Distribution of cardiac output in different models of hypertension in the conscious rat

The distribution of cardiac output was determined by 15 m radioactive microspheres in all the major organs of spontaneous, DOCA/NaCl and one kidney Goldblatt hypertensive rats and compared to normotensive Wistar rats. Although there were alterations in cardiac output distribution which were characteristic of each model of hypertension significant changes were common to all three were an increased distribution to skeletal muscle with decreases to the lungs, spleen and hepatosplanchnic tissues. The results suggest that alterations in peripheral resistance induced by hypertension are of unequal importance in the different vascular beds with certain vascular resistance changes occurring irrespective of the origin of the hypertension.Abbreviations used in this paper SHR spontaneously hypertensive rats - DOCA deoxycorticosterone acetate Supported by I.C.I. Pharmaceutical Ldt and the Mersey Regional Health Authority (Research Schemes No. 338).     

Irreversible shock of rats after acute renal vein thrombosis

Summary After occlusion of the renal veins rats die quickly in progressive shock (within 4.5 h), but after ligating the renal hilum of both Kidneys they survive 27 h. To learn why renal vein occlusion is so rapidly lethal, and what substances are given off and by what method from the hemorrhagically infarcted kidneys, we studied eight groups of rats, each containing at least seven animals. The groups differed in the combination of hilar structures (renal veins, ureters, lymphatics) ligated. We compared: survival times, changes in blood pressure, blood volume, levels of plasma kinins, adenosine, and lactate, changes of blood pH, responses to Indomethacin, Trasylol^®, and plasma expanders, tubular and capillary flow rates, histopathological changes in organs and cerebral blood flow and changes in the blood coagulation system. Our results suggest that the venous stasis, anoxia, and hemorrhagic necrosis caused by bilateral venous occlusion release into renal lymphatics toxic substances which reach the systemic circulation and induce irreversible shock. We have excluded prostaglandins and adenosine as the toxic substances inducing shock but could not rule out an action of the kallikrein-kinin-system. We postulate that the striking degenerative changes occurring in the arterioles of the brain after bilateral venous occlusion may mean these vessels are especially susceptible to high levels of lactic acid and that this may explain why these animals die so quickly. Our conclusions should help not only in understanding why high levels of lactate in shock portend a poor prognosis but also help in formulating appropriate therapy for circulatory failure of renal origin and for protracted hypotension after extensive tissue injury.The studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres SystemPresented in part: Jäckh and Steinhausen, 1976; Dallenbach et al., 1978; Zimmerhackl et al., 1979We dedicate this paper to Wilhelm Doerr, Dr. med., Professor of Pathology, University of Heidelberg on the occasion of his 65th birthday (August 25th, 1979)     

Neural basis of visually guided head movements studied with fMRI

We used event-related fMRI to measure brain activity while subjects performed saccadic eye, head, and gaze movements to visually presented targets. Two distinct patterns of response were observed. One set of areas was equally active during eye, head, and gaze movements and consisted of the superior and inferior subdivisions of the frontal eye fields, the supplementary eye field, the intraparietal sulcus, the precuneus, area MT in the lateral occipital sulcus and subcortically in basal ganglia, thalamus, and the superior colliculus. These areas have been previously observed in functional imaging studies of human eye movements, suggesting that a common set of brain areas subserves both oculomotor and head movement control in humans, consistent with data from single-unit recording and microstimulation studies in nonhuman primates that have described overlapping eye- and head-movement representations in oculomotor control areas. A second set of areas was active during head and gaze movements but not during eye movements. This set of areas included the posterior part of the planum temporale and the cortex at the temporoparietal junction, known as the parieto-insular vestibular cortex (PIVC). Activity in PIVC has been observed during imaging studies of invasive vestibular stimulation, and we confirm its role in processing the vestibular cues accompanying natural head movements. Our findings demonstrate that fMRI can be used to study the neural basis of head movements and show that areas that control eye movements also control head movements. In addition, we provide the first evidence for brain activity associated with vestibular input produced by natural head movements as opposed to invasive caloric or galvanic vestibular stimulation.     

Learning in escape/avoidance tasks in female rats does not vary with reproductive condition

To determine whether the development of novel stimulus-response associations by the mother during the periparturient period is attributable to a general facilitation of learning produced by the hormonal milieu during that period, learning ability under various reproductive conditions was assessed in two tasks unrelated to the periparturitional situation. The two tasks, selected because they equalized the various groups for motivation and performance variables, were acquisition of a water-maze escape (including two reversals), and acquisition and retention of an unsignalled shuttlebox shock avoidance. The groups tested in the water maze were a midpregnant group, an immediately prepartum group, and an immediately postpartum group. In the shuttlebox, the same conditions (different rats) were compared, together with a nonpregnant estrus condition, and a nonpregnant diestrus condition. The results of both experiments indicate that although learning occurred, the characteristics of acquisition and retention were not influenced by reproductive condition.     

The cholinergic nervous system and immediate hypersensitivity: I. Eccrine sweat responses in allergic patients

The cholinergically innervated human eccrine sweat gland is a readily available organ permitting the assessment in allergic patients of cholinergic reactivity with few or no adrenergic influences. The sweat responses of four matched groups (male allergic, female allergic, male control, and female control) to intradermal Mecholyl from 0.1 μg to 100 μg was compared; the 45 male and 45 female allergic patients demonstrated statistically significant increases in sweat responses to essentially all concentrations of Mecholyl examined. No difference in the sweat responses of patients with allergic rhinitis alone as compared with patients with both allergic rhinitis and allergic asthma was noted. Five patients with intrinsic asthma most closely resembled the allergic groups in their responses and 8 patients with vasomotor rhinitis sweated at or below the control groups. The increased sensitivity of allergic patients to cholinergic stimulation as measured by eccrine sweat responses suggests that this hyperresponsiveness may be one of the underlying defects in allergic disease.     

Interactions of Respiratory and Cardiovascular Adjustments to Behavioral Stressors

The relationships among a variety of cardiovascular and respiratory measures were examined in young college males subjected to a cold pressor task, reaction-time shock avoidance task, and three levels of graded exercise. As expected, the relationships between cardiovascular (e.g., heart rate and cardiac output) and respiratory (e.g., oxygen uptake and minute ventilation) variables were tightly linear when considering rest and exercise values. However, the range of individual cardiopulmonary responses during cold pressor and reaction time was considerable, often leading to disruptions in the cardiovascular/respiratory interactions. Analyses of extreme high and low ventilation reactors during both reaction time and cold pressor revealed that the excessive ventilation responders in cold pressor showed clear signs of hyperventilation. Increases in ventilation by the high reactors during reaction time were of smaller magnitude than during cold pressor, with potential hyperventilation much less clear. Increases in minute ventilation by reactors during the cold pressor task were primarily due to large increases in tidal volume, with only modest increases in respiratory rate. For reaction time, however, the increases in ventilation by reactive individuals stemmed from rate increases with tidal volume remaining essentially unchanged.     

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input–output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input–output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.     

Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient.

BACKGROUND: Hepatitis B Virus (HBV) infection is a leading cause of chronic hepatitis and liver cirrhosis worldwide, and efficient protection can usually be achieved by vaccination that is based on recombinant HBsAg protein from HBV genotype A and D. RESULTS: Here we report the case of a fully immune-competent German patient that acquired a symptomatic acute HBV infection during adulthood despite a complete and formally successful vaccination, which had resulted in anti-HBs titers considered protective. Further phylogentic analysis identified an infection with the rare genotype F of HBV, possibly acquired in Spain, without apparent aberrations in the immunodominant 'a' determinant domain of the envelope gene. However, sequence comparisons revealed that all reported genotype F isolates display marked differences from the other genotypes in this domain which serves as an epitope for humoral immune responses. CONCLUSIONS: The rare HBV genotype F, as detected in this immune-competent, previously vaccinated patient, has marked sequences differences in the envelope/polymerase gene. Therefore, current HBV vaccines based on genotype A and D may not result in full protective immunity towards viral strains from genotype F.