Search

Unlabelled: We evaluated dynamic cardiovascular control by spectral analytical methods in 20 young adults anesthetized with propofol (2.5 mg/kg, followed by continuous infusion of 0.1 mg/kg/min) and in an awake control group during cyclic stimulation of the carotid baroreceptors via sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and at 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity). During anesthesia and mechanical ventilation at 0.25 Hz, major underdampened hemodynamic oscillations occurred at 0.055 +/- 0.012 Hz. The response of RR intervals to baroreceptor stimulation at 0.2 Hz was markedly decreased during anesthesia (median of transfer function magnitude between neck suction and RR intervals 3% of the awake control). Blood pressure response to baroreceptor stimulation at 0.1 Hz was significantly decreased during anesthesia to 26% (systolic blood pressure), and 44% (diastolic blood pressure) of the awake control. There was a significant delay in baroreflex effector responses during anesthesia. Our results demonstrate a markedly depressed vagally mediated heart rate response and an impaired blood pressure response to cyclic baroreceptor stimulation during propofol anesthesia in mechanically ventilated patients. The disturbed baroreflex control is accompanied by an irregular dynamic behavior of cardiovascular regulation, indicating a decreased stability of the control system., Implications: An irregular dynamic behavior of the cardiovascular control system, associated with an impaired baroreflex control of heart rate and blood pressure, can be observed during propofol anesthesia in mechanically ventilated subjects.

The question of whether respiratory sinus arrhythmia (RSA) originates mainly from a central coupling between respiration and heart rate, or from baroreflex mechanisms, is a subject of controversy. If there is a major contribution of baroreflexes to RSA, cardiocirculatory coupling during breathing and during cyclic baroreflex stimulation should show similarities. We applied a sinusoidal stimulus to the carotid baroreceptors and generated heart rate fluctuations of the same magnitude as RSA with a frequency similar to, but different from, the breathing frequency (0.2 Hz, compared with 0.25 Hz), and at 0.1 Hz, in 17 supine healthy subjects (age 28-39 years). The data were analysed using discrete Fourier-transform and transfer function analysis. Respiratory fluctuations in systolic blood pressure preceded RSA with a time lag equal to that between baroreceptor stimulation and oscillations in RR interval (0.62+/-0.18 s compared with 0.57+/-0.28 s at 0.2 Hz neck suction). The response of systolic blood pressure to neck suction at 0.2 Hz was 5 times less than the respiratory blood pressure fluctuations. Neck suction at 0.1 Hz largely increased fluctuations in blood pressure and RR interval, whereas the spontaneous phase relationship between blood pressure and RR interval remained unchanged. Our results are not consistent with the hypothesis that the origin of RSA is predominantly a central phenomenon which secondarily generates fluctuations in blood pressure, but suggest that, under the condition of fixed-frequency breathing at 0.25 Hz, baroreflex mechanisms contribute to respiratory fluctuations in RR interval.

1. In bovine adrenal chromaffin cells made permeable either to molecules less than or equal to 3 kDa with alphatoxin or to proteins less than or equal to 150 kDa with streptolysin O, the GTP analogues guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG) and guanosine 5'-[gamma-thio]triphosphate (GTP[S]) differently modulated Ca(2+)-stimulated exocytosis. 2. In alphatoxin-permeabilized cells, p[NH]ppG up to 20 microM activated Ca(2+)-stimulated exocytosis. Higher concentrations had little or no effect. At a free Ca2+ concentration of 5 microM, 7 microM-p[NH]ppG stimulated exocytosis 6-fold. Increasing the free Ca2+ concentration reduced the effect of p[NH]ppG. Pretreatment of the cells with pertussis toxin prevented the activation of the Ca(2+)-stimulated exocytosis by p[NH]ppG. 3. In streptolysin O-permeabilized cells, p[NH]ppG did not activate, but rather inhibited Ca(2+)-dependent catecholamine release under all conditions studied. In the soluble cytoplasmic material that escaped during permeabilization with streptolysin O, different G-protein alpha-subunits were detected using an appropriate antibody. Around 15% of the cellular alpha-subunits were detected in the supernatant of permeabilized control cells. p[NH]ppG or GTP[S] stimulated the release of alpha-subunits 2-fold, causing a loss of about 30% of the cellular G-protein alpha-subunits under these conditions. Two of the alpha-subunits in the supernatant belonged to the G(o) type, as revealed by an antibody specific for G(o) alpha. 4. GTP[S], when present alone during stimulation with Ca2+, activated exocytosis in a similar manner to p[NH]ppG. Upon prolonged incubation, GTP[S], in contrast to p[NH]ppG, inhibited Ca(2+)-induced exocytosis from cells permeabilized by either of the pore-forming toxins. This effect was resistant to pertussin toxin. 5. The p[NH]ppG-induced activation of Ca(2+)-stimulated release from alphatoxin-permeabilized chromaffin cells may be attributed to one of the heterotrimeric G-proteins lost during permeabilization with streptolysin O. The inhibitory effect of GTP[S] on exocytosis is apparently not mediated by G-protein alpha-subunits, but by another GTP-dependent process still occurring after permeabilization with streptolysin O.