Klaus Pleschka

Structural and functional characteristics of individual phrenic motoneurons.

SummaryIntracellular recording and staining techniques were applied to the study of cat phrenic motoneurons. Spontaneously driven phrenic cells possessed individualistic depolarization and spiking patterns that were a function of the conduction velocity in the different motor axons. Staining of phrenic motoncurons with Procion yellow indicated that fast conducting cells with small slow-wave depolarizations were large in size while slow conducting cells with large depolarizations were small in size. This implicated differences in membrane input resistance between large and small cells, although an unequal distribution of inputs to the individual components could not be discounted.On the average, phrenic motoneurons had a smaller dendritic surface area and smaller dendritic dominance than lumbosacral motoneurons. These factors help to explain the higher membrane resistances and longer time constants of phrenic cells.Phrenic dendrites were found to project in all directions away from the cell body and form ellipsoidal receptive fields that overlapped with other phrenic fields. It is speculated that the close approximation of phrenic dendrites with one another could, in part, be responsible for the high degree of synchronization among the different phrenic units.

Differential vasomotor adjustments in the evaporative tissues of the tongue and nose in the dog under heat load

Abstract1.Nasal and lingual blood flow were synchronously recorded with respiratory rate and arterial blood pressure in 14 anesthetized spontaneously breathing dogs in which blood temperature was raised by radiant heat. The blood flow responses of the infraorbital and sphenopalatine arteries to increasing heat load were characterized by a continuous increase which resulted from significant decreases in local vascular resistances. The final values during panting exceeded the resting values by 3 times. In contrast, lingual blood flow remained nearly unaffected as long as panting did not occur. With the onset of panting, lingual blood flow increased in close correlation with the increase in respiratory rate. This increase also resulted from a significant decrease in local vascular resistance.2.The preoptic-anterior hypothalamic region was heated with a water perfused thermode in 10 other dogs at normal (38.4°C) and elevated (39.4°C) blood temperature. Hypothalamic heating at a normal blood temperature induced vasodilatation only in the nasal vessels, while lingual blood flow and respiratory rate were nearly unaffected. However, in animals at an elevated blood temperature hypothalamic heating stimulated the full heat defense response, i.e. a marked increase in both nasal and lingual blood flow associated with polypnea.3.The results suggest that under normal conditions, in which the dog is breathing with the mouth closed, the graded enhancement of convective heat transfer to the respiratory mucous surfaces of the nose enables a continuous control of evaporative heat loss from these surfaces. During panting, when the dog is breathing with the mouth opened, the additional increase of heat transfer to the surface of the protruded tongue further increases the efficiency of evaporative heat loss. In addition the results confirm the hypothesis that the upper brainstem coordinates the differential patterns of circulatory adjustments in evaporative tissues.

Vasodilatory response of arteriovenous anastomoses to local cold stimuli in the dog's tongue.

In anesthetized dogs total tongue blood flow and its distribution to mucosa and muscle capillaries and to arteriovenous anastomoses (AVA) was determined by combining venous outflow measurements with the radioactive microsphere technique.Local temperature changes of the tongue surface in the physiological range revealed an inverse relationship between lingual blood flow (8.6–30.4 ml·min−1) and tongue surface temperature (40.5 to 27.7°C). The temperature dependent changes of tongue blood flow were exclusively due to changes of AVA blood flow (6.3–21.4 ml·min−1).

Lingual Blood Flow and Its Hypothalamic Control in the Dog during Panting

Summary1.The effects of increased ambient temperature (Ta) on blood-flow and-temperatures of the tongue were studied in the unanaesthetized dog. At Ta of 20° C and a relative humidity (rh) of 30% the mean lingual blood flow was 11 ml · min−1 (0.15 ml · g−1 · min−1) and the temperature difference between the lingual artery and vien (ΔTLAV) was 1.0° C. Accordingly, a heat loss of 48.6 J · min−1 was calculated even for the dog breathing with the mouth closed. When Ta was elevated to 38° C at constant rh, panting ensued. In parallel fashion lingual blood flow increased to 60.4 ml · min−1 (0.81 ml · g−1 · min−1) in mean and to 74.7 ml · min−1 (0.99 ml · g−1 · min−1) at peak rate of thermal tachypnoea (272 breaths · min−1). This flow increase resulted from a decrease in the local vascular resistance since the driving systemic pressure remained constant. It was accompanied by an increase in TLAV to 1.5° C equivalent to a heat loss of 400.7 J · min−1 in mean and 496.2 J · min−1 at maximum respiratory rate.2.The preoptic/anterior hypothalamic (PO/AH) region was heated with a water perfused thermode in urethane anaesthetized dogs at constant body temperature in order to study the relationship in time between the increase in lingual blood flow and the onset of thermal panting. Lingual blood flow was found to be 20 ml · min−1 at a respiratory rate of 60 breaths/min. During hypothalamic heating both respiratory rate and lingual blood flow increased markedly. At maximum respiratory rates (244 breaths · min−1) lingual blood flow reached a level of 60 ml · min−1. When perfusion of the thermode was stopped, both respiratory rate and lingual blood flow synchronously returned to control values within 5 min. Similar changes did not occur in dogs in which a ventilatory response failed to be elicited during hypothalamic heating.3.The results suggest that the tongue contributes to the evaporative heat loss mechanism and they confirm the concept that panting, associated with increased lingual blood flow, is induced by a common autonomic outflow pattern which is mediated by the central mechanism controlling thermal homeostasis.

Vasodilatory mechanisms in the tongue and nose of the dog under heat load

Blood flow in vessels running to the nose and tongue was measured with electromagnetic flowmeters in anaesthetized dogs. In initial experiments the effect of electrical stimulation of the stellate ganglion on blood flow to the nose and tongue was studied and suitable doses of antagonist drugs to adrenergic and cholinergic receptors determined. In subsequent experiments the effect of receptor blockade on blood flow response was examined in animals subjected to hypothalamic heating at different body temperatures induced by whole body warming. It was found that heat load provoked an increase in blood flow to the nose which was due to a decrease in the activity of nerves supplying alpha adrenergic receptors. The heat induced vasodilatation observed in the tongue occurred by the same mechanism as in the nose when the thermal load was small and respiration rate was not increased from resting levels. However, when the thermal load was greater and panting was induced, a secondary “active” component became evident, and this was mediated neither by adrenergic nor cholinergic muscarinic receptors. Fibres responsible for this active vasodilatation to the tongue were postganglionic and ran apart from the vagosympathetic trunk.

Der Einflu des Lungenvolumens auf die Spontanatmung und die ventilatorische CO2-Reaktion beim Hund

SummaryThe effects of inflating or deflating the lungs on the spontaneous ventilation and the CO2 response curve were investigated in 16 dogs under light anesthesia (Chloralose or Pernocton) using positive or negative pressure breathing. Negative pressure breathing caused an increase of respiratory rate and total ventilation whereas tidal volume and arterial CO2 tension decreased. The opposite effect was observed with positive pressure breathing. The CO2 response curve for the total ventilation and for the respiratory rate were shifted to lower values of arterial CO2 tensions with negative pressure breathing and to higher values of CO2 tensions with positive pressure breathing. The slope of the CO2 response curves however was not influenced systematically by changing the lung volume. After cutting both vagus nerves changes in lung volume did not influence the spontaneous ventilation and the position of the CO2 response curve. Rising the arterial CO2 tension increased the respiratory rate both before and after vagotomy. It is concluded that vagal afferent impulses and CO2 are additive in producing the net respiratory drive rather than interacting in a multiplicative manner.ZusammenfassungDer Einfluß der Lungenblähung auf die Spontanatmung und die CO2-Antwortkurve wurde bei 16 Hunden in leichter Pernocton- oder Chloralosenarkose aufgrund des Verhaltens bei Überdruckatmung (+9 cm H2O) und Unterdruckatmung (−8 cmH2O) untersucht. Verkleinerung des Lungenvolumens führte zu einer Zunahme der Atemfrequenz und des Atemminutenvolumens und zu einer Abnahme der Atemtiefe und des arteriellen CO2-Druckes. Das entgegengesetzte Verhalten ergab sich bei Vergrößerung des Lungenvolumens. Die CO2-Antwortkurven für das Atemminutenvolumen und die Atemfrequenz lagen bei Unterdruckatmung im Bereich niedrigerer CO2-Drucke verglichen mit den CO2-Antwortkurven bei Überdruckatmung. Eine unterschiedliche Steilheit fand sich jedoch nicht. Nach doppelseitiger Vagotomie fehlten die Sofortreaktionen der Atmung und die Verlagerung der CO2-Antwortkurve bei Änderung des Lungenvolumens. Erhöhung des arteriellen CO2-Druckes führte jedoch auch nach Vagotomie zu einer Frequenzzunahme. Die Ergebnisse lassen auf eine additive Wechselwirkung zwischen dem CO2-Antrieb und den vagalen Afferenzen von den Lungendehnungs-receptoren schließen. Eine multiplikative Komponente konnte nicht nachgewiesen, jedoch auch nicht mit Sicherheit ausgeschlossen werden.

Der Einfluß der Temperatur auf die CO2-Schwelle des Atemsystems

SummaryThe effect of body temperature on the CO2 response threshold was determined in 41 anesthetized, artificially ventilated dogs. The threshold was assessed by observing the cessation and the return of the action potentials of the phrenic nerve due to hyperventilation and return to normal ventilation respectively. Body temperature was changed by cooling or heating the blood by means of an arterio-venous by-pass and a controllable heat exchanger. Shivering was abolished by administration of succinylcholine. The threshold value of the arterial CO2 tension at 38° C was 41 Torr. During hypothermia the threshold CO2 decreased to a minimum of 31–34 Torr at 32° C and then increased to 67 Torr at 25° C. During hyperthermia the threshold pCO2 decreased to 29 Torr at 40° C. With still higher body temperatures panting frequently occurred. Overventilation apnea could not be obtained during this stage even with arterial CO2 tensions as low as 5 Torr. The direct and indirect effects of temperature on the respiratory center and the interaction of temperature regulation and the respiratory regulation are briefly discussed.ZusammenfassungDer Einfluß der Körpertemperatur auf die CO2-Schwelle der Atmung wurde an 41 narkotisierten, künstlich beatmeten Hunden untersucht. Dabei wurde die CO2-Schwelle durch das Erlöschen bzw. durch die Wiederkehr der Aktionspotentiale des N. phrenicus bei Hyperventilation bzw. Rückkehr zur normalen Ventilation definiert. Die Körpertemperatur wurde durch Kühlung bzw. Erwärmung des Blutes mit Hilfe eines arterio-venösen Kurzschlusses und eines Wärmeaustauschers geändert. Bei 38° C lag die Schwelle bei einer arteriellen CO2-Spannung von 41 Torr. Bei Senkung der Körpertemperatur sank die CO2-Schwelle zunächst ab und erreichte bei 32° C ein Minimum von 31–34 Torr. Bei weiterer Temperatursenkung stieg die Schwelle steil an bis auf 67 Torr bei 25° C. Erhöhung der Körpertemperatur führte zu einer Schwellensenkung auf 29 Torr bei 40° C. Bei höheren Temperaturen trat häufig Hecheln auf. Dabei konnte eine Hyperventilationsapnoe nicht mehr erzwungen werden, auch wenn die arterielle CO2-Spannung bis auf 5 Torr gesenkt wurde. Die direkten und indirekten Temperatureffekte sowie die Wechselwirkung zwischen Temperatur- und Atmungsregulation werden diskutiert.

Der Einfluß der Temperatur auf die elektrische Aktivität des Nervus phrenicus

SummaryThe effect of a decreased body temperature on respiration was investigated in 9 anaesthetized dogs. Shivering was abolished by succinyl choline which also inhibited spontaneous ventilation. The respiratory feedback loop was thereby opened. Information about the activity of the respiratory center was obtained from the discharges of the phrenic nerve, the integrated electric activity serving as equivalent to the tidal volume. Arterial blood gases were adjusted by altering the artificial ventilation. In order to analyse CO2-reactivity, short increases ofPaCO2 were used.The following results were obtained:1.The number of discharges per minute decreased with blood temperature.2.Phrenic nerve activity ceased below 24°C blood temperature.3.The duration of inspiratory activity increased linearily with decreasing blood temperature, whereas the duration of the expiratory pauses increased nearly exponentially.4.The integrated electric activity per burst increased until the blood temperature reached 27°C. Below 27°C the integrated electric activity decreased without returning to the initial value at 38°C.5.The product of burst frequency and integrated electric activity, serving as equivalent to the total ventilation, did not change until 30°C blood temperature. Below this temperature it decreased markedly.6.Responses to increased arterial CO2 pressure were observed even at 24°C. It is concluded that during hypothermia the increase in ventilation is not only due to an increase in oxygen consumption, but also due to a directly acting neural factor.ZusammenfassungBei neun gelähmten und künstlich beatmeten Hunden wurde der Einfluß erniedrigter Körpertemperatur auf die Atmung bei aufgehobener Kältegegenregulation untersucht. Dabei stand im Vordergrund der Untersuchung die Frage nach der Reaktionsweise des Atemzentrums unter den Bedingungen des aufgeschnittenen Regelkreises. Die Auftrennung des Regelkreises erfolgte zwischen dem Atemzentrum als Regler und der Ventilation als Stellglied durch die pharmakologische Blockierung der motorischen Endplatten. Als aussagekräuftiges Äquivalent für Atemfrequenz, Atemzugsvolumen und Atemminutenvolumen diente das Phrenicogramm. Dabei entsprachen die Zahl der Phrenicussalven der Atemfrequenz und die Integrationswerte der Massenableitung dem Atemzugsvolumen. Das Produkt beider Meßgrößen kennzeichnete das Atemminutenvolumen.Zur Überprüfung der Reaktivität wurde als Reiz die kurzfristige Erhöhung des arteriellen CO2-Druckes gewählt und die daraus resultierenden Änderungen der Spontanaktivität des N. phrenicus als Reizantwort des Atemzentrums gedeutet.Danach konnten inHypothermie bei normalen Kreislaufverhältnissen die folgenden charakteristischen Änderungen beobachtet werden:1.Die Zahl der Phrenicussalven nahm kontinuierlich ab.2.Ein Ausbleiben der elektrischen Aktivität bei noch normalen Blutdrucjwerten wurde erst unterhalb von 24°C Bluttemperatur beobachtet.3.Die Inspirationsdauer nahm annähernd linear, die Exspirationsdauer annähernd exponentiell zu.4.Die dem Atemzugsvolumen entsprechende integrierte elektrische Aktivität ließ im Mittel eine deutliche Zunahme bis in einen Temperaturbereich von 27°C erkennen, danach trat eine Abnahme ein, die den Ausgangswert jedoch nicht wieder erreichte.5.Die das Atemminutenvolumen repräsentierende Größe {ie334-1} blieb im Mittel bis 30°C unverändert, bei Temperaturen unter 30°C field sie jedoch steil ab.6.Die CO2-Reaktivität des Atemzentrums blieb bis 24°C erhalten. Die Analyser der in Hypothermie zu beobachtenden Änderungen führte zu der Annahme, daß die initiale Atemsteigerung des intakten Tieres unter Kältebelastung nicht nur über die Stoffwechselsteigerung, sondern auch durch eine direkte nervale Komponente ausgelöst wird.

Die alveolar-arterielle Sauerstoffdifferenz (AaD O2) und die alveolare Ventilation beim wachen Hund in Abhngigkeit von der Umgebungstemperatur

SummaryAlveolar ventilation, oxygen consumption and arterial blood O2 and CO2 tensions were measured repeatedly in two unanesthetized well-trained dogs at different ambient temperatures without disturbing the natural breathing pattern. At neutral ambient temperature (25°C) oxygen consumption was 5–6 ml/(kg min), alveolar ventilation was 20 ml/ml oxygen consumption, arterial CO2 tension was 38 Torr, arterial pH 7.36 and AaD O2 was 14 Torr. At lower ambient temperature (20 and 10°C) oxygen consumption and alveolar ventilation increased in parallel thus leaving alveolar O2 and CO2 tension unchanged. The arterial O2 tension decreased slightly with the AaD O2 rising well above 20 Torr. At elevated ambient temperatures (up to 38°C) oxygen consumption and alveolar ventilation increased almost in parallel until the respiratory rate reached peak values of 250–300/min under which conditions respiratory alcalosis (arterial CO2 tension of 28 Torr and pH of 7.44) was encountered. The AaD O2 was again well above the control values. Total ventilation was estimated indirectly to increase by 500–900% of the control value.Zusammenfassung1. In 26 Versuchen an zwei trainierten Carotisschlingenhunden wurden die arteriellen Blutgase sowie der Gasstoffwechsel bei Indifferenztemperatur sowie bei milder Kältebelastung und Wärmebelastung untersucht.2. Bei Indifferenztemperatur betrug der Sauerstoffverbrauch 5,1 bzw. 6,7 ml/min kg, der respiratorische Quotient war mit 0,84 normal, ebenso unterschieden sich die Werte für den arteriellen CO2-Druck, das arterielle pH, das Kohlensäurebindungsvermögen des Blutes und für den arteriellen Sauerstoffdruck nicht von den beim Menschen bekannten Normalwerten. Die alveolare Ventilation betrug 2,8 bzw. 2,2 l/min (entsprechend etwa 0,1 l/min kg). Der arterielle Sauerstoffdruck betrug im Mittel 88 Torr, so daß bei einem alveolären O2-Druck von 102 Torr eine durchschnittliche AaD O2 von 14 Torr unter Ruhebedingungen resultierte.3. Bei milder Kältebelastung (Umgebungstemperatur von 20 bzw. 10°C für 150 min) steigerte sich der Sauerstoffverbrauch um 56 bzw. 75%. Parallel damit stieg die alveolare Ventilation an, so daß keine Änderungen der arteriellen CO2- und pH-Werte eintraten. Bei leicht erhöhtem, alveolarem Sauerstoffdruck blieb der arterielle Sauerstoffdruck niedrig oder nahm sogar etwas ab, so daß die AaD O2-Werte zwischen 20 bis 27 Torr erreichte.4. Unter Wärmebelastung stieg die alveolare Ventilation stärker an als der Sauerstoffverbrauch, so daß eine respiratorische Alkalose mit einem durchschnittlichen CO2-Druck von 28,8 Torr und einem pH-Wert von 7,44 bei einer Atemfrequenz von etwa 300/min resultierte. Bei nur wenig erhöhtem, arteriellem Sauerstoffdruck stieg der alveolare Sauerstoffdruck auf 116 Torr an, so daß sich die AaD O2 auf im Mittel 23 Torr vergrößerte. Die Änderung der Gesamtventilation wurde aufgrund früher gefundener, gesetzmäßiger Beziehungen zwischen Gesamtventilation, alveolarer Ventilation, Sauerstoffverbrauch und Atemfrequenz auf das 5- bis 9 fache des Ruhewertes geschätzt.

The somatostatin system of the brain and hibernation in the European hamster (Cricetus cricetus).

The depression of physiological processes characteristic of mammalian hibernation is precisely regulated by the central nervous system, especially by the neuropeptidergic apparatus of the hypothalamus. Because of inhibitory influences on neuronal circuits within the brain and suppressive effects on the metabolism via the endocrine axis, somatostatin has been implicated in the regulation of hibernation. The somatostatin system of the brain was investigated with immunocytochemistry, in situ hybridization, and radioimmunoassays in euthermic summer, euthermic winter, and hibernating European hamsters (Cricetus cricetus). Numerous somatostatin-immunoreactive perikarya were observed in the periventricular hypothalamic nucleus. The striatum, amygdala, and cortex contained only scattered immunoreactive perikarya. These entities also contained immunoreactive fiber profiles, although the highest density of immunoreactive fibers was found in the median eminence. Immunocytochemistry and radioimmunoassays showed that the number of somatostatin-immunoreactive perikarya and fibers and the content of somatostatin in the hypothalamus and the median eminence was conspicuously lower in euthermic winter animals than in euthermic summer animals. This decrease was more pronounced in hibernating specimens. In situ hybridization also demonstrated a decrease in the expression and synthesis rate of somatostatin in euthermic winter animals; again, this was even more dramatic in hibernating hamsters. These changes were less pronounced or non-significant in the extrahypothalamic somatostatin-immunoreactive perikarya and fiber systems, as shown by immunocytochemistry and radioimmunoassay, respectively.