Yukie Ueyama

Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.

Effects of intravenous administration of lactated Ringer's solution on hematologic, serum biochemical, rheological, hemodynamic, and renal measurements in healthy isoflurane-anesthetized dogs

OBJECTIVE To determine the hematologic, serum biochemical, rheological, hemodynamic, and renal effects of IV administration of lactated Ringers solution (LRS) to healthy anesthetized dogs. DESIGN 4-period, 4-treatment cross-over study. ANIMALS 8 healthy mixed-breed dogs. PROCEDURES Each dog was anesthetized, mechanically ventilated, instrumented, and randomly assigned to receive LRS (0, 10, 20, or 30 mL/kg/h [0, 4.5, 9.1, or 13.6 mL/lb/h]), IV, on 4 occasions separated by at least 7 days. Blood hemoglobin concentration and serum total protein, albumin, lactate, and electrolyte concentrations; PCV; colloid osmotic pressure; arterial and venous pH and blood gases (Po2; Pco2); whole blood and plasma viscosity; arterial and venous blood pressures; cardiac output; results of urinalysis; urine production; glomerular filtration rate; and anesthetic recovery times were monitored. Oxygen delivery, vascular resistance, stroke volume, pulse pressure, and blood and plasma volume were calculated. RESULTS Increasing rates of LRS administration resulted in dose-dependent decreases in PCV; blood hemoglobin concentration and serum total protein and albumin concentrations; colloid osmotic pressure; and whole blood viscosity. Plasma viscosity; serum electrolyte concentrations; data from arterial and venous blood gas analysis; glomerular filtration rate; urine production; heart rate; pulse, central venous, and arterial blood pressures; pulmonary vascular resistance; and oxygen delivery did not change. Pulmonary artery pressure, stroke volume, and cardiac output increased, and systemic vascular resistance decreased. CONCLUSIONS AND CLINICAL RELEVANCE Conventional IV infusion rates of LRS to isoflurane-anesthetized dogs decreased colligative blood components; increased plasma volume, pulmonary artery pressure, and cardiac output; and did not change urine production or oxygen delivery to tissues.

Evaluation of oscillometric and vascular access port arterial blood pressure measurement techniques versus implanted telemetry in anesthetized cats

OBJECTIVE To compare the use of a semi-invasive vascular access port (VAP) device or noninvasive oscillometry versus invasive telemetry for blood pressure measurements in cats. ANIMALS 6 healthy cats. PROCEDURES 30 days before the study, all cats received an implanted telemeter and a VAP device. During normotension and experimentally induced hypertension, blood pressure was measured with the implanted devices and with noninvasive oscillometry at 4 time points. RESULTS Compared with invasive telemetry, VAP had a correlation coefficient from 0.8487 to 0.9972, and noninvasive oscillometry had a correlation coefficient from 0.7478 to 0.9689. CONCLUSIONS AND CLINICAL RELEVANCE Use of the VAP device and noninvasive oscillometry had a high degree of correlation with invasive telemetry as the gold standard for blood pressure measurement. Use of a VAP device resulted in a slightly higher degree of correlation, compared with noninvasive oscillometry.

Arterial blood pressure as a predictor of the response to fluid administration in euvolemic nonhypotensive or hypotensive isoflurane-anesthetized dogs

OBJECTIVE To determine the effects of rapid small-volume fluid administration on arterial blood pressure measurements and associated hemodynamic variables in isoflurane-anesthetized euvolemic dogs with or without experimentally induced hypotension. DESIGN Prospective, randomized, controlled study. ANIMALS 13 healthy dogs. PROCEDURES Isoflurane-anesthetized dogs were randomly assigned to conditions of nonhypotension or hypotension (mean arterial blood pressure, 45 to 50 mm Hg) and treatment with lactated Ringers solution (LRS) or hetastarch (3 or 10 mL/kg [1.4 or 4.5 mL/lb] dose in a 5-minute period or 3 mL/kg dose in a 1-minute period [4 or 5 dogs/treatment; ≥ 10-day interval between treatments]). Hemodynamic variables were recorded before and for up to 45 minutes after fluid administration. RESULTS IV administration of 10 mL/kg doses of LRS or hetastarch in a 5-minute period increased right atrial and pulmonary arterial pressures and cardiac output (CO) when dogs were nonhypotensive or hypotensive, compared with findings before fluid administration; durations of these effects were greater after hetastarch administration. Intravenous administration of 3 mL of hetastarch/kg in a 5-minute period resulted in an increase in CO when dogs were nonhypotensive. Intravenous administration of 3 mL/kg doses of LRS or hetastarch in a 1-minute period increased right atrial pressure and CO when dogs were nonhypotensive or hypotensive. CONCLUSIONS AND CLINICAL RELEVANCE Administration of LRS or hetastarch (3 or 10 mL/kg dose in a 5-minute period or 3 mL/kg dose in a 1-minute period) improved CO in isoflurane-anesthetized euvolemic dogs with or without hypotension. Overall, arterial blood pressure measurements were a poor predictor of the hemodynamic response to fluid administration.

VASOMERA™, A NOVEL VPAC2-SELECTIVE VASOACTIVE INTESTINAL PEPTIDE AGONIST, ENHANCES CONTRACTILITY AND DECREASES MYOCARDIAL DEMAND IN DOGS WITH BOTH NORMAL HEARTS AND WITH PACING-INDUCED DILATED CARDIOMYOPATHY

The natural vasoactive intestinal peptide (VIP) has been proposed as a therapeutic agent for heart failure via the activation of the G-protein-coupled VPAC1 and VPAC2 receptors; however, VIPs clinical utility is limited due to its short half-life and VPAC1-mediated side-effects. Vasomera™ is a

A Systematic Review of the Quality of IV Fluid Therapy in Veterinary Medicine

Objective To evaluate the quality of the veterinary literature investigating IV fluid therapy in dogs, cats, horses, and cattle. Design Systematic review. Procedures The preferred reporting of items for systematic review and meta-analysis protocols (PRISMA-P) was employed for systematic review of all relevant IV fluid therapy manuscripts published from January 1969 through December 2016 in the Commonwealth Agricultural Bureaux International (CABI) database. Independent grading systems used to evaluate manuscripts included the updated CONsolidated Standards of Reporting Trials 2012 checklist, risk of bias for animal intervention studies, criteria for levels of evidence, and methodological quality (Jadad scale). The quality of articles published before and after 2010 was compared. Results One hundred and thirty-nine articles (63 dogs, 7 cats, 39 horses, 30 cattle) from 7,258 met the inclusion criteria. More than 50% of the manuscripts did not comply with minimal requirements for reporting randomized controlled trials. The most non-compliant items included identification of specific predefined objectives or a hypothesis, identification of trial design, how sample size was determined, randomization, and blinding procedures. Most studies were underpowered and at risk for selection, performance, and detection bias. The overall quality of the articles improved for articles published after 2010. Conclusion and clinical relevance Most of the veterinary literature investigating the administration of IV fluid therapy in dogs, cats, horses, and cattle is descriptive, does not comply with standards for evidence, or provide adequate translation to clinical practice. Authors should employ and journal editors should enforce international consensus recommendations and guidelines for publication of data from animal experiments investigating IV fluid therapy.

Cardiac Unloading with an Implantable Interatrial Shunt in Heart Failure: Serial Observations in an Ovine Model of Ischemic Cardiomyopathy

ABSTRACT Background: Patients with dilated cardiomyopathy often have progressive heart failure with systolic dysfunction, ventricular remodeling and clinical decompensation heralded by elevations of filling pressures. Our hypothesis is that an interatrial shunt device can regulate left atrial pressure and stabilize left ventricular function without overloading the right heart. Methods: Sheep (N = 21) were subjected to repeat coronary microembolization until left ventricular dysfunction with reduced LVEF was documented. After study group assignment, animals were chronically instrumented during thoracotomy. Shunts were implanted in n = 14 and n = 7 were sham controls. Hemodynamic and echocardiographic responses were serially evaluated for 12 weeks. Results: Comparisons at study termination showed improved outcomes with interatrial shunting (LVEF 46 ± 11% vs. 18 ± 3%; fractional shortening 19 ± 6% vs. 6 ± 1%; ventricular septal thickness 1.2 ± 0.2 cm vs. 1.0 ± 0.3 cm; left atrial pressure 14 ± 3 mmHg vs. 25 ± 5 mmHg; mean pulmonary artery pressure 24 ± 4 mmHg vs. 37 ± 8 mmHg; right atrial pressure 8 ± 4 mmHg vs. 15 ± 4 mmHg; LV dP/dtmax 1515 ± 391 mmHg·s−1 vs. 879 ± 333 mmHg−s−1; LV dP/dtmin −2116 ± 569 mmHg·s−1 vs. −1138 ± 545 mmHg·s−1; p ≤ 0.03 for all comparisons). These findings were supported by gross pathological observations and there was a survival advantage with shunting (13/14 vs. 4/7 at 12 weeks, p = 0.047). Shunts were small with Qp:Qs 1.2 ± 0.1 and all devices were patent at necropsy. Conclusion: In an animal model of ischemic cardiomyopathy, interatrial shunting selectively unloaded the left-heart leading to sustained reductions in left-atrial pressure, improved left ventricular performance, preserved inotropic and lusitropic function with blunted remodeling. Secondary pulmonary hypertension was absent and right-sided cardiac pressures and function were preserved.

CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction—A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat

The nitroxyl (HNO) prodrug, CXL-1020, induces vasorelaxation and improves cardiac function in canine models and patients with systolic heart failure (HF). HNOs unique mechanism of action may be applicable to a broader subset of cardiac patients. This study investigated the load-independent safety and efficacy of CXL-1020 in two rodent (rat) models of diastolic heart failure and explored potential drug interactions with common HF background therapies. In vivo left-ventricular hemodynamics/pressure-volume relationships assessed before/during a 30 min IV infusion of CXL-1020 demonstrated acute load-independent positive inotropic, lusitropic, and vasodilatory effects in normal rats. In rats with only diastolic dysfunction due to bilateral renal wrapping (RW) or pronounced diastolic and mild systolic dysfunction due to 4 weeks of chronic isoproterenol exposure (ISO), CXL-1020 attenuated the elevated LV filling pressures, improved the end diastolic pressure volume relationship, and accelerated relaxation. CXL-1020 facilitated Ca2+ re-uptake and enhanced myocyte relaxation in isolated cardiomyocytes from ISO rats. Compared to milrinone, CXL-1020 more effectively improved Ca2+ reuptake in ISO rats without concomitant chronotropy, and did not enhance Ca2+ entry via L-type Ca2+ channels nor increase myocardial arrhythmias/ectopic activity. Acute-therapy with CXL-1020 improved ventricular relaxation and Ca2+ cycling, in the setting of chronic induced diastolic dysfunction. CXL-1020s lusitropic effects were greater than those seen with the cAMP-dependent agent milrinone, and unlike milrinone it did not produce chronotropy or increased ectopy. HNO is a promising new potential therapy for both systolic and diastolic heart failure.

A pilot study evaluating adaptive closed-loop fluid resuscitation during states of absolute and relative hypovolemia in dogs: Closed-Loop Fluid Resuscitation in Dogs

OBJECTIVE To evaluate and determine the performance of a partially automated as well as a fully automated closed-loop fluid resuscitation system during states of absolute and relative hypovolemia. DESIGN Prospective experimental trial. SETTING Research laboratory. ANIMALS Five adult Beagle dogs. METHODS Isoflurane anesthetized mechanically ventilated dogs were subjected to absolute hypovolemia (controlled: 2 trials; uncontrolled: 3 trials), relative hypovolemia (2 trials), and the combination of relative and absolute controlled hypovolemia (2 trials). Controlled and uncontrolled hypovolemia were produced by withdrawing blood from the carotid or femoral artery. Relative hypovolemia was produced by increasing the isoflurane concentration (1 trial) or by infusion of intravenous sodium nitroprusside (1 trial). Relative hypovolemia combined with controlled absolute hypovolemia was produced by increasing the isoflurane concentration (1 trial) and infusion of IV sodium nitroprusside (1 trial). Hemodynamic parameters including stroke volume variation (SVV) were continuously monitored and recorded in all dogs. A proprietary closed-loop fluid administration system based on fluid distribution and compartmental dynamical systems administered a continuous infusion of lactated Ringers solution in order to restore and maintain SVV to a predetermined target value. MEASUREMENTS AND MAIN RESULTS A total of 9 experiments were performed on 5 dogs. Hemodynamic parameters deteriorated and SVV increased during controlled or uncontrolled hypovolemia, relative hypovolemia, and during relative hypovolemia combined with controlled hypovolemia. Stroke volume variation was restored to baseline values during closed-loop fluid infusion. CONCLUSIONS Closed-loop fluid administration based on IV fluid distribution and compartmental dynamical systems can be used to provide goal directed fluid therapy during absolute or relative hypovolemia in mechanically ventilated isoflurane anesthetized dogs.

Effects of propofol on intraocular pressure in premedicated and nonpremedicated dogs with and without glaucoma

OBJECTIVE To establish a study cutoff for evidence of glaucoma on the basis of IOP measurements from a large population of healthy dogs and to assess the effects of IV propofol administration on IOPs in premedicated and nonpremedicated dogs with and without glaucoma defined by this method. DESIGN Prospective, descriptive study. ANIMALS 234 client-owned dogs. PROCEDURES IOPs measured in 113 healthy dogs (226 eyes) were used to calculate an IOP value indicative of glaucoma. The IOPs were measured in an additional 121 dogs (237 eyes) undergoing ophthalmic surgery. Midazolam-butorphanol was administered IV as preanesthetic medication to 15 and 87 dogs with and without glaucoma, respectively. A placebo (lactated Ringer solution) was administered IV to 8 and 11 dogs with and without glaucoma, respectively. Anesthesia of surgical patients was induced with propofol IV to effect. The IOPs and physiologic variables of interest were recorded before (baseline) and after preanesthetic medication or placebo administration and after propofol administration. RESULTS An IOP > 25 mm Hg was deemed indicative of glaucoma. Compared with baseline measurements, mean IOP was increased after propofol administration in nonpremedicated dogs without glaucoma and unchanged in nonpremedicated dogs with glaucoma. Propofol-associated increases in IOP were blunted in premedicated dogs without glaucoma; IOP in affected eyes of premedicated dogs with glaucoma was decreased after preanesthetic medication and after propofol administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that preexisting IOP influences the response to anesthetic drugs, and administration of preanesthetic medication with muscle-relaxing properties may blunt or reduce propofol-induced increases in IOP. Further research with a larger number of dogs is needed to confirm our results in dogs with glaucoma.