首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 31 毫秒
1.
Moxifloxacin has been shown to induce QT prolongation in both clinical and preclinical models. However, the ability to observe this effect at clinically relevant concentration in normal conscious dogs has not been reported. The purpose of this study was to investigate the effects of moxifloxacin on the QT interval in conscious, healthy dogs. Four male mongrel dogs were chronically instrumented for the measurement of arterial blood pressure, left ventricular blood pressure, cardiac output, electrocardiograms (ECGs), and body temperature. Animals were administered a 1-h i.v. infusion of moxifloxacin once per day via a catheter in the cephalic vein. Each dog received all doses (0, 1, 10, 25 and 50 mg/kg) in an escalating fashion. Moxifloxacin caused a statistically significant increase in arterial blood pressure at 50 mg/kg. A dose-response effect on QT and QTc prolongation was observed. A statistically significant prolongation in the QT interval was observed at 10, 25 and 50 mg/kg and a prolongation of QTc was observed at 25 and 50 mg/kg. These effects occurred at clinically relevant plasma concentrations. This study demonstrate that a study design with four dogs was sensitive enough to measure moxifloxacin-induced QT prolongation at clinically relevant plasma concentrations.  相似文献   

2.
OBJECTIVE: To evaluate cardiac electrical function in dogs with tick toxicity. DESIGN: A prospective clinical investigation of 39 client-owned dogs treated for naturally occurring tick toxicity. PROCEDURE: An ECG was performed on each dog on several occasions; at admission to hospital with tick toxicity, 24 h later, at discharge from hospital when clinically normal and approximately 12 months later. RESULTS: The mean QT interval corrected for heart rate (QTc) was prolonged at admission, 24 h and at discharge compared to the QTc measured 12 months later. T wave morphology was altered in dogs at admission. All other parameters were within normal limits. CONCLUSIONS: The prolonged QTc interval and altered T wave morphology of dogs with tick toxicity reflects delayed cardiac repolarisation and is comparable with long QT syndrome (LQTS) in people who are predisposed to polymorphic ventricular tachycardia and sudden death. Resolution of ECG changes lagged behind clinical recovery.  相似文献   

3.
Comparison of the QT interval and corrected QT interval values that were calculated by the methods of Bazett (QTc1) and Fridericia (QTc2) were made between dogs with or without cardiac diseases to determine the influence of the QT interval on canine heart failure. Upon comparison of the measured values on ECG between the cardiac disease and non-cardiac disease groups, it was observed that the heart rate(HR) was significantly higher in the cardiac disease group than in the non-cardiac disease group, although the QT interval was similar in the two groups. The QTc1 and QTc2 were significantly longer in the cardiac disease group than in the non-cardiac disease group. With the progression of the New York Heart Association Class, the HR tended to increase. The QTc1 and QTc2 became significantly prolonged with the progression of heart failure. Nevertheless, because Bazett's correction formula is known to overcorrect when the HR is high, it was considered that the QTc1 was actually overcorrected by high HR with the progression of heart failure. The QTc2, on the other hand, was only slightly influenced by HR, suggesting that the prolongation was due to the progression of heart failure. These results suggest that the prolongation of QTc2 in cardiac disease reflects the substantial prolongation of the QT interval without the influence of HR. It is suggested that the QTc2 could be a useful parameter for assessing the degree of heart failure in dogs with cardiac disease.  相似文献   

4.
The characteristics of ECG changes with representative antiarrhythmic drugs; procainamide (PA) (class Ia), lidocaine (LC) (class Ib), propranolol (PN) (class II), and verapamil (VP) (class IV) were investigated in adult rats. Action potential (AP) was also recorded from myocardial cells during electrical stimuli with frequencies of 1-5 Hz. All the four drugs produced ECG abnormalities which contained AV and SA blocks at middle and high dose levels. Three drugs except VP induced a prolongation of QRS complex and notched QRS at low or middle dose level. As compared such effects with those in dogs and humans, some differences were noted as follows: (1) a dose-dependent prolongation of QT interval by LC and PN, and (2) a shortening of RR interval by VP at the dose of 0.6 mg/kg or less. LC and PN elongated the QT interval in the unipolar precordial chest lead ECGs at right anterior chest positions. These two drugs did not affect the duration of AP (APD90), whereas maximum upstroke velocity (Vmax) decreased. These results suggest that the prolongation of QT interval with LC and PN was due to a delay in local ventricular conduction time, especially on the right ventricle. The shortening of RR interval by VP was clearly blocked by the pretreatment with PN, indicating that this shortening reflected the sympathetic nervous reflex presumably due to the peripheral vasodilation effect of VP.  相似文献   

5.
We previously reported that D0870 induced QT prolongation and sudden death due to torsades de pointes (TdP) in dogs and that catecholamines played an important part in the development of the sudden death. In the present study, we analyzed in detail the ambulatory electrocardiographic recordings obtained from the just-mentioned study to elucidate the mechanism of the onset of TdPs and conducted an in vitro study using isolated canine Purkinje fibers to assess the effect of D0870 on repolarization. The hearts with TdPs observed before the sudden death showed a higher sinus rate for 5 and 10 sec before the onset, a shorter coupling interval, and a higher ventricular tachycardia rate compared with those having the non-sustained TdPs. These findings suggest that D0870-induced fatal TdPs may be provoked by a triggered activity developed from delayed after depolarizations. In contrast, as the pause-dependent, non-sustained TdPs in bradycardia showed a typical "short-long-short" sequence, they may be developed from early afterdepolarization . Moreover, the results of the in vitro study supported our contention that D0870 induced QT prolongation in a reverse use-dependent manner in vivo and suggested that it may inhibit not only rapidly activating delayed rectifier potassium current (Ik(r)) but also L-type Ca current (I(ca-L)).  相似文献   

6.
OBJECTIVE: To measure QT interval duration and QT dispersion in Boxers and to determine whether QT variables correlate with indices of disease severity in Boxers with familial ventricular arrhythmias, including the number of ventricular premature complexes per day, arrhythmia grade, and fractional shortening. ANIMALS: 25 Boxers were evaluated by ECG and echocardiography. PROCEDURE: The QT interval duration was measured from 12-lead ECG and corrected for heart rate (QTc), using Fridericia's formula. The QT and QTc were calculated for each lead, from which QT and QTc dispersion were determined. Echocardiography and 24-hour ambulatory ECG were performed to evaluate for familial ventricular arrhythmias. Total number of ventricular premature complexes, arrhythmia grade, and fractional shortening were determined and used as indices of disease severity. RESULTS: There was no correlation between any QT variable and total number of ventricular premature complexes, arrhythmia grade, or fractional shortening. No difference between QT dispersion and QTc dispersion was identified, and correction for heart rate did not affect the results. CONCLUSIONS AND CLINICAL RELEVANCE: QT interval duration and dispersion did not correlate with indices of disease severity for familial ventricular arrhythmias. Heart rate correction of the QT interval did not appear to be necessary for QT dispersion calculation in this group of dogs. QT dispersion does not appear to be a useful noninvasive diagnostic tool in the evaluation of familial ventricular arrhythmias of Boxers. Identification of affected individuals at risk for sudden death remains a challenge in the management of this disease.  相似文献   

7.
OBJECTIVE: To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs. ANIMALS: 6 healthy 8-month-old Beagles. PROCEDURE: Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography. RESULTS: The mean peak concentration during MBF infusion was 34.2 +/- 6.4 microg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment. CONCLUSIONS AND CLINICAL RELEVANCE: MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given.  相似文献   

8.
The antiarrhythmic compound disopyramide has been shown to possess negative inotropic effects. The present study was conducted to establish the effects of graded doses of disopyramide on ventricular function and electrocardiograms from healthy, awake dogs. Electrocardiograms and echocardiograms were obtained during a control period, and during an experimental period in which the six dogs on test received 7.5, 15 or 30 mg disopyramide per kg body weight orally three times per day. Six other dogs served as vehicle controls. No changes of statistical significance occurred in heart rate. The PQ interval was prolonged at all doses, the QRS complex was prolonged only at the highest dose, and the QT interval was prolonged at the intermediate and high doses. Left ventricular pre-ejection period (PEP) was prolonged in a dose-dependent relationship, and the left ventricular ejection time (ET) was shortened only at the highest dose. The percent shortening fraction of the left ventricle (% delta D) decreased significantly at intermediate and high doses, while the ratio of pre-ejection period to ejection time increased in a dose-dependent relationship. Conclusions are that even in therapeutic levels disopyramide produces significant reduction in left ventricular function, and that ratio of PEP/ET correlates better with the dose of disopyramide than did % delta D. This study demonstrates the feasibility of evaluating cardiac effects of compounds by non-invasive means.  相似文献   

9.
Ci 744 (20 mg/kg, given intramuscularly (IM) produced a reliable level of surgical anesthesia in both dogs and cats. Animals anesthetized in this way did not have an increased sensitivity to cardiac fibrillation after they were given epinephrine. Epinephrine-induced ventricular arrhythmia observed in C1 744-anesthetized animals was eliminated in cats and was markedly reduced in dogs by bilateral vagotomy. Myocardial fibrillation was not produced by epinephrine (0.1 to 100 mug/kg, intravenously (IV) in dogs and cats anesthetized with C1 744 alone. Pentobarbital anesthesia, like C1 744 anesthesia, did not sensitize the heart, whereas a significant number of thiamylal-halothane-anesthetized animals died from cardiac fibrillation after they had been given epinephrine. Additional dogs were anesthetized with C1 744 or pentobarbital and given a series of pressor and depressor agents (isoproterenol, epinephrine, tyramine, 1, 1-dimethyl-4-phenylpiperazium iodide (DMPP) plus bilateral carotid occlusion) before and after vagotomy. The responses with either anesthetic were similar with the exception that the reflex bradycardia to pressor agents was more evident in C1 744- than in pentobarbital-anesthetized dogs.  相似文献   

10.
Amiodarone, a class III antiarrhythmic with beta-adrenergic blocking and antimuscarinic properties, has a wide spectrum of clinical use in humans. This study was conducted to establish the effects of a 25 mg/kg q12h loading dose and a 30 mg/kg q24h maintenance dose of amiodarone, each given PO for 3.5 weeks, on systemic arterial pressure, echocardiographic (ECHO) indices of left ventricular function, ECGs, exercise tolerance, and serum biochemistries in adult, clinically normal dogs. Means were calculated and were compared by analysis of variance with repeated measures. When a significant F statistic was identified, specific means were compared by Bonferroni's post hoc test. Body weight and heart rate (HR) decreased, and PQ, QT, and corrected QT (QTc) increased significantly (P < .05) for the weeks that the dogs received the loading dose, but all parameters returned to values the same as those in the pretest for the weeks when dogs received the maintenance dose. Serum activity of hepatic enzyme activities and cholesterol concentrations increased, and serum concentrations of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), phosphorous, and total carbon dioxide decreased. The changes in PQ, QT, and QTc are similar to those obtained previously, but the detailed ECG and ECHO observations have not been reported. A dose of 25 mg/kg q12h, but not 30 mg/kg q24h, is an appetite suppressant, and the lower dose produces neither ECG nor ECHO changes of clinical or toxicological significance in normal dogs.  相似文献   

11.
Hemodynamic Effects of Intravenous Midazolam-Xylazine-Butorphanol in Dogs   总被引：1，自引：0，他引：1  
The hemodynamic effects of a mixture of midazolam (1.0 mg/kg), xylazine (0.44 mg/kg), and butorphanol (0.1 mg/kg) were evaluated in six adult dogs. The dogs were anesthetized with isoflurane for instrumentation. As the dogs returned to consciousness, baseline values were recorded and the midazolam-xylazine-butorphanol mixture and glycopyrrolate (0.01 mg/kg) were administered intravenously (IV). Hemodynamic data were recorded 3, 10, 20, 30, 40, 50, and 60 minutes after injection. Mean arterial pressure (AP), mean pulmonary arterial pressure (PAP), heart rate (HR), rate-pressure product (RPP), mean pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), and right ventricular stroke work index (RVSWI) were increased significantly above baseline values. Cardiac output (CO), stroke volume (SV), cardiac index (CI), stroke index (SI), mean central venous pressure (CVP), and left ventricular stroke work index (LVSWI) were decreased significantly below baseline values. When administered IV at the dosages used in this study, midazolam-xylazine-butorphanol-glycopyrrolate induced profound acute alterations in several critical hemodynamic variables.  相似文献   

12.
OBJECTIVE: To evaluate histamine release and selected physiologic variables during constant rate infusion (CRI) of morphine in dogs. ANIMALS: Five healthy, conscious, intact female dogs. MATERIAL AND METHODS: Using a Latin square, repeated-measures design, dogs were randomly assigned to three treatment groups to receive a 4-hour CRI of saline (SAL), or a loading dose of morphine at 0.3 mg kg(-1) (LM), or 0.6 mg kg(-1) (HM), followed by an infusion of 0.17 mg kg(-1) hour(-1) (LM) and 0.34 mg kg(-1) hour(-1) (HM) respectively. Dogs received each of the three treatments at intervals of at least 7 days. Plasma histamine concentration, skin flushing, edema and wheals, heart rate and rhythm and non-invasive arterial blood pressure were measured before the loading dose and at 1, 2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI, or at the time of occurrence. RESULTS: The loading dose induced the highest histamine release in the HM group being statistically higher than the SAL group. The histamine release obtained in the LM group after the loading dose did not differ from SAL. During the infusion, plasma histamine levels were numerically higher in the LM group. Besides one dog that developed hypotension for 2 minutes after the loading dose in the HM group and one dog that showed occasional ventricular premature contractions during both morphine infusions, cardiovascular variables were similar among the three treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of morphine induced variable histamine release with minimal adverse cardiovascular effects in these conscious, healthy dogs. The plasma histamine levels obtained may be associated with significant hemodynamic changes in patients with limited cardiovascular reserve and sympathetic nervous tone.  相似文献   

13.
We investigated the effects of graded dosages of magnesium given i.v. to anesthetized dogs on blood pressure, cardiac output, and electrophysiology. Magnesium was infused at 0.12 mEq/kg/minute until ventricular fibrillation occurred naturally or was provoked by programmed electrical stimulation or until arrest of the sinuatrial node in 8 dogs. Plasma total magnesium concentrations doubled in 1 minute of that infusion rate, and a hemodynamically safe plasma concentration of 12.2 mEq/L was achieved after 16 minutes of infusion. Heart rate, inotropy, lusitropy, and cardiac output increased up to a cumulative infusion dosage of magnesium of 1.0-2.0 mEq/kg, which produced plasma magnesium concentrations of 8.5-12.2 mEq/L (n = 5). Above the cumulative infusion dosage, inotropy decreased and lusitropy increased until death occurred between cumulative infusion dosages of 5.9 mEq/kg and 10.9 mEq/kg. Arterial pressure and vascular resistance decreased, and PQ interval and QRS complex increased, in a dose-dependent fashion. The relationship between ionized and total magnesium was y = 0.624x - 0.542 (r2 = .986), where y is ionized and x is total magnesium in mEq/L in 3 dogs. In conclusion, a cumulative infusion dosage of 0.1-0.2 mEq/kg of magnesium may be given without changing hemodynamic parameters, but with higher cumulative infusion doses heart rate accelerates. Hemodynamic parameters except those related to blood pressure continued to increase to a cumulative infusion dosage of 2.0 mEq/kg. At higher cumulative infusion dosages dogs became hypotensive and the PQ interval was prolonged. However, dangerous arrhythmias were not provoked until a total dosage of 3.9 mEq/kg.  相似文献   

14.
The objective of the study was to assess the cardiovascular effects of intravenous (IV) dosing with robenacoxib (Onsior®) in conscious adult healthy beagle dogs. The study employed a randomized, open, placebo‐controlled, four‐phase Latin square design. A total of eight dogs received a single dose of 2 mg/kg and 4 mg/kg IV robenacoxib (test groups), 2 mg/kg subcutaneous (SC) robenacoxib (reference dose and route), and IV isotonic saline (control). There were no significant differences between groups for clinical observations, buccal mucosal bleeding time or blood hematology, coagulation, and clinical chemistry variables in all eight dogs. In a subset of four dogs, no significant differences between groups were detected using telemetric assessment for arterial blood pressure, heart rate, electrocardiogram, or body temperature over 8 hr postdose. In conclusion, no significant cardiovascular effects were detected after a single IV dose of 2 or 4 mg/kg robenacoxib in conscious healthy dogs.  相似文献   

15.
OBJECTIVE: To evaluate the effect of medetomidine on minimum alveolar concentration (MAC), respiratory rate, tidal volume, minute volume (V(M)), and maximum inspiratory occlusion pressure (IOCP(max)) in halothane- and isoflurane-anesthetized dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females). PROCEDURE: The MAC of both inhalants was determined before and 5, 30, and 60 minutes after administration of medetomidine (5 microg/kg, IV). Dogs were subsequently anesthetized by administration of halothane or isoflurane and administered saline (0.9% NaCl) solution IV or medetomidine (5 microg/kg, IV). Respiratory variables and IOCP(max) were measured at specific MAC values 15 minutes before and 5, 30, and 60 minutes after IV administration of medetomidine while dogs breathed 0% and 10% fractional inspired carbon dioxide (FICO2). Slopes of the lines for VM/FICO2 and IOCP(max)/FICO2 were then calculated. RESULTS: Administration of medetomidine decreased MAC of both inhalants. Slope of V(M)/FICO2 increased in dogs anesthetized with halothane after administration of medetomidine, compared with corresponding values in dogs anesthetized with isoflurane. Administration of medetomidine with a simultaneous decrease in inhalant concentration significantly increased the slope for V(M)/FICO2, compared with values after administration of saline solution in dogs anesthetized with halothane but not isoflurane. Values for IOCP(max) did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Equipotent doses of halothane and isoflurane have differing effects on respiration that are most likely attributable to differences in drug effects on central respiratory centers. Relatively low doses of medetomidine decrease the MAC of halothane and isoflurane in dogs.  相似文献   

16.
Atrial fibrillation (AF) was induced in anesthetized Beagle hounds to determine the dose of diltiazem (D) that resulted in hemodynamic function similar to that observed during sinus rhythm (SR). Dogs were instrumented to record hemodynamic and electrophysiological parameters. Six dogs were given D, IV at cumulative doses of 0.063, 0.188, 0.438, 0.938, and 1.938 mg/kg, whereas 6 other dogs received vehicle in equivalent volumes. Plasma concentrations (PC) of D were measured. A cumulative dose of D between 0.438 and 0.938 mg/kg produced PC of 67.8 to 117.4 ng/mL and resulted in a heart rate (HR) closest to that observed during SR. At doses up to 0.938 mg/kg, no parameter of systolic function fell below that obtained during SR. At a dose of 0.938 mg/kg, the left ventricular end-diastolic and right atrial pressures exceeded those during SR. The rate-pressure product did not differ from that during SR at a dose of 0.938 mg/kg and fell below that during SR at the dose of 1.938 mg/kg. Left ventricular efficiency decreased from SR to AF, returned to values not different from those during SR at a dose of 0.938 mg/kg, and increased to values above those observed during SR at a dose of 1.938 mg/kg. In AF, slowing the HR with 0.438-0.938 mg/kg of D with resultant PC of 67.8-117.4 ng/mL results in cardiovascular function not different from that observed during SR.  相似文献   

17.
OBJECTIVE: To evaluate the effect of the tiletamine/zolazepam (TZ) combination (Zoletil 100; Virbac, Carros, France) with and without atropine on blood gas values and acid-base status in dogs. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: Six healthy adult cross-bred dogs, weighing 11.0-18.5 kg. MATERIALS AND METHODS: Each dog received four different drug treatments at intervals of at least 15 days: (i) 5 mg kg(-1) intravenous (IV) TZ (TZ.IV); (ii) 10 mg kg(-1) intramuscular (IM) TZ (TZ.IM); (iii) atropine, 20 microg kg(-1) IV, followed 5 minutes later by 5 mg kg(-1) TZ IV (A.TZ.IV); and (IV) atropine (same dose) given 5 minutes before 10 mg kg(-1) TZ IM (A.TZ.IM). Arterial blood samples were collected from each dog before drug administration (baseline) at induction of anaesthesia (time 0) and 2, 5, 10 and 30 minutes thereafter. RESULTS: Transient hypoxaemia and respiratory acidosis were observed just after induction. PaO(2) and SaO(2) dropped, while H(+) concentration and PaCO(2) rose significantly above baseline values. In groups TZ.IV and A.TZ.IV, PaO(2) values as low as 6.0-6.4 kPa (45-48 mm Hg) were recorded. However, there was no significant difference in blood gas variables among the groups encountered during the evaluation period. The overall change in [HCO(3) (-)] and base excess (BE) was not significant among groups. Atropine did not affect the above variables. CONCLUSIONS AND CLINICAL RELEVANCE: Tiletamine/zolazepam injection may induce transient hypoxaemia and respiratory acidosis, but acid-base status changes are clinically unimportant. Particularly, close observation of dogs is recommended during the first 5-10 minutes after induction with TZ, especially in animals with cardiopulmonary disease. TZ should perhaps not be used in animals intolerant of tachycardia.  相似文献   

18.
OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.  相似文献   

19.
Background: Elsamitrucin, the most potent topoisomerase II inhibitor available, is unique in that it does not cause neutropenia or cardiotoxicosis. It has antitumor activity in human patients with relapsed or refractory non‐Hodgkin's lymphoma. Objectives: To determine the maximum tolerated dose (MTD), safety, and toxicity of elsamitrucin when administered to tumor‐bearing dogs and to evaluate the incidence and severity of adverse events. Animals: Twenty client‐owned dogs with spontaneous malignant solid tumors or lymphoma that were refractory to, or for which the owner declined, conventional therapy were enrolled. Methods: Prospective, open‐label, single‐agent study. Escalating doses of elsamitrucin were administered once weekly IV for up to 16 weeks in a modified 3 + 3 Phase I design. The starting dose was 0.06 mg/kg with escalation to 0.08 and 0.09 mg/kg. Dogs that remained on the study were monitored for evidence of toxicoses for at least 4 weeks and for survival every 2 months. Results: Serious adverse events (SAEs) possibly attributable to elsamitrucin include: 1 dog developed heart failure and another developed hepatotoxicosis manifested by increased alanine aminotransferase, alkaline phosphatase, and total bilirubin (0.06 mg/kg dose); 1 dog developed severe anorexia and diarrhea, another developed severe diarrhea alone, and a 3rd dog went into cardiac arrest (0.09 mg/kg dose). A dose of 0.08 mg/kg was well tolerated with no SAEs. Conclusions and Clinical Importance: The MTD and recommended dose for Phase II trials of elsamitrucin is 0.08 mg/kg IV weekly. Elsamitrucin might be considered for combination protocols with myelosuppressive chemotherapy agents.  相似文献   

20.
OBJECTIVE: To determine the relationship between bispectral index (BIS) and minimum alveolar concentration (MAC) multiples of isoflurane after IM injection of medetomidine or saline (0.9% NaCl) solution in anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: Each dog was anesthetized 3 times with isoflurane. First, the MAC of isoflurane for each dog was determined by use of the tail clamp method. Second, anesthetized dogs were randomly assigned to receive an IM injection of medetomidine (8 microg x kg(-1)) or an equal volume of isotonic saline (0.9% NaCl) solution 30 minutes prior to beginning BIS measurements. Last, anesthetized dogs received the remaining treatment (medetomidine or isotonic saline solution). Dogs were anesthetized at each of 4 MAC multiples of isoflurane. Ventilation was controlled and atracurium (0.2 mg/kg followed by 6 microg/kg/min as a continuous infusion, IV) administered. After a 20-minute equilibration period at each MAC multiple of isoflurane, BIS data were collected for 5 minutes and median values of BIS calculated. RESULTS: BIS significantly decreased with increasing MAC multiples of isoflurane over the range of 0.8 to 2.0 MAC. Mean (+/- SD) MAC of isoflurane was 1.3 +/- 0.2%. During isoflurane-saline anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 65 +/- 8, 60 +/- 7 52 +/- 3, and 31 +/- 28, respectively. During isoflurane-medetomidine anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 77 +/- 4, 53 +/- 7, 31 +/- 24, and 9 +/- 20, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: BIS monitoring in dogs anesthetized with isoflurane has a predictive value in regard to degree of CNS depression. During isoflurane anesthesia, our results support a MAC-reducing effect of medetomidine.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号