Pulmonary fluid balance following pulmocutaneous baroreceptor denervation in the toad

Pulmonary hemodynamics and net transcapillary fluid flux (NTFF) were measured in conscious toads before and following bilateral denervation of the recurrent laryngeal nerves (rLN), which contain afferents from baroreceptors located in the pulmocutaneous arteries. Denervation caused an acute doubling of the arterial-venous pressure gradient across the lung and a threefold increase in pulmonary blood flow. Calculated pulmonary vascular resistance fell and remained below control values through the period of experimentation. NTFF increased by an order of magnitude (0.74-7.77 ml X kg-1 X min-1), as filtration increased in response to the hemodynamic changes caused by rLN denervation. There was a better correlation between NTFF and pulmonary blood flow than between NTFF and pulmonary driving pressure. Our results support the view that tonic neural input from pulmocutaneous baroreceptors protects the anuran lung from edema by restraining pulmonary driving pressure and blood flow and perhaps by reflexly maintaining vascular tone in the extrinsic pulmonary artery, therefore tending to increase the pre-to-postpulmonary capillary resistance ratio and biasing the Starling relationship in the pulmonary capillaries against filtration.     

Stephen Hales: neglected respiratory physiologist

Stephen Hales was an eminent early 18th century scientist and minister of the parish of Teddington near London. He is well known for his early work on blood pressure. However, he made many contributions to respiratory physiology. He clarified the nature of the respiratory gases, distinguishing between their free (gaseous) and fixed (chemically combined) forms, demonstrated that rebreathing from a closed circuit could be extended if suitable gas absorbers were included (to remove carbon dioxide), suggested a similar device as a respirator for noxious atmospheres, invented the pneumatic trough for collecting gases, measured the size of the alveoli, calculated the surface area of the interior of the lung, calculated the time spent by the blood in a pulmonary capillary, invented the U-tube manometer, and measured intrathoracic pressures during normal and forced breathing. Hale's work is remarkable for its emphasis on the "statical" method, i.e., meticulous attention to detail in measurement and careful calculations. In his later life he made important contributions in the area of public health. He was a trustee of the new colony of Georgia and willed his own library of books to the colony though their whereabouts is unknown. He deserves more recognition in the history of respiratory physiology.     

Fetal pulmonary vasodilation and vasoreactivity during metabolic acidaemia

We studied the pulmonary vascular response to progressive metabolic acidaemia and to an abrupt increase in oxygen tension during metabolic acidaemia in 8 chronically-prepared fetal sheep. Left pulmonary artery blood flow was measured by electromagnetic flow transducer. Two and a half hour infusion of NH4Cl into the fetal inferior vena cava caused pH to fall to 6.94 +/- 0.01 from 7.37 +/- 0.01 (P less than 0.001). During this period of progressive metabolic acidaemia, left pulmonary artery blood flow increased from a baseline value of 60 +/- 8 to 105 +/- 14 ml.min-1 (P less than 0.002). Pulmonary artery pressure did not change significantly and calculated pulmonary vascular resistance fell indicating fetal pulmonary vasodilation. PO2 rose significantly (19.8 +/- 0.7 to 24.1 +/- 1.8 torr; P less than 0.03) and oxygen saturation fell (54.6 +/- 2.8% to 38.9 +/- 3.5%; P less than 0.001) confirming a rightward shift of the oxyhaemoglobin dissociation curve. During acidaemia, administration of 100% oxygen to the ewe further increased fetal PO2 to 37.9 +/- 2.3 torr within 10 min (P less than 0.001) and this increase in PO2 was accompanied by an increase in left pulmonary artery blood flow (P less than 0.001), a fall in pulmonary artery pressure (P less than 0.03) and a decrease in pulmonary vascular resistance (P less than 0.001) indicating further vasodilation. The response of the fetal pulmonary circulation to a 2-h period of increased oxygen tension was qualitatively similar in acidaemic and non-acidaemic fetuses. We conclude that the progressive metabolic acidaemia imposed by these experimental conditions increases pulmonary blood flow likely through an increase in fetal PO2 and that metabolic acidaemia does not block the normal vasodilatory response to an increase in oxygen tension.     

Effects of BAY 41-2272, a soluble guanylate cyclase activator, on pulmonary vascular reactivity in the ovine fetus

Nitric oxide (NO)-cGMP signaling plays a critical role during the transition of the pulmonary circulation at birth. BAY 41-2272 is a novel NO-independent direct stimulator of soluble guanylate cyclase that causes vasodilation in systemic and local circulations. However, the hemodynamic effects of BAY 41-2272 have not been studied in the perinatal pulmonary circulation. We hypothesized that BAY 41-2272 causes potent and sustained fetal pulmonary vasodilation. We performed surgery on 14 fetal lambs (125-130 days gestation; term = 147 days) and placed catheters in the main pulmonary artery, aorta, and left atrium to measure pressures. An ultrasonic flow transducer was placed on the left pulmonary artery (LPA) to measure blood flow, and a catheter was placed in the LPA for drug infusion. Pulmonary vascular resistance (PVR) was calculated as pulmonary artery pressure minus left atrial pressure divided by LPA blood flow. BAY 41-2272 caused dose-related increases in pulmonary blood flow up to threefold above baseline and reduced PVR by 75% (P < 0.01). Prolonged infusion of BAY 41-2272 caused sustained pulmonary vasodilation throughout the 120-min infusion period. The pulmonary vasodilator effect of BAY 41-2272 was not attenuated by N(omega)-nitro-l-arginine, a NO synthase inhibitor. In addition, compared with sildenafil, a phosphodiesterase 5 inhibitor, the pulmonary vasodilator response to BAY 41-2272 was more prolonged. We conclude that BAY 41-2272 causes potent and sustained fetal pulmonary vasodilation independent of NO release. We speculate that BAY 41-2272 may have therapeutic potential for pulmonary hypertension associated with failure to circulatory adaptation at birth, especially in the setting of impaired NO production.     

Pulmonary vascular response to prostacyclin in fetal lambs.

Eighteen prostacyclin injections (19.4 +/- 1.5 micrograms/kg) were performed in five chronically instrumented, intact fetal lambs in order to study the effects on pulmonary blood flow. These resulted in a brief period of bradycardia followed by a more prolonged period of increased pulmonary blood flow. In this latter phase, pulmonary blood flow increased from a baseline value of 49 +/- 4 ml/(kg min) to 122 +/- 10 ml/(kg min). Systolic/diastolic pulmonary arterial pressure simultaneously fell from 73 +/- 2/48 +/- 1 to 68 +/- 2/42 +/- 1 mm Hg. Flow through the ductus arteriosus was unchanged and right ventricular output increased to account for the increased pulmonary blood flow. Thus, prostacyclin causes pulmonary vasodilation in intact fetal lambs and may participate in the control of fetal pulmonary blood flow and the circulatory adjustments to extra-uterine life.     

HIV epidemiology: past, present, and future

The worldwide pandemic of acquired immunodeficiency syndrome (AIDS) has the potential to cause catastrophic medical and social effects that will influence world health well into the 21st century. The causative agent, a lentiretrovirus called human immunodeficiency virus (HIV-1), is spread by intimate exposure to blood and bodily fluids through sexual, parenteral, and mother-to-infant exposure. The natural history from exposure to disease has a median incubation period of 8-10 years and is characterized by progressive depletion of CD-4 positive T lymphocytes as well as effects on other immune and central nervous system cell populations. The World Health Organization (WHO) estimates that between 8 and 10 million persons are currently infected with the virus worldwide, with 8 to 10 times this level projected by some estimates into the 21st century. Recent leveling off of AIDS incidence in the U.S. appears to represent the positive benefits of antiretroviral therapy, and considerable benefit could be seen if such therapies were made more widely available to medically underserved populations. With prolonged survival, however, other long-term sequelae such as cancer and lymphoma may emerge as significant complications of prolonged immunodeficiency. Furthermore, the large pool of already infected persons and continued spread of the virus make the development of additional therapies and an effective anti-HIV vaccine priorities of medical research.     

Hebrew and Latin astrology in the twelfth century: the example of the location of pain

The formative period of Latin and Hebrew astrology occurred virtually simultaneously in both cultures. In the second quarter of the twelfth century the terminology of the subject was established and the textbooks which became authoritative were written. The responsibility for this lay almost entirely with two scholars: John of Seville for the Latins, and Abraham ibn Ezra for the Jews. It is unlikely to have been by coincidence that the same developments in astrology occurred in these two cultures. John of Seville and Abraham ibn Ezra were both brought up within the Islamic culture of Spain, and their astrology was Arabic astrology. Moreover, some scholars have thought that John’s origins were Jewish, while Ibn Ezra is known to have collaborated with Latin scholars (whose names are not recorded). It cannot be a coincidence that they forged the science of astrology for their respect co-religionists at almost the same time. Yet, very little research has been done on the possible relations between the two scholars. The purpose of this paper is to begin to explore this relationship, and to illustrate it in particular by their shared doctrine concern the location of pain.     

Vascular resistance and vasoactivity of gills and pulmonary artery of the salamander,Ambystoma tigrinum

Summary In order to understand the blood flow patterns and their regulation in the gills and pulmonary artery ofAmbystoma tigrinum, the vascular resistance and vasoactivity of the two major branchial perfusion pathways and a vascular plexus in the pulmonary artery were investigated using an isolated-tissue perfusion method. Acetylcholine and epinephrine were both pressor agents in all three vascular segments. Angiotensin II also constricted the branchial respiratory vasculature. Norephinephrine was primarily a vasodilator in the branchial respiratory vasculature, however, it had no effect on the shunt vessels of the gill or the pulmonary arterial plexus. Both gill circulations were insensitive to alterations in CO₂ and pH. Anoxia produced a slight vasodilation of the branchial respiratory vessels but had no effect on the shunt vasculature. Mild hypoxia had no effect on either branchial circulations. The results suggest that: (1) blood flow through the respiratory section of the gill may vary between 8 and 47% of total gill flow, (2) the major perfusion pathway to the lung is probably from the efferent artery of the third gill through the ductus arteriosus and then into the pulmonary artery, (3) O₂, CO₂ and pH exert no local control of branchial perfusion, (4) both cholinergic and adrenergic regulation of branchial and proximal pulmonary arterial vascular resistance is possible, (5) a rise in circulating norepinephrine should increase blood flow to the respiratory section of the gill.Abbreviations AII angiotensin II - ACh acetylcholine - EPi epinephrine - NE norepinephrine     

Fasudil inhibits the myogenic response in the fetal pulmonary circulation

In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent vasodilation in the developing lung circulation are unknown. We studied the effects of fasudil, a ROCK inhibitor, on the hemodynamic response during acute compression of the ductus arteriosus (DA) in chronically prepared, late-gestation fetal sheep. Acute DA compression simultaneously induces two opposing responses: 1) blood flow-induced vasodilation through increased shear stress that is mediated by NO release and 2) stretch-induced vasoconstriction (i.e., the myogenic response). The myogenic response was assessed during acute DA compression after treatment with N(omega)-nitro-L-arginine, an inhibitor of nitric oxide synthase, to block flow-induced vasodilation and unmask the myogenic response. Intrapulmonary fasudil infusion (100 microg over 10 min) did not enhance flow-induced vasodilation during brief DA compression but reduced the myogenic response by 90% (P<0.05). During prolonged DA compression, fasudil prevented the time-dependent decline in left pulmonary artery blood flow at 2 h (183+/-29 vs. 110+/-11 ml/min with and without fasudil, respectively; P<0.001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation.     

An anatomy lesson and the quality of intermittence

Not only in the second century AD but also at the end of the second millennium, there was much debate on the structural and functional characteristics of the heart in different-sized mammals. Galen commented on the dissection of the heart of an elephant, whereas Meijler, a Dutch cardiologist, set out on a whale-ECG expedition to prove pre-existing assumptions too. The chain of thoughts is remarkably similar, in as far as human nature is driven by the aspiration to fill in the voids in pre-existing learning. As appreciation for our heritage of knowledge has somewhat receded into the background, a plea is made for reappraisal and the quality of being intermittent. (Neth Heart J 2007;15:239-41.).     

Effect of pulmonary blood flow on leukocyte uptake and release by dog lung

The effect of pulmonary blood flow on leukocyte uptake and release by the lung was examined in 10 anesthetized spontaneously breathing dogs. Pulmonary arterial and pulmonary venous blood was sampled with catheters placed into the right ventricle and aorta, respectively. Pulmonary blood flow was lowered by inflating a balloon catheter located in the inferior vena cava. In five experiments simultaneous blood samples were drawn from the right ventricle and aorta at 10-s intervals during a control period, a 2- to 3-min period of low flow, and a recovery period. In five additional experiments, less frequent samples were taken over periods of 15-60 min. Total leukocyte concentrations and differential counts were determined for each blood sample. The study shows that large numbers of leukocytes become sequestered within the lung when pulmonary blood flow is low and that an equivalent number of cells are released from the lung after deflation of the balloon catheter. Both the polymorphonuclear leukocytes and the lymphocytes were taken up by the lung when pulmonary blood flow was reduced. We conclude that pulmonary blood flow has a marked effect on the uptake and release of leukocytes by the dog lung.     

Evidence for pulmonary CO2 chemosensitivity: effects on ventilation

To determine whether there is a pulmonary chemoreceptor for CO2 that influences spontaneous ventilation (VE), we separated the systemic and pulmonary circulations and controlled partial pressure of CO2 (PCO2) independently in each circuit under hyperoxic conditions and measured VE. Dogs were anesthetized with ketamine and maintained with 1% halothane. Systemic venous return was drained from the right atrium and passed through an oxygenator and heat exchanger; blood was returned to the ascending aorta. An identical bypass was established for the pulmonary circulation, draining blood from the left atrium and returning it to the pulmonary artery. The heart was fibrillated; all cannulas were brought through the chest wall; and the median sternotomy was closed. Blood flow through both circuits was maintained at 0.080 l . kg-1 . min-1. Systemic PCO2 (PSCO2) was held constant at three different nonoscillatory levels. At each level, pulmonary PCO2 (PpCO2) was randomly varied between approximately 7 and 85 Torr. With PSCO2 at 43.5 +/- 0.4 Torr, VE increased 2.67 +/- 0.61 l . min-1 as PpCO2 was varied between these limits. With PSCO2 at 63.8 +/- 2.5 Torr, VE increased 3.95 +/- 0.73 l . min-1 over these same limits of PpCO2. With PSCO2 below 25--30 Torr, the dogs were apneic and no longer responded to changes in PpCO2. The effect of PpCO2 on VE was abolished by vagotomy. These results suggest the presence of a CO2 chemoreceptor in the lung that interacts with the nonpulmonary chemoreceptors in the control of VE.     

Economic Botany and ethnobotany in al-Andalus (Iberian Peninsula: Tenth-fifteenth centuries), an unknown heritage of Mankind

The Hispano-Arabic culture in the Iberian Middle Ages is a major chapter in the history of the use and knowledge of plants. The Andalusi agronomists, botanists and physicians assimilated their heritage of Iberian, Hispano-Roman, and Hispano-Visigothic cultures with North-African and Eastern influences. They developed a profound knowledge of the plant world and managed a high diversity of species. A part of this ethnobotanical and agronomic heritage was transmitted not only to the local cultures and generations that followed, but also to peoples on the other side of the Atlantic Ocean by the Spanish colonists in the New World. This paper presents a study of the principal works of the so-called Andalusi Agronomic School (10th-15th centuries) and their agronomist authors: Arib ben Said, Ibn Wafid, Ibn Hayyay, Abu l-Jayr, Ibn Bassal, al-Tignari, Ibn al-Awwam and Ibn Luyun. We also raise questions about Andalusi ethnobotany, the introduction of Oriental species in the Iberian Peninsula and the prospects for ethnobotanical research through the philological study of Hispano-Arabic writings.     

The main trends in the palaeodemography of the 7th-18th century population of Latvia

The study represents palaeodemographic research of osteological material of 3304 individuals from the funds of the Anthropological Laboratory of the Institute of History of the University of Latvia in Riga, dating from the 7th to the 18th century AD. Compensated life expectancy at birth is varying between 20.3 and 22.2 years during the research period. Crude mortality has changed between 49.3 and 45% per hundred. In the early period (7th-13th century) there is a significant male prevalence (2.2-1.4); female life expectancy at the age of 20 is on average 6.6 years less than for males. This difference decreases to 5.4 years in the 13th-18th century. According to historical demography, female life span exceeded male only in the 2nd half of 19th century. The palaeodemographic data indicate that in the 7th-18th century, women in Latvia gave birth to a mean of 4-5 children (the figure includes childless women), of whom half, at most 2-2.5, reached reproductive age, on account of high child mortality. The net reproductive rate R0 (the number of descendants per individual of the parents' generation) varies between 1 and 1.25 in the study period. Concerning the completely excavated cemeteries of Lejasbiteni (7th-10h century) and Daudziesi (16th-17th century), it was possible to calculate the size and structure of the populations that had used these cemeteries. They were similar, having 45.3-49.9% of children up to an age of 14 and 24-28% individuals over the age of 30. According to historical demography, radical improvement of the demographic situation in Latvia began in the second half of the 19th century, when the process of demographic transition in Latvia started.     

Genetic diversity, population structure, effective population size and demographic history of the Finnish wolf population

The Finnish wolf population (Canis lupus) was sampled during three different periods (1996-1998, 1999-2001 and 2002-2004), and 118 individuals were genotyped with 10 microsatellite markers. Large genetic variation was found in the population despite a recent demographic bottleneck. No spatial population subdivision was found even though a significant negative relationship between genetic relatedness and geographic distance suggested isolation by distance. Very few individuals did not belong to the local wolf population as determined by assignment analyses, suggesting a low level of immigration in the population. We used the temporal approach and several statistical methods to estimate the variance effective size of the population. All methods gave similar estimates of effective population size, approximately 40 wolves. These estimates were slightly larger than the estimated census size of breeding individuals. A Bayesian model based on Markov chain Monte Carlo simulations indicated strong evidence for a long-term population decline. These results suggest that the contemporary wolf population size is roughly 8% of its historical size, and that the population decline dates back to late 19th century or early 20th century. Despite an increase of over 50% in the census size of the population during the whole study period, there was only weak evidence that the effective population size during the last period was higher than during the first. This may be caused by increased inbreeding, diminished dispersal within the population, and decreased immigration to the population during the last study period.     

Pulmonary vascular response to prostacyclin in fetal lambs

Eighteen prostacyclin injections (19.4±1.5 μg/kg) were performed in five chronically instrumented, intact fetal lambs in order to study the effects on pulmonary blood flow. These resulted in a brief period of bradycardia followed by a more prolonged period of increased pulmonary blood flow. In this latter phase, pulmonary blood flow increased from a baseline value of 49±4 ml/(kg min) to 122±10 ml/(kg min). Systolic/diastolic pulmonary arterial pressure simultaneously fell from to mm Hg. Flow through the ductus arteriosus was unchanged and right ventricular output increased to account for the increased pulmonary blood flow. Thus, prostacyclin causes pulmonary vasodilation in intact fetal lambs and may participate in the control of fetal pulmonary blood flow and the circulatory adjustments to extra-uterine life.     

Measurement of bronchial blood flow with radioactive microspheres in awake sheep

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)     

The galenic and hippocratic challenges to Aristotle's conception theory

Conclusion As a result of this case study, additional questions arise. These can be cast into at least three groups. The first concerns the development of critical empiricism in the ancient world: a topic of much interest in our own century, expecially with regard to the work of the logical empiricists. Many of the same arguments are present in the ancient world and were hotly debated from the Hippocratic writers through and beyond Galen. Some of the ways in which Galen reacts to Hippocratic and Aristotelian influences may, in part, be explained by Galen's own posture as a so-called Dogmatist. Both the Empirics and the Methodists offered alternative viewpoints on the place, role, and limits of observation in biomedical research. Though I have written on this relationship in the Hippocratic writers and Aristotle,⁴⁴ it remains to be discussed in detailed fashion just how critical empiricism acted in Galen's evaluation of biomedical problems (aporiai). Contrasts between Galen and his predecessors might further clarify this issue both as a historical question and as it affects the construction of biological theory.The second area explores the question of how one develops comprehensive theories. In this respect Galen follows Aristotle's methodology rather closely. Both look at what theories are available to them and then systematically review the problems raised, at the same time refuting what they find inadequate. This is an effective strategy, for it permits utilizing the best features of earlier work to fashion a new whole. Indeed, Galen himself seems to attribute his use of such a methodology to his ecletic medical and philosophical training. Both Aristotle and Galen endeavor to employ techniques of theory integration. That is, they use aspects of theories they have already espoused to deal with new problems. This suggests the emergence of formal, logical coherence as an element in theory evaluation. The obvious drawback is that it can cause mistakes in one area to be repeated and ingrained in other areas. Such errors, because they are at the very core of an explanatory framework, may take centuries to correct. Future studies may shed light on how theory integration acts both in a positive and in a negative way.Finally, this case study offers a glimpse of how science progresses. Even though the advances in medical technology were comparatively minor, there is a great deal more sophistication in the conception theoreis of Aristotle and Galen than was present in the Hippocratic writers. Some of this (in Galen's case) had to do with increased anatomic and physiological knowledge, but most, I believe, is due to the evolution of scientific knowledge. If further work were done specifically on this question, it might document more completely how scientific knowledge on a specific topic evolves. The mode of advancement is primarily through gradual refinement of the types of questions being asked by these ancient authors, and the ramifications of their answers.Ancient theories of conception offer a fine case study in the history and philosophy of how a theory begins the develops. I have tried to suggest some interrelationships among the more important theories, as they focused upon Aristotle's own conception theory. There has been renewed interest in such cases in recent years. It is my hope that future specialized studies will increase our knowledge of method and practice in these important case studies and thereby augment our understanding of the genesis and application of biological theories.     

The hemodynamics of the lesser circulation and blood indices in rats under long-term high-altitude hypoxia

Pulmonary hemodynamics in anesthetized rats was studied during long-term residence (2,5 and 10 months) at high altitude (3,200 m, Tien Shan). Transbronchial regional electroplethysmography and catheterization of pulmonary artery was used. It has been shown that at all periods of adaptation there was increased systolic pressure in pulmonary artery and practically unchanged diastolic one. Some regional redistributions of pulmonary blood flow and blood volume for five different lung parts were demonstrated. Hemoglobin content in erythrocytes was steadily increased while specific electric blood resistance, hematocrit, and number of erythrocytes did not change so significantly. The role of pulmonary arterial hypertension and changes of other studied indices of hemodynamics and red blood in adaptation to chronic high-altitude hypoxia are being discussed.