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Biomedical subjects

R Mukkamala

Publications and source records attributed to R Mukkamala.

14 recordsLinked to original sources
PubMed2002

Effects of prolonged bed rest on the total peripheral resistance baroreflex.

Orthostatic intolerance following prolonged exposure to microgravity continues to be a primary concern of the human space program. Reduced autonomic tone has been demonstrated to contribute to this phenomenon, and the heart rate baroreflex, in particular, has been repeatedly shown to be impaired. However, only the works of Yelle et al. have attempted to address the role of the total peripheral resistance (TPR) baroreflex, a potentially more significant contributor to blood pressure regulation. We applied a previously developed method for estimating the static gains of both the arterial and cardiopulmonary TPR baroreflexes to data obtained before and after 16-day bed rest. Reductions in the estimated static gains of the arterial (statistically significant) and cardiopulmonary TPR baroreflexes were found after bed rest. This study supports the works of Yelle et al, which imply that the TPR baroreflex is reduced after spaceflight.

Adult↗
PubMed2002

A computational model-based validation of Guyton's analysis of cardiac output and venous return curves.

Guyton developed a popular approach for understanding the factors responsible for cardiac output (CO) regulation in which 1) the heart-lung unit and systemic circulation are independently characterized via CO and venous return (VR) curves, and 2) average CO and right atrial pressure (RAP) of the intact circulation are predicted by graphically intersecting the curves. However, this approach is virtually impossible to verify experimentally. We theoretically evaluated the approach with respect to a nonlinear, computational model of the pulsatile heart and circulation. We developed two sets of open circulation models to generate CO and VR curves, differing by the manner in which average RAP was varied. One set applied constant RAPs, while the other set applied pulsatile RAPs. Accurate prediction of intact, average CO and RAP was achieved only by intersecting the CO and VR curves generated with pulsatile RAPs because of the pulsatility and nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR curves generated with pulsatile RAPs were also practically independent. This theoretical study therefore supports the validity of Guyton's graphical analysis.

Atrial Function, Right↗
PubMed2001

A forward model-based validation of cardiovascular system identification.

We present a theoretical evaluation of a cardiovascular system identification method that we previously developed for the analysis of beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure, and instantaneous lung volume. The method provides a dynamical characterization of the important autonomic and mechanical mechanisms responsible for coupling the fluctuations (inverse modeling). To carry out the evaluation, we developed a computational model of the cardiovascular system capable of generating realistic beat-to-beat variability (forward modeling). We applied the method to data generated from the forward model and compared the resulting estimated dynamics with the actual dynamics of the forward model, which were either precisely known or easily determined. We found that the estimated dynamics corresponded to the actual dynamics and that this correspondence was robust to forward model uncertainty. We also demonstrated the sensitivity of the method in detecting small changes in parameters characterizing autonomic function in the forward model. These results provide confidence in the performance of the cardiovascular system identification method when applied to experimental data.

Autonomic Nervous System↗
PubMed2001

Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.

Adrenergic alpha-Agonists↗
PubMed2001

Do nonlinearities play a significant role in short term, beat-to-beat variability?

Numerous studies of short-term beat-to-beat variability in cardiovascular signals have not resolved the debate about the completeness of linear analysis techniques. This aim of this paper is to evaluate further the role of nonlinearities in short-term, beat-to-beat variability. We compared linear autoregressive moving average (ARMA) and nonlinear neural network (NN) models for predicting instantaneous heart rate (HR) and mean arterial blood pressure (BP) from past HR and BP. To evaluate these models, we used HR and BP time series from the MIMIC database. Experimental results indicate that NN-based nonlinearities do not play a significant role and suggest that ARMA linear analysis techniques provide adequate characterization of the system dynamics responsible for generating short-term, beat-to-beat variability.

Algorithms↗
PubMed2001

Introduction of computational models to PhysioNet.

PhysioNet is a national research resource that provides experimental data sets and open-source software for their analysis. Computational modeling can complement studies of these experimental data sets so as to facilitate the advancement of physiologic research. Thus, in order to introduce computational models to PhysioNet, we have developed and posted a cardiovascular model designed for research that generates reasonable human pulsatile hemodynamic waveforms, cardiac output and venous return curves, and beat-to-beat variability. Some of the key features of the software include: 1) compatibility with PhysioNet's open-source data analysis software; 2) online viewing and parameter updating as the data are being calculated; 3) off-line viewing after completion of the simulation; 4) pre-compiled Linux binaries; 5) open-source code that may be compiled on other platforms; and 6) an extensive user's manual and software guide.

Cardiac Output↗
PubMed2000

A noninvasive method for total peripheral resistance baroreflex identification.

We developed a noninvasive method for estimating the static gains of the arterial and cardiopulmonary total peripheral resistance (TPR) baroreflexes. The method involves a system identification analysis of beat-to-beat fluctuations in arterial blood pressure (ABP), cardiac output (CO), and stroke volume (SV) in order to identify two transfer functions relating CO fluctuations to ABP fluctuations and SV fluctuations to ABP fluctuations. The static gains of each of the TPR baroreflexes may then be computed from the static gains of the two identified transfer functions. In order to evaluate the method, we constructed a computer model of the human cardiovascular system. We applied the method to data generated from the computer model and found close agreement between the estimated and actual static gains of the model TPR baroreflexes. We also applied the method to experimental human data and obtained encouraging results. These results motivate the experimental validation of the method.

Baroreflex↗
PubMed1999

System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy.

We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.

Adult↗
PubMed1998

Multifunctional cytokine expression by human coronary endothelium and regulation by monokines and glucocorticoids.

Human endothelium is capable of expressing a variety of molecules, including cytokines and growth factors, critical to inflammation. This aspect of coronary endothelium has not been studied in detail. In this study, we report, for the first time, expression of multifunctional cytokines by human coronary artery endothelial cells (HCAEC) and their regulation by inflammatory cytokines and glucocorticoids. We also compared expression of cytokine transcripts in two additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein (HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP-1 was seen following treatment with TNFalpha. We found no expression of IL-1RA, IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1 production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found even after maximal stimulation of HCAEC. No significant differences were seen in the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC. Glucocorticoids inhibited IL-8 production from all three cell lines. This study demonstrates that human coronary endothelial cells are capable of expressing a wide variety of multifunctional cytokines which may be of relevance to vascular inflammation.

Cell Line↗
PubMed1997

Pulmonary blastomycosis with acute respiratory failure as predominant clinical feature.

Two previously healthy young adults came to our community hospital with rapidly progressive respiratory failure. Investigation confirmed Blastomyces as the responsible etiologic agent. Despite adequate antifungal chemotherapy and intensive supportive care, both patients died, one within 24 hours and the other after 14 days. Overwhelming infection with Blastomyces dermatitidis can cause acute respiratory failure, possibly the adult respiratory distress syndrome, even in immunocompetent hosts.

Acute Disease↗
PubMed1997

System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade.

We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

Adult↗
PubMed1996

Persistent urticarial eruption in an asthmatic patient.

This case demonstrates the importance of recognizing urticarial vasculitis in patients with chronic urticarial eruptions. The salient points in history that point towards the diagnosis of urticarial vasculitis include the presence of painful urticarial lesions that last longer than 24 hours and that heal leaving residual pigmentation. In some cases the urticaria may evolve into palpable purpura. An associated systemic illness that may resemble systemic lupus erythematosus should also suggest the diagnosis, which is established by skin biopsy. Histopathology reveals a leukocytoclastic vasculitis involving postcapillary venules. When associated with systemic vasculitis, the urticaria is likely to be of the hypocomplementemic variety, with immunoglobulin and complement deposition on biopsies, and with serum complement studies demonstrating classical pathway activation, low C1q levels, and anti-C1q precipitins. A variety of agents have been used in the management of urticarial vasculitis, including aspirin, nonsteroidal anti-inflammatory agents, corticosteroids, colchicine, dapsone, hydroxychloroquine, and cytotoxic agents such as cyclophosphamide and azathioprine.

Adult↗
PubMed1996

Pulmonary abscess due to Corynebacterium striatum.

Non-diphtheria corynebacteria are normal commensals of the skin and mucous membranes of humans. Increasingly, however, these saprophytic organisms are being recognized as pathogens. Patients infected with these bacteria typically have an underlying immunosuppressive process and/or an indwelling venous catheter. Pleuropulmonary infection with Corynebacterium striatum is rare. We present a patient with diabetes mellitus who developed an intrapulmonary abscess due to C. striatum.

Aged↗