Effects of increasing infusion rates of dopamine, dobutamine, epinephrine, and phenylephrine in healthy anesthetized cats

OBJECTIVE: To determine the cardiopulmonary effects of increasing doses of dopamine, dobutamine, epinephrine, and phenylephrine and measure plasma concentrations of norepinephrine, epinephrine, and dopamine in cats anesthetized with isoflurane. ANIMALS: 6 healthy adult cats. PROCEDURES: Each cat was anesthetized with isoflurane (1.5 X minimum alveolar concentration) on 4 occasions. Cardiopulmonary measurements were obtained after a 30-minute stabilization period; 20 minutes after the start of each infusion dose; and 30, 60, and 90 minutes after the infusion was discontinued. Cats received 5 progressively increasing infusions of epinephrine or phenylephrine (0.125, 0.25, 0.5, 1, and 2 microg/kg/min) or dobutamine or dopamine (2.5, 5, 10, 15, and 20 microg/kg/min). The order of treatment was randomly allocated. Results-All 4 treatments increased oxygen delivery. Heart rate (HR) increased during administration of all drugs except phenylephrine, and mean arterial pressure increased during administration of all drugs except dobutamine. A progressive metabolic acidosis was detected, but whole-blood lactate concentration only increased during administration of epinephrine and dobutamine. Systemic vascular resistance index increased during administration of phenylephrine, decreased during administration of dobutamine, and remained unchanged during administration of dopamine and epinephrine. A positive inotropic effect was detected with all treatments. CONCLUSIONS AND CLINICAL RELEVANCE: During anesthesia in cats, administration of dopamine, dobutamine, and epinephrine may be useful for increasing cardiac output, with dopamine having the most useful effects. Administration of phenylephrine increased cardiac and systemic vascular resistance indexes with minimal effect on HR and may be useful for increasing mean arterial pressure without increasing HR.     

Cardiovascular effects of vasopressors in isoflurane-anesthetized dogs before and after hemorrhage

Exogenously administered vasopressors (sympathomimetics) were evaluated in isoflurane-anesthetized dogs to determine the effects of these drugs on cardiovascular function before and after hemorrhage. Six dogs were anesthetized with thiamylal sodium (20 mg/kg of body weight) and isoflurane (1.25 minimal alveolar concentration) in 100% oxygen. After instrumentation, cardiac output, systemic arterial blood pressure, heart rate (HR), left ventricular pressure, pulmonary arterial pressure, and an index of cardiac contractility (dP/dT) were measured. Stroke volume, cardiac index (CI), stroke index (SI), rate-pressure product, and systemic vascular resistance (SVR) were calculated. Epinephrine (0.1, 0.3, and 0.5 micrograms/kg/min [low, medium, and high doses, respectively]) and dobutamine (1, 5, and 10 micrograms/kg/min [low, medium, and high doses, respectively]) were infused. Methoxamine was given in a bolus of 0.22 mg/kg, IV. All measurements were taken at 2.5 minutes after infusion, and were repeated after removal of 40% of the estimated blood volume. Before hemorrhage, administration of high doses of dobutamine and medium and high doses of epinephrine were equally effective at increasing CI and SI. The dP/dT was increased to the greatest degree by administration of high doses of dobutamine. Administration of the low dose of dobutamine increased dP/dT, whereas administration of the low dose of epinephrine increased CI, HR, and SI, and decreased SVR. The HR and SVR were not increased by administration of any dose of dobutamine or of the medium and high doses of epinephrine. However, methoxamine increased SVR and decreased HR. Methoxamine decreased CI, SI, and dP/dT, but increased systemic arterial pressure to the same degree as that attributed to administration of high doses of dobutamine and epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of dopamine or dobutamine infusions on cardiovascular variables after rapid blood loss and volume replacement during isoflurane-induced anesthesia in dogs

OBJECTIVE: To determine the cardiovascular effects of dopamine and dobutamine infusions during nor-movolemia, hypovolemia (HV) through blood loss of 10 mL/kg (HV(10)), further loss to 25 mL/kg (HV(25)), and volume replacement (VR) in isoflurane-anesthetized dogs. ANIMALS: 7 healthy young dogs. PROCEDURES: Dogs were anesthetized with isoflurane 2 times (3 weeks apart). Cardiovascular measurements were obtained for each volume state. The cardiac index (CI) determined by the lithium dilution technique was compared with CI assessed by the arterial pulse contour technique. At each volume state, random treatment with dobutamine or dopamine was assessed (CI by the arterial pulse contour technique). Ten-minute treatments with 3 and 6 microg of dobutamine/kg/min or 7 and 14 microg of dopamine/kg/min (low and high doses, respectively) were administered sequentially. Differences from baseline were determined for volume, drug, and dose effects. RESULTS: Significant proportional changes in blood pressure (BP), stroke index (SI), and CI were evident with changes in volume state. Systemic vascular resistance (SVR) decreased after VR. Dobutamine induced little change in BP; increased heart rate (HR), SI, and CI; and decreased SVR (high dose). Dopamine increased BP and SI, did not change CI, and increased SVR (high dose). The arterial pulse contour technique underestimated changes in CI associated with volume changes. CONCLUSIONS AND CLINICAL RELEVANCE: Isoflurane eliminates clinically obvious compensatory increases in HR during HV. Dopamine is suitable for temporary management of blood loss in isoflurane-anesthetized dogs. Dobutamine increased CI without an associated improvement in BP. The arterial pulse contour monitor should be recalibrated when volume status changes.     

Effect of dobutamine in postperfusion cardiac failure in the dog.

The effect of dobutamine on cardiac function of dogs was investigated. Sixteen dogs were submitted to cardiopulmonary bypass. The aorta of each dog was cross-clamped for 1 hour; attempt was not made to perfuse the heart. After 1 hour, 8 of the 16 dogs were randomly selected and treated with dobutamine (5 mug/kg/min). The other 8 dogs were designated the control group and were given placebo. Postperfusion failure and death were used as end point criteria. Dogs given dobutamine responded remarkably well, with significantly decreased postperfusion low output syndrome. Evidence of cardiac function 5 minutes after the removal of the bypass was the criterion used to determine survival of the surgical cross-clamp procedure; however, this did not necessarily indicate survival of the dog. Of the 8 dogs given dobutamine, 6 (75%) survived the surgical cross-clamp, whereas of the 8 dogs not given dobutamine, 3 (37.5%) survived the surgical procedure. Seemingly, the effect of dobutamine is not mainly chronotropic, but is rather a direct aid to myocardial strength.     

The effects of pre-anesthetic administration of xylazine on the cardiovascular responses to dobutamine in halothane anaesthetized horses

Studies evaluating the effects of dobutamine in horses do not consistently report increases in cardiac output despite increases in arterial blood pressure. The concurrent administration of the α₂ agonist clonidine, in people, inhibited the chronotropic effects of dobutamine and increased left ventricular stroke work ( Zimpfer et al. 1982 ). Our study was performed to determine if pre‐medication with an α₂ agonist affects the response to dobutamine in anaesthetized horses. Eleven horses were anaesthetized on four separate occasions for one of four randomly assigned treatments; (I) no xylazine, no dobutamine (II) xylazine, no dobutamine (III) no xylazine, dobutamine, and (IV) xylazine, dobutamine. Horses received 0.02 mg kg^?1 of butorphanol IV 10 minutes prior to anesthetic induction. Two minutes prior to induction, groups II and IV received 0.5 mg kg^?1 of IV xylazine. Anaesthesia was induced with 6–7 mg kg^?1 of thiopental and maintained with halothane. End‐tidal halothane concentrations were maintained between 1.1 and 1.2% in groups I and III, and 0.9–1.0% for groups II and IV. Heart rate, cardiac output, right atrial pressure, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure were recorded 30 minutes after beginning halothane anaesthesia (T10). Cardiac output was estimated using Lithium dilution ( Linton et al. 2000 ). Baseline measurements were repeated twice, at 5‐minute intervals (T5 and T0). At time 0 (T0), an IV infusion of either saline (100 mL hour^?1) or dobutamine (0.001 mg kg^?1 minute^?1) was started and data recorded at 5‐minute intervals for 30 minutes (T5 – T30). Stroke volume and systemic vascular resistance (SVR) were calculated. Data were analysed using repeated measures anova (p < 0.01 significant) and Newman–Keuls for multiple comparisons. Cardiac output and stroke volume increased over time in groups III and IV. Cardiac index was higher in groups III and IV than in groups I and II from T10 until completion of the study. Estimates of cardiac index at T30 for groups I–IV were 45 ± 9, 46 ± 11, 71 ± 11, and 78 ± 19 mL kg^?1 minute^?1, respectively (mean ± SD). Stroke index was higher in groups III and IV than in groups I and II from T15 to T30. Values for stroke index at T30 for groups I–IV were 0.98 ± 0.19, 1.11 ± 0.18, 1.46 ± 0.21, 1.74 ± 0.33 mL kg^?1. Heart rate decreased from T10–T30 in groups I and II. Heart rate was greater in groups I and III than in groups II and IV at T5 and T0. Values for heart rate at T0 for groups I–IV were 48 ± 5, 42 ± 5, 50 ± 4, 43 ± 4 beats minute^?1. Systolic arterial pressure, DAP and MAP were higher in groups III and IV than in groups I and II from T5 to T30. There were no differences in SVR between groups. Dobutamine at 0.001 mg kg^?1 minute^?1 increased cardiac output, blood pressure, and stroke volume. Premedication with xylazine at 0.5 mg kg^?1 did not appear to affect the response to dobutamine.     

Cardiovascular effects of vasopressors in halothane-anesthetized dogs before and after hemorrhage

Exogenously administered vasopressors (sympathomimetics) were evaluated in halothane-anesthetized dogs to determine the effects of these drugs on cardiovascular function before and after hemorrhage. Six dogs were anesthetized with thiamylal sodium (20 mg/kg of body weight) and halothane (1.25 minimal alveolar concentration) in 100% oxygen. After instrumentation, cardiac output, systemic arterial blood pressure (SAP), heart rate (HR), left ventricular pressure, pulmonary arterial pressure, and an index of cardiac contractility (dP/dT) were measured. Stroke volume, cardiac index (CI), stroke index (SI), rate-pressure product, and systemic vascular resistance (SVR) were calculated. Epinephrine (0.1, 0.3, and 0.5 micrograms/kg/min [low, medium, and high doses, respectively]) and dobutamine (1, 5, and 10 micrograms/kg/min [low, medium, and high doses, respectively]) were infused. Methoxamine was given in a bolus of 0.22 mg/kg, IV. All measurements were taken at 2.5 minutes after infusion, and were repeated after removal of 40% of the estimated blood volume. Dobutamine administered at the low dose before hemorrhage increased SAP and dP/dT. At the high and medium dose, dobutamine significantly increased CI, dP/dT, and SAP, with no significant change in HR or SVR. The medium dose of epinephrine was the most effective dose of epinephrine at increasing key variables (CI, SI, dP/dT). The response of CI and SI to this dose was not significantly different from the changes seen with high-dose administration of dobutamine. The dP/dT was significantly lower with epinephrine than with dobutamine, and SVR and HR were unchanged with epinephrine, except at the low dose, which decreased SVR.     

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.     

Response of hypotensive dogs to dopamine hydrochloride and dobutamine hydrochloride during deep isoflurane anesthesia

OBJECTIVE: To evaluate the dose-related cardiovascular and urine output (UrO) effects of dopamine hydrochloride and dobutamine hydrochloride, administered individually and in combination at various ratios, and identify individual doses that achieve target mean arterial blood pressure (MAP; 70 mm Hg) and cardiac index (CI; 150 mL/kg/min) in dogs during deep isoflurane anesthesia. ANIMALS: 10 young clinically normal dogs. PROCEDURES: Following isoflurane equilibration at a baseline MAP of 50 mm Hg on 3 occasions, dogs randomly received IV administration of dopamine (3, 7, 10, 15, and 20 microg/kg/min), dobutamine (1, 2, 4, 6, and 8 microg/kg/min), and dopamine-dobutamine combinations (3.5:1, 3.5:4, 7:2, 14:1, and 14:4 microg/kg/min) in a crossover study. Selected cardiovascular and UrO effects were determined following 20-minute infusions at each dose. RESULTS: Dopamine caused significant dose-dependent responses and achieved target MAP and CI at 7 microg/kg/min; dobutamine at 2 microg/kg/min significantly affected only CI values. At any dose, dopamine significantly affected UrO, whereas dobutamine did not. Target MAP and CI values were achieved with a dopamine-dobutamine combination at 7:2 microg/kg/min; a dopamine-related dose response for MAP and dopamine- and dobutamine-related dose responses for CI were identified. Changes in UrO were associated with dopamine only. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized dogs, a guideline dose for dopamine of 7 microg/kg/min is suggested; dobutamine alone did not improve MAP. Data regarding cardiovascular and UrO effects indicated that the combination of dopamine and dobutamine did not provide greater benefit than use of dopamine alone in dogs.     

Effects of norepinephrine and a combined norepinephrine and dobutamine infusion on systemic hemodynamics and indices of renal function in normotensive neonatal thoroughbred foals

BACKGROUND: Norepinephrine is a potent vasopressor that increases arterial blood pressure but may have adverse effects on renal blood flow. The combination of norepinephrine and dobutamine may lead to improved renal perfusion compared to an infusion of norepinephrine alone. The effects of these drugs in the normotensive neonatal foal have not been reported. HYPOTHESIS: Norepinephrine increases arterial blood pressure. Adding dobutamine to a norepinephrine infusion will change the renal profile during the infusions without changing the arterial blood pressure. ANIMALS: Eight conscious Thoroughbred foals were used in this study. METHODS: Each foal received norepinephrine (0.1 microg/kg/min), combined norepinephrine (0.1 microg/kg/min) and dobutamine (5 microg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate, arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance, stroke volume, cardiac index, and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of sodium, potassium, and chloride were measured. RESULTS: Norepinephrine and a combined norepinephrine and dobutamine infusion increased arterial blood pressure and systemic vascular resistance and decreased heart rate and cardiac index as compared to saline. The combination resulted in higher arterial pressure than norepinephrine alone. There was no significant difference in urine output, creatinine clearance, or fractional excretion of electrolytes with either infusion as compared to saline. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that norepinephrine and a combined norepinephrine and dobutamine infusion cause unique hemodynamic effects without affecting indices of renal function, and this effect warrants further investigation.     

Effects of glycopyrrolate on cardiorespiratory function in horses anesthetized with halothane and xylazine

OBJECTIVE: To evaluate cardiopulmonary effects of glycopyrrolate in horses anesthetized with halothane and xylazine. ANIMALS: 6 horses. PROCEDURE: Horses were allocated to 2 treatment groups in a randomized complete block design. Anesthesia was maintained in mechanically ventilated horses by administration of halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, i.v.). Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of glycopyrrolate or saline (0.9% NaCl) solution. Glycopyrrolate (2.5 microg/kg, i.v.) was administered at 10-minute intervals until heart rate (HR) increased at least 30% above baseline or a maximum cumulative dose of 7.5 microg/kg had been injected. Recovery characteristics and intestinal auscultation scores were evaluated for 24 hours after the end of anesthesia. RESULTS: Cumulative dose of glycopyrrolate administered to 5 horses was 5 microg/kg, whereas 1 horse received 7.5 microg/kg. The positive chronotropic effects of glycopyrrolate were accompanied by an increase in cardiac output, arterial blood pressure, and tissue oxygen delivery. Whereas HR increased by 53% above baseline values at 20 minutes after the last glycopyrrolate injection, cardiac output and mean arterial pressure increased by 38% and 31%, respectively. Glycopyrrolate administration was associated with impaction of the large colon in 1 horse and low intestinal auscultation scores lasting 24 hours in 3 horses. CONCLUSIONS AND CLINICAL RELEVANCE: The positive chronotropic effects of glycopyrrolate resulted in improvement of hemodynamic function in horses anesthetized with halothane and xylazine. However, prolonged intestinal stasis and colic may limit its use during anesthesia.     

Effects of dobutamine on cardiac index and arterial blood pressure in isoflurane-anaesthetized horses under clinical conditions

Volatile agent-induced hypotension may contribute to anaesthetic-related morbidity and mortality in horses. Dobutamine is commonly used to support arterial blood pressure (ABP) but little is known about its cardiovascular effects under clinical conditions. The aim of this clinical study was to elucidate the relationship between cardiovascular function and dobutamine infusion in isoflurane-anaesthetized horses. Forty-four horses anaesthetized for a variety of surgical procedures were studied. Premedication with acepromazine, methadone and detomidine was followed by induction of anaesthesia with ketamine and midazolam. Anaesthesia was maintained with isoflurane vaporized in oxygen. Routine anaesthetic monitoring was applied and cardiac output was measured by lithium dilution. Dobutamine was infused to maintain mean ABP above 70 mmHg. The relationship between dobutamine infusion rate, heart rate (HR), ABP and cardiac index was investigated immediately prior to ( T ₀) and 15 min ( T ₁) after dobutamine infusion started, followed at 30 min intervals ( T ₂, etc.). Arterial blood pressure increased significantly after dobutamine infusion started, HR and cardiac index increased significantly only with dobutamine infusion in combination with surgical stimulus. Although isoflurane decreases blood pressure mainly by vasodilation, dobutamine is an effective treatment for hypotension under clinical conditions in isoflurane-anaesthetized horses. The effect of dobutamine is not directly proportional to dose and surgical stimulus probably contributes to the cardiovascular improvement.     

Evaluation of Echocardiographic Parameters During Increasing Infusion Rates of Dobutamine in Isoflurane-Anesthetized Horses

The purpose of this study was to evaluate changes in echocardiographic parameters during increasing infusion rates of dobutamine in isoflurane-anesthetized horses and to compare our results with those of previous studies. Six Standardbred female healthy horses were included in this study. All animals were anesthetized and infused with dobutamine at different rates. mean arterial pressure (MAP), heart rate (HR), and some echocardiographic measurements were recorded. Statistical analysis was applied. Under basal conditions (time 0 [T0]), HR ranged between 32 and 42 beats per minute (bpm), and MAP was between 39 and 63 mm Hg. MAP increased significantly from T0 compared with values at T2, T2, and T3 in a dose-dependent manner, while HR increased significantly only at T3 if compared to the other measuring times. Left ventricular internal diameter during diastole (LVDs) decreased significantly in a dose-dependent manner, with increasing of the infusion rate of dobutamine. Interventricular septal dimension during diastole (IVSs) increased significantly, and end-systole left ventricular volumes (LVVols) decreased significantly at T2 and T3 compared to T1. Ejection fraction (%) increased significantly between T0 and T1, T2, and T3. Cardiac output increased significantly only at the higher dosage (T3 vs. others) of dobutamine, but cardiac power output was enhanced significantly at T2 versus that at T0 and T1 and at T3 versus all the previous measurements. Arrhythmias were diagnosed in 5 of 6 (83.3%). In this study, the increase of MAP was found to be dose-dependent, according with literature. The HR and MAP values registered at T0 were comparable to previous results obtained both in anesthetized and conscious horses, while at T1, T2, and T3, HR and MAP values were similar only too those reported in anesthetized horses. IVSs increased and LVDs decreased significantly with the increment of dobutamine infusion rate. These findings suggest that dobutamine, even at low infusion rates, induces an enhancement in cardiac systolic function. The dose-dependent increase of IVSs and decrease of LVDs measurements are in line with those reported for dobutamine administered in conscious horses but with lower values. The LVVols dose-dependent reduction obtained in this study is in line with that in other reports, but both LVold and LVVols values after dobutamine infusion at different dosages are lower if compared to previous studies. The low LVol values and the wide standard deviation have influenced consequently the derived indices values (stroke volume [SV], EF, cardiac output [CO]). In the present study, SV did not significantly increase during dobutamine infusion. These results disagree with those reported by others. The increment of CO might be due mainly to the enhanced HR rather than to the weak changes of SV. Cardiac power output increased significantly from the 5 mcg/kg/min dosage in a dose-dependent manner, as reported by others.     

Hemodynamic Effects of Atropine, Dobutamine, Nitroprusside, Phenylephrine, and Propranolol in Conscious Horses

The authors investigated the cardiovascular effects of low doses of nitroprusside, dobutamine, and phenylephrine and a beta-adrenergic blocking dose of propranolol in conscious, healthy horses with and without prior atropine administration. A parasympathetic blocking dose of atropine produced significant increases in heart rate and arterial pressures, and decreased stroke volume, ejection fraction, pulse pressure, and right-ventricular end-diastolic pressure and volume. Cardiac output was not changed by atropine administration. Nitroprusside reduced arterial pressures to a greater extent in atropinized horses but increased heart rate in both atropinized and non-atropinized horses. Dobutamine increased mean arterial pressure in both non-atropinized and atropinized horses but increased heart rate, diastolic arterial pressure, and systemic vascular resistance only in atropinized horses. Propranolol did not affect any of the hemodynamic variables that were measured. Phenylephrine, in the presence of beta-adrenergic blockade, increased mean arterial pressure and reduced cardiac output. This study showed that low doses of nitroprusside, dobutamine, and phenylephrine produce significant hemodynamic effects in conscious, healthy horses and that these effects are modified by prevailing parasympathetic tone.     

Effects of dopamine, dobutamine, amrinone and milrinone on regional blood flow in isoflurane anesthetized dogs

The effects of cyclic AMP increasing cardiotonics (dopamine, dobutamine, amrinone and milrinone) on the blood flow in most organs were compared using colored microsphere technique in isoflurane-anesthetized dogs. Dopamine increased blood flow in ventricular myocardium. Furthermore dopamine induced the increase in blood flow in intestine and kidney at low to middle dose, but not at high dose. Dobutamine induced the highest increase in blood flow in ventricular myocardium and skeletal muscle among the drugs evaluated at middle and high doses. Amrinone and milrinone increased blood flow in ventricular myocardium almost same with catecholamines, and milrinone decreased vascular resistance moderately in most other organs. Milrinone might be more useful than catecholamines for improvement of congestive heart failure or peripheral circulatory failure accompanied with exceeded vasoconstriction.     

Cardiovascular and renal effects of carvedilol in dogs with heart failure

To determine the acute effects of carvedilol (beta-blocker) on cardiovascular and renal function and its pharmacokinetics in dogs. Fifteen mature mongrel dogs (7-15 kg) of both sexes were used in these experiments. Eight dogs served as controls, and seven dogs served as iatrogenic mitral regurgitation (MR) experimental animals. Carvedilol (0.2, 0.4, and 0.8 mg/kg, P.O.) was administered, and the blood carvedilol concentration was analyzed by reverse-phase high-performance liquid chromatography. The response to isoproterenol or phenylephrine was also evaluated. Isoproterenol (0.025 microg/kg/min) was infused via the saphenous vein for 5 min, and phenylephrine (5 microg/kg) was injected with carvedilol (0.2, 0.4 mg/kg) or placebo for 4 days. The heart rate and arterial blood pressure were measured, and LV fractional shortening was measured by echocardiography. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate. Carvedilol (0.2 mg/kg) decreased the heart rate, whereas renal function, arterial blood pressure, and left ventricular contractile function were not affected. Carvedilol (0.4 mg/kg) decreased heart rate, blood pressure, and renal function. The tachycardic response to isoproterenol was significantly diminished for 36 hr by 0.4 mg/kg carvedilol. Carvedilol 0.2 mg/kg inhibited this effect for 24 hr. Thus, it is necessary to titrate the dosage of carvedilol, it should be initiated at less than 0.2 mg/kg and titrated up to 0.4 mg/kg for heart failure dogs.     

Comparison of arterial pressure waveform analysis with the lithium dilution technique to monitor cardiac output in anesthetized dogs

OBJECTIVE: To assess agreement between arterial pressure waveform-derived cardiac output (PCO) and lithium dilution cardiac output (LiDCO) systems in measurements of various levels of cardiac output (CO) induced by changes in anesthetic depth and administration of inotropic drugs in dogs. ANIMALS: 6 healthy dogs. PROCEDURE: Dogs were anesthetized on 2 occasions separated by at least 5 days. Inotropic drug administration (dopamine or dobutamine) was randomly assigned in a crossover manner. Following initial calibration of PCO measurements with a LiDCO measurement, 4 randomly assigned treatments were administered to vary CO; subsequently, concurrent pairs of PCO and LiDCO measurements were obtained. Treatments included a light plane of anesthesia, deep plane of anesthesia, continuous infusion of an inotropic drug (rate adjusted to achieve a mean arterial pressure of 65 to 80 mm Hg), and continuous infusion of an inotropic drug (7 microg/kg/min). RESULTS: Significant differences in PCO and LiDCO measurements were found during deep planes of anesthesia and with dopamine infusions but not during the light plane of anesthesia or with dobutamine infusions. The PCO system provided higher CO measurements than the LiDCO system during deep planes of anesthesia but lower CO measurements during dopamine infusions. CONCLUSIONS AND CLINICAL RELEVANCE: The PCO system tracked changes in CO in a similar direction as the LiDCO system. The PCO system provided better agreement with LiDCO measurements over time when hemodynamic conditions were similar to those during initial calibration. Recalibration of the PCO system is recommended when hemodynamic conditions or pressure waveforms are altered appreciably.     

Initial Experience with Norepinephrine Infusion in Hypotensive Critically III Foals

Seven critically ill foals that continued to be hypotensive despite fluid resuscitation and the infusion of dobutamine and/or dopamine were treated with an infusion of norepinephrine (noradrenaline). The norepinephrine was administered concurrently with dobutamine, and the combination therapy was titrated by use of indirect mean arterial pressure measurements. The highest dose of norepinephrine used was 1.5 mcg/kg/min. In six foals the administration of norepinephrine was associated with an increase in blood pressure. In one foal the mean arterial pressure did not increase in response to the doses of norepinephrine administered. All of the foals experienced an increase in urine output coincident with the start of the norepinephrine infusion. Three of the foal survived to hospital discharge.     

Pharmacodynamics of carvedilol in conscious, healthy dogs

The purpose of the study reported here was to determine the magnitude and duration of beta-blocking efficacy, determine an effective dose and dosing interval, and document safety and tolerability of carvedilol given orally in clinically normal dogs. Pharmacodynamic data were evaluated in conscious, unrestrained, healthy hound dogs at baseline and after long-term oral administration of carvedilol (1.5 mg/kg of body weight PO q12h for >5 days). At baseline, heart rate (HR) and blood pressure (BP) data were collected continuously for 24 hours, and complete echocardiography was performed. This protocol was repeated after long-term oral carvedilol administration. Additionally, isoproterenol was administered to evaluate the magnitude and duration of the nonselective beta-blocking efficacy of carvedilol. An isoproterenol challenge was performed 0.75, 1.5, 2.25, 4, 6, 12, and 24 hours after carvedilol administration, with echocardiography being performed once at 2 hours. Plasma samples were obtained prior to each challenge time point for determination of plasma carvedilol concentration. Time series regression analysis indicated no difference between baseline and carvedilol-induced HR or BP trend lines in 6 of 8 dogs. In 2 of 8 dogs, HR, after long-term carvedilol administration, was reduced. Carvedilol attenuated isoproterenol-induced changes in HR by 54-76% through 12 hours and by 30% at 24 hours. The BP changes were attenuated by 80-100% through 12 hours. These data suggest that carvedilol (1.5 mg/kg PO q12h) in healthy, conscious dogs confers nonselective beta blockade for 12 hours, with minimal effects on resting HR, BP, and echocardiographic variables. Additionally, the magnitude of beta blockade correlated strongly to peak plasma carvedilol concentration, suggesting that therapeutic drug monitoring may be clinically useful.     

Catecholamine infusion in vagotomized dogs during thiamylal-halothane and pentobarbital anesthesia

The cardiac arrhythmogenic infusion rate of epinephrine, dopamine, and dobutamine in vagotomized dogs was determined during thiamylal-halothane and pentobarbital anesthesia. Epinephrine, dopamine, and dobutamine were administered until 4 or more ventricular arrhythmias on duplicated trials were produced or until a predetermined maximum infusion rate was attained. The mean ventricular arrhythmogenic infusion rates (micrograms X kg-1 X min-1) during thiamylal-halothane anesthesia were: epinephrine, 0.57 +/- 0.24; dopamine, 23.7 +/- 8.26; and dobutamine, 10.21 +/- 3.54. Few arrhythmias were produced at the maximum administered infusion rate during pentobarbital anesthesia (2 of 6 with epinephrine, 3 of 6 with dopamine, and 0 of 6 administered dobutamine). Heart rate and blood pressure increased progressively with increasing infusion rates for all 3 catecholamines during thiamylal-halothane anesthesia. Heart rate and blood pressure changes were similar during pentobarbital anesthesia except for blood pressure changes during dobutamine infusion.     

Effects of dobutamine on cardiovascular function and oxygen delivery in standing horses

Dobutamine is routinely used to improve cardiovascular function in anaesthetized horses. However, dobutamine in conscious horses is insufficiently investigated. Ten research horses that were already instrumented for a preceding trial were included into the study. Cardiovascular variables were recorded and blood samples taken after instrumentation (Baseline), before starting dobutamine and after 10 min of dobutamine infusion (2 µg kg⁻¹ min⁻¹). A significant increase in systemic blood pressure, mean pulmonary artery pressure and right atrial pressure, and a decrease in heart rate were observed with dobutamine compared with baseline measurements. Arterial and mixed venous haemoglobin and oxygen content, as well as mixed venous partial pressure of oxygen increased. No significant changes in cardiac output, stroke volume, systemic vascular resistance, arterial partial pressure of oxygen, or oxygen consumption, delivery and extraction ratio were detected. Concluding, dobutamine increased systemic blood pressure without detectable changes in stroke volume, cardiac output or systemic vascular resistance in conscious horses.