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Abstract: This review examines selected areas of cardiovascular physiology where there have been impressive gains of knowledge and indicates fertile areas for future research. Because arterial blood is usually fully saturated with oxygen, increasing cardiac output is the only means for transferring substantially more oxygen to tissues. Consequently, any behavioural or environmental change that alters oxygen uptake typically involves a change in cardiac output, which in fishes can amount to a threefold change. During exercise, not all fishes necessarily have the same ability as salmonids to increase cardiac output by increasing stroke volume; they rely more on increases in heart rate instead. The benefits associated with increasing cardiac output via stroke volume or heart rate are unclear. Regardless, all fishes examined so far show an exquisite cardiac sensitivity to filling pressure and the cellular basis for this heightened cardiac stretch sensitivity in fish is being unraveled. Even so, a fully integrated picture of cardiovascular functioning in fishes is hampered by a dearth of studies on venous circulatory control. Potent positive cardiac inotropy involves stimulation of sarcolemmal β-adrenoceptors, which increases the peak trans-sarcolemmal current for calcium and the intracellular calcium transient available for binding to troponin C. However, adrenergic sensitivity is temperature-dependent in part through effects on membrane currents and receptor density. The membrane currents contributing to the pacemaker action potential are also being studied but remain a prime area for further study. Why maximum heart rate is limited to a low rate in most fishes compared with similarsized mammals, even when [Q.sub.10] effects are considered, remains a mystery. Fish hearts have up to three oxygen supply routes. The degree of coronary capillarization circulation is of primary importance to the compact myocardium, unlike the spongy myocardium, where venous oxygen partial pressure appears to be the critical factor in terms of oxygen delivery. Air-breathing fishes can boost the venous oxygen content and oxygen partial pressure by taking an air breath, thereby providing a third myocardial oxygen supply route that perhaps compensates for the potentially precarious supply to the spongy myocardium during hypoxia and exercise. In addition to venous hypoxemia, acidemia and hyperkalemia can accompany exhaustive exercise and acute warming, perhaps impairing the heart were it not for a cardiac protection mechanism afforded by β-adrenergic stimulation. With warming, however, a mismatch between an animal's demand for oxygen (a [Q.sub.10] effect) and the capacity of the circulatory and ventilatory systems to delivery this oxygen develops beyond an optimum temperature. At temperature extremes in salmon, it is proposed that detrimental changes in venous blood composition, coupled with a breakdown of the cardiac protective mechanism, is a potential mechanism to explain the decline in maximum and cardiac arrhythmias that are observed. Furthermore, the fall off in scope for heart rate and cardiac output is used to explain the decrease in aerobic scope above the optimum temperature, which may then explain the field observation that adult sockeye salmon (Oncorhynchus nerka (Walbaum in Artedi, 1792)) have difficulty migrating to their spawning area at temperatures above their optimum. Such mechanistic linkages to lifetime fitness, whether they are cardiovascular or not, should assist with predictions in this era of global climate change. Resume : Notre retrospective examine certains domaines choisis de la physiologie cardiovasculaire qui ont connu un avancement impressionnant des connaissances et elle signale des avenues prometteuses pour la recherche future. Parce que le sang arteriel est en general completement sature en oxygene, le seul moyen de transferer plus d'oxygene aux tissus est d'augmenter le debit cardiaque. En consequence, tout changement comportemental ou environnemental qui modifie l'apport d'oxygene implique typiquement une variation du debit cardiaque, ce qui chez les poissons peut representer un changement de l'ordre de trois fois. Durant l'exercice, tous les poissons ne possedent pas necessairement la capacite qu'ont les salmonides d'accroitre le debit cardiaque en augmentant le volume systolique; ils utilisent plutot une acceleration du rythme cardiaque. Les benefices associes a l'augmentation du debit cardiaque par le debit systolique ou par le rythme cardiaque ne sont pas clairs. Neanmoins, tous les poissons examines a ce jour montrent une tres grande sensibilite a la pression de remplissage; la base cellulaire de cette sensibilite accrue a l'etirement cardiaque chez les poissons est en train d'etre elucidee. Malgre tout, l'obtention d'une image totalement integree de la fonction cardiovasculaire chez les poissons est retardee par le manque d'etudes sur le controle circulatoire veineux. La puissante inotropie positive du coeur implique la stimulation des recepteurs b-adrenergiques du sarcolemme, qui augmente le courant de pointe du calcium a travers le sarcolemme et le calcium intracellulaire transitoire disponible pour la fixation a la troponine C. Cependant, la sensibilite adrenergique est fonction de la temperature en partie par les effets sur les courants membranaires et la densite des recepteurs. Les courants membranaires contribuant au potentiel d'action du centre d'automatisme cardiaque font aussi l'objet d'etudes, mais restent toujours des sujets de premier ordre pour des travaux futurs. C'est encore un mystere de savoir pourquoi le rythme cardiaque maximal de la plupart des poissons est confine a des valeurs basses, par comparaison a celui des mammiferes de taille semblable, meme apres correction pour les effets du [Q.sub.10]. Les coeurs de poissons beneficient de jusqu'a trois voies d'approvisionnement en oxygene. Le degre de circulation dans la capillarisation coronaire est de premiere importance dans le myocarde compact; au contraire, dans le myocarde spongieux, la pression partielle d'oxygene veineux semble etre le facteur critique en ce qui concerne l'apport d'oxygene. Les poissons a respiration aerienne peuvent faire augmenter le contenu en oxygene et la pression partielle d'oxygene veineux par une aspiration d'air, procurant ainsi une troisieme voie d'approvisionnement du myocarde en oxygene, ce qui compense peut-etre l'apport potentiellement fragile au myocarde spongieux durant l'hypoxie et l'exercice. En plus de l'hypoxemie veineuse, l'acidemie et l'hyperkaliemie peuvent accompagner un exercice epuisant et un rechauffement aigu, ce qui affaiblirait peut-etre le coeur si ce n'etait du mecanisme de protection cardiaque apporte par la stimulation β-adrenergique. Dans le cas du rechauffement cependant, il se developpe au-dela d'une temperature optimale un mesappariement entre la demande d'oxygene de l'animal (un effet du [Q.sup.10]) et la capacite des systemes de circulation et de ventilation a fournir cet oxygene. Chez le saumon, aux temperatures extremes, nous croyons que les changements nuisibles dans la composition du sang veineux, combines a une panne du processus de protection cardiaque, peuvent etre un mecanisme pour expliquer le declin du debit cardiaque maximal et les arythmies cardiaques que l'on observe. De plus, la chute de l'etendue des debit et rythme cardiaques sert a expliquer la diminution de la portee aerobie au-dela de la temperature optimale, ce qui peut expliquer a son tour les observations de terrain qui indiquent que les saumons rouges (Oncorhynchus nerka (Walbaum in Artedi, 1792)) adultes ont du mal a migrer vers leur site de fraie aux temperatures superieures a l'optimum. Ces liens mecanistes a la fitness de la vie entiere, qu'ils soient cardiovasculaires ou non, devraient aider a formuler des predictions dans la periode actuelle de changement climatique global., Introduction Some 20 years ago, a review on fish cardiovascular physiology appeared in this journal (Farrell 1984). At the time there were just two relevant chapters in the treatise Fish [...]

The objective monitoring of cough for extended periods of time has long been recognized as an important step towards a better understanding of this symptom, and a better management of chronic cough patients. In this paper, we present a system for the automatic analysis of 24-h, continuous, ambulatory recordings of cough. The system uses audio recordings from a miniature microphone and the detection algorithm is based on statistical models of the time-spectral characteristics of cough sounds. We validated the system against manual counts obtained by a trained observer on 40 ambulatory recordings and our results show a median sensitivity value of 85.7%, median positive predictive value of 94.7% and median false positive rate of 0.8 events/h. An analysis application was developed, with a graphical user interface, allowing the use of the system in clinical settings by technical or medical staff. The result of the analysis of a recording session is presented as a concise, graphical-based report. The modular nature of the system interface facilitates its enhancement with the integration of further modules. Index Terms--Algorithms, biomedical monitoring, biomedical signal detection, cough, hidden Markov models, respiratory system.

We investigated the time-dependent modulation of arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) that occurs during isometric handgrip exercise (1HG). Thirteen healthy subjects performed a 3-min IHG at 30% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between spontaneous variations in diastolic arterial pressure (DAP) and MSNA during supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear relations between DAP and MSNA variables were shifted progressively rightward until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA relations were shifted upward and were shifted further upward at IHG3; 3) the sensitivity of the ABR control of total MSNA was increased at IHG2 and increased further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly higher than at IHG2, and the sensitivity of the control of total MSNA was the same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP-burst incidence relation remained at the IHG3 level. These results indicate that during IHG, ABR control of MSNA is modulated in a time-dependent manner. We suggest that this modulation of ABR function is one of the mechanisms underlying the progressive increase in blood pressure and MSNA during the course of isometric exercise. arterial blood pressure; sympathetic nervous system; integrated circulatory regulation

The 'hemodynamic inverse problem' is the determination of arterial system properties from pressures and flows measured at the entrance of an arterial system. Conventionally, investigators fit reduced arterial system models to data, and the resulting model parameters represent putative arterial properties. However, no unique solution to the inverse problem exists--an infinite number of arterial system topologies result in the same input impedance ([Z.sub.in]) and, therefore, the same pressure and flow. Nevertheless, there are exceptions to this theoretical limitation; total peripheral resistance ([R.sub.tot]), total arterial compliance ([C.sub.tot]), and characteristic impedance ([Z.sub.o]) can be uniquely determined from input pressure and flow. [Z.sub.in] is determined completely by [C.sub.tot] and [R.sub.tot] at low frequencies, [Z.sub.o] at high frequencies, and arterial topology and reflection effects at intermediate frequencies. We present a novel method to determine the relative contribution of [Z.sub.o], [C.sub.tot], [R.sub.tot] and arterial topology/reflection to [Z.sub.in] without assuming a particular reduced model. This method is tested with a large-scale distributed model of the arterial system, and is applied to illustrative cases of measured pressure and flow. This work, thus, lays the theoretical foundation for determining the arterial properties responsible for increased pulse pressure with age and various arterial system pathologies. Index Terms--Apparent arterial compliance, hemodynamics, mathematical modeling, pulse wave reflection.

In conventional one-dimensional single-path models, radially averaged concentration is calculated as a function of time and longitudinal position in the lungs, and coupled convection and diffusion are accounted for with a dispersion coefficient. The axisymmetric single-path model developed in this paper is a two-dimensional model that incorporates convective-diffusion processes in a more fundamental manner by simultaneously solving the Navier-Stokes and continuity equations with the convection-diffusion equation. A single airway path was represented by a series of straight tube segments interconnected by leaky transition regions that provide for flow loss at the airway bifurcations. As a sample application, the model equations were solved by a finite element method to predict the unsteady state dispersion of an inhaled pulse of inert gas along an airway path having dimensions consistent with Weibel's symmetric airway geometry. Assuming steady, incompressible, and laminar flow, a finite element analysis was used to solve for the axisymmetric pressure, velocity and concentration fields. The dispersion calculated from these numerical solutions exhibited good qualitative agreement with the experimental values, but quantitatively was in error by 20%-30% due to the assumption of axial symmetry and the inability of the model to capture the complex recirculatory flows near bifurcations. [DOI: 10.1115/1.2133762] Keywords: dispersion, finite element, single path, lungs

The pulsatile flow and gas transport of a Newtonian passive fluid across an array of cylindrical microfibers are numerically investigated. It is related to an implantable, artificial lung where the blood flow is driven by the right heart. The fibers are modeled as either squared or staggered arrays. The pulsatile flow inputs considered in this study are a steady flow with a sinusoidal perturbation and a cardiac flow. The aims of this study are twofold: identifying favorable array geometry/spacing and system conditions that enhance gas transport; and providing pressure drop data that indicate the degree of flow resistance or the demand on the right heart in driving the flow through the fiber bundle. The results show that pulsatile flow improves the gas transfer to the fluid compared to steady flow. The degree of enhancement is found to be significant when the oscillation frequency is large, when the void fraction of the fiber bundle is decreased, and when the Reynolds number is increased; the use of a cardiac flow input can also improve gas transfer. In terms of array geometry, the staggered array gives both a better gas transfer per fiber (for relatively large void fraction) and a smaller pressure drop (for all cases). For most cases shown, an increase in gas transfer is accompanied by a higher pressure drop required to power the flow through the device. [DOI: 10.1115/1.2133761] Keywords: pulsatile flow, gas transfer, artificial lung, cylinder array

Spectral analysis of cardiovascular signals has been extensively used to investigate circulatory homeostatic mechanisms. However, the nature of very low-frequency (VLF) fluctuations remains unclear. Because we previously observed enhanced VLF fluctuations in blood pressure (BP) in the sympathectomized rat (a model characterized by markedly increased plasma epinephrine levels), the aims of our study were to assess whether the genesis of VLF fluctuations in BP depends on circulating catecholamines and to determine which adrenergic receptor(s) and which membrane ion channel(s) are involved. We used continuous intra-arterial BP recordings from unanesthetized unrestrained rats to compute the power of VLF fluctuations in BP in the intact condition, during acute ganglionic blockade with hexamethonium, and after restoration of BP levels by infusion (in addition to hexamethonium) of adrenergic agonists (epinephrine, norepinephrine, and clonidine) or nonadrenergic vasoconstrictors (vasopressin). Effects of infusion of specific adrenergic receptor blockers (propranolol, prazosin, and yohimbine) with hexamethonium and catecholamines and infusion of various membrane ion channel blockers on VLF fluctuations in BP were also evaluated. Our results are as follows. 1) Ganglionic blockade drastically reduced BP levels and VLF fluctuations. 2) All vasoconstrictors restored BP levels, but only adrenergic vasoconstrictors generated striking VLF fluctuations in BP. 3) Catecholamine-induced fluctuations were abolished by [[alpha].sub.2]-, but not [[alpha].sub.1]- or [beta]-, adrenergic receptor blockade and by [Ba.sup.2+]-sensitive [K.sup.+] channel or L-type [Ca.sup.2+] channel, but not by other ion channel, blockers. We conclude that, in the conscious, unrestrained ganglion-blocked rat, catecholamine infusion generates VLF fluctuations in BP through stimulation of [[alpha].sub.2]-receptors and activation of [Ba.sup.2+]-sensitive [K.sup.+] channels. These fluctuations may have (patho)physiological relevance under conditions of disrupted circulatory homeostasis. catecholamines; spectral analysis; ganglionic blockade; adrenergic receptors

Compared with arterial hemodynamics, there has been relatively little study of venous hemodynamics. We propose that the venous system behaves just like the arterial system: waves propagate on a time-varying reservoir, the windkessel, which functions as the reverse of the arterial windkessel. During later diastole, pressure increases exponentially to approach an asymptotic value as inflow continues in the absence of outflow. Our study in eight open-chest dogs showed that windkessel-related arterial resistance was ~62% of total systemic vascular resistance, whereas windkessel-related venous resistance was only ~7%. Total venous compliance was found to be 21 times larger than arterial compliance (n = 3). Inferior vena caval compliance (0.32 [+ or -] 0.015 ml x [mmHg.sup.-1] x [kg.sup.-1]; mean [+ or -] SE) was ~14 times the aortic compliance (0.023 [+ or -] 0.002 ml x [mmHg.sup.-1] x [kg.sup.-1]; n = 8). Despite greater venous compliance, the variation in venous windkessel volume (i.e., compliance x windkessel pulse pressure; 7.8 [+ or -] 1.1 ml) was only ~32% of the variation in aortic windkessel volume (24.3 [+ or -] 2.9 ml) because of the larger arterial pressure variation. In addition, and contrary to previous understanding, waves generated by the right heart propagated upstream as far as the femoral vein, but excellent proportionality between the excess pressure and venous outflow suggests that no reflected waves returned to the right atrium. Thus the venous windkessel model not only successfully accounts for variations in the venous pressure and flow waveforms but also, in combination with the arterial windkessel, provides a coherent view of the systemic circulation. systemic circulation

Male Sprague-Dawley rats were studied using Fos immunocytochemistry to investigate the brain regions triggered by isotonic volume expansion. The rats subjected to volume expansion showed substantially greater Fos activation in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus and perinuclear zone of the supraoptic nucleus. The neurons in brain regions that were found to inhibit both vasopressin release and sympathetic activity demonstrated a rise in Fos expression after isotonic volume expansion.

A major theme of many papers in this symposium is the identification of broad physiological trends and patterns that extend beyond the boundaries of data from individual studies. Recognizing patterns in everything from hypoxic ventilatory patterns to regulation of blood gases not only helps the investigator understand specific data sets, but also helps place those data in a broad context. Yet, recognizing physiological patterns is confounded by two factors: phylogenetic relationships and physiological state. Fortunately, the last decade has seen infiltration of sound evolutionary theory, including tools of cladisitic analysis and population genetics, into more and more studies of comparative physiology. However, even when an experimenter carefully accounts for phylogeny, differences in physiological state in the experimental animals can still obscure physiological patterns. Two informal categories of physiological state are described, the first obvious and frequently controlled for, and the second less obvious and typically not controlled for. Examples of the latter, including seasons, rhythms, prandial effects and sex of the animal, are developed to show how ignoring these can lead to considerable misleading variation in cardiorespiratory data sets. Considering physiological state is vital in producing reliable data that can be used meaningfully for delineating broad physiological patterns.

The purposes of this research were: (1) to carry out the comparative evaluation of indices of the morphofunctional condition of the cardiovascular system (CVS) in patients with arterial hypertension (AH) exposed to ionizing radiation, taking into account the occurrence of peripheral arterial atherosclerosis and the spread of traditional risk factors of cardiovascular diseases (CVD); (2) to determine interaction between the structural and functional indices of the CVS and IR influence. Unbiased sampling of patients with mild and moderate AH (n = 100) in the cohort exposed to sources of IR in the workplace was undertaken, with investigation of heart rate variability, and scintiangiography of large arteries of elastic type to evaluate their elastic-tonic properties and the functional condition of the endothelium. Comparison of the spread rate of risk factors of cardiovascular pathology formation revealed a more frequent occurrence of tobacco smoking, shiftwork, and a high level of psychoemotional overstrain in persons in contact with IR sources in the workplace. The results revealed a tendency to increased arterial blood pressure, longer duration of AH, and more significant structural and functional changes in the CVS in an unbiased sample of persons suffering from AH exposed to IR.

Nakanishi, Kuniaki, Fumiko Tajima, Hiroshi Itoh, Yasuko Nakata, Norio Hama, Osamu Nakagawa, Kazuwa Nakao, Toshiaki Kawai, Chikao Torikata, Tatsuko Suga, Kunio Takishima, Takashi Aurues, and Tomosumi Ikeda. Expression of C-type natriuretic peptide during development of rat lung. Am. J. Physiol. 277 (Lung Cell. Mol. Physiol. 21): L996-L1002, 1999.--C-type natriuretic peptide (CNP), recently found to be secreted from vascular endothelial cells, is now viewed as a novel endothelium-derived relaxing peptide. However, the distribution and expression of CNP during cardiopulmonary development is unclear. To follow changes in the expression of CNP during lung development, we examined rat embryos and neonates using Northern blot analysis and in situ hybridization for CNP mRNA and radioimmunoassay and immunohistochemistry for CNP protein. A substantial expression of CNP mRNA was first detected on postnatal day 2, and it thereafter remained fairly steady. The level of CNP protein also increased rapidly after postnatal day 1, reaching a settled level on postnatal day 4. CNP protein and mRNA were detected in the endothelium and smooth muscle cells of blood vessels and in bronchial airway and alveolar epithelia. Immunoreactivity for CNP protein in the endothelium of blood vessels increased to an intense level after the saccular stage. These results suggest that the changes in CNP levels may be related to the occurrence of pulmonary vasodilation after birth. cardiopulmonary system