Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea.

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model (n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 +/- 1.7% decrease after apnea with arousal (P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 +/- 1.0 vs. 4.1 +/- 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 +/- 2.3 mmHg vs. 10.3 +/- 1.6 mmHg, REM vs. non-REM, respectively, P < 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation.     

Effects of systemic arterial hypoperfusion on splanchnic hemodynamics and hepatic arterial buffer response in pigs

The hepatic arterial buffer response (HABR) tends to maintain liver blood flow under conditions of low mesenteric perfusion. We hypothesized that systemic hypoperfusion impairs the HABR. In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 ml. kg(-1). min(-1) for 1 h (short-term tamponade) and further to 30 ml. kg(-1). min(-1) for another hour (prolonged tamponade). Twelve pigs without tamponade served as controls. Portal venous blood flow decreased from 17 +/- 3 (baseline) to 6 +/- 4 ml. kg(-1). min(-1) (prolonged tamponade; P = 0.012) and did not change in controls, whereas hepatic arterial blood flow decreased from 2 +/- 1 (baseline) to 1 +/- 1 ml. kg(-1). min(-1) (prolonged tamponade; P = 0.050) and increased from 2 +/- 1 to 4 +/- 2 ml. kg(-1). min(-1) in controls (P = 0.002). The change in hepatic arterial conductance (DeltaC(ha)) during acute portal vein occlusion decreased from 0.1 +/- 0.05 (baseline) to 0 +/- 0.01 ml. kg(-1). min(-1). mmHg(-1) (prolonged tamponade; P = 0.043). In controls, DeltaC(ha) did not change. Hepatic lactate extraction decreased, but hepatic release of glutathione S-transferase A did not change during cardiac tamponade. In conclusion, during low systemic perfusion, the HABR is exhausted and hepatic function is impaired without signs of cellular damage.     

Effects of carnosine on systemic hemodynamics and myocardial metabolism in rats in the early postresuscitation period]

It was demonstrated in experiments on male rats that acute lethal blood loss and subsequent resuscitation after 4- and 6-min clinical death induce lipid peroxidation processes, decreased antioxidant enzyme activity, cause activation of anaerobic glycolysis in the myocardium. This metabolic heart impairment causes hemodynamic instability in postresuscitation period. 25 mg/kg of carnosine injected during resuscitation decreased functional-metabolic heart impairments and hemodynamic disarrangement as well as early postresuscitation lethality. The authors attribute positive carnosine effect to its significant antioxidant activity.     

Effects of rottlerin on silica-exacerbated systemic autoimmune disease in New Zealand mixed mice

Environmental crystalline silica exposure has been associated with formation of autoantibodies and development of systemic autoimmune disease, but the mechanisms leading to these events are unknown. Silica exposure in autoimmune-prone New Zealand mixed (NZM) mice results in a significant exacerbation of systemic autoimmunity as measured by increases in autoantibodies and glomerulonephritis. Previous studies have suggested that silica-induced apoptosis of alveolar macrophages (AM) contributes to the generation of the autoantibodies and disease. Rottlerin has been reported to inhibit apoptosis in many cell types, possibly through direct or indirect effects on PKCdelta. In this study, rottlerin reduced silica-induced apoptosis in bone marrow-derived macrophages as measured by DNA fragmentation. In NZM mice, RNA and protein levels of PKCdelta were significantly elevated in AM 14 wk after silica exposure. Therefore, rottlerin was used to reduce apoptosis of AM and evaluate the progress of silica-exacerbated systemic autoimmune disease. Fourteen weeks after silica exposure, NZM mice had increased levels of anti-histone autoantibodies, high proteinuria, and glomerulonephritis. However, silica-instilled mice that also received weekly instillations of rottlerin had significantly lower levels of proteinuria, anti-histone autoantibodies, complement C3, and IgG deposition within the kidney. Weekly instillations of rottlerin in silica-instilled NZM mice also inhibited the upregulation of PKCdelta in AM. Together, these data demonstrate that in vivo treatment with rottlerin significantly decreased the exacerbation of autoimmunity by silica exposure.     

The effect of different doses of mexamine on systemic hemodynamics

The method of thermodilution was used to study the influence of mexamine on the systemic haemodynamics in rats. The radioprotective and cardiovascular effects of the agent within the dose range (2-11 mg/kg) under study were shown to be relatively independent.     

Alteration of systemic hemodynamics in dogs with adrenal hypertension

Arterial hypertension was reproduced in 20 dogs by suturing the adrenal glands with ligature. Arterial pressure showed a significant fall in 2 weeks; cardiac output diminished, and the general peripheral resistance displayed a sharp elevation. The phasic syndrome of hypodynamia, a reduction of the contractility index, of the volumetric rate of cardiac output, of the cardiac index, and of the rate of increase of the intraventricular pressure pointed to reduction of the myocardial contractility. Three months after the suturing there was an even greater elevation of arterial pressure, and hemodynamic shifts were analogous to the two-week hypertension period.     

Effects of local anesthetics on bacterial cells.

The membrane effects of chlorpromazine, nupercain, tetracain, and procain were studied using Bacillus cereus, B. megaterium, B. subtilis, and Streptococcus faecalis, protoplasts from S. faecalis, and isolated membranes from B. subtilis. Chlorpromazin, nupercain, and tetracain produced characteristic micromorphological alterations after treatment for 5 to 30 min at pH 7.0 and 20 degrees C; the membrane staining pattern changed from asymmetric to symmetric, complex mesosome-like structures appeared, and membrane fractures and solubilization occurred. Procain at concentrations up to 100 mM did not induce detectable alterations. Protoplasts were quickly lysed by 10 mM tetracain. A rapid and extensive leakage of K+ was induced by chlorpromazin, nupercain, and tetracain. Procain (100 mM) induced a slight K+ leakage. The membrane respiratory activity of intact B. cereus cells (as measured by the triphenyl tetrazolium reduction) and the succinic dehydrogenase activity of B. subtilis isolated membranes were found to be inhibited by the four local anesthetics. The concentrations that produced 50% inhibition of those activities are correlated with the hydrophobicities of the anesthetic molecules.     

Effect on the systemic hemodynamics of polymers that decrease hydrodynamic resistance

It has been shown that intravenous injections of drug-reducing polymers (at a dose of 2 x1 0(-6) g/ml) to rabbits produced a decrease in the total peripheral resistance with an increase in the cardiac output and simultaneous diminution of the mean blood pressure. These hemodynamic effects did not depend on vasodilatation as it had previously been shown. The alterations were retained for not less than 72 hours after one polymer injection; the effects were due to the influence of polymers on the flow structure.     

Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response.

We previously showed that chronic administration of recombinant human relaxin (rhRLX; 4 microg/h) to conscious female, nonpregnant rats to reach serum levels corresponding to early to midgestation (approximately 20 ng/ml) increases cardiac output (CO) and global arterial compliance (AC) and decreases systemic vascular resistance (SVR), comparable to changes observed in midterm pregnancy. The goals of this study were to test whether chronic administration of rhRLX (4 microg/h) to conscious male rats will yield similar changes in CO and systemic arterial load and to determine whether higher infusion rates of rhRLX (50 microg/h) administered to nonpregnant female rats yielding serum concentrations corresponding to late pregnancy ( approximately 80 ng/ml) will further modify CO and SVR and global AC comparable to late gestation. CO and systemic arterial load, as quantified by SVR and AC, were obtained by using the same methods as in our previous studies. With respect to baseline, chronic rhRLX administration to male rats over 10 days at 4 mug/h increased both CO (20.5 +/- 4.2%) and AC (19.4 +/- 6.9%) and reduced SVR (12.7 +/- 3.9%). These results were comparable to those elicited by the hormone in nonpregnant female rats. In contrast, neither acute (over 4 h) nor chronic (over 6 days) infusion of the higher dose of rhRLX administered to conscious female rats resulted in significant changes in CO, AC, or SVR from baseline. We conclude that 1) rhRLX increases CO and AC and reduces SVR irrespective of sex, and 2) the rhRLX dose response is biphasic insofar as significant alterations in CO and systemic arterial load fail to occur at high serum concentrations.     

Effects of general anesthetics on search in memory in man.

Recovery of search functions in long-term memory following several hours of anesthesia was studied on human volunteers. Verbal as well as visual search was assessed. The anesthetics used, fluroxene and halothane, slowed down considerably the verbal search for the first few hours following anesthesia, but had very little effect on the following day. No effect was observed a week later. Visual search was not affected at all, in accordance with previous findings indicating a selective effect of low concentrations of inhalation anesthetics on verbal memory.     

Endothelium-dependent mechanism of formation of the systemic hemodynamics responses

In anaesthetised rats, effects of blockade of the NO-synthetase upon hemodynamic shifts were studied (arterial pressure, cardiac output, general peripheral vascular resistance), the shifts being evoked either by increase (infusion of polyglucon) or by decrease (orthostasis) in the cardiac output. Under the blockade of the NO-synthetase, the pressor effects of polyglucon increased by 27% and the orthostatic hypotension by 72%. Responses of general peripheral vascular resistance changed in the same direction. The findings suggest importance of the NO secretion by the vessels' endothelium for formation of the systemic hemodynamics responses.