Dynamic detection and reversal of myocardial ischemia using an artificially intelligent bioelectronic medicine.

Myocardial ischemia is spontaneous, frequently asymptomatic, and contributes to fatal cardiovascular consequences. Importantly, myocardial sensory networks cannot reliably detect and correct myocardial ischemia on their own. Here, we demonstrate an artificially intelligent and responsive bioelectronic medicine, where an artificial neural network (ANN) supplements myocardial sensory networks, enabling reliable detection and correction of myocardial ischemia. ANNs were first trained to decode spontaneous cardiovascular stress and myocardial ischemia with an overall accuracy of ~92%. ANN-controlled vagus nerve stimulation (VNS) significantly mitigated major physiological features of myocardial ischemia, including ST depression and arrhythmias. In contrast, open-loop VNS or ANN-controlled VNS following a caudal vagotomy essentially failed to reverse cardiovascular pathophysiology. Last, variants of ANNs were used to meet clinically relevant needs, including interpretable visualizations and unsupervised detection of emerging cardiovascular stress. Overall, these preclinical results suggest that ANNs can potentially supplement deficient myocardial sensory networks via an artificially intelligent bioelectronic medicine system.

Closed-Loop Control for Fluid Resuscitation: Recent Advances and Future Challenges.

Fluid therapy is extensively used to treat traumatized patients as well as patients during surgery. The fluid therapy process is complex due to interpatient variability in response to therapy as well as other complicating factors such as comorbidities and general anesthesia. These complexities can result in under- or over-resuscitation. Given the complexity of the fluid management process as well as the increased capabilities in hemodynamic monitoring, closed-loop fluid management can reduce the workload of the overworked clinician while ensuring specific constraints on hemodynamic endpoints are met with higher accuracy. The goal of this paper is to provide an overview of closed-loop control systems for fluid management and highlight several key steps in transitioning such a technology from bench to the bedside.

Understanding Volume Kinetics: The Role of Pharmacokinetic Modeling and Analysis in Fluid Therapy.

Fluid therapy is a rapidly evolving yet imprecise clinical practice based upon broad assumptions, species-to-species extrapolations, obsolete experimental evidence, and individual preferences. Although widely recognized as a mainstay therapy in human and veterinary medicine, fluid therapy is not always benign and can cause significant harm through fluid overload, which increases patient morbidity and mortality. As with other pharmaceutical substances, fluids exert physiological effects when introduced into the body and therefore should be considered as "drugs." In human medicine, an innovative adaptation of pharmacokinetic analysis for intravenous fluids known as volume kinetics using serial hemoglobin dilution and urine output has been developed, refined, and investigated extensively for over two decades. Intravenous fluids can now be studied like pharmaceutical drugs, leading to improved understanding of their distribution, elimination, volume effect, efficacy, and half-life (duration of effect) under various physiologic conditions, making evidence-based approaches to fluid therapy possible. This review article introduces the basic concepts of volume kinetics, its current use in human and animal research, as well as its potential and limitations as a research tool for fluid therapy research in veterinary medicine. With limited evidence to support our current fluid administration practices in veterinary medicine, a greater understanding of volume kinetics and body water physiology in veterinary species would ideally provide some evidence-based support for safer and more effective intravenous fluid prescriptions in veterinary patients.

Myocardial Contractility: Historical and Contemporary Considerations.

The term myocardial contractility is thought to have originated more than 125 years ago and has remained and enigma ever since. Although the term is frequently used in textbooks, editorials and contemporary manuscripts its definition remains illusive often being conflated with cardiac performance or inotropy. The absence of a universally accepted definition has led to confusion, disagreement and misconceptions among physiologists, cardiologists and safety pharmacologists regarding its definition particularly in light of new discoveries regarding the load dependent kinetics of cardiac contraction and their translation to cardiac force-velocity and ventricular pressure-volume measurements. Importantly, the Starling interpretation of force development is length-dependent while contractility is length independent. Most historical definitions employ an operational approach and define cardiac contractility in terms of the hearts mechanical properties independent of loading conditions. Literally defined the term contract infers that something has become smaller, shrunk or shortened. The addition of the suffix "ility" implies the quality of this process. The discovery and clinical investigation of small molecules that bind to sarcomeric proteins independently altering force or velocity requires that a modern definition of the term myocardial contractility be developed if the term is to persist. This review reconsiders the historical and contemporary interpretations of the terms cardiac performance and inotropy and recommends a modern definition of myocardial contractility as the preload, afterload and length-independent intrinsic kinetically controlled, chemo-mechanical processes responsible for the development of force and velocity.

A pilot study evaluating adaptive closed-loop fluid resuscitation during states of absolute and relative hypovolemia 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.

Anesthesia-Associated Relative Hypovolemia: Mechanisms, Monitoring, and Treatment Considerations.

Although the utility and benefits of anesthesia and analgesia are irrefutable, their practice is not void of risks. Almost all drugs that produce anesthesia endanger cardiovascular stability by producing dose-dependent impairment of cardiac function, vascular reactivity, and compensatory autoregulatory responses. Whereas anesthesia-related depression of cardiac performance and arterial vasodilation are well recognized adverse effects contributing to anesthetic risk, far less emphasis has been placed on effects impacting venous physiology and venous return. The venous circulation, containing about 65-70% of the total blood volume, is a pivotal contributor to stroke volume and cardiac output. Vasodilation, particularly venodilation, is the primary cause of relative hypovolemia produced by anesthetic drugs and is often associated with increased venous compliance, decreased venous return, and reduced response to vasoactive substances. Depending on factors such as patient status and monitoring, a state of relative hypovolemia may remain clinically undetected, with impending consequences owing to impaired oxygen delivery and tissue perfusion. Concurrent processes related to comorbidities, hypothermia, inflammation, trauma, sepsis, or other causes of hemodynamic or metabolic compromise, may further exacerbate the condition. Despite scientific and technological advances, clinical monitoring and treatment of relative hypovolemia still pose relevant challenges to the anesthesiologist. This short perspective seeks to define relative hypovolemia, describe the venous system's role in supporting normal cardiovascular function, characterize effects of anesthetic drugs on venous physiology, and address current considerations and challenges for monitoring and treatment of relative hypovolemia, with focus on insights for future therapies.

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.

Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs.

OBJECTIVE: To examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Six adult healthy sevoflurane-anaesthetized Beagle dogs. METHODS: Dogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were mechanically ventilated after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined during six stages of graded venous blood withdrawal (5 mL kg-1 increments) and six stages of graded blood infusion (5 mL kg-1 increments). The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. RESULTS: Blood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in MAP, CVP, TPTDCO, SV and PI and decreases in PPV and PVI. PPV and PVI showed a relevant correlation (p < 0.001, r2 = 0.62) and threshold values of PPV ≥ 16% (sensitivity 71%, specificity 82%) and PVI ≥ 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. CONCLUSIONS AND CLINICAL RELEVANCE: Noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV ≥ 16% and PVI ≥ 12%. Clinical trials are needed to confirm these threshold values in dogs.

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.

Stroke volume variation (SVV) and pulse pressure variation (PPV) as indicators of fluid responsiveness in sevoflurane anesthetized mechanically ventilated euvolemic dogs.

Changes in stroke volume variation (SVV) and pulse pressure variation (PPV) in response to fluid infusion were experimentally evaluated during vecuronium infusion and sevoflurane anesthesia in 5 adult, mechanically ventilated, euvolemic, beagle dogs. Sequential increases in central venous pressure (CVP; 3-7[baseline], 8-12, 13-17, 18-22 and 23-27 mmHg) were produced by infusing lactated Ringer's solution and 6% hydroxyethyl starch solution. Heart rate (beats/min), right atrial pressure (RAP, mmHg), pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), transpulmonary thermodilution cardiac output (TPTDCO, l/min), stroke volume (SV, ml/beat), arterial blood pressure (ABP, mmHg), extravascular lung water (EVLW, ml), pulmonary vascular permeability index (PVPI, calculated), SVV (%), PPV (%) and systemic vascular resistance (SVR, dynes/sec/cm5) were determined at each predetermined CVP range. Heart rate (P=0.019), RAP (P<0.001), PAP (P<0.001), PCWP (P<0.001), TPTDCO (P=0.009) and SV (P=0.04) increased and SVR (P<0.001), SVV (P<0.001) and PPV (P<0.001) decreased associated with each stepwise increase in CVP. Arterial blood pressure, EVLW, PVPI and the arterial partial pressures of oxygen and carbon dioxide did not change. The changes in SVV and PPV directly reflected the fluid load and the minimum threshold values for detecting fluid responsiveness were SVV ≥11% and PPV ≥7% in dogs.

Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs.

We determined the dose-dependent effects of OC99, a novel, stabilized hemoglobin-based oxygen-carrier, on hemodynamics, systemic and pulmonary artery pressures, surrogates of tissue oxygen debt (arterial lactate 7.2 ± 0.1 mM/L and arterial base excess -17.9 ± 0.5 mM/L), and tissue oxygen tension (tPO2) in a dog model of controlled severe oxygen-debt from hemorrhagic shock. The dose/rate for OC99 was established from a pilot study conducted in six bled dogs. Subsequently twenty-four dogs were randomly assigned to one of four groups (n = 6 per group) and administered: 0.0, 0.065, 0.325, or 0.65 g/kg of OC99 combined with 10 mL/kg lactated Ringers solution administered in conjunction with 20 mL/kg Hextend IV over 60 minutes. The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99. The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure. Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.

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 Ringer's 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.

Anesthetic and cardiorespiratory effects of propofol, medetomidine, lidocaine and butorphanol total intravenous anesthesia in horses.

Anesthetic and cardiorespiratory effects of medetomidine, lidocaine, butorphanol and propofol total intravenous anesthesia (MLBP-TIVA) were evaluated in horses undergoing an experimental surgery. Ten horses were premedicated with an intravenous injection (IV) of medetomidine (5 µg/kg) and butorphanol (20 µg/kg). Anesthesia was induced by administration of 1% propofol (3 mg/kg, IV) at a rate of 1 mg/kg/min (n=5, group-1) or 2% propofol administered at a rate of 6 mg/kg/min (n=5, group-2) following administration of lidocaine (1 mg/kg, IV) and then maintained by infusions of propofol, medetomidine (3.5 µg/kg/hr), lidocaine (3 mg/kg/hr) and butorphanol (24 µg/kg/hr). The mean durations of anesthesia and propofol infusion rate required for maintaining surgical anesthesia were 130 ± 17 min and 0.10 ± 0.01 mg/kg/min in group 1 and 129 ± 14 min and 0.10 ± 0.02 mg/kg/min in group 2. Four horses in group 1 and 2 horses in group 2 paddled following recumbency during induction of anesthesia. The median quality scores for induction (0-4: poor-excellent) and recovery (0-5: unable to stand-excellent) were 3 and 4 for both groups, respectively. Transition to anesthesia (the first 20-min period after induction) was uneventful in group 2, while all horses showed a light plane of anesthesia in group 1. The quality score (0-3: poor-excellent) for the transition to anesthesia in group 2 was significantly higher than in group 1 (median 3 versus 1, P=0.009). Heart rate and arterial blood pressure were maintained within acceptable ranges, but hypercapnia occurred during anesthesia in both groups. In conclusion, MLBP-TIVA may provide clinically useful surgical anesthesia in horses. A rapid induction with propofol may improve the qualities of induction and transition to MLBP-TIVA.

Cardiorespiratory, gastrointestinal, and analgesic effects of morphine sulfate in conscious healthy horses.

OBJECTIVE: To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variables; intestinal motility; and response to thermal and electrical noxious stimuli. Adverse effects and horse behavior were also recorded. Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid chromatography-mass spectrometry. RESULTS: No significant differences in any variable were evident after saline solution administration. Intravenous and IM administration of morphine resulted in minimal and short-term cardiorespiratory, intestinal motility, and behavioral changes. A decrease in gastrointestinal motility was detected 1 to 2 hours after IM administration of morphine at doses of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1 mg/kg. Morphine administration yielded no change in any horse's response to noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were detected in plasma after IV and IM administration of morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Clinically relevant doses of morphine sulfate yielded minimal and short-term behavioral and intestinal motility effects in healthy horses with no signs of pain. Neither dose of morphine affected their response to a noxious stimulus.

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 Ringer's 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.

Effect of 50% and maximal inspired oxygen concentrations on respiratory variables in isoflurane-anesthetized horses.

BACKGROUND: The purpose of this study was to compare the effects of 0.5 fraction of inspired oxygen (FiO2) and >0.95 FiO2 on pulmonary gas exchange, shunt fraction and oxygen delivery (DO2) in dorsally recumbent horses during inhalant anesthesia. The use of 0.5 FiO2 has the potential to reduce absorption atelectasis (compared to maximal FiO2) and augment alveolar oxygen (O2) tensions (compared to ambient air) thereby improving gas exchange and DO2. Our hypothesis was that 0.5 FiO2 would reduce ventilation-perfusion mismatching and increase the fraction of pulmonary blood flow that is oxygenated, thus improving arterial oxygen content and DO2. RESULTS: Arterial partial pressures of O2 were significantly higher than preanesthetic levels at all times during anesthesia in the >0.95 FiO2 group. Arterial partial pressures of O2 did not change from preanesthetic levels in the 0.5 FiO2 group but were significantly lower than in the >0.95 FiO2 group from 15 to 90 min of anesthesia. Alveolar to arterial O2 tension difference was increased significantly in both groups during anesthesia compared to preanesthetic values. The alveolar to arterial O2 tension difference was significantly higher at all times in the >0.95 FiO2 group compared to the 0.5 FiO2 group. Oxygen delivery did not change from preanesthetic values in either group during anesthesia but was significantly lower than preanesthetic values 10 min after anesthesia in the 0.5 FiO2 group. Shunt fraction increased in both groups during anesthesia attaining statistical significance at varying times. Shunt fraction was significantly increased in both groups 10 min after anesthesia but was not different between groups. Alveolar dead space ventilation increased after 3 hr of anesthesia in both groups. CONCLUSIONS: Reducing FiO2 did not change alveolar dead space ventilation or shunt fraction in dorsally recumbent, mechanically ventilated horses during 3 hr of isoflurane anesthesia. Reducing FiO2 in dorsally recumbent isoflurane anesthetized horses does not improve oxygenation or oxygen delivery.

Vital organ tissue oxygenation after serial normovolemic exchange transfusion with HBOC-201 in anesthetized swine.

This study determined the effects of serial, normovolemic, stepwise exchange transfusions with either 6% human serum albumin (HSA) or the hemoglobin-based oxygen carrier, HBOC-201, on tissue oxygenation of the heart, brain, and kidney in intact anaesthetized pigs. Exchange transfusions to 10%, 30%, and 50% of the pigs' total blood volume were completed at a withdrawal rate of 1.0 mL·kg(-1)·min(-1) followed by an infusion rate of 0.5 mL·kg(-1)·min(-1) of HBOC-201 or iso-oncotically matched 6% HSA. Measurements included invasive systemic hemodynamic (blood pressures, left ventricular end-diastolic pressure), hematolic (hemoglobin, hematocrit, methemoglobin), acid-base (pH, PCO2), and biochemistry (serum lactate) measurements. Brain and kidney tissue oxygenation (tPO2) was determined by electron paramagnetic resonance and heart tPO2 by O2 sensitive fiberoptic probe. The main results demonstrated that tPO2 after HBOC-201 remained stable despite significant decreases in hematocrit and changing hemodynamics. In vivo tPO2 measurements (heart tPO2 average ≥22 mmHg, brain tPO2 average ≥8 mmHg, and kidney tPO2 average ≥10 mmHg) were maintained in all groups at all times. Blood pressures were 20 to 30 mmHg higher after HBOC-201 compared with HSA controls. Heart rate and left ventricular end-diastolic pressure were not different among treatment groups. In conclusion, the administration of HBOC-201 maintained tPO2 in three vital organs after profound hemodilution.