Frank Jacono - Academia.edu (original) (raw)

Papers by Frank Jacono

American journal of respiratory and critical care medicine, 2015

Sleep, 2010

Studies of the genetics of obstructive sleep apnea may be facilitated by identifying intermediate... more Studies of the genetics of obstructive sleep apnea may be facilitated by identifying intermediate traits with high heritability that quantify etiological pathways, such as those related to respiratory control. Electrocardiogram (ECG)-based sleep spectrograms, measuring the coupling between respiratory modulation of ECG QRS-wave amplitude and heart rate variability, may provide measures of sleep state and ventilatory dynamics during sleep. We evaluated the familial aggregation of distinctive spectrographic biomarkers of unstable sleep, related to elevated-low frequency cardiopulmonary coupling (e-LFC), to assess their utility in genetic studies. 622 participants from 137 families from the Cleveland Family Study underwent standardized polysomnography (PSG). From the ECG signal on the PSG, the interbeat interval time series and the corresponding ECG-derived respiratory signal were extracted, and the low frequency (0.01-0.1 Hz) component of their coupling was computed using a fully auto...

J Appl Physiol, 2005

The objective of the present study was to examine the impact of early stages of lung injury on ve... more The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial Po(2), and arterial Pco(2) were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole body plethysmography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals, as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.

Chest Journal, Aug 1, 2009

Anatomic right-to-left shunt causes hypoxemia that can pose a diagnostic challenge to clinicians.... more Anatomic right-to-left shunt causes hypoxemia that can pose a diagnostic challenge to clinicians. Among the many possible causes of right-to-left shunt, persistent left-sided superior vena cava (PLSVC) with an "unroofed" coronary sinus represents an uncommon congenital anomaly in which detection by saline-contrast echocardiogram (bubble echo) or contrast-enhanced CT scan requires injection of contrast in the left arm. We present the case of an elderly man with hypoxemia on the basis of a right-to-left shunt accompanying a PLSVC with unroofed coronary sinus in whom the shunt escaped initial detection following a bubble echo with contrast injected into the right arm. This case reminds pulmonary clinicians, who are frequently called on to assess the cause of hypoxemia, that specifying a contrast injection into the left arm is required in the pursuit of this specific shunt-producing anomaly.

Http Dx Doi Org 10 1089 Ham 2005 6 112, Feb 1, 2005

Chronic hypoxia leads to adaptations in the respiratory system manifested as a persistent increas... more Chronic hypoxia leads to adaptations in the respiratory system manifested as a persistent increase in resting ventilation, termed ventilatory acclimatization to hypoxia (VAH). Increased afferent nerve activity from carotid bodies and the ensuing reflex activation of ventilation are critical for eliciting VAH. In this review we highlight recent information on the cellular and molecular mechanisms associated with chronic hypoxia-induced functional and structural changes in the carotid body. Chronic hypoxia leads to hypersensitivity of the carotid bodies and induces morphological changes, including enlargement of the organ, hyperplasia of glomus cells, and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities, as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin- 1, ET-1) in glomus cells. Morphological alterations are in part due to upregulation of growth factors (e.g., VEGF). VAH is markedly attenuated in mice partially deficient in HIF-1 transcription factor, which regulates several downstream genes, including VEGF, ET-1, and Ca(2+) channels. The finding that VAH is also blunted in mice deficient in the fosB gene led to the suggestion that the magnitude and time course of VAH depend on complex interactions between more than one transcription factor, resulting in coordinated regulation of several downstream genes and their protein products.

The Faseb Journal, Apr 1, 2013

Journal of Applied Physiology, Apr 28, 2011

Physiological rhythms, including respiration, exhibit endogenous variability associated with heal... more Physiological rhythms, including respiration, exhibit endogenous variability associated with health, and deviations from this are associated with disease. Specific changes in the linear and nonlinear sources of breathing variability have not been investigated. In this study, we used information theory-based techniques, combined with surrogate data testing, to quantify and characterize the vagal-dependent nonlinear pattern variability in urethane-anesthetized, spontaneously breathing adult rats. Surrogate data sets preserved the amplitude distribution and linear correlations of the original data set, but nonlinear correlation structure in the data was removed. Differences in mutual information and sample entropy between original and surrogate data sets indicated the presence of deterministic nonlinear or stochastic non-Gaussian variability. With vagi intact (n = 11), the respiratory cycle exhibited significant nonlinear behavior in templates of points separated by time delays ranging from one sample to one cycle length. After vagotomy (n = 6), even though nonlinear variability was reduced significantly, nonlinear properties were still evident at various time delays. Nonlinear deterministic variability did not change further after subsequent bilateral microinjection of MK-801, an N-methyl-D-aspartate receptor antagonist, in the Kölliker-Fuse nuclei. Reversing the sequence (n = 5), blocking N-methyl-D-aspartate receptors bilaterally in the dorsolateral pons significantly decreased nonlinear variability in the respiratory pattern, even with the vagi intact, and subsequent vagotomy did not change nonlinear variability. Thus both vagal and dorsolateral pontine influences contribute to nonlinear respiratory pattern variability. Furthermore, breathing dynamics of the intact system are mutually dependent on vagal and pontine sources of nonlinear complexity. Understanding the structure and modulation of variability provides insight into disease effects on respiratory patterning.

The Faseb Journal, Mar 1, 2008

Canadian respiratory journal : journal of the Canadian Thoracic Society, Jan 17, 2015

The Poincaré plot is a popular two-dimensional visualization tool for time series due to its intu... more The Poincaré plot is a popular two-dimensional visualization tool for time series due to its intuitive display of dynamic system behavior. Poincaré plots have been used successfully to visualize heart rate variability and to distinguish between health and disease. However, the conventional quantitative analysis relies on linear measurements of the cumulative distribution of points making it difficult to interpret irregular or complex plots. Moreover, the plots are constructed to reflect the highly correlated regions of the time series, minimizing the amount of nonlinear information presented and thereby hiding potentially relevant features.

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stress... more Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardioventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. and Vodovotz Y Linking inflammation, cardiorespiratory variability, and neural control in acute inflammation via computational modeling. Front. Physio. 3:222.

Open Journal of Molecular and Integrative Physiology, 2012

Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hy... more Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hypertension in some patients. In this study we examined the effects of daily hypoxia (10% oxygen; 8h/day for 14 days) on two strains of rats to simulate sleep related hypoxia in pulmonary diseases expecting to find differences in vascular responses, the development of right ventricular hypertrophy and pulmonary hypertension according to genetic background. In response to daily hypoxia, Sprague Dawley rats developed right ventricular hypertrophy while Brown Norway rats did not. Both strains developed pulmonary hypertension (elevated right ventricular pressure) although the increase was significantly greater in the Sprague Dawley strain. Pulmonary artery (first branch) vasoconstrictive responses to potassium chloride were increased equally in both strains and the subsequent vasodilation with acetylcholine were reduced equally with daily hypoxia in both strains. Taken together, these findings suggest that the genetic makeup of the rats contributed significantly to the development of right ventricular hypertrophy and the degree of pulmonary hypertension. Moreover, this response is not secondary to differences in the intralobar pulmonary vascular reactivity. Genetic background could explain why certain patients do worse with hypoxia inducing pulmonary vascular diseases.

TheScientificWorldJournal, 2015

There is a broad consensus that 21st century health care will require intensive use of informatio... more There is a broad consensus that 21st century health care will require intensive use of information technology to acquire and analyze data and then manage and disseminate information extracted from the data. No area is more data intensive than the intensive care unit. While there have been major improvements in intensive care monitoring, the medical industry, for the most part, has not incorporated many of the advances in computer science, biomedical engineering, signal processing, and mathematics that many other industries have embraced. Acquiring, synchronizing, integrating, and analyzing patient data remain frustratingly difficult because of incompatibilities among monitoring equipment, proprietary limitations from industry, and the absence of standard data formatting. In this paper, we will review the history of computers in the intensive care unit along with commonly used monitoring and data acquisition systems, both those commercially available and those being developed for res...

C76. CONTROL OF VENTILATION AND RESPIRATORY MUSCLES, 2011

... R. Balaji , D. Nethery , C. Campanaro , D. Baekey , T. Dick , FJ Jacono MF Knoch1 2 3 2 2 2 4... more ... R. Balaji , D. Nethery , C. Campanaro , D. Baekey , T. Dick , FJ Jacono MF Knoch1 2 3 2 2 2 4 ... Following the 2 2 protocol, bronchoalveolar lavage (BAL) was performed to measure cell count, protein and cytokine levels, and the lungs were removed for wet-to-dry weight ratios. ...

A43. INTERESTING CASES IN INTERVENTIONAL PULMONARY: TECHNIQUES AND COMPLICATIONS, 2010

Rett syndrome, a severe X-linked neurodevelopmental disorder caused by mutations in the gene enco... more Rett syndrome, a severe X-linked neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (Mecp2), is associated with a highly irregular respiratory pattern including severe upper-airway dysfunction. Recent work suggests that hyperexcitability of the Hering-Breuer reflex (HBR) pathway contributes to respiratory dysrhythmia in Mecp2 mutant mice. To assess how enhanced HBR input impacts respiratory entrainment by sensory afferents in closed-loop in vivo-like conditions, we investigated the input (vagal stimulus trains) -output (phrenic bursting) entrainment via the HBR in wildtype and MeCP2-deficient mice. Using the in situ perfused brainstem preparation, which maintains an intact pontomedullary axis capable of generating an in vivo-like respiratory rhythm in the absence of the HBR, we mimicked the HBR feedback input by stimulating the vagus nerve (at threshold current, 0.5 ms pulse duration, 75 Hz pulse frequency, 100 ms train duration) at an inter-burst frequency matching that of the intrinsic oscillation of the inspiratory motor output of each preparation. Using this approach, we observed significant input-output entrainment in wild-type mice as measured by the maximum of the cross-correlation function, the peak of the instantaneous relative phase distribution, and the mutual information of the instantaneous phases. This entrainment was associated with a reduction in inspiratory duration during feedback stimulation. In contrast, the strength of input-output entrainment was significantly weaker in Mecp2 −/+ mice. However, Mecp2 −/+ mice also had a reduced inspiratory duration during stimulation, indicating that reflex behavior in the HBR pathway was intact. Together, these observations suggest that the respiratory network compensates for enhanced sensitivity of HBR inputs by reducing HBR input-output entrainment.

Brain and Behavior, 2013

c-Aminobutyric acid type A (GABA A ) receptor plasticity participates in mediating adaptation to ... more c-Aminobutyric acid type A (GABA A ) receptor plasticity participates in mediating adaptation to environmental change. Previous studies in rats demonstrated that extrasynaptic GABA A receptor subunits and receptors in the pons, a brainstem region involved in respiratory control, are upregulated by exposure to sustained hypobaric hypoxia. In these animals, expression of the mRNA encoding the extrasynaptic a4 subunit rose after 3 days in sustained hypoxia, while those encoding the a6 and d subunits increased dramatically by 2 weeks. However, the participation of extrasynaptic subunits in maintaining respiration in normoxic conditions remains unknown. To examine the importance of a4 in a normal environment, respiratory function, motor and anxiety-like behaviors, and expression of other GABA A receptor subunit mRNAs were compared in wild-type (WT) and a4 subunit-deficient mice. Loss of the a4 subunit did not impact frequency, but did lead to reduced ventilatory pattern variability. In addition, mice lacking the subunit exhibited increased anxiety-like behavior. Finally, a4 subunit loss resulted in reduced expression of other extrasynaptic (a6 and d) subunit mRNAs in the pons without altering those encoding the most prominent synaptic subunits. These findings on subunit-deficient mice maintained in normoxia, in conjunction with earlier findings on animals maintained in chronic hypoxia, suggest that the expression and regulation of extrasynaptic GABA A receptor subunits in the pons is interdependent and that their levels influence respiratory control as well as adaptation to stress.

American journal of respiratory and critical care medicine, 2015

Sleep, 2010

Studies of the genetics of obstructive sleep apnea may be facilitated by identifying intermediate... more Studies of the genetics of obstructive sleep apnea may be facilitated by identifying intermediate traits with high heritability that quantify etiological pathways, such as those related to respiratory control. Electrocardiogram (ECG)-based sleep spectrograms, measuring the coupling between respiratory modulation of ECG QRS-wave amplitude and heart rate variability, may provide measures of sleep state and ventilatory dynamics during sleep. We evaluated the familial aggregation of distinctive spectrographic biomarkers of unstable sleep, related to elevated-low frequency cardiopulmonary coupling (e-LFC), to assess their utility in genetic studies. 622 participants from 137 families from the Cleveland Family Study underwent standardized polysomnography (PSG). From the ECG signal on the PSG, the interbeat interval time series and the corresponding ECG-derived respiratory signal were extracted, and the low frequency (0.01-0.1 Hz) component of their coupling was computed using a fully auto...

J Appl Physiol, 2005

The objective of the present study was to examine the impact of early stages of lung injury on ve... more The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial Po(2), and arterial Pco(2) were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole body plethysmography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals, as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.

Chest Journal, Aug 1, 2009

Anatomic right-to-left shunt causes hypoxemia that can pose a diagnostic challenge to clinicians.... more Anatomic right-to-left shunt causes hypoxemia that can pose a diagnostic challenge to clinicians. Among the many possible causes of right-to-left shunt, persistent left-sided superior vena cava (PLSVC) with an "unroofed" coronary sinus represents an uncommon congenital anomaly in which detection by saline-contrast echocardiogram (bubble echo) or contrast-enhanced CT scan requires injection of contrast in the left arm. We present the case of an elderly man with hypoxemia on the basis of a right-to-left shunt accompanying a PLSVC with unroofed coronary sinus in whom the shunt escaped initial detection following a bubble echo with contrast injected into the right arm. This case reminds pulmonary clinicians, who are frequently called on to assess the cause of hypoxemia, that specifying a contrast injection into the left arm is required in the pursuit of this specific shunt-producing anomaly.

Http Dx Doi Org 10 1089 Ham 2005 6 112, Feb 1, 2005

Chronic hypoxia leads to adaptations in the respiratory system manifested as a persistent increas... more Chronic hypoxia leads to adaptations in the respiratory system manifested as a persistent increase in resting ventilation, termed ventilatory acclimatization to hypoxia (VAH). Increased afferent nerve activity from carotid bodies and the ensuing reflex activation of ventilation are critical for eliciting VAH. In this review we highlight recent information on the cellular and molecular mechanisms associated with chronic hypoxia-induced functional and structural changes in the carotid body. Chronic hypoxia leads to hypersensitivity of the carotid bodies and induces morphological changes, including enlargement of the organ, hyperplasia of glomus cells, and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities, as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin- 1, ET-1) in glomus cells. Morphological alterations are in part due to upregulation of growth factors (e.g., VEGF). VAH is markedly attenuated in mice partially deficient in HIF-1 transcription factor, which regulates several downstream genes, including VEGF, ET-1, and Ca(2+) channels. The finding that VAH is also blunted in mice deficient in the fosB gene led to the suggestion that the magnitude and time course of VAH depend on complex interactions between more than one transcription factor, resulting in coordinated regulation of several downstream genes and their protein products.

The Faseb Journal, Apr 1, 2013

Journal of Applied Physiology, Apr 28, 2011

Physiological rhythms, including respiration, exhibit endogenous variability associated with heal... more Physiological rhythms, including respiration, exhibit endogenous variability associated with health, and deviations from this are associated with disease. Specific changes in the linear and nonlinear sources of breathing variability have not been investigated. In this study, we used information theory-based techniques, combined with surrogate data testing, to quantify and characterize the vagal-dependent nonlinear pattern variability in urethane-anesthetized, spontaneously breathing adult rats. Surrogate data sets preserved the amplitude distribution and linear correlations of the original data set, but nonlinear correlation structure in the data was removed. Differences in mutual information and sample entropy between original and surrogate data sets indicated the presence of deterministic nonlinear or stochastic non-Gaussian variability. With vagi intact (n = 11), the respiratory cycle exhibited significant nonlinear behavior in templates of points separated by time delays ranging from one sample to one cycle length. After vagotomy (n = 6), even though nonlinear variability was reduced significantly, nonlinear properties were still evident at various time delays. Nonlinear deterministic variability did not change further after subsequent bilateral microinjection of MK-801, an N-methyl-D-aspartate receptor antagonist, in the Kölliker-Fuse nuclei. Reversing the sequence (n = 5), blocking N-methyl-D-aspartate receptors bilaterally in the dorsolateral pons significantly decreased nonlinear variability in the respiratory pattern, even with the vagi intact, and subsequent vagotomy did not change nonlinear variability. Thus both vagal and dorsolateral pontine influences contribute to nonlinear respiratory pattern variability. Furthermore, breathing dynamics of the intact system are mutually dependent on vagal and pontine sources of nonlinear complexity. Understanding the structure and modulation of variability provides insight into disease effects on respiratory patterning.

The Faseb Journal, Mar 1, 2008

Canadian respiratory journal : journal of the Canadian Thoracic Society, Jan 17, 2015

The Poincaré plot is a popular two-dimensional visualization tool for time series due to its intu... more The Poincaré plot is a popular two-dimensional visualization tool for time series due to its intuitive display of dynamic system behavior. Poincaré plots have been used successfully to visualize heart rate variability and to distinguish between health and disease. However, the conventional quantitative analysis relies on linear measurements of the cumulative distribution of points making it difficult to interpret irregular or complex plots. Moreover, the plots are constructed to reflect the highly correlated regions of the time series, minimizing the amount of nonlinear information presented and thereby hiding potentially relevant features.

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stress... more Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardioventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. and Vodovotz Y Linking inflammation, cardiorespiratory variability, and neural control in acute inflammation via computational modeling. Front. Physio. 3:222.

Open Journal of Molecular and Integrative Physiology, 2012

Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hy... more Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hypertension in some patients. In this study we examined the effects of daily hypoxia (10% oxygen; 8h/day for 14 days) on two strains of rats to simulate sleep related hypoxia in pulmonary diseases expecting to find differences in vascular responses, the development of right ventricular hypertrophy and pulmonary hypertension according to genetic background. In response to daily hypoxia, Sprague Dawley rats developed right ventricular hypertrophy while Brown Norway rats did not. Both strains developed pulmonary hypertension (elevated right ventricular pressure) although the increase was significantly greater in the Sprague Dawley strain. Pulmonary artery (first branch) vasoconstrictive responses to potassium chloride were increased equally in both strains and the subsequent vasodilation with acetylcholine were reduced equally with daily hypoxia in both strains. Taken together, these findings suggest that the genetic makeup of the rats contributed significantly to the development of right ventricular hypertrophy and the degree of pulmonary hypertension. Moreover, this response is not secondary to differences in the intralobar pulmonary vascular reactivity. Genetic background could explain why certain patients do worse with hypoxia inducing pulmonary vascular diseases.

TheScientificWorldJournal, 2015

There is a broad consensus that 21st century health care will require intensive use of informatio... more There is a broad consensus that 21st century health care will require intensive use of information technology to acquire and analyze data and then manage and disseminate information extracted from the data. No area is more data intensive than the intensive care unit. While there have been major improvements in intensive care monitoring, the medical industry, for the most part, has not incorporated many of the advances in computer science, biomedical engineering, signal processing, and mathematics that many other industries have embraced. Acquiring, synchronizing, integrating, and analyzing patient data remain frustratingly difficult because of incompatibilities among monitoring equipment, proprietary limitations from industry, and the absence of standard data formatting. In this paper, we will review the history of computers in the intensive care unit along with commonly used monitoring and data acquisition systems, both those commercially available and those being developed for res...

C76. CONTROL OF VENTILATION AND RESPIRATORY MUSCLES, 2011

... R. Balaji , D. Nethery , C. Campanaro , D. Baekey , T. Dick , FJ Jacono MF Knoch1 2 3 2 2 2 4... more ... R. Balaji , D. Nethery , C. Campanaro , D. Baekey , T. Dick , FJ Jacono MF Knoch1 2 3 2 2 2 4 ... Following the 2 2 protocol, bronchoalveolar lavage (BAL) was performed to measure cell count, protein and cytokine levels, and the lungs were removed for wet-to-dry weight ratios. ...

A43. INTERESTING CASES IN INTERVENTIONAL PULMONARY: TECHNIQUES AND COMPLICATIONS, 2010

Rett syndrome, a severe X-linked neurodevelopmental disorder caused by mutations in the gene enco... more Rett syndrome, a severe X-linked neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (Mecp2), is associated with a highly irregular respiratory pattern including severe upper-airway dysfunction. Recent work suggests that hyperexcitability of the Hering-Breuer reflex (HBR) pathway contributes to respiratory dysrhythmia in Mecp2 mutant mice. To assess how enhanced HBR input impacts respiratory entrainment by sensory afferents in closed-loop in vivo-like conditions, we investigated the input (vagal stimulus trains) -output (phrenic bursting) entrainment via the HBR in wildtype and MeCP2-deficient mice. Using the in situ perfused brainstem preparation, which maintains an intact pontomedullary axis capable of generating an in vivo-like respiratory rhythm in the absence of the HBR, we mimicked the HBR feedback input by stimulating the vagus nerve (at threshold current, 0.5 ms pulse duration, 75 Hz pulse frequency, 100 ms train duration) at an inter-burst frequency matching that of the intrinsic oscillation of the inspiratory motor output of each preparation. Using this approach, we observed significant input-output entrainment in wild-type mice as measured by the maximum of the cross-correlation function, the peak of the instantaneous relative phase distribution, and the mutual information of the instantaneous phases. This entrainment was associated with a reduction in inspiratory duration during feedback stimulation. In contrast, the strength of input-output entrainment was significantly weaker in Mecp2 −/+ mice. However, Mecp2 −/+ mice also had a reduced inspiratory duration during stimulation, indicating that reflex behavior in the HBR pathway was intact. Together, these observations suggest that the respiratory network compensates for enhanced sensitivity of HBR inputs by reducing HBR input-output entrainment.

Brain and Behavior, 2013

c-Aminobutyric acid type A (GABA A ) receptor plasticity participates in mediating adaptation to ... more c-Aminobutyric acid type A (GABA A ) receptor plasticity participates in mediating adaptation to environmental change. Previous studies in rats demonstrated that extrasynaptic GABA A receptor subunits and receptors in the pons, a brainstem region involved in respiratory control, are upregulated by exposure to sustained hypobaric hypoxia. In these animals, expression of the mRNA encoding the extrasynaptic a4 subunit rose after 3 days in sustained hypoxia, while those encoding the a6 and d subunits increased dramatically by 2 weeks. However, the participation of extrasynaptic subunits in maintaining respiration in normoxic conditions remains unknown. To examine the importance of a4 in a normal environment, respiratory function, motor and anxiety-like behaviors, and expression of other GABA A receptor subunit mRNAs were compared in wild-type (WT) and a4 subunit-deficient mice. Loss of the a4 subunit did not impact frequency, but did lead to reduced ventilatory pattern variability. In addition, mice lacking the subunit exhibited increased anxiety-like behavior. Finally, a4 subunit loss resulted in reduced expression of other extrasynaptic (a6 and d) subunit mRNAs in the pons without altering those encoding the most prominent synaptic subunits. These findings on subunit-deficient mice maintained in normoxia, in conjunction with earlier findings on animals maintained in chronic hypoxia, suggest that the expression and regulation of extrasynaptic GABA A receptor subunits in the pons is interdependent and that their levels influence respiratory control as well as adaptation to stress.