Clinical aspects of septic shock and comprehensive approaches to treatment in dogs and cats.
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Animals↗
Biomedical subjects
W W Muir
Publications and source records attributed to W W Muir.
Electrophysiologic interactions of procainamide and N-acetylprocainamide in isolated canine cardiac Purkinje fibers.
The study objective was to characterize the electrophysiologic interactions of procainamide (PA) and its metabolite, N-acetylprocainamide (NAPA), in canine Purkinje fibers. Cell (N = 43) action potentials were measured in Tyrode's solution (K+ = 4.0 mM, 36 degrees C) at a basic cycle length of 1,000 ms using standard microelectrode techniques. Six PA concentrations (0.020-0.32 mM) and six NAPA concentrations (0.010-0.24 mM) were studied alone and in combination. PA caused concentration-dependent decreases in Vmax and APD50 but did not alter APD90, ERP, or RMP. NAPA caused a small but not significant concentration-dependent decrease in Vmax, no change in RMP, and significant concentration-dependent increases in APD50, APD90, and ERP. Low NAPA concentrations increased, intermediate concentrations did not affect, and high NAPA concentrations again increased PA's effect on Vmax. PA-NAPA combinations resulted in concentration-dependent changes in APD50 that were intermediate between the effects of PA or NAPA alone. PA did not significantly alter NAPA's effects on APD90 at NAPA concentrations less than or equal to 0.040 mM, while it antagonized NAPA's effect at higher concentrations. The effects of PA-NAPA combinations on ERP were generally similar to their effects on APD90. The electrophysiologic effects of PA-NAPA combinations in normal canine Purkinje fibers are complex functions of the relative and absolute concentrations of the two compounds.
Acecainide↗
The pharmacology and pharmacokinetics of high-dose methocarbamol in horses.
The haemodynamic, respiratory and behavioural effects and pharmacokinetics of methocarbamol were studied in eight healthy, adult horses after intravenous (i.v.) and oral administration of large dosages. Heart rate, cardiac output, mean pulmonary arterial blood pressure, systolic, diastolic and mean aortic blood pressure, respiratory rate and arterial blood gases did not change after either i.v. (30 mg/kg bodyweight [bwt]) or oral (50 and 100 mg/kg bwt) dosages of methocarbamol. Mild to moderate depression was observed in five of eight horses administered i.v. methocarbamol, and in all horses administered oral methocarbamol. Plasma methocarbamol concentration declined very rapidly during the initial or rapid disposition phase after i.v. administration; the terminal elimination half-life ranged from 59 to 90 mins. Peak plasma methocarbamol concentrations following oral administration occurred within 15 to 45 mins and oral bioavailability ranged from 50.7 to 124 percent.
Administration, Oral↗
Pharmacokinetics and metabolism of intravenous doxapram in horses.
The pharmacokinetics and metabolism of doxapram in horses administered intravenous (iv) doses of 0.275, 0.55 and 1.1 mg doxapram/kg bodyweight (bwt) were investigated. Plasma doxapram concentrations decreased rapidly after drug administration and the disappearance of doxapram from plasma was best described by a polyexponential equation. Median values of total body clearance were 10.9, 10.6 and 10.9 ml/min/kg bwt for the three doses and were independent of dose. The steady-state volume of distribution was approximately 1,200 ml/kg bwt and the median biological half-life ranged from 121 to 178 mins. Plasma protein binding of doxapram ranged from 76.0 to 85.4 per cent. The blood:plasma doxapram concentration ratio was approximately 0.8 and the affinity of the red blood cells for doxapram ranged from 2.0 to 2.8 indicating sequestration of doxapram in erythrocytes. Renal clearance of doxapram was a minor route of elimination. Metabolic clearance of doxapram appeared to be a major route of elimination. Four metabolites of doxapram were isolated from urine and were identified. The metabolites were: a) 1-ethyl-4-[(2-hydroxyethyl) amino]ethyl-3,3-diphenyl-2-pyr-rolidinone, b) a glucuronic acid or sulphuric acid conjugate of 1-ethyl-3-(hydroxyphenyl)-4-(2-morpholinoethyl)-3-phenyl-pyrrolidinone, c) 3,3-diphenyl-4-(2-morpholinoethyl)-2-pyrrolidinone and d) 1-(2-hydroxyethyl)-3,3-diphenyl-4-(2-morpholinoethyl)-2-pyr-rolidinon e. The rapid disappearance of doxapram from plasma immediately after iv administration was attributed to redistribution of the drug from plasma to other tissues. The short duration of clinical effect from doxapram may be attributed to redistribution of the drug from plasma and other well-perfused tissues, such as the brain, to less well-perfused tissues such as the skeletal muscles and adipose tissue. Continuous or repeated administration of doxapram could prolong the duration of clinical effect because re-distribution is less important as steady-state conditions are approached.
Adipose Tissue↗
Lung innervation and the hemodynamic response to 7% sodium chloride in hypovolemic dogs.
A pulmonary vagal reflex triggered by passage of hypertonic saline through the pulmonary circulation has been proposed as one of the mechanisms by which hypertonic saline resuscitates dogs in hemorrhagic shock. Thirteen anesthetized dogs with denervated left lung lobes were subjected to a standard hemorrhage model to evaluate this purported reflex. We then infused 7% NaCl (4 ml/kg) into either the innervated (six dogs) or the denervated (seven dogs) pulmonary circulation. There were no differences in cardiac output, mean arterial pressure, right atrial pressure, heart rate, or peripheral vascular resistance between groups during a 1 hr period after 7% NaCl infusion. Changes in hematocrit, total plasma protein, and osmolality after 7% NaCl administration suggested that plasma volume expansion had occurred and was similar between groups. We conclude that a pulmonary reflex elicited by hypertonic saline does not contribute to the beneficial hemodynamic effects associated with administration of 7% NaCl during hemorrhagic shock.
Animals↗
Inotropic mechanisms of dopexamine hydrochloride in horses.
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 micrograms/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 1, and beta 2-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/dtmax). Right atrial pressure and systemic vascular resistance decreased. Parasympathetic and ganglionic blockade attenuated cardiac output, systolic and mean aortic blood pressures, and +dP/dtmax responses to dopexamine infusion. Dopexamine-induced increase in heart rate was potentiated by parasympathetic and ganglionic blockade. beta 1-Adrenergic receptor blockade decreased heart rate, cardiac output, arterial blood pressure, and +dP/dtmax from baseline values and markedly reduced the response to dopexamine infusion. beta 2-Adrenergic receptor blockade induced further decrease in hemodynamic variables from baseline values and completely abolished the cardiostimulatory effects of dopexamine on +dP/dtmax. These data indicate that baroreflex activity, beta 1- and beta 2-adrenergic receptor stimulation may be an important cause of dopexamine's positive inotropic effects in horses.
Adrenergic Agonists↗
Effects of ketamine infusion on halothane minimal alveolar concentration in horses.
Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectrometry under electron-impact ionization conditions, using lidocaine as the internal standard. Halothane minimal alveolar concentration (MAC; concentration at which half the horses moved in response to an electrical stimulus) and plasma ketamine concentration were determined after steady-state concentrations of each ketamine infusion had been reached. Plasma ketamine concentrations > 1.0 microgram/ml decreased halothane MAC. The degree of MAC reduction was correlated directly with the square root of the plasma ketamine concentration, reaching a maximum of 37% reduction at a plasma ketamine concentration of 10.8 +/- 2.7 micrograms/ml. Heart rate, mean arterial blood pressure, and the rate of increase of right ventricular pressure did not change with increasing plasma ketamine concentration and halothane MAC reduction. Cardiac output increased significantly during ketamine infusions and halothane MAC reduction. Our findings suggest that plasma ketamine concentrations > 1.0 micron/ml reduce halothane MAC and produce beneficial hemodynamic effects.
Anesthesia↗
Arterial-venous difference in atrial natriuretic peptide concentration during exercise in horses.
Six nontrained mares were subjected to steady-state, submaximal treadmill exercise to examine the effect of exercise on the plasma concentration of atrial natriuretic peptide (ANP) in arterial, compared with mixed venous, blood. Horses ran on a treadmill up a 6 degree grade for 20 minutes at a speed calculated to require a power equivalent to 80% of maximal oxygen uptake (VO2MAX). Arterial and mixed venous blood samples were collected simultaneously from the carotid and pulmonary arteries of horses at rest and at 10 and 20 minutes of exercise. Plasma was stored at -80 C and was later thawed; ANP was extracted, and its concentration was determined by radioimmunoassay. Exercise caused significant (P < 0.05) increases in arterial and venous plasma ANP concentrations. Mean +/- SEM arterial ANP concentration increased from 25.2 +/- 4.4 pg/ml at rest to 52.7 +/- 5.2 pg/ml at 10 minutes of exercise and 62.5 +/- 5.2 pg/ml at 20 minutes of exercise. Mean venous ANP concentration increased from 24.8 +/- 4.3 pg/ml at rest to 67.2 +/- 14.5 pg/ml at 10 minutes of exercise and 65.3 +/- 13.5 pg/ml at 20 minutes of exercise. Significant differences were not evident between arterial or mixed venous ANP concentration at rest or during exercise, indicating that ANP either is not metabolized in the lungs or is released from the left atrium at a rate matching that of pulmonary metabolism.
Animals↗
Effect of xylazine on the arrhythmogenic dose of epinephrine in thiamylal/halothane-anesthetized horses.
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 micrograms/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 micrograms/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 micrograms/kg/min; xylazine, 1.21 +/- 0.46 micrograms/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.
Anesthesia, General↗
Plasma renin activity and aldosterone and vasopressin concentrations during incremental treadmill exercise in horses.
Six untrained mares were subjected to incremental treadmill exercise to examine exercise-induced changes 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 degree 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 less than 0.05) and PRA (r = 0.93, P less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aldosterone↗
Cardiovascular effects of dopexamine HCl in conscious and halothane-anaesthetised horses.
The cardiovascular effects of serial increasing infusions of dopexamine HCl were investigated in six conscious (1, 2, 4, 6, 10 micrograms/kg bodyweight [bwt]/min) and eight (0.5, 1, 5, 10, 20 micrograms/kg bwt/min) halothane-anaesthetised horses. Dopexamine produced dose-dependent increases in heart rate, +dP/dtmax' -dP/dtmax and cardiac output, and a decrease in systemic vascular resistance in conscious and halothane-anaesthetised horses. Mean arterial blood pressure did not change in conscious horses but increased to a maximum value at 10 micrograms/kg bwt/min in halothane-anaesthetised horses. Thereafter, median artery blood flow decreased. Ventricular arrhythmias occurred in two conscious horses during the infusion of 10 micrograms/kg bwt/min dopexamine HCl. No cardiac arrhythmias other than sinus tachycardia were observed in halothane-anaesthetised horses. The administration of propanolol eliminated the haemodynamic response to the infusion of 5 and 10 micrograms/kg bwt/min dopexamine HCl in halothane-anaesthetised horses. The haemodynamic effects of dopexamine HCl offer specific advantages over dopamine and dobutamine for the treatment of low cardiac output states in horses.
Adrenergic beta-Agonists↗
Antiarrhythmic drugs. Treatment of cardiac arrhythmias.
This article focuses on drugs that have been specifically developed for the treatment of cardiac arrhythmias. A brief overview of the principal mechanisms responsible for the development of cardiac arrhythmias is also included, because it has been the goal of pharmacologists and clinical cardiologists to develop drugs and prescribe specific antiarrhythmic therapy based on a knowledge of these mechanisms with the assumption that specific antiarrhythmic therapy will be the most efficacious in restoring and maintaining normal sinus rhythm.
Animals↗
Thiamylal- and halothane-sparing effect of diazepam in dogs.
The thiamylal- and halothane-sparing effect of diazepam was studied in two experiments using 32 conditioned dogs. Twenty-four dogs received 0.05, 0.1 or 0.2 ml/kg diazepam or 0.9% saline (placebo) prior to the administration of thiamylal sodium i.v. Eight dogs received 0.1 or 0.2 mg/kg diazepam i.v. or placebo prior to or during halothane anesthesia. All three doses of diazepam significantly decreased the amount of thiamylal required to allow orotracheal intubation. The 0.2 mg/kg i.v. dose of diazepam produced the most significant effects. Premedication of dogs with diazepam did not reduce the concentration of halothane required to maintain anesthesia. The administration of 0.1 and 0.2 mg/kg diazepam i.v. during halothane anesthesia decreased the concentration of halothane required to maintain anesthesia. These studies demonstrate that diazepam reduces the amount of thiamylal required for orotracheal intubation, and when given intra-operatively reduces the concentration of halothane required to maintain anesthesia.
Animals↗
Furosemide-induced changes in plasma and blood volume of horses.
The effect of furosemide administration (1 mg/kg body weight, i.v.) on plasma and blood volumes in 6 intact and 4 splenectomized horses was measured using Evans blue dye dilution, hematocrit, and hemoglobin and plasma total solids concentrations. Body weight decreased by 33.6 +/- 3.3 and 33.7 +/- 0.8 g/kg 4 h after furosemide administration to intact and splenectomized mares, respectively. Plasma volume, estimated by Evans blue dye dilution, was reduced by 8.3 +/- 3.3% (mean +/- SE) 4 h after furosemide administration. The reduction in plasma volume was first detectable 5-10 min after furosemide administration and was greatest 15-30 min (13.0 +/- 0.8%) after dosing. This study demonstrates that furosemide produces significant and rapid reductions in plasma volume in horses. These decreases in plasma volume only partially resolve 4 h after furosemide administration.
Animals↗
Xylazine and tiletamine-zolazepam for induction of anaesthesia maintained with halothane in 19 horses.
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Anesthesia↗
A technique for production of complete atrioventricular block in dogs.
A simple and reliable technique for producing complete atrioventricular (AV) block in dogs by the injection of a 38% formaldehyde solution into the area of the AV node is described. This technique, a modification of previous methods utilizing formaldehyde injection for the production of complete AV block, uses the coronary sinus as the major landmark. Complete heart block was produced in 20 of 20 dogs. The technique is simple and associated with few problems, does not require special equipment, is associated with little or no hemorrhage from the injection site, and does not enter a cardiac chamber. The only side effect noted was the development of ventricular arrhythmias in 2 of 20 dogs. A detailed description of the technique is included with comparisons to previous techniques utilizing injection of a 40% formaldehyde solution.
Animals↗
Renal tubular function in horses during submaximal exercise.
Exercise-induced changes in renal function were examined during steady-state submaximal treadmill exercise in six unfit mares. Horses were randomly assigned to either an exercise or parallel control (no exercise) trial on day 1 and the alternate trial 1 wk later. The mares ran on a treadmill, set at a 6 degrees incline, for 1 h at 55-60% of maximal heart rate. Exercise significantly (P less than 0.05) increased plasma osmolality, plasma [K+], urine flow (+ 45%), Na+ excretion (+ 371%), K+ excretion (+ 57%), osmotic clearance (+ 32%), Na+ clearance (+ 391%), K+ clearance (+ 33%), and fractional Na+ excretion (+ 320%) and significantly decreased plasma [Cl-], Cl- excretion (-46%), Cl- clearance (-41%), and fractional Cl- excretion (-47%). Glomerular filtration rate, fractional K+ excretion, and free water clearance did not change during exercise. Atrial natriuretic peptide increased during exercise from 11 +/- 1 pg/ml at rest to a peak of 40 +/- 9 pg/ml (264%, P less than 0.05) at 40 min. Increases in plasma renin activity (66%, P less than 0.05) were accompanied by increases in plasma aldosterone concentration (760%, P less than 0.05). Vasopressin concentration increased (P less than 0.05) steadily over the 60-min period of exercise. It was concluded that, in horses, submaximal exercise-induced increases in urine flow and sodium excretion are associated with a concurrent increase in the plasma concentration of atrial natriuretic peptide.
Animals↗
Alpha-adrenoceptor stimulation in the presence of halothane: effects on impulse propagation in cardiac Purkinje fibers;.
Halothane effects on action potential characteristics and conduction were determined in canine Purkinje fibers, before and during alpha-adrenergic stimulation. Halothane significantly decreased effective refractory period and action potential duration in Purkinje fibers. alpha-Adrenergic stimulation restored effective refractory period and action potential duration in Purkinje fibers exposed to halothane via an alpha 1-adrenoceptor mediated effect antagonized by prazosin. Halothane significantly slowed propagation of impulses initiated at a basic cycle length of 500 ms, and conduction of premature impulses, in Purkinje fibers. In the presence of halothane, alpha-adrenergic stimulation had no additional effects on normal impulse propagation; however, alpha-adrenergic stimulation significantly slowed the conduction of premature impulses in Purkinje fibers exposed to halothane. These data refute a previous report that alpha-adrenergic stimulation enhances halothane's negative dromotropic effect in Purkinje fibers paced at a basic drive cycle length. alpha-Adrenergic prolongation of the conduction times of premature stimuli in Purkinje fibers exposed to halothane is a new finding.
Action Potentials↗