Cardio- and hemodynamics of dogs during the development of postischemic shock reaction

Experiments on dogs have shown that tension of peripheral capacitive vessels decreased and development of the blood deposition reaction in the venous part of the vascular bed occurred immediately after beginning of long-ischemized tissue perfusion. This leads to limitation of venous blood return to the heart, decrease of the cardiac output and development of the system hypotension. Lowering in the perfusion coronary pressure induced limitation of the coronary blood flow and inhibition of the myocardial contractility. Indicated constriction of resistive vessels and dilatation of the capacitive ones may be due to an increase of the prostacyclin and thromboxane A2 blood levels. Described disturbances achieved their maximum 3 hours later and were accompanied by arterial hypoxemia, metabolic acidosis and hypercapnia.     

Nitric oxide and sympathoexcitatory cardiovascular neurons of the ventrolateral medulla in cats

In acute experiments on cats, the effects of injections of nitric oxide (NO) donors and an inhibitor of its synthesis into the sympathoexcitatory neuronal structures in the ventrolateral medulla (VLM) were studied to examine their effects on the peripheral mechanisms of the cardiovascular control. Unilateral injections of NO donors, nitroglycerine (1.3–5.2 nmol) or sodium nitroprusside (1.1–4.6 nmol) into the sites of the sympathoexcitatory neurons residing in the VLM induced the lowering of the systemic arterial pressure (SAP) in a dose-depended fashion. Two types of the hypotensive responses have been distinguished. In the first type responses, lowering of the SAP level was mainly due to a decrease in the peripheral vascular resistance (PVR), while the heart rate (HR) and stroke volume (SV) were only slightly reduced. In the second type responses, the drop in SAP level resulted mainly from a decrease in the HR and myocardial contractivity. These effects were induced by the limitation of the descending excitatory influences to the heart and vessels from the VLM sympathoexcitatory systems. An increase in the NO concentrations in the neuronal structures located 2.5–4.5 mm caudally to the trapezold bodies resulted in the first type responses, while that in the sites immediately adjacent to the caudal sympathoinhibitory area (0.5–1.5 mm rostrally to the XIIth cranial nerve roots) was associated with the second type of reactions. Stimulation of the endogenous NO release from the neurons after injections of L-arginine induced the same cardiovascular shifts as exogenic NO did, and attenuation of NO synthesis following injections of NO antagonist L-NMMA into the VLM neuronal structures evoked hemodynamic shifts of a reverse direction. Injections of NO donors inhibited the reflex responses induced by the activation of the carotid sinus receptors. Our data give further evidence for NO involvement in the inhibitory control of the cardiac activity and vascular tone through those VLM sympatoexcitatory neurons, which are involved in the system of central neurogenic cardiovascular control and the activity of which prevent the development of hypertension.Neirofiziologiya/Neurophysiology, Vol. 28, No. 2/3, pp. 111–120, March–June, 1996.     

Hemodynamic responses induced by modulation of the nitric oxide system and mitochondrial permeability in the medullary cardiovascular nuclei of rats

In acute experiments on normotensive rats and those with genetically determined hypertension (urethane anesthesia), we studied hemodynamic effects resulting from modulation of the activities of neuronal NO synthase (NOS-1), arginase II, and superoxide dismutase, and also of the mitochondrial permeability in medullary cardiovascular neurons. Unilateral microinjections of either a nitric oxide (NO) donor, sodium nitroprusside, or a substrate for endogenous NO synthesis, L-arginine, into the medullary cardiovascular nuclei (nucl. tractus solitarius, NTS, nucl. ambiguous, AMB, paramedian nucleus, PMn, and lateral reticular nucleus LRN) were shown to induce hemodynamic responses with rather similar dynamics in both normotensive and spontaneously hypertensive rats, although in the latter the reactions were more intense. Injections of an antagonist of NOS-1, N^G nitro-L-arginine (L-NNA), into the medullary nuclei under study in spontaneously hypertensive rats resulted in shifts of the systemic arterial pressure (SAP), which did not differ dramatically from those observed in normotensive animals. The data obtained serve as the background for the suggestion that the functional activity of NOS-1 is not fundamentally impaired under hypertension conditions, but, probably, the amount of the substrate for adequate synthesis of NO via the NO-synthase pathway of metabolism of L-arginine is insufficient. Considering this, we examined the functional activity of arginase, an enzyme that also, similarly to NOS, uses L-arginine for metabolic transformation. Injections of antagonists of arginase, norvaline or α-difluoromethylornithine hydrochloride (DFMO), into populations of the medullary neurons under study induced similar shifts of the SAP in normotensive and spontaneously hypertensive rats, and those responses did not differ significantly from the effects of inhibition of the NOS-1 activity. Thus, both the above-mentioned enzymes are potentially active in normotensive and spontaneously hypertensive rats; so, a possibility for their competition for L-arginine in certain situations does exist. Modulation of the mitochondrial permeability in medullary cardiovascular neurons in normotensive and spontaneously hypertensive rats induced significant hemodynamic effects. In particular, an increase in the mitochondrial permeability in the medullary cardiovascular nuclei by injections of an inductor of mitochondrial permeability transition pore (mPTP) opening, phenylarsine oxide (PAO), was accompanied by SAP drops in both normotensive and spontaneously hypertensive rats; the effects were dose-dependent and, in some cases, irreversible. A decrease in the mitochondrial permeability in the neurons under study by injections of an inhibitor of mPTP, melatonin, induced mostly hypertensive responses, although in some experiments we observed hypotensive and two-phase responses. Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 232–244, May–June, 2007.     

Role of endothelin-1 in the central neural cardiovascular control

In acute experiments on cats, endothelin-1 (ET-1) was injected into the sympathoexcitatory neuronal structures of the ventrolateral medulla (VLM) and the effects of injections on the peripheral mechanisms of circulation control were studied. Effects of ET-1 appeared to be dose-dependent. Injections of 200 pmol ET-1 into the structures of the tested brain zone resulted in considerable regular hypertensive responses due to an increase in the common peripheral vascular resistance (PVR), which corresponds to vasospasm. ET-1 in a smaller dose (100 pmol) could cause either hypertensive or, in some cases, hypotensive responses. Hemodynamic responses induced by injections of 100 pmol ET-1 into the sites of localization of vasomotor neurons in the VLM were based on less expressed shifts in the peripheral vascular resistance, as compared with the effects of ET-1 in the dose of 200 pmol. The effects were related to either facilitation or suppression (in the cases of hypertensive or hypotensive responses, respectively) of descending sympathoexcitatory influences from the VLM on different vascular pools. The threshold for excitation of vasomotor neurons in the tested brain area is likely to be considerably lower as compared with that for medullary “cardiac” neurons, because injections of 200 pmol ET-1 in the site of localization of cardiac neurons were followed by either enhancement, or suppression of the contractile myocardiac activity, while the heart rate usually decreased. The effects of ET-1 were facilitated after blocking of GABAa receptors with bicuculline and attenuated after preliminary application of GABA to the ventral surface of the medulla. The results indicate the possibility of interaction ET-1 and GABA on the neurons in the VLM. Such interaction is likely to be directed toward providing an optimum mode of regulation of the blood circulation.     

Caffeine-induced electrical responses of intact endothelial cells

The mechanism of caffeine-induced endothelial-dependent relaxation of vascular smooth muscle cells has been studied by recording caffeine application-induced electrical responses from intact guinea pig aortic endothelial cells. Depending on the values of the membrane potential, caffeine evoked either hyperpolarizing responses (V _m<−45 mV, 88.9% of the cells tested), or depolarizing reactions (V _m>−45 mV). The mean amplitude of caffeine-induced hyperpolarization of endothelial cells was 11.2±5.5 mV, which is comparable with the amplitude of ATP-induced hyperpolarization. The amplitude of caffeine-induced depolarization was 8.9±3.4 mV, on average. It was shown that caffeine-induced hyperpolarization of endothelial cells is a result of calcium release from the intracellular stores with subsequent activation of calcium-dependent potassium channels. Intracellular calcium stores involved in caffeine-induced responses are different from those involved in ATP responses. It is concluded that calcium mobilization from the intracellular stores of endothelial cells and, possibly, activation of calcium entry contributes to the caffeine-induced endothelial-dependent relaxation of vascular smooth muscle cells.     

Effect of Adaptation to Graduated Physical Exercises on the Function of the Rat Myocardium

On isolated hearts obtained from control rats and rats subjected to regular physical exercises (forced swimming) during 6 weeks, we studied the contractile activity of the heart, resistance of the myocardium to ischemia/reperfusion-induced injuries, as well as the dependence of the developed and end-diastolic pressures in the aortic ventricle (AV) on the strain of the myocardium (by means of a dosed increase in the volume of a polyethylene reservoir inserted into the ventricle). It was demonstrated that adaptation to regular graduated physical exercises exerts a positive effect on the functional state of the AV myocardium and its contractile function. This was manifested in intensification of the contractile activity of the myocardium, a decrease in its oxygen “job cost,” and an increase in the resistance to injuries induced by ischemia-reperfusion. In addition, regular physical trainings led to an increase in the resistance of the AV myocardium to the strain. In trained rats, the plateau of the Frank–Starling plot was significantly greater than that in control animals, while the rigidity of the AV myocardium was significantly lower. Neirofiziologiya/Neurophysiology, Vol. 41, No. 1, pp. 41–47, January–February, 2009.     

Salmonella in Broiler Litter and Properties of Soil at Farm Location

Contamination of litter in a broiler grow-out house with Salmonella prior to placement of a new flock has been shown to be a precursor of the flock''s Salmonella contamination further down the production continuum. In the southern USA, broiler grow-out houses are primarily built on dirt pad foundations that are placed directly on top of the native soil surface. Broiler litter is placed directly on the dirt pad. Multiple grow-out flocks are reared on a single litter batch, and the litter is kept in the houses during downtime between flocks. The effects of environmental determinants on conditions in broiler litter, hence Salmonella ecology within it, has received limited attention. In a field study that included broiler farms in the states of Alabama, Mississippi and Texas we assessed Salmonella in broiler litter at the end of downtime between flocks, i.e. at the time of placement of a new flock for rearing. Here we utilized these results and the U.S. General Soil Map (STATSGO) data to test if properties of soil at farm location impacted the probability of Salmonella detection in the litter. The significance of soil properties as risk factors was tested in multilevel regression models after accounting for possible confounding differences among the farms, the participating broiler complexes and companies, and the farms'' geographical positioning. Significant associations were observed between infiltration and drainage capabilities of soil at farm location and probability of Salmonella detection in the litter.     

Sheep Movement Networks and the Transmission of Infectious Diseases

Background and Methodology

Various approaches have been used to investigate how properties of farm contact networks impact on the transmission of infectious diseases. The potential for transmission of an infection through a contact network can be evaluated in terms of the basic reproduction number, R ₀. The magnitude of R ₀ is related to the mean contact rate of a host, in this case a farm, and is further influenced by heterogeneities in contact rates of individual hosts. The latter can be evaluated as the second order moments of the contact matrix (variances in contact rates, and co-variance between contacts to and from individual hosts). Here we calculate these quantities for the farms in a country-wide livestock network: >15,000 Scottish sheep farms in each of 4 years from July 2003 to June 2007. The analysis is relevant to endemic and chronic infections with prolonged periods of infectivity of affected animals, and uses different weightings of contacts to address disease scenarios of low, intermediate and high animal-level prevalence.

Principal Findings and Conclusions

Analysis of networks of Scottish farms via sheep movements from July 2003 to June 2007 suggests that heterogeneities in movement patterns (variances and covariances of rates of movement on and off the farms) make a substantial contribution to the potential for the transmission of infectious diseases, quantified as R ₀, within the farm population. A small percentage of farms (<20%) contribute the bulk of the transmission potential (>80%) and these farms could be efficiently targeted by interventions aimed at reducing spread of diseases via animal movement.     

Gaba-ergic mechanisms in the caudal ventrolateral region of the cat medulla regulating vascular tonus and cardiac activity

In acute experiments on anesthetized cats data are obtained attesting to the fact that injections of GABA (0.5–50 µmoles/liter) into neuronal structures of the caudal ventrolateral medulla (CVLM) are accompanied by the development of hypertensive reactions caused by an increase in spontaneous activity in the sympathetic fibers of the renal and inferior cardiac nerves. An asymmetry is discovered in the realization of the inhibitory chrono- and inotropic influences on the heart emanating from the region investigated. Blocking of the GABA receptors with bicuculline (0.2–5.0 µmoles/liter) causes a sharp drop in the level of the systemic arterial pressure, a decrease in the strength and frequency of cardiac contractions, and a falling-off of the background activity in the peripheral symphathetic nerves. The findings suggest that the sympathoinhibitory CVLM neurons are under the constant inhibitory control of the GABA-ergic neurons.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 698–703, November–December, 1991.