Julius H. Comroe, Jr., Distinguished Lecture: Central chemoreception: then … and now

The 2010 Julius H. Comroe, Jr., Lecture of the American Physiological Society focuses on evolving ideas in chemoreception for CO2/pH in terms of what is “sensed,” where it is sensed, and how the sensed information is used physiologically. Chemoreception is viewed as involving neurons (and glia) at many sites within the hindbrain, including, but not limited to, the retrotrapezoid nucleus, the medullary raphe, the locus ceruleus, the nucleus tractus solitarius, the lateral hypothalamus (orexin neurons), and the caudal ventrolateral medulla. Central chemoreception also has an important nonadditive interaction with afferent information arising at the carotid body. While ventilation has been viewed as the primary output variable, it appears that airway resistance, arousal, and blood pressure can also be significantly affected. Emphasis is placed on the importance of data derived from studies performed in the absence of anesthesia.

Assessment of renal autoregulation

The kidney displays highly efficient autoregulation so that under steady-state conditions renal blood flow (RBF) is independent of blood pressure over a wide range of pressure. Autoregulation occurs in the preglomerular microcirculation and is mediated by two, perhaps three, mechanisms. The faster myogenic mechanism and the slower tubuloglomerular feedback contribute both directly and interactively to autoregulation of RBF and of glomerular capillary pressure. Multiple experiments have been used to study autoregulation and can be considered as variants of two basic designs. The first measures RBF after multiple stepwise changes in renal perfusion pressure to assess how a biological condition or experimental maneuver affects the overall pressure-flow relationship. The second uses time-series analysis to better understand the operation of multiple controllers operating in parallel on the same vascular smooth muscle. There are conceptual and experimental limitations to all current experimental designs so that no one design adequately describes autoregulation. In particular, it is clear that the efficiency of autoregulation varies with time and that most current techniques do not adequately address this issue. Also, the time-varying and nonadditive interaction between the myogenic mechanism and tubuloglomerular feedback underscores the difficulty of dissecting their contributions to autoregulation. We consider the modulation of autoregulation by nitric oxide and use it to illustrate the necessity for multiple experimental designs, often applied iteratively.

Propofol Reduces Perioperative Remifentanil Requirements in a Synergistic Manner

Background Remifentanil is often combined with propofol for induction and maintenance of total intravenous anesthesia. The authors studied the effect of propofol on remifentanil requirements for suppression of responses to clinically relevant stimuli and evaluated this in relation to previously published data on propofol and alfentanil. Methods With ethics committee approval and informed consent, 30 unpremedicated female patients with American Society of Anesthesiologists physical status class I or II, aged 18-65 yr, scheduled to undergo lower abdominal surgery, were randomly assigned to receive a target-controlled infusion of propofol with constant target concentrations of 2, 4, or 6 microg/ml. The target concentration of remifentanil was changed in response to signs of inadequate anesthesia. Arterial blood samples for the determination of remifentanil and propofol concentrations were collected after blood-effect site equilibration. The presence or absence of responses to various perioperative stimuli were related to the propofol and remifentanil concentrations by response surface modeling or logistic regression, followed by regression analysis. Both additive and nonadditive interaction models were explored. Results With blood propofol concentrations increasing from 2 to 7.3 microg/ml, the C(50) of remifentanil decreased from 3.8 ng/ml to 0 ng/ml for laryngoscopy, from 4.4 ng/ml to 1.2 ng/ml for intubation, and from 6.3 ng/ml to 0.4 ng/ml for intraabdominal surgery. With blood remifentanil concentrations increasing from 0 to 7 ng/ml, the C(50) of propofol for the return to consciousness decreased from 3.5 microg/ml to 0.6 microg/ml. Conclusions Propofol reduces remifentanil requirements for suppression of responses to laryngoscopy, intubation, and intraabdominal surgical stimulation in a synergistic manner. In addition, remifentanil decreases propofol concentrations associated with the return of consciousness in a synergistic manner.

Interaction of rearing temperature and maternal influence on egg development rates and larval size at hatch in yellowtail flounder (Pleuronectes ferrugineus)

We assessed the extent to which temperature interacts with maternal contributions to egg size to affect development time and size of yellowtail flounder (Pleuronectes ferrugineus) larvae at hatch. Maternal effects contributed significantly to differences in egg sizes produced by four females. Eggs from each female were incubated at five temperatures. Development time was most significantly affected by temperature, and female effects were minimal. However, the variance in development time within a population was significantly affected by an interaction between female and temperature effects. Average length at hatch varied significantly among temperatures and females, as did the variance in hatching length within a population. Variance in hatching length explained by maternal effects peaked at intermediate temperatures (~38% explained variance at 7°C), while variance explained by covariation with development time increased linearly with temperature, explaining ~40% variance at 13°C. Overall, the nonadditive interaction between maternal contributions and the environment suggests that female effects must be considered over the entire range of environmental conditions experienced by their progeny. In addition, our results support the idea that it is inappropriate to quantify female effects among eggs and extrapolate these differences to larvae.

Postural vascular response vs. sympathetic vasoconstriction in human skin during orthostasis

Sympathetic activation and local vascular smooth muscle reactions to vessel distension contribute to the increase in vascular resistance in the skin during orthostasis. The relative contribution of these two mechanisms to the changes of skin blood flow along the body axis on standing was investigated in healthy male subjects by laser-Doppler (LD) fluxmetry. Compared with recumbency, LD flux (LDF) in the standing subjects was reduced by -19.6 +/- 7.2% at the forehead and by -69.6 +/- 9.6% in the leg. In the absence of hydrostatic pressure changes, the LDF changes on standing averaged -29 +/- 13%, independent of skin region, reflecting the effect of vasoconstriction due to sympathetic activation. The postural vascular response, elicited by lowering the arm or the leg from heart level, was significantly attenuated in orthostasis compared with recumbency. The vessel reaction to local alteration of transmural pressure was studied in the skin of the forehead and lower leg by application of external pressure in supine subjects. No difference in vessel responsiveness to changes of transmural pressure was found between these skin sites. The findings suggest that the changes of skin perfusion in orthostasis result from a nonadditive interaction of height-dependent and -independent mechanisms.