OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired portosystemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.

Objective--To determine whether larkspur-derived N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids alter heart rate and electrically evoked electromyographic (eEMG) response of the external anal sphincter (EAS) in cattle and whether these effects can be reversed by acetylcholinesterase inhibitors. Animals--12 beef heifers and 4 cows. Procedures--3 or 4 heifers were used in 1 or 2 of 7 dose-response experiments; heart rate and EAS eEMG response were assessed before and 24 hours after oral treatment with larkspur (doses equivalent to 0.5 to 15 mg of MSAL-type alkaloids/kg). In 3 subsequent experiments, 3 heifers (1 of which was replaced with another heifer in the control experiment) each received 10 mg of MSAL-type alkaloids/kg and were injected IV with physostigmine (0.04 mg/kg), neostigmine (0.04 mg/kg), or saline (0.9% NaCl) solution 24 hours later, prior to assessment. Additionally, EAS eEMG response was measured in 4 cows before and after epidural administration of 2% lidocaine hydrochloride. Results--Larkspur-treated heifers developed dose-related increases in heart rate and decreases in EAS eEMG response. Twenty-four hours after administration of MSAL-type alkaloids, neostigmine decreased heart rate but did not affect eEMG response, whereas physostigmine did not affect heart rate but caused a 2-fold increase in eEMG response. In cows, epidural anesthesia did not alter eEMG response, suggesting that transdermal stimulation of the EAS pudendal innervation did not occur. Conclusions and Clinical Relevance--In cattle, cardiac effects and muscle weakness or loss of EAS eEMG response induced by larkspur-derived MSAL-type alkaloids were reversed by neostigmine or physostigmine, respectively. Treatment with anticholinesterase inhibitors may alter the clinical effects of larkspur poisoning in cattle.

The effects of hypertonic saline solution (HSS) and hyperosmotic dextrose (HD; 2,400 mosm/L, 4 ml/kg of body weight) on left ventricular afterload were determined in normovolumic, chloralose-anesthetized, autonomically blocked dogs (n = 8). Solutions were infused IV over 3 minutes. Left ventricular afterload was assessed by use of a dual-tipped micromanometer catheter with an electromagnetic fluid-velocity sensor located in the ascending aorta, and the impedance spectrum was calculated after Fourier analysis of signal-averaged aortic pressure and flow signals. Hypertonic saline solution and HD decreased peripheral resistance, reflection coefficient at zero frequency, and frequency of the first zero crossing of the phase angle for 3 to 5 minutes after either fluid was administered. Characteristic impedance was not altered by HSS or HD. These impedance spectrum changes indicate transient vasodilatation and afterload reduction. We conclude that the vascular effect of an ionic hyperosmotic solution (HSS) is similar to that of a nonionic hyperosmotic solution (HD), and that HSS and HD transiently decrease afterload in normovolumic dogs. The duration of the afterload reduction after HSS administration appeared to be too short to be of great clinical benefit.

Eighteen dogs undergoing lateral thoracotomy at the left fifth intercostal space were randomly assigned to 1 of 3 postoperative analgesic treatment groups of 6 dogs each as follows: group A, morphine, 1.0 mg/kg of body weight, IM; group B, 0.5% bupivacaine, 1.5 mg/kg given interpleurally; and group C, morphine, 1.0 mg/kg given interpleurally. Heart rate, respiratory rate, arterial blood pressure, arterial blood gas tensions, alveolar-arterial oxygen differences, rectal temperature, pain score, and pulmonary mechanics were recorded hourly for the first 8 hours after surgery, and at postoperative hours 12, 24, and 48. These values were compared with preoperative (control) values for each dog. Serum morphine and cortisol concentrations were measured at 10, 20, and 30 minutes, hours 1 to 8, and 12 hours after treatment administration . All dogs had significant decreases in pHa, PaO2, and oxygen saturation of hemoglobin, and significant increases in PaCO2 and alveolar-arterial oxygen differences in the postoperative period, but these changes were less severe in group-B dogs. Decreases of 50% in lung compliance, and increases of 100 to 200% in work of breathing and of 185 to 383% in pulmonary resistance were observed in all dogs after surgery. Increases in work of breathing were lower, and returned to preoperative values earlier in group-B dogs. The inspiratory time-to-total respiratory time ratio was significantly higher in group-B dogs during postoperative hours 5 to 8, suggesting improved analgesia. Blood pressure was significantly lower in group-A dogs for the first postoperative hour. Significant decreases in rectal temperature were observed in all dogs after surgery, and hypothermia was prolonged in dogs of groups A and C. Significant differences in pain score were not observed between treatment groups. Cortisol concentration was high in all dogs after anesthesia and surgery, and was significantly increased in group-B dogs at hours 4 and 8. Significant differences in serum morphine concentration between groups A and C were only observed 10 minutes after treatment administration. In general, significant differences in physiologic variables between groups A and C were not observed. Results of the study indicate that anesthesia and thoracotomy are associated with significant alterations in pulmonary function and lung mechanics. Interpleurally administered bupivacaine appears to be associated with fewer blood gas alterations and earlier return to normal of certain pulmonary function values. Interpleural administration of morphine does not appear to provide any advantages, in terms of analgesia or pulmonary function, compared with its IM administration.

Cardiopulmonary responses were evaluated in 12 dogs undergoing endoscopy (gastroscopy and enteroscopy). Constant endoscopic insufflation was used to distend the stomach and small intestine for 30 minutes in groups of small (< 10 kg n = 4), medium (10 to 20 kg n = 4), and large (> 20 kg n = 4) dogs. Cardiopulmonary measurements within groups prior to gastric distention (preendoscopy) were compared with postendoscopy measurements and with those made during endoscopy. After distending the stomach and small intestine, increased luminal pressure within the body of the stomach and in the descending duodenum (P < 0.05) and increased abdominal girth (P < 0.05) were observed, with the greatest changes in small dogs. Caudal vena cava pressures and mean arterial and pulmonary artery pressures increased (P < 0.05) during endoscopy. Cardiac index varied, with small dogs having greater cardiac index (P < 0.05) during endoscopy, compared with that in medium and large dogs. Minute volume remained unchanged during insufflation, despite a decrease in tidal volume (P < 0.05), because of an increase in respiratory rate (P < 0.05). Arterial blood gas analysis revealed a mild, mixed metabolic/respiratory acidosis in all groups. Although cardiopulmonary changes associated with gastrointestinal tract endoscopy were common, the changes were often small and of little clinical significance.

Pharmacokinetic variables of bupivacaine (BPV) were determined after IV and epidural administrations in the same 6 dogs. Plasma BPV concentration curves after IV administration were adjusted to biexponential kinetics: a rapid distribution phase was followed by a slower elimination phase, with half-life of 34.5 +/- 7.8 minutes. Mean plasma clearance was 20.2 +/- 7.4 ml/min/kg of body weight, and mean volume of distribution at steady state was 0.7 +/- 0.2 L/kg. After epidural administration, absorption was rapid. Peak plasma concentration, 1.4 +/- 0.4 microgram/ml, was detected approximately 5 minutes after BPV administration. The half-life corresponding to epidural administration (179 +/- 33.6 minutes) was 5 to 6 times longer than that observed after IV administration, possibly because of the slow release of BPV from the epidural space. Induction times were short (2.3 +/- 2.2 minutes); anesthesia quickly began and lasted for more than 2 hours (158 +/- 48.8 minutes). During that period, BPV plasma concentration ranged between 1.4 and 0.2 microgram/ml. Changes in systolic blood pressure and heart rate were correlated to high plasma concentration of BPV. These modifications were observed for the first 30 minutes, reaching baseline values after 60 minutes.

Effects of endotoxemia on left ventricular contractility and systemic hemodynamics were determined in pentobarbital-anesthetized swine. A multielectrode conductance (volume) catheter and a high-fidelity pressure transducer catheter were passed retrograde into the left ventricle to continuously measure pressure and volume. End-systolic pressure-volume relationships were determined during transient (8 to 10 s) caudal vena caval balloon occlusion. Lactated Ringer's solution was administered at a rate sufficient to maintain left ventricular end-diastolic pressure > 6 mm of Hg. Following baseline measurements, Escherichia coli endotoxin (O55-B5) was infused IV at 2.5 micrograms/kg of body weight/h for 3 hours. Left ventricular end-systolic elastance (Ees), the slope of the end-systolic pressure-volume relationship; end-systolic elastance normalized for left ventricular end-diastolic volume (Ees norm); the rate of increase of left ventricular pressure (dP/dtmax); and preload recruitable stroke work (PRSW, stroke work-to-end-diastolic volume relationship) did not change in endotoxemic swine, compared with baseline measurements or with values from control (physiologic saline solution-treated) swine. Left ventricular pressures and volumes had marked pig-to-pig variability in the control and endotoxin-treated groups. Determination of Ees, Ees norm, and PRSW was further confounded by development of frequent premature ventricular contractions during caudal vena caval balloon occlusion. Endotoxin significantly (P < 0.05) decreased left ventricular end-diastolic pressure, compared with that in control swine, and significantly (P < 0.01) decreased left ventricular end-diastolic volume, compared with baseline. Endotoxin decreased cardiac index and arterial blood pressure, whereas heart rate, central venous pressure, and mean pulmonary arterial pressure increased. Endotoxin did not decrease myocardial contractility, as measured by Ees, Ees norm, dP/dtmax, or PRSW in anesthetized swine.

Effects of differential ventilation on gas exchange were studied in 7 isoflurane-anesthetized, laterally recumbent horses, and were compared with effects of conventional ventilation, using similar minute volume. A tracheal tube-in-tube intubation technique allowed each lung to be connected separately to an anesthetic circle system with a ventilator. Two distribution patterns of tidal volume were investigated; half the tidal volume was distributed to each lung and two-thirds the tidal volume was distributed to the dependent lung. Effects of the combination of these patterns with positive end-expiratory pressure (PEEP) of 10 and 20 cm of H20 to the dependent lung were investigated. Differential ventilation maintained PaCO2, but significantly increased PaO2, from 180 to 270 mm of Hg (+44%) and decreased shunt perfusion from 22 to 19% (-15%), regardless of the distribution pattern used. Mean airway pressure was lower than the value detected during conventional ventilation. The combination of differential ventilation with selective PEEP was followed by a decrease in PaCO2 and further increase of PaO2 and decrease of shunt, which were similar for both distribution patterns. Effects of PEEP of 20 cm of H2O were more pronounced than those of PEEP of 10 cm of H2O. Owing to the combined effects of differential ventilation and selective PEEP, PaO2 increased to 399 mm of Hg and shunt decreased to 15%. This represents increase of 112% and decrease of 33% respectively, compared with values for conventional ventilation. Mean airway pressure increased maximally to 23 cm of H2O, which was 11 cm of H2O greater than the value for conventional ventilation. During differential ventilation, alveolar dead space in the dependent lung became greater than that in the nondependent lung and maximum was 39%. There were no significant changes in arterial blood pressure. Beneficial effects on gas exchange can be explained by improved matching of ventilation and perfusion, possibly attributable to reopening of previously dosed units in the dependent lung.

The hemodynamic effects of 2 dosages of ephedrine were studied in 6 dogs anesthetized with isoflurane only (end-tidal concentration equivalent to 1.5 times minimum alveolar concentration). Following instrumentation, baseline (time 0) measurements included heart rate (HR), respiratory rate, mean arterial blood pressure (MAP), cardiac output, and blood gas tensions. Cardiac index (CI), stroke volume (SV), systemic vascular resistance (SVR), arterial oxygen content (CaO2), and oxygen delivery and consumption (DO2 and VO2, respectively) were calculated. Three dogs were given ephedrine IV at a dosage of 0.1 mg/ kg of body weight, and 3 dogs were given ephedrine IV at a dosage of 0.25 mg/kg. Measurements were recorded at 5, 10, 15, 30, and 60 minutes. Each dog then received the alternate dosage of ephedrine, and measurements were again recorded at the same intervals. Effects of ephedrine varied with dosage. Neither dosage was associated with significant changes in pH, PaO2, PaCO2, VO2, or respiratory rate. Ephedrine at a dosage of 0.1 mg/kg caused transient significant increases in MAP, CI, SV, CaO2, and DO2, significant decreases in HR and SVR, and a late, slight decrease in CaO2. Ephedrine at a dosage of 0.25 mg/kg caused a greater and more prolonged increase in MAP, as well as increases in CI, SV, and SVR, and a decrease in HR. The higher dosage of ephedrine also caused a pronounced increase in hemoglobin concentration and CaO2, resulting in a 20 to 35% increase in DO2 throughout the 60-minute experiment.

We evaluated the effects of clenbuterol HCl (0.8 micrograms/kg, of body weight, IV), a beta 2, agonist, on ventilation-perfusion matching and hemodynamic variables in anesthetized (by IV route), laterally recumbent horses. The multiple inert gas elimination technique was used to assess pulmonary gas exchange. Clenbuterol HCl induced a decrease in arterial oxygen tension (from 57.0 +/- 1.8 to 49.3 +/- 1.2 mm of Hg; mean +/- SEM) as a result of increased shunt fraction (from 6.6 +/- 2.1 to 14.4 +/- 3.1%) and ventilation to regions with high ventilation-perfusion ratios. In contrast, no changes in these variables were found in horses given sterile water. In horses given clenbuterol HCl, O2 consumption increased from 2.23 +/- 0.18 to 2.70 +/- 0.14 ml . min-1 . kg-1, and respiratory exchange ratio decreased from 0.80 +/- 0.02 to 0.72 +/- 0.01. Respiratory exchange ratio and O2 consumption were not significantly modified in sterile water-treated (control) horses. Clenbuterol HCl administration was associated with increased cardiac index (from 57.4 +/- 4.0 to 84.2 +/- 6.3 ml . min-1 . kg- 1), decreased total peripheral vascular resistance (from 108.3 +/- 9.3 to 47.6 +/- 2.8 mm of Hg . s . kg . ml-1), and decreased pulmonary vascular resistance (from 31.3 +/- 3.8 to 13.6 +/- 0.7 mm of Hg . s . kg . ml-1). Our findings indicated that clenbuterol HCl may potentiate hypoxemia as a result of increased shunt fraction in horses anesthetized by the IV route, and caused changes in hemodynamic variables that were consistent with its ability to stimulate beta 2-adrenergic receptors.