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Biomedical subjects

F S Grodins

Publications and source records attributed to F S Grodins.

At least 19 recordsLinked to original sources

Ventilatory response to CO2 and O2 near eupnea in awake dogs.

The problem faced in determining the ventilatory response to CO2 near eupnea has been the difficulty of unloading metabolically produced CO2 from the subject in the steady state. Previous methods using extracorporeal circuits to unload CO2 are technically difficult and provide a limited number of experimental states per experiment. Using the method of high-frequency ventilation to unload CO2, we were able to obtain a large number of determinations in the same subject under conditions of hypoxia, normoxia, and hyperoxia. Data collected in five awake dogs show that the ventilatory response to CO2 is linear down to apnea during normoxic conditions but exhibits nonlinear behavior dependent on the level of arterial O2 tension. During hyperoxic conditions, the response was concave curvilinear, with a statistically significant decrease in slope near apnea. In contrast, mild hypoxia led to a convex curvilinear response with an increased slope near apnea.

Animals

Role of VCO2 in control of breathing of awake exercising dogs.

Steady-state ventilatory responses to CO2 inhalation, intravenous CO2 loading (loading), and intravenous CO2 unloading (unloading) were measured in chronic awake dogs while they exercised on an air-conditioned treadmill at 3 mph and 0% grade. End-tidal PO2 was maintained at control levels by manipulation of inspired gas. Responses obtained in three dogs demonstrated that the response to CO2 loading [average increase in CO2 output (Vco2) of 216 ml/min or 35%] was a hypercapnic hyperpnea in every instance. Also, the response to CO2 unloading [average decrease in Vco2 of 90 ml/min or 15% decrease] was a hypocapnic hypopnea in every case. Also, the analysis of the data by directional statistics indicates that there was no difference in the slopes of the responses (change in expiratory ventilation divided by change in arterial Pco2) for loading, unloading, and inhalation. These results indicate that the increased CO2 flow to the lung that occurs in exercise does not provide a direct signal to the respiratory controller that accounts for the exercise hyperpnea. Therefore, other mechanisms must be important in the regulation of ventilation during exercise.

Animals

Effects of small changes in PaO2 on the ventilatory response to CO2 infusion.

The steady-state ventilatory responses to CO2 inhalation and two levels of intravenous CO2 infusion were examined in chronic awake dogs. Responses were obtained for four treatments: 1) air breathing, in which arterial O2 tension (PaO2) increased during infusion; 2) normoxia, PaO2 maintained at control levels; 3) hypoxia, PaO2 = 70 Torr; and 4) hyperoxia, PaO2 = 160 Torr. In three dogs, the ventilatory responses were obtained for treatments 1, 2, and 4 and in an additional three dogs for treatments 2, 3, and 4. Analysis of the data by directional statistics indicates that the response to infusion was hypercapnic for all treatments, and the slope of the response (change in minute ventilation divided by change in arterial CO2 tension) was identical to that of CO2 inhalation. Also, the slopes of the responses for the low infusion rate, CO2 output (VCO2) = 50%, and the high infusion rate, VCO2 = 270%, were identical, which suggests that the CO2 response is not significantly curvilinear near the eucapnic region. Finally, changing PaO2 between 70 and 160 Torr had no significant effect on the response slopes. Thus the ventilatory response to CO2 infusion in the awake dog is a hypercapnic hyperpnea that is not due to ventilatory inhibition arising from an increase in PaO2.

Animals

Intrapulmonary Co2 receptors and ventilatory response to lung Co2 loading.

The possible role of intrapulmonary CO2 receptors (IPC) in arterial CO2 partial pressure (PaCO2) homeostasis was investigated by comparing the arterial blood gas and ventilatory responses to CO2 loading via the inspired gas and via the venous blood. Adult male Pekin ducks were decerebrated 1 wk prior to an experiment. Venous CO2 loading was accomplished with a venovenous extracorporeal blood circuit that included a silicone-membrane blood oxygenator. The protocol randomized four states: control (no loading), venous CO2 loading, inspired CO2 loading, and venous CO2 unloading. Intravenous and inspired loading both resulted in hypercapnic hyperpnea. Comparison of the ventilatory sensitivity (delta VE/delta PaCO2) showed no significant difference between the two loading regimes. Likewise, venous CO2 unloading led to a significant hypocapnic hypopnea. Sensitivity to changes in PaCO2 could explain the response of ventilation under these conditions. The ventilatory pattern, however, was differentially sensitive to the route of CO2 loading; inspired CO2 resulted in slower deeper breathing than venous loading. It is concluded that IPC play a minor role in adjusting ventilation to match changes in pulmonary CO2 flux but rather are involved in pattern determination.

Animals

Ventilatory responses to intravenous and airway CO2 administration in anesthetized dogs.

The ventilatory responses to steady-state venous CO2 loading (iv CO2) and CO2 inhalation have been observed in chloralose-urethan-anesthetized dogs. Intravenous CO2 was administered by increasing the CO2 fraction of gas ventilating a membrane gas exchanger in an arteriovenous bypass; blood flow rate was fixed at 30 ml/min. During the study, we identified a time-dependent hyperventilation in all 14 experimentally treated dogs and in 4 additional sham-treated dogs. When we tested 8 of these animals with a protocol having small progressive increments in iv CO2 loading rate, we observed a response approaching isocapnia during iv CO2 and a large hypocapnia when we returned to control conditions. The use of a randomized protocol in 6 animals demonstrated the necessity of accounting for this systematic base-line shift, because before doing so the response depended more on the passage of time than on the nature of the CO2 load. After this analytical adjustment was made, there was no significant difference between the respiratory controller gains (delta nu E/delta Paco2) for inhaled and iv CO2.

Anesthesia

Arterial PCO2 response to intravenous CO2 in awake dogs unencumbered by external breathing apparatus.

The steady-state arterial CO2 tension (PaCO2) was examined during control and intravenous CO2 loading in awake dogs unencumbered by any breathing apparatus. The dogs inhaled air while undergoing intravenous CO2 loading, and we estimated the gain, delta VA/delta PACO2. CO2 was introduced into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow was maintained constant at 0.5 l/min. A total of 11 experiments were performed in 3 dogs comprising 93 control observations and 83 CO2 loading observations. Intravenous CO2 produced a significant increase in the steady state PaCO2, a finding consistent with our previous study in tracheostomized awake dogs. We conclude that intravenous CO2 produces hypercapnia in the awake dog with an intact airway unencumbered by external respiratory apparatus.

Acidosis, Respiratory

Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs.

Ventilatory responses to CO2 inhalation and CO2 infusion were compared in the awake dog. The CO2 was introduced directly into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow, QX, was maintained constant at one of two rates: low, 0.5 l/min; or high, 2.0 l/min. A total of 13 experiments was performed in four dogs comprising 50 control and 25 inhalation and infusion observations at each of the two flow rates. Comparison of CO2-response curve slopes, S = delta V E/delta PaCO2, between CO2 inhalation and infusion showed no significant difference either within or between flow rates. The mean value of S for all conditions was 1.88 l/min per Torr with a 95% confidence interval of 1.66 -2.14. An independent additive ventilatory drive amounting to 28% of low-flow control VE was found at the highflow rate. We conclude that at constant blood flow the responses to both CO2 inhalation and infusion are hypercapnic and not significantly different.

Animals

Mechanism of respiratory responses to intravenous NaHCO3, HCl, and KCN.

We studied the mechanism by which respiratory responses are produced by rapid injection of NaHCO3, HCl, or KCN into the superior vena cava of lightly anesthetized dogs. To estimate independently circulatory transit time to receptor sites, the solutions were injected at 0 degrees C and their arrival time at the ascending aorta and carotid sinus was detected by thermocouples. All of the ventilatory responses were observed to begin after the substances had reached the ascending aorta and 94% began after the carotid sinus had been reached. The injections were repeated following bilateral vagotomy and/or carotid body resection. Vagotomy produced no significant changes in ventilatory responses, but carotid body resection considerably reduced them. Following both procedures, few ventilatory responses were observed, and the time lag to the onset of the response increased greatly. We conclude that all of the observed ventilatory responses can be accounted for by the known arterial and central chemoreceptors, and that no evidence for pulmonary chemoreceptors was obtained.

Animals

Dynamic analysis of gravimetric response of isolated dog hindlimb.

Previous gravimetric studies of transcapillary fluid movement have been based on capillary filtration coefficient (CFC) estimates. In these studies only a single CFC value is estimated for the entire isolated vascular bed. We have analyzed the dynamic gravimetric responses of isolated dog hindlimb to venous pressure steps and found it possible to estimate two different CFC values. Under control conditions, one CFC value averaged .0049 ml/mmHg min per 100g tissue wt, whichagrees with results of previous investigators. The other CFC value averaged 90304, which is very close to estimates we have previously made by an independent frequency-response methods. Changes in hindlimb properties to intra-arterial infusions of acetylcholine, papaverine, isoproterenol, and norepinephrine were also studied. Drug infusion results and the presence of similar dynamic components in experiments on gracilis muscle support the existence of inhomogeneous pathwaysin tissue, which lead to fluid-exchange nonuniformity.

Acetylcholine

Effect of histamine on microvasculature of isolated dog gracilis muscle.

Isogravimetric capillary pressure (Pci), capillary filtration coefficient (CFC), and plasma protein concentration were measured before and during adminisistration of histamine in an isolated, independently perfused canine gracilis muscle. Histamine produced an average decrease in Pci of 14.1 mmHg, an increase in CFC of 36-fold, and an increased rate of plasma protein escape of at least 24-fold. These results suggest that histamine reduces the reflection coefficient for protein at the capillary wall and are consistent with predictions of the theory of restricted diffusion assuming that 1-2.5% of available pores increase in radious from 40 to 240 A.

Animals

Total work rate of breathing optimization in CO-2 inhalation and exercise.

The hypothesis that respiratory frequency and the relative durations of inspiration and expiration are regulated according to a total cycle work rate minimization criterion was explored. Effects of negative work performed by the respiratory muscles and dead space variation as a function of tidal volume were included in a formulation which yielded a theoretically predictable optimal frequency and relative duration of inspiration and expiration at all levels of ventilation. Predicted cycle characteristics based on measured mechanical parameters were compared with data taken during CO-2 inhalation (3 and 5%) and moderate exercise (MRR = 3 and 6) in three normal human subjects. No major difference in breathing pattern was observed between CO-2 inhalation and exercise. Results suggest that conditions for minimization of total cycle work rate are achieved asympototically as the level of ventilation rises above the resting level. At rest and at low levels of hyperpnea complete work rate optimization is not achieved.

Adult