Pulsatile Features of Major Arteries in Rats during Hypotension Caused by Acute Blood Loss.

The study examined the modes of pulsations of the femoral and carotid arteries of rats in situ (n=14) during acute blood loss, which sequentially caused a deep BP drop, cardiac and respiration arrest, and termination of ECG signals. When BP dropped to 19 (13; 26) mm Hg, the mechanosensitivity of passively pulsing arteries determined by the ratio of the swing range of electroimpedance oscillations of arterial segment to pulse pressure increased by 3.2 (2 ; 4) times (p<0.05). During the decrease of BP to the threshold value of 13 (8; 15) mm Hg, the arterial pulsing mode changed from passive to intermediate and then to the active one characterized by constriction of arterial segment in response to systolic elevation of BP. After cardiac arrest and BP drop almost to zero, the arterial pulsing switched to autonomic rhythmical vasomotions with the rate, which was greater than the frequency of still sustained QRS pulses of ECG. The observed phenomena are explained by transarterial hypotensive transition hypothesis, which argues that peculiarities of pulsations and vasomotions of major arteries during deep BP drop are typical of arterioles under normal or diminished BP. The study refined the hypothesis of "peripheral heart" and its role in hypo- and hypertension.

Chronic Effects of Modeled Myocardial Infarction, Thoracic Trauma, and Denervation of Hind Limb on Rheographic Parameters of Rat Femoral Arteries In Situ.

In experiments on narcotized male rats (n=85), the mean electroimpedance Z and peak-to-peak magnitudes (the swing ranges) of passive (ΔZp) and active (ΔZa) pulsatile electroimpedance oscillations of isolated segment of femoral arteries were determined in situ. These rheographic parameters (RP) were measured in intact animals and in those with modeled chronic myocardial infarction, chronic denervation of the right hind leg, as well as in rats subjected to sham operations to mimic denervation or infarction (with thoracic trauma). The rats with modeled myocardial infarction demonstrated decreasing trends of all RP. In sham-operated rats with thoracic trauma, ΔZp increased significantly on postsurgery months 2-4 by 4.3 times in comparison with the control. No essential correlation was found in denervated rats between RP of any femoral artery and severity of neuropathic pain syndrome assessed by autotomy of the operated leg. In these rats, the mean electroimpedance Z of any femoral artery was significantly greater than the control level. They demonstrated especially high values of ΔZp with significant difference between ΔZp of innervated and denervated hind leg. In denervated rats, ΔZa was significantly greater than the control value without significant difference between ΔZa of both femoral arteries. The paradoxically great increase of ΔZp (100- and 50-fold for innervated and denervated legs, respectively) and a significant 3-fold increment of ΔZa in both hind legs provoked by denervation of one of them are discussed in relation to searching for the ways of systemic influences on vascular network in clinics and experiments.

Relationship between Passive and Active Pulsations of Rat Artery as Vascular Extension of Frank-Starling Law.

The experiments on narcotized male rats (n=30) determined the parameters of passive and active pulsatile modes of isolated segment of femoral artery in situ. Rheographic elasticity (RE) and reactivity (RR) were correspondingly determined as the ratios of peak-to-peak (p2p) magnitudes of passive and active pulsatile oscillations of arterial electroimpedance (AEI) to p2p magnitude of BP undulations. The medians and interquartile ranges of RE and RR were 6 (3; 11) and 70 (40; 110) mΩ/mm Hg, respectively. The maximal and minimal values of RE and RR in various rats differed by 50 and 80 times, respectively, and were bimodally distributed: in major group (n=23), the values were RE<15 and RR<200 mΩ/mm Hg, whereas in minor group (n=7), these parameters were RE>20 and RR>300 mΩ/mm Hg. The above ranges of RE and RR parameters were considered as the diagnostic signs of normal and pseudo-healthy rats with pathologically augmented AEI oscillations, respectively. Statistical analysis of all rats (n=30) revealed the positive correlation between RE and RR (r=0.76) with linear regression RR=31+7.6×RE. It is hypothesized that this correlation is underlain by a mechanism similar to that described by the Frank-Starling law for myocardium.

Effect of Alternating Electric Current on Pulsation Mode of Rat Major Arteries In Situ.

In experiments on narcotized rats, the electrical potential and impedance of isolated segment of the right femoral and/or carotid artery were simultaneously recorded in situ via two extracellular nonpolarizable Ag/AgCl electrodes mounted along the arteries at the interelectrode distance of 4 mm. The active, passive, and intermediate pulsing modes of arterial segment were determined according to the phase relations between its electrical impedance and BP, which was simultaneously measured in the symmetrical part of the respective left artery and used to assess pressure in the examined segment. The study assessed the effect of amplitude (0.2-2.0 mA) of alternating probe current (100 kHz), which was used to measure the electrical impedance of arterial segment, on its pulsing mode. The pulsing mode determined at the initial minimal probe current of 0.2 mA was passive with out-of-phase pulsatile oscillations of electrical impedance and BP. After elevation of the probe current amplitude to maximal level of 2 mA, these oscillations became in-phase indicating transition of the arterial segment to active pulsing mode. This transition was accompanied by appearance of arterial voltage impulses synchronized with BP upstrokes and an 11-fold median increase in the peak-to-peak value of electrical impedance oscillations with the interdecile range of 7-15 (N=28). Under moderate amplitude of probe current (0.3-0.5 mA), the intermediate mode of arterial pulsing was observed featured by a delayed, weak, and short active constriction during BP front, which was insufficient to resist and counterbalance the dilating effect of rising BP. In this case, the pulsatile oscillations of electrical impedance were smaller than those observed in active or passive pulsing modes indicating a possibility to stabilize the arterial diameter during pulsatile oscillations of BP. The effect of alternating electric current on the mode of arterial pulsation is explained with electrical model of smooth muscle cell membrane reflecting the rectifying features of potassium channels and predicting membrane hyperpolarization in response to external alternating current passing across the cell. The visibilities of therapeutic neurotropic and angiotropic stimulation with alternating electric current are discussed.

Bimodal Electrical Properties of Rat Major Artery Segment In Situ.

In experiments on narcotized rats, BP in the left femoral artery as well as local electrical potential and electrical impedance of the symmetric segment of the right femoral artery were simultaneously recorded in situ with two extracellular nonpolarizable Ag/AgCl electrodes located along the artery at a distance of 3 mm from each other. The pulsatile arterial electrical potentials with amplitude of 100-200 µV and duration of about 50 msec were recorded, which coincided with the front of BP wave corrected for a 10-msec delay of the pressure transducer. Under normal conditions, the pulsatile oscillations of arterial electroimpedance were in-phase with BP oscillations, so the rising phase of BP was paralleled by elevation of electroimpedance reflecting constriction of the arterial segment. This finding is viewed as indicative of periodic myogenic Ostroumov-Bayliss effect triggered by arterial pulse. After local application of tetrodotoxin (3×10-7 М), procaine (0.5%), or lidocaine (spray 10%) to isolated arterial segment, its electroimpedance oscillated out-of-phase with BP, so the changes of electroimpedance were similar to the response of a passive elastic tube to pulsatile BP. The applied agents completely (tetrodotoxin) or pronouncedly (procaine, lidocaine) inhibited the pulsatile arterial electrical potential. The present data indicate the possibility of passive and active modes of arterial pulsing, which differ by the amplitude of pulsatile arterial electrical potential as well as by phasic relations between BP and electroimpedance. The possible physiological role of various modes of pulsing in major arteries is discussed.

Pro- and Antioxidant Systems in the Lower Portion of Rat Brainstem during Hydroxybutyrate-Induced Pathological Periodic Breathing.

Activities of superoxide dismutase and catalase characterizing antioxidant status of the nervous tissue and its resistance to free radical oxidation were measured in the brainstem of rats with hydroxybutyrate-induced pathological periodic breathing. Hydroxybutyrate modified the pro- and antioxidant status in the brainstem respiratory center. It markedly inhibited catalase activity; in rats without the signs of periodic breathing, hydroxybutyrate up-regulated superoxide dismutase activity and to a lesser extent increased the resistance of the membrane structures in the medulla oblongata to induction of free radical oxidation. In rats with periodic breathing pattern, hydroxybutyrate induced more pronounced increase in the sensitivity of membrane structures in the medulla oblongata to induction of free radical oxidation.

[The role of opioidergic and GABAergic systems in the mechanosensitivity regulation of the respiratory system in rats].

In anaesthetized white outbred male rats we investigated the change of respiratory mechanoreceptors sensitivity to morphine and phenibut. Bilateral transection of the vagus nerves causes a severely slowdown of respiratory rate in 30 minutes after the systemic administration of morphine, however after administration of phenibut the respiratory rate and other respiration parameters have not changed significantly. It means that the activation of opioid receptors by morphine does not significantly affect the function of the respiratory mechanoreceptor control loop, and transection of the vagus nerves on this background increases the probability of respiratory rhythm disorders. Activation of GABAergic system by phenibut significantly weakened the impact of the regulating contour of the respiratory mechanoreceptor on breathing parameters, up to effect of "central vagotomy": that is, to no changes in respiratory parameters after cutting the vagus nerves.

[The resistance of low brainstem tissue to free radical oxidation in rats during periodic breathing following hydroxybutyrate treatment].

We evaluated tissue resistance to free radical oxidation, in pentobarbital-anesthetized mongrel albino male rats during pathologic periodic breathing following hydroxybutyrate (GHBA) administration. It was shown that GHBA modulated pro- and antioxidant status of brain tissue. In the absence of periodic breathing after GHBA, decreases in resistance of brainstem tissue membranes to induction of free radical oxidation were slightly pronounced. Rats with GHBA-induced periodic breathing exhibited increased membrane sensitivity of medullar neurons to induction of free radical oxidation. We suggest that cellular metabolism and/or membrane mechanisms of respiratory rhythm-generating neurons play a role in the pathogenesis of periodic breathing.

Effect of opioids on mechanoreflexive respiration control.

The effects of opioids (morphine and fentanyl) on the function of mechanoreceptive respiration regulatory loop were demonstrated. In most opioid-treated rats (74% cases) vagotomy was followed by apneustic respiration with inspiration pause. Excess of opioids in rat CNS produced minor disturbances in the respiration rhythm, but in the absence afferent input from the mechanoreceptors of respiratory pathways and lungs, pronounced periodic apneustic respiration with inspiration pauses developed. The opioidergic system is involved in the formation of respiratory rhythm, but had no appreciable effect on transmission of mechanoreceptive nerve pulses from respiratory pathways and the lungs to the respiratory center.