Measurement of cardiac output by transesophageal Doppler ultrasonography in anesthetized dogs - comparison with thermodilution

Objective: To compare cardiac outputs (CO) measured by a transesophageal Doppler ultrasound technique (TED, Hemosonic 100[Superscript TM], Arrow Int) and CO measured by thermodilution (TD) in anesthetized dogs. Design: Interventional studies. Settings: Veterinary Teaching Laboratory-Iowa State University. Animals: The study included 10 canines weighing from 18.5 kg to 32.5 kg. Set criteria for inclusion were adequate body size of the dogs for placement of the esophageal probe (body weight\u3e18.5 kg) and stable anesthesia maintenance period. Interventions: Simultaneous TED and TD measurements of CO were obtained during initial baseline period. The baseline CO was then altered by constant rate intravenous infusion of dobutamine, dopamine and norepinephrine; and by caudal vena cava occlusion. Results: Each measurement of CO allowed a comparison of TED and TD values. Forty-nine CO paired comparisons were made with the CO ranging from 0.73 l/min to 10.9 l/min (obtained by TD). Simple linear regression was used to determine the correlation between the two techniques (rò=0.53). Bland and Altman statistical method was used for assessing agreement between the two methods. The difference between the TD and TED was 0.82 l/min (bias) and SD was 1.63 l/min. At baseline and low CO levels (caudal vena cava occlusion) the correlation coefficient (rò) was 0.77 and at high CO levels (dobutamine, dopamine and norepinephrine infusions) the correlation coefficient (rò) was 0.45. Conclusion: The TED might be a useful method for detecting low CO trends and aid in determining the cause of hypotension

Assessment of Cardiorespiratory Interactions during Apneic Events in Sleep via Fuzzy Kernel Measures of Information Dynamics

Apnea and other breathing-related disorders have been linked to the development of hypertension or impairments of the cardiovascular, cognitive or metabolic systems. The combined assessment of multiple physiological signals acquired during sleep is of fundamental importance for providing additional insights about breathing disorder events and the associated impairments. In this work, we apply information-theoretic measures to describe the joint dynamics of cardiorespiratory physiological processes in a large group of patients reporting repeated episodes of hypopneas, apneas (central, obstructive, mixed) and respiratory effort related arousals (RERAs). We analyze the heart period as the target process and the airflow amplitude as the driver, computing the predictive information, the information storage, the information transfer, the internal information and the cross information, using a fuzzy kernel entropy estimator. The analyses were performed comparing the information measures among segments during, immediately before and after the respiratory event and with control segments. Results highlight a general tendency to decrease of predictive information and information storage of heart period, as well as of cross information and information transfer from respiration to heart period, during the breathing disordered events. The information-theoretic measures also vary according to the breathing disorder, and significant changes of information transfer can be detected during RERAs, suggesting that the latter could represent a risk factor for developing cardiovascular diseases. These findings reflect the impact of different sleep breathing disorders on respiratory sinus arrhythmia, suggesting overall higher complexity of the cardiac dynamics and weaker cardiorespiratory interactions which may have physiological and clinical relevance

Classification of Physiological States Through Machine Learning Algorithms Applied to Ultra-Short-Term Heart Rate and Pulse Rate Variability Indices on a Single-Feature Basis

This study investigates the feasibility of classifying physiological stress states usingMachine Learning (ML) algorithms on short-term (ST,∼5min) and ultra-short-term (UST, < 5 min, down to 10 heartbeats) heart rate (HRV) or pulse rate variability (PRV) features computed from inter-beat interval time series. Three widely employed ML algorithms were used, i.e. Naive Bayes Classifier, Support Vector Machines, and Neural Networks, on various time-, frequency and information domain HRV/PRV indices on a single-feature basis. Data were collected from healthy individuals during different physiological states including rest, postural and mental stress. Results highlighted comparable values using either HRV or PRV indices, and higher accuracy (>65% for most features and all classifiers) when classifying postural than mental stress. While decreasing the time series length, time-domain indices resulted still reliable down to ∼10 s, contrary to UST frequency-domain features which reported lower accuracy below 60 heartbeats

Detection and characterization of glaucoma-like canine retinal tissues using Raman spectroscopy

Early detection of pathological changes and progression in glaucoma and other neuroretinal diseases remains a great challenge and is critical to reduce permanent structural and functional retina and optic nerve damage. Raman spectroscopy is a sensitive technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, spectroscopic analysis was conducted on the retinal tissues of seven beagles with acute elevation of intraocular pressure (AEIOP), six beagles with compressive optic neuropathy (CON), and five healthy beagles. Spectroscopic markers were identified associated with the different neuropathic conditions. Furthermore, the Raman spectra were subjected to multivariate discriminate analysis to classify independent tissue samples into diseased/healthy categories. The multivariate discriminant model yielded an average optimal classification accuracy of 72.6% for AEIOP and 63.4% for CON with 20 principal components being used that accounted for 87% of the total variance in the data set. A strong correlation (R2\u3e0.92) was observed between pattern electroretinography characteristics of AEIOP dogs and Raman separation distance that measures the separation of spectra of diseased tissues from normal tissues; however, the underlining mechanism of this correlation remains to be understood. Since AEIOP mimics the pathological symptoms of acute/early-stage glaucoma, it was demonstrated that Raman spectroscopic screening has the potential to become a powerful tool for the detection and characterization of early-stage disease

Monocytic/Macrophagic Pneumonitis after Intrabronchial Deposition of Vascular Endothelial Growth Factor in Neonatal Lambs

Preterm and young neonates are prone to inadequate surfactant production and are susceptible to respiratory distress syndrome characterized by alveolar damage and hyaline-membrane formation. Glucocorticoid therapy is commonly used in preterm and young infants to enhance lung maturation and surfactant synthesis. Recently, vascular endothelial growth factor (VEGF) was suggested to be a novel therapeutic agent for lung maturation that lacked adverse effects in mice. The purpose of this study was to assess the safety of incremental concentration (0.0005, 0.005, and 0.05 mg/ml) and duration (16, 24, and 32 hours) of recombinant human VEGF after bronchoscopic instillation (10 ml) in neonatal lambs. High-dose VEGF caused locally extensive plum-red consolidation that was microscopically characterized by interstitial and alveolar infiltrates of cells that were morphologically and phenotypically (CD68+) consistent with monocytes/macrophages. T cells (CD3+) and B cells (CD79+) were located primarily in bronchus/bronchiole-associated lymphoid tissue and were not consistently altered by treatment with VEGF. The dose of VEGF had significant effects on both gross lesions (P \u3c .0047) and microscopic monocyte/macrophage recruitment scores (P \u3c .0001). Thus, the VEGF dose instilled into the lung greatly influenced cellular recruitment and lesion development. The post-dosing interval of VEGF in this study had minor impact (no statistical significance) on cellular recruitment. This study showed that airway deposition of VEGF in the neonatal lamb induces monocyte/macrophage recruitment to the lung and high doses can cause severe lesions. The cellular recruitment suggests further research is needed to define dosages that are efficacious in enhancing lung maturation while minimizing potential adverse effects

Maternal alcohol ingestion reduces SP-A expression by pre-term fetal lung epithelia

In addition to neurodevelopmental effects, alcohol consumption at high levels during pregnancy is associated with immunomodulation and premature birth. Premature birth, in turn, is associated with increased susceptibility to various infectious agents such as Respiratory Syncytial Virus (RSV). The initial line of pulmonary innate defense includes the mucociliary apparatus, which expels microorganisms trapped within the airway secretions. Surfactant proteins A and D (SP-A and SP-D, respectively) are additional components of pulmonary innate immunity and have an important role in pulmonary defense against inhaled pathogens. The purpose of this study was to determine if chronic alcohol consumption during the third trimester of pregnancy alters the function of the mucociliary apparatus and expression of SP-A and SP-D of fetal lung epithelia. Sixteen, date-mated ewes were assigned to two different groups; an ethanol exposed group in which ewes received ethanol through surgically implanted intra-abomasal cannula during the third trimester of pregnancy, and a control group in which ewes received the equivalent amount of water instead of ethanol. Within these two groups, ewes were further randomly assigned to a full-term group in which the lambs were naturally delivered, and a pre-term group in which the lambs were delivered prematurely via an abdominal incision and uterotomy. Ethanol was administered 5 times a week as a 40% solution at 1gr/kg of body weight. The mean maternal serum alcohol concentration (SAC) measured 6 hr post administration was 16.3 +/− 4.36 mg/dL. Tracheas from 6 full-term lambs were collected to assess ciliary beat frequency (CBF). The lung tissue from all (24) lambs was collected for immunohistochemistry (IHC) analysis of SP-A and SP-D protein production and fluorogenic real-time quantitative polymerase chain reaction analysis (qPCR) of SP-A and SP-D mRNA levels. Exposure to ethanol during pregnancy significantly blocked stimulated increase in CBF though ethanol-mediated desensitization of cAMP-dependant protein kinase (PKA). In addition, pre-term born/ethanol-exposed lambs showed significantly decreased SP-A m-RNA expression when compared to the pre-term born/control group (p=0.004); no significant changes were seen with SP-D. The full-term/ethanol exposed lambs had no significant alterations in mRNA levels, but had significantly less detectable SP-A protein when compared to the full-term/control lambs (p=0.02). These findings suggest that chronic maternal ethanol consumption during the third trimester of pregnancy alters innate immune gene expression in fetal lung. These alterations may underlie increased susceptibility of pre-term infants, exposed to ethanol in utero, to RSV and other microbial agents

Differential Expression of Ovine Innate Immune Genes by Preterm and Neonatal Lung Epithelia Infected with Respiratory Syncytial Virus

Preterm infants have increased susceptibility to severe manifestations of respiratory syncytial virus (RSV) infection. The cause(s) for this age-dependent vulnerability is/are not well-defined, but alterations in innate immune products have been implicated. In sheep, RSV disease severity has similar age-dependent characteristics and sheep have several related innate molecules for study during pulmonary infection including surfactant protein A (SP-A), surfactant protein D (SP-D), sheep beta defensin 1 (SBD1), monocyte chemotactic protein 1 (MCP1), and Toll-like receptor 4 (TLR4). However, the in vivo cellular gene expression as a response to RSV infection is poorly understood. In this study, the effect of RSV infection on expression of these innate immune genes was determined for bovine RSV-infected (bRSV+ fluorescence) epithelial cells, adjacent cells lacking bRSV antigen (adjoining cells lacking fluorescence), and control cells from non-infected lung using laser capture microdissection (LCM) and real-time RT-PCR. Control lambs had increased expression of innate immune molecules in full term (term) compared to preterm epithelia with statistical significance in SBD1, SP-D, and TLR4 mRNA. Infected cells (bRSV+ fluorescent cells) had consistently higher mRNA levels of SP-A (preterm and term), MCP1 (preterm and term), and SP-D (preterm). Interestingly, bRSV- cells of infected term lambs had significantly reduced SP-D mRNA expression compared to bRSV+ and control epithelia, suggesting that RSV infected cells may regulate the adjacent epithelial SP-D expression. This study defines specific innate immune components (e.g., SBD1, SP-D, and TLR4) that have differential age-dependent expression in the airway epithelia. Furthermore, cellular bRSV infection enhanced certain innate immune components while suppressing adjacent cellular SP-D expression in term animals. These in vivo gene expression results provide a framework for future studies on age-dependent susceptibility to RSV and RSV pathogenesis