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Biomedical subjects

E R Schertel

Publications and source records attributed to E R Schertel.

34 records · Page 2Linked to original sources

Reflex cardiovascular effects of continuous prostacyclin administration into an isolated in situ lung in the dog.

Bolus administration of prostacyclin (PGI2), an inflammatory product produced by the arachidonic acid cyclooxygenase pathway, into the pulmonary circulation is known to stimulate pulmonary C-fibers and to produce transient reflex cardiovascular depression. We used an isolated perfused in situ left lung preparation to examine the reflex cardiovascular effects of continuous administration of PGI2 into the isolated pulmonary circulation of dogs. PGI2 was infused for 30 min (5 micrograms.kg-1 x min-1) into the innervated isolated left pulmonary circulation in six dogs and into the denervated isolated circulation in seven dogs. Mean arterial pressure and cardiac output were significantly decreased from baseline values during the final 20 min of PGI2 infusion. There were no significant changes in maximum rate of change of left ventricular pressure during systole and in heart rate. All variables returned to baseline levels within 15 min of discontinuation of PGI2 infusion. PGI2 infusion produced no significant measured hemodynamic changes in the denervated group. Control experiments demonstrated that the observed response was not affected by duration of the preparation, lung denervation, or infusion vehicle. These findings suggest that continuous infusion of PGI2 into the isolated pulmonary circulation produces sustained cardiovascular depression via a vagal reflex mechanism that is probably mediated by pulmonary C-fibers.

Animals↗

Comparative effects of 7.5% NaCl in 6% Dextran 70 and 0.9% NaCl on cardiorespiratory parameters after cardiac output-controlled resuscitation from canine hemorrhagic shock.

We resuscitated severely hemorrhaged (mean arterial pressure at 40 mm Hg for 30 min) pentobarbital-anesthetized dogs to 120% of control cardiac output with 7.5% NaCl in 6% Dextran 70 (HSD) or 0.9% NaCl (IS) to compare the effects on hemodynamic and oxygen transport parameters. Hemodynamic parameters and oxygen delivery did not differ between groups. Oxygen consumption and oxygen extraction ratio tended to be higher, and mixed venous oxygen tension lower (P < 0.05) for HSD during the first hour of the postresuscitation period. Resuscitation of the HSD group required significantly less time (10.4 +/- 2.0 vs. 23.6 +/- 1.7 min; P < 0.01) and fluid volume (8.0 +/- 1.1 vs. 47.0 +/- 3.3 ml.kg-1; P < 0.01). We conclude that the resuscitation of hypovolemic dogs with HSD and IS to equivalent cardiac output results in identical improvements in hemodynamics and oxygen delivery but that HSD may provide a better oxygen supply/demand balance during the first hour postresuscitation.

Animals↗

Lung innervation and the hemodynamic response to 7% sodium chloride in hypovolemic dogs.

A pulmonary vagal reflex triggered by passage of hypertonic saline through the pulmonary circulation has been proposed as one of the mechanisms by which hypertonic saline resuscitates dogs in hemorrhagic shock. Thirteen anesthetized dogs with denervated left lung lobes were subjected to a standard hemorrhage model to evaluate this purported reflex. We then infused 7% NaCl (4 ml/kg) into either the innervated (six dogs) or the denervated (seven dogs) pulmonary circulation. There were no differences in cardiac output, mean arterial pressure, right atrial pressure, heart rate, or peripheral vascular resistance between groups during a 1 hr period after 7% NaCl infusion. Changes in hematocrit, total plasma protein, and osmolality after 7% NaCl administration suggested that plasma volume expansion had occurred and was similar between groups. We conclude that a pulmonary reflex elicited by hypertonic saline does not contribute to the beneficial hemodynamic effects associated with administration of 7% NaCl during hemorrhagic shock.

Animals↗

Hypertonic saline/dextran resuscitation of dogs with experimentally induced gastric dilatation-volvulus shock.

We investigated small-volume (5 ml/kg) 7% NaCl in 6% dextran 70 (HS/D70) as an alternative to large-volume (60 ml/kg) 0.9% NaCl for treatment of experimentally induced canine gastric dilatation-volvulus (GDV) shock. The stomach was surgically displaced and then distended with an intragastric balloon in 11 dogs anesthetized with pentobarbital. All dogs were subjected to GDV for 180 minutes before partial decompression and resuscitation. Hemodynamic values, blood gas values, and plasma volume were measured during control, shock, and resuscitation periods. Resuscitation started with 1 group (n = 6) receiving 5 ml of HS/D70/kg, iv, over 5 minutes, and the other group (n = 5) receiving 60 ml of 0.9% NaCl/kg, IV, over 60 minutes. Both groups received a surgical maintenance dosage (20 ml/kg/h) of 0.9% NaCl after initial resuscitation. Resuscitative effects of small-volume HS/D70 were similar to large-volume 0.9% NaCl during the first hour of treatment; however, cardiac output was significantly higher in the HS/D70 group for the last 2 hours of resuscitation. Changes in heart rate, left ventricular pressure change, and systemic vascular resistance appeared to be responsible for improved perfusion. Mixed venous oxygen partial pressure data supported improved perfusion in the HS/D70 group. Packed cell volume remained higher in the HS/D70 group, indicating less hemodilution and improved oxygen delivery. Resuscitation of this GDV-induced shock model was better sustained with small-volume HS/D70, compared with conventional large-volume 0.9% NaCl.

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Vagotomy alters the hemodynamic response of dogs in hemorrhagic shock.

We examined the hemodynamic response of severely hemorrhaged dogs to vagotomy to further define the role of vagal innervation in circulatory control during severe hemorrhage. When the cervical vagi were severed in severely hemorrhaged, pentobarbital-anesthetized dogs, MAP decreased immediately after vagotomy and remained lower than in vagal-intact dogs. Cardiac output (CO) and heart rate (HR) also remained lower in the vagotomized dogs. When 45 ml/kg of 0.9% NaCl was administered to vagal-intact or vagotomized, severely hemorrhaged dogs, the MAP and CO increases were attenuated by vagotomy. Blood flow increases in the renal and splanchnic, but not femoral, vascular beds were inhibited by vagotomy. Vagotomy attenuates the hemodynamic response of severely hemorrhaged dogs, limits the effectiveness of isotonic fluid therapy, and exerts a differential effect on blood flow distribution.

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Influence of 7% NaCl on the mechanical properties of the systemic circulation in the hypovolemic dog.

We examined the effects of hypertonic saline (7%) administration during hypovolemia in the anesthetized dog on the mechanical properties of the systemic circulation that constitute the major determinants of venous return. By using a right-heart bypass preparation in which venous return from the splanchnic and non-splanchnic vascular beds was isolated and drained into a common reservoir, venous resistance, venous compliance, and blood flow distribution measurements were made during control conditions and during a period of lowered systemic blood flow (30 min at a mean arterial pressure of 50 mm Hg). These measurements were repeated following hypertonic saline administration at the reduced and control levels of systemic blood flow. Hypertonic saline administration (8 ml/kg) produced an average increase in reservoir volume of 23 ml/kg and osmolality of 25.5 mOsm/kg. Changes in venous compliance, venous resistance, and blood flow distribution in response to hypertonic saline accounted for no more than 5% of the reservoir volume increase. Furthermore, plasma volume expansion estimated from hematocrit dilution suggests that hypertonic saline does not alter unstressed vascular volume. The most likely mechanism by which hypertonic saline enhances venous return is by plasma volume expansion and not by alterations of the mechanical properties of the systemic circulation.

Animals↗

Effect of pulmonary arterial PCO2 on breathing pattern.

We studied breathing patterns and tidal volume (VT)-inspiratory time (TI) relationships at three steady-state levels of pulmonary arterial PCO2 (PpCO2) in 10 anesthetized dogs. To accomplish this we isolated and then separately pump perfused the pulmonary and systemic circulations, which allowed us to control blood gases in each circuit independently. To ventilate the lungs at a rate and depth determined by central drive, we used an electronically controlled positive-pressure ventilator driven by inspiratory phrenic neural activity. Expiratory time (TE) varied inversely with PpCO2 over the range of PpCO2 from approximately 20 to 80 Torr. VT and TI increased with rising PpCO2 over the range from approximately 20 to 45 Torr but did not change further as PpCO2 was raised above the middle level of approximately 45 Torr. Thus minute ventilation increased as a function of TE and VT as PpCO2 was increased over the lower range and increased solely as a function of TE as PpCO2 was increased over the upper range. The VT-TI relationship shifted leftward on the time axis as PpCO2 was lowered below the middle level but did not shift in the opposite direction as PpCO2 was raised above the middle level. In addition to its effect on breathing pattern, we found that pulmonary hypocapnia depressed inspiratory drive.

Animals↗

Respiratory reflexes in the anesthetized miniature swine.

To assess the suitability of the miniature swine for studies of the control of breathing we evaluated the response of these animals to commonly used respiratory stimuli. Hanford miniature pigs were anesthetized with alpha chloralose and allowed to breathe spontaneously. Rapid lung inflations induced a prolonged expiratory pause proportional to load. Mechanical stimulation of the upper airways induced coughing. Central venous injections of C-fiber stimulants produced bradycardia, hypotension with apnea and/or rapid shallow breathing. CO2 rebreathing increased ventilation primarily through an increase in tidal volume; inspiratory time was not changed. Bilateral vagotomy caused a slower, deeper pattern of breathing, and significantly attenuated the ventilatory response to CO2; all other reflexes were abolished by vagotomy. Cooling the vagus nerves caused reversible blockade of the cough, inflation and C-fiber mediated reflexes in that order. We conclude that the pig can serve as a useful animal in which to study the control of breathing.

Anesthesia↗

Effects of end-expired pressure on phrenic output in servo-ventilated dogs.

The pattern of breathing induced by increases in end-expired lung volume (EEVL) was determined in 9 anesthetized dogs. The pulmonary and systemic circulations were separately pump-perfused and the lungs were ventilated with a servo-ventilator actuated from the phrenic neurogram. EEVL was increased as a continuous ramp by slowly raising end-expired transpulmonary pressure from 1.5 to 12 cm H2O. Tidal volume (VT), inspiratory time (TI), and expiratory time (TE) were measured at vagal temperatures of 39 degrees C and 7 degrees C and following vagotomy. At a vagal temperature of 39 degrees C, increasing EEVL produced significant reductions in VT and TI while greatly prolonging TE. Vagal cooling to 7 degrees C, substantially altered the reflex response to increased EEVL. At 7 degrees C, VT decreased as EEVL increased, but the reduction was not so pronounced as at 39 degrees C. In addition, both TI and TE shortened. Increasing EEVL following vagotomy had no consistent effects on breathing pattern. We conclude that increasing EEVL stimulates tachypneic promoting pulmonary afferent nerves, most likely pulmonary C-fibers, but at normal vagal temperature their effect is masked by the stronger reflex inhibition of slowly adapting pulmonary stretch receptors.

Animals↗

A phrenic nerve-actuated electronically controlled positive-pressure ventilator.

We have constructed an electronically controlled positive-pressure ventilator actuated by phrenic neural activity for use in open-chested or paralyzed experimental animals for the study of breathing pattern. A Bird Mark 14 positive-pressure ventilator was modified such that flow is a linear function of a command signal. Flow is delivered by advancing an air valve with a servo-motor that is controlled by one of three different operational modes. In two of the modes, the difference between the electronic average of inspiratory phrenic activity (moving average) and a feedback signal determines the inspiratory flow. The feedback signal is derived from either tracheal pressure or an electronic measure of inspired volume. In the third mode, the moving average is differentiated to provide control of inspiratory flow and volume. Physiological flow profiles were created using all three operational modes. Integration of an air-valve position signal provides an electronic measure of tidal volume. An additional feature of this ventilator allows inspiratory flow and duration to be predetermined for a given breath.

Animals↗

Effect of pulmonary arterial PCO2 on slowly adapting pulmonary stretch receptors.

We recorded pulmonary stretch receptor (PSR) activity in anesthetized dogs and examined the effect of varying pulmonary arterial PCO2 (PpCO2) in both the naturally perfused and vascularly isolated pulmonary circulations while ventilating the lungs with room air. Steady-state increases in PpCO2 from approximately 25 to 50 Torr and from 50 to 70 Torr decreased PSR activity (impulses/ventilatory cycle) by 15 and 9%, respectively (P less than 0.001). Rapid increases in PpCO2 from approximately 50 to 80 Torr in a right-heart bypass preparation (with pulmonary blood flow constant) decreased PSR activity by 27%. Depression of firing, which was proportionately greater in deflation, was not dependent on changes in lung mechanics. Results show that loading CO2 intravascularly depresses PSR activity, the effects extending above as well as below resting PpCO2. Rapidly increasing PpCO2 above the resting level markedly depresses PSR activity during the transient. We conclude that PSRs may contribute to altered breathing resulting from changes in mixed venous PCO2 over the physiological range.

Adaptation, Physiological↗

Rapid shallow breathing evoked by capsaicin from isolated pulmonary circulation.

Recently Green et al. (J. Appl. Physiol. 57:562-567, 1984) reported that pulmonary C-fibers initiate the prompt apnea evoked by pulmonary arterial injections of capsaicin; however, their role in the subsequent rapid shallow breathing of the pulmonary chemoreflex is still in dispute. To determine whether this reflex tachypnea is triggered by pulmonary C-fibers rather than by afferents further downstream, we separately perfused the pulmonary and systemic circulations in dogs anesthetized with either halothane or alpha-chloralose as the lungs were ventilated with a servo-controlled ventilator driven by phrenic nerve activity. Injection of capsaicin (10 micrograms/kg) into the pulmonary artery of the isolated pulmonary circulation evoked an immediate apnea followed by rapid shallow breathing. Injection of the same dose of capsaicin into the left atrium of the isolated pulmonary circulation had no effect. By contrast, when capsaicin was administered at a slower rate into the pulmonary artery (10-20 micrograms X kg-1 X min-1) rapid shallow breathing occurred but without apnea. Our results are consistent with the hypothesis that in spontaneously breathing animals, stimulation of pulmonary C-fibers can evoke rapid shallow breathing.

Anesthesia↗

Effect of p-chlorophenylalanine on thermoregulation in unrestrained rats.

p-Chlorophenylalanine (PCPA), a serotonin depletor, was used to investigate thermoregulation of unrestrained unanesthetized rats exposed to warm (approximately 32 degrees C) and cold (approximately 3 degrees C) environments. PCPA (300 mg/kg, ip) was administered approximately 48-96 h prior to the experimental trials. After 60 min of warm exposure, PCPA-treated rats had a significantly smaller increase in mean tail temperature (3.05 degrees C) and a greater increase in mean core temperature (1.47 degrees C) than did the control rats (6.13 and 1.20 degrees C, respectively) as measured via chronically implanted thermistors. A noninvasive method, infrared photography, was also used to monitor skin temperatures following heat exposure. Changes were qualitatively similar to those seen with thermistors, although differences between control and PCPA-treated groups were not statistically significant. During cold exposure, thermistor measurements indicated that the decrease in mean core temperature of the PCPA-treated rats (0.62 degrees C) did significantly differ from that of the controls (1.11 degrees C), whereas tail temperatures did not. These data confirm other studies implicating serotonin in the thermoregulation of rats. In particular, these results show that in a warm environment, PCPA may alter, albeit subtly, peripheral vasodilation in unrestrained rats.

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Effects of gravitational profiles on the rat's thermoregulatory response to cold.

Unrestrained rats were subjected to a 1-h period of cold exposure during centrifugation to characterize their ability to regulate core temperature (Tc) and to determine if this regulation was dependent on the amplitude of the hypergravic field before the cold exposure. Tc was measured in unrestrained rats by the use of a thermistor implanted adjacent to the carotid artery. One hour of cold exposure applied over the last hour of either a 1-, 4-, 7-, 13-, 19-. 25-, or 37-h period at 3 G evoked a decrease in Tc of about 3 degrees C. This fall in Tc was significantly greater than changes in Tc in cold-exposed rats at 1 G. No significant differences were found between the measured decreases in Tc observed for the 1-h cold exposures during the first 37 h at 3 G. However, when rats were subjected concurrently to cold and acceleration after 8 days at 3 G, they exhibited a smaller fall in Tc, suggesting a partial recovery of the acceleration-induced impairment of temperature regulation. In another series of experiments, the gravitational field profile was changed in amplitude in three different ways during the 3-h period preceding the 1-h cold exposure at 3 G. Despite the different gravitation field profiles before cold, the magnitude of the fall in Tc over the 1-h period of cold exposure was the same of all cases. These results suggest that the thermoregulatory impairment has a rapid onset, it a manifestation of an ongoing effect of hypergravity, and is not dependent on the prior G profile. The inability of rats to maintain Tc when cold exposed may be transient as indicated by the partial recovery of regulation by the 8th day.

Animals↗