Studies on the Central Integration of Excitatory Chemoreceptor Influences and Inhibitory Baroreceptor and Cardiac Receptor Influences

Experiments were performed on cats to explore the integrated cardiovascular responses when excitatory (chemoreceptor) and inhibitory (baroreceptor or cardiac receptor) influences are simultaneously presented to the medullary cardiovascular areas. At a given sinus pressure in the low or medium pressure range, the systemic blood pressure and the vascular resistance were higher when the chemoreceptors were stimulated, while a high, pulsating sinus pressure, i.e. a strong baroreceptor stimulation, could suppress completely even an intense chemoreceptor activation. Thus, the set point and the gain of the baroreflex were increased by a concomitant chemoreceptor activation. These effects are compatible with a simple, mutual ‘summation’ of excitatory and inhibitory influences on a common population of central vasomotor neurons. The reflex vasodilator effects elicited via vagal cardiac afferents were found to be more effectively suppressed by a concomitant chemoreceptor stimulation than were the baroreceptor effects, provided a primary chemoreceptor response (bradycardia) was at hand, while the heart rate responses were essentially uninfluenced by the prevailing chemoreceptor activity. This chemoreceptor suppression of the reflex vasodilatation from cardiac receptors, which may be of great importance in hypoxic situations, e.g. during a dive, suggests a more complex, neuronal interaction between the two reflex mechanisms in the CNS.     

Interaction between the Hypothalamic Defence Reaction and Cardiac Ventricular Receptor Reflexes

The interference with regard to the cardiovascular and gastric motility responses which follows stimulation of the hypothalamic defence area (D.A.) and a simultaneous afferent input from cardiac ventricular receptors was analysed in chloralose-anesthetized cats. In spinalized animals with only the vagal efferent innervation of autonomic effectors from supraspinal structures intact, a D.A. stimulation increased the heart rate to the same level irrespective whether the cardiac receptor afferents were stimulated or not. This suggests that the vagal component of the reflex bradycardia of cardiac receptor origin was completely suppressed by the D.A. stimulation. The reflex gastric relaxation to cardiac receptor activation, mediated via vagal efferent non-adrenergic fibres, was similarly completely blocked by D.A. stimulation. In contrast, the reflex inhibition of the sympathetic outflow to the heart and vessels from cardiac receptors was still effective during a D.A. stimulation, a phenomenon which seems compatible with a simple summation of excitatory D.A. and inhibitory cardiac receptor influences on the sympathetic neurons. The modifying influence from ventricular receptors on D.A. responses closely resembles that exerted by the arterial baroreceptors. The two reflex mechanisms thus work in concert and synergistically with the hypothalamic influences to produce maximal cardiac output and skeletal muscle perfusion without undue increases of pressure load on the pump during a defence reaction.     

Differentiated Interaction between the Hypothalamic Defence Area and Baroreceptor Reflexes

In experiments on cats, the interaction between the oppositely directed hypothalamic defence reaction and the baroreceptor reflexes was analysed with particular regard to the effects on aortic blood flow, left ventricular work load and muscle blood flow. Because of their differentiated interaction — suppression of the baroreceptor reflex effect on the heart with preservation of the reflex modulation of the vascular bed (Djojosugito et al. 1969) — the baroreceptor reflex so modifies the primary defence reaction, with its intense neurogenic drive on the heart, that a greater cardiac output is gained for a given left ventricular work load. This particularly favours muscle blood supply. It follows that such a differentiated interaction between two basically opposite autonomic patterns causes them to act in synergism with respect to efficient cardiovascular performance in states of emergency.     

Differentiated Interaction between the Hypothalamic Defence Reaction and Baroreceptor Reflexes

As the interrelationship of autonomic patterns involving cortico-hypothalamic and bulbar levels is of general interest, the interaction between the hypothalamic defence reaction and the homeostatic baroreceptor reflexes was explored in cats with respect to cardiac as well as vascular effects. The results suggest, in conformity with Hilton's observations (1963), that defence area stimulation suppresses the baroreceptor reflex inhibition of the heart. On the other hand, the baroreceptor influence on vasoconstrictor fibre discharge was largely the same, whether defence area stimulations were performed or not. This had important haemodynamic consequences, especially for muscle blood flow, since the reflex inhibition of regional constrictor fibre tone could greatly enhance the cholinergic vasodilatation. Therefore such a differentiated interaction between oppositely directed central and reflex autonomic mechanisms has the consequence that the baroreceptor reflexes, rather than damping the defence reaction, act in synergism with it with respect to net haemodynamic effects; some further implications of this are dealt with in the subsequent paper (Kylstra and Lisander 1969).     

Vasoconstrictor Fibre Discharge to Skeletal Muscle,Kidney, Intestine and Skin at Varying Levels of Arterial Baroreceptor Activity in the Cat

Estimations of the average discharge rates in vasoconstrictor fibres to skeletal muscle, kidney, intestine and skin at varying levels of arterial baroreceptor activity were made by comparing quantitatively the reflexly induced vascular responses with those obtained with stimulations of the regional vasoconstrictor fibres at known frequencies. The results indicate that withdrawal of baroreceptor restraint was normally followed by a considerably lower firing rate in renal vasoconstrictor fibres than in e.g. skeletal muscle vasoconstrictor fibres. A complete elimination of the inhibitory influence induced vasoconstrictor fibre discharge rates up to 8 imp/s in skeletal muscle but only at most 4 imp/s in the kidney. Intestinal vasomotor fibres were found to be activated to approximately the same extent as those to skeletal muscle. The vasomotor fibres to the cutaneous arterio-venous anastomoses were evidently not activated when the baroreceptors were unloaded. The reason for this non-uniform activation of the different sets of vasoconstrictor fibres seems to be different levels of spontaneous activity in the respective “neuron pools” in the bulbar vasomotor centre. The renal vascular responses to baroreceptor unloading became augmented when the excitatory level in the vasomotor centre was enhanced, as e.g. when the animal became acidotic.     

Exteroceptive Influences on the Lumbar Back Muscle Tone and Reflexes in the Cat

The exteroceptive influences on tonic activity and on stretch reflexes of the longissimus dorsi and multifidus spinae muscles were investigated in decerebrate, spinal and chloralose-anesthetized cats. Adequate skin stimulation was used to map out facilitatory and inhibitory skin areas on the trunk and the extremities. On the trunk facilitatory areas are relatively large and located at the dorsal side while inhibitory areas are confined to the ventrolateral part of the contralateral body half. The facilitatory skin fields are of approximately the same size in decerebrate and spinal cats. On leg skin stimulation facilitation can be evoked from the ipsilateral hind limb while inhibition results from stimulation of the other limbs. Spinal cord transection increased excitatory effects of ipsilateral hind limb stimulation. Reflex responses in the back muscles to applied stretch are described. These reflexes were used as test reflexes in experiments with conditioning stimulation of the peripheral nerves supplying skin areas from which effects on back muscle activity were evoked by adequate stimulation. The conditioning-test experiments and those using adequate stimulation show that the longissimus dorsi and multifidus spinae are activated or facilitated by an ipsilateral stimulus to skin afferents. The extent of the effects induced by stimulation of skin differs in the types of preparation used. These differences may be accounted for by assuming a supraspinal control of the reflex pathways studied.     

Chronotropic and Inotropic Components of Cardiac Reflexes in Cats

The relationship between chronotropic and inotropic components of cardiac reflexes were studied in cats using intravenous blood injections, occlusion of the abdominal aorta, pressing on eyeballs (Aschner maneuver), and occlusion of the carotid arteries. Inotropic reactions were characterized by the contractility index DP×HR/MSAP. Different reflexes were shown to be characterized by different ratio of chronotropic and inotropic components, in addition, heart rate and contractility were often altered in opposite directions.     

Technical and Metrological Aspects of Arterial Pressure Measurement Using the Oscillometric Method

The accuracy of arterial pressure (AP) measurement is a critical parameter of noninvasive blood pressure monitors. The procedure of testing of blood pressure monitors is labor-consuming; moreover, it includes human factor as an object of measurement. An alternative method including experimental estimation of errors and distortions is suggested. This is added to the result of measurements of basic elements of the measuring system, which uses an oscillometric method for determining AP.     

Effects of Long-term Right Ventricular Apical Pacing on Left Ventricular Remodeling and Cardiac Function

Objective： To investigate the impacts of long-term right ventricular apical pacing on the ventricular remodeling and cardiac functions of patients with high-grade and third-degree atrioventricular blockage with normal heart structures and cardiac functions. In addition, we provide many evidences for choosing an optimal electrode implantation site.Methods： Study participants included patients who were admitted for pacemaker replacements and revisited for examinations of implanted pacemakers at outpatient. Pacemakers were implanted to treat high-grade and third-degree atrioventricular blockage. At the time of pacemaker implantation, patients had normal cardiac functions and showed no serious heart diseases or cardiac dilatation. The durations from the implantation to follow-up were more than 5 years. The pacing rate was higher than 80%. Patients with a left ventricular ejection fraction （LVEF） 〈 50% and a left ventricular end-diastolic diameter （LVEDD） 〉 55 mm were excluded. Ventricular remodeling was defined as follows：increase of LVEDD by 10% and a reduction of LVEF by 25% for five years after implantation. Cardiac functions were evaluated according to New York Heart Association （NYHA） classification.Results：A total of 82 patients with a mean age of （66.97±13.19） years （range, 12 to 91 years old）,among which 39 male and 43 female were enrolled in this study. The average duration between two assessments was 8.7 years （104.4 months）. Before pacemaker implantation, the average left atrial diameter （LA）, LVEDD and LVEF were 37.0 mm, 50.23 mm and 64.87%, respectively. After the implantation, these values were 39.39 mm （P=0.000163）, 50.82 mm （P=0.177842） and 60.50% （P=0.000104）, respectively. Four patients （4.87%） had ventricular remodeling with deteriorations of cardiac function, three of which had anterior wall myocardial infarction after implantation and one had type II diabetes. Clinical symptoms of heart failure were not found among the patients who did not exhibit ventricular remodeling. Conclusion： Through a long-period follow-up study, we found that long-term right ventricular apical pacing in patients with normal heart structure and cardiac function would not generally cause ventricular remodeling and clinical deteriorations of cardiac function. Right ventricular apical is a safe and effective site for pacing electrode wire implantation.     

Characteristics of Aortic Baroreceptor C-Fibres in the Rabbit

The characteristics of 40 C-fibres arising from the aortic arches of 15 normotensive rabbits have been investigated. The conduction velocity of the fibres varied between 0.5-1.8 m/s (0.91±0.05, mean ± S.E.). The activation threshold for all the fibres lay between 70–140 mmHg. 32 medullated fibres from the same animals had thresholds between 35 and 90 mmHg. After correction for the time delay in conduction the firing in the C-fibres occurs in early systole. Pressure response curves were constructed for 10 medullated and 18 C-fibres. The mean activity at 100 mmHg was, for the C-fibres 5.0 Hz and for the medullated fibres 34 Hz. At 130 mmHg the activity in the C-fibres was 13 Hz and in the medullated fibres 68 Hz. Thus C-fibres from the aortic baroreceptor regions are activated at higher pressures than the medullated fibres and have lower discharge frequencies. Noradrenaline did not influence the pressure response curves of the C-fibres. It is concluded that the arterial baroreceptor C-fibres may exert a weak tonic influence on the vasomotor centre at normal pressures but are likely to be of greater importance when the arterial pressure rises acutely.     

High-Resolution Computed Tomography Imaging of the Cranial Arterial System and Rete Mirabile of the Cat (Felis catus)

The objective of this study was to investigate the possibility of obtaining high-resolution multiplanar computed tomography (CT) imaging of the cranial arterial circulation of the cat (Felis catus), the rete mirabile, and components of the skull, utilizing preserved cat specimens with an arterial system that was injected with a radiopaque contrast compound in the early 1970s. Review of the literature shows no high-resolution CT studies of the cat's cranial circulation, with only few plain radiographic studies, all with limited cranial vascular visualization. In view of the inability of the radiographic techniques available from 1970s to mid-2000s to provide high-resolution imaging of the arterial circulation within the intact skull and brain of the cat, without dissection and histologic sectioning and disruption of tissues, no further imaging was performed for many years. In 2010, a high-resolution micro CT scanner became available, large enough to scan the entire nondissected head of the arterially injected cats. All the obtained CT images were processed with a software program that provided 3D volume rendering and multiplanar reconstruction with the ability to change the plane angulation and slab thickness. These technical features permitted more precise identification of specific arterial and bony anatomy. The obtained images demonstrated, with a nondestructive method, high-resolution vascular anatomy of the cerebral, orbital, facial arterial system, the rete mirabile, and skull bone components of the cat, with details not previously described in the literature. Anat Rec, 302:1958–1967, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.     

Impact of Acute Pulmonary Embolization on Arterial Stiffening and Right Ventricular Function in Dogs

Pulmonary hypertension (PH) can impact right ventricular (RV) function and alter pulmonary artery (PA) stiffness. The response of the RV to an acute increase in pulmonary pressure is unclear. In addition, the relation between total pulmonary arterial compliance and local PA stiffness has not been investigated. We used a combination of right heart catheterization (RHC) and magnetic resonance imaging (MRI) to assess PA stiffening and RV function in dogs before and after acute embolization. We hypothesized that in moderate, acute PH the RV is able to compensate for increased afterload, maintaining adequate coupling. Also, we hypothesized that in the absence of PA remodeling the relative area change in the proximal PA (RAC, a noninvasive index of local area strain) correlates with the total arterial compliance (stroke volume-to-pulse pressure ratio). Our results indicate that, after embolization, RV function is able to accommodate the demand for increased stroke work without uncoupling, albeit at the expense of a reduction of efficiency. In this acute model, RAC showed excellent correlation with total arterial compliance. We used this correlation to assess PA pulse pressure (PP) from noninvasive MRI measurements of stroke volume and RAC. We demonstrated that in acute pulmonary embolism MRI estimates of PP are remarkably close to measurements from RHC. These results, if confirmed in chronic PH and clinically, suggest that monitoring of PH progression by noninvasive methods may be possible.     

Effects of Lesions in the Parabrachial Nucleus on the Mechanisms for Central and Reflex Termination of Inspiration in the Cat

The effects of PCO₂ and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory ‘off-switch’ threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO₂, and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory ‘off-switch’ threshold was raised in the apneustic animals as in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory ‘off-switch’ mechanism.     

Effects of Decreases in Dopamine (D1 and D2) Receptor Expression in the Basolateral Amygdala of Rats on Conditioned Defensive Reflexes

Neuroscience and Behavioral Physiology - RNA interference studies using lentivirus transduction were performed to investigate the effects of decreased expression of dopamine receptors (D1R and D2R)...     

Baroreceptor sensitive neurones in the anterior hypothalamus of the cat

1. The activity of 372 neurones, located within or close to the hypothalamic depressor area, was recorded on raising the pressure within a vascularly isolated carotid sinus.2. When the intrasinusal pressure was raised abruptly to 200 mm Hg the activity of fifteen neurones was enhanced and of six inhibited.3. The neurones exhibiting excitation on baroreceptor afferent stimulation were broadly divisible into two groups. Nine neurones responded with a marked increase in discharge frequency, the other six responded with a ;burst-on' discharge with a minimum latency of 90 msec. Excitation in both cases was always within 500 msec of the presentation of the stimulus. No functional distinction has been drawn from these responses.4. Evidence has been obtained suggesting that the responses of both types of neurone showing excitation may be potentiated using a pulsatile rather than static stimulus.5. The role of the neurones in the integration of the carotid sinus baroreceptor reflex is discussed. It is suggested that the hypothalamic depressor area represents the rostral extension of the integrative centre for the reflex.     

Chronobiology of Cardiac Ventricular Fibrillation Development in Experimental Acute Coronary Failure

Numerous experiments on simulation of acute coronary failure in initially intact rabbits showed that under the same experimental conditions irreversible ventricular fibrillation developed in some animals and did not develop anothers. We hypothesize that the probability of fibrillation development was determined by the time of the day, during which acute coronary failure developed. The study was carried out on 2 groups of rabbits in winter in Moscow. In group 1, the failure was induced by ligation of the left descending coronary artery at the interface between its middle and lower thirds at 11.00-18.00 with 30-min intervals. In group 2, the microcirculatory status of the left-ventricular myocardium was studied by light microscopy and morphometry at 12.00 and 18.00. Induction of coronary failure during the period from 15.30 to 18.00 led to irreversible ventricular fibrillation and death in 100% cases. Modeling of the condition from 11.00 to 15.00 caused no ventricular fibrillation in 89% cases, and the animals survived. The area of left-ventricular myocardial capillaries at 12.00 virtually 2-fold surpassed that at 18.00. Presumably, the electrolyte balance and metabolic characteristics of the myocardium switch over to the nocturnal mode of functioning at 15.30 due to changes in blood filling of the myocardium. The appearance of an ischemic focus in the myocardium during this period inevitably leads to the development of irreversible ventricular fibrillation.