoxide dismutase-like activity and are extremely inexpensive, compared with enzymatic superoxide dismutase preparations. In this study, we explored the use of Mn salts as antioxidant drugs. We used the percentage of inhibition of nitroblue tetrazolium reduction by superoxide as a measure of the amount of superoxide dismutase-like activity. We found concentration-related increases in superoxide scavenging activity in simple buffer solutions upon addition of 1.25, 2.5, and 5.0 microM MnSO4. To determine whether Mn salts can inhibit oxidative damage in tissues, we used an in vitro model of lipid peroxidation in ischemic and reoxygenated rat liver slices. Concentrations of 10, 100, and 1000 micromoles MnCl2/L of buffer significantly decreased indicators of lipid peroxidation believed to be initiated by intracellular superoxide. We then determined the effectiveness of MnCl2 as a superoxide scavenger in conscious horses by measuring the superoxide scavenging ability of equine plasma before and during intravenous infusions of 1.0 L volumes of 0.9% saline solution containing 0, 12.5, or 25 mM MnCl2. Plasma Mn concentrations, which were determined by atomic absorption spectrophotometry, increased as a function of time and dose. Intravenously administered MnCl2 concomitantly produced dose-related increases in superoxide scavenging ability of equine plasma at 15, 30, 45, and 60 minutes after the onset of infusion, compared with preinfusion control values. Heart rate and blood pressure of the treated horses, which were monitored to measure toxicity of MnCl2, gradually increased in both treatment groups. Clinical adverse effects of MnCl2 administration included defecation, pawing, hyperexcitability, flank watching, and sweating. The results of this study indicate that simple Mn salts may scavenge superoxide radicals in vivo with minimal adverse reactions and at a trivial cost.
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