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PubMed2000

Permissive hypercapnia impairs pulmonary gas exchange in the acute respiratory distress syndrome.

Current recommendations for mechanical ventilation in the acute respiratory distress syndrome (ARDS) include the use of small tidal volumes (VT), even at the cost of respiratory acidosis. We evaluated the effects of this permissive hypercapnia on pulmonary gas exchange with the multiple inert gas elimination technique (MIGET) in eight patients with ARDS. After making baseline measurements, we induced permissive hypercapnia by reducing VT from 10 +/- 2 ml/kg to 6 +/- 1 ml/kg (mean +/- SEM) at constant positive end-expiratory pressure. After restoration of initial VT, we infused dobutamine to increase cardiac output (Q) by the same amount as with hypercapnia. Permissive hypercapnia increased Q by an average of 1.4 L. min(-)(1). m(2), decreased arterial oxygen tension from 109 +/- 10 mm Hg to 92 +/- 11 mm Hg (p < 0.05), markedly increased true shunt (Q S/Q T), from 32 +/- 6% to 48 +/- 5% (p < 0.0001), and had no effect on the dispersion of VA/Q.VA/Q. On reinstatement of baseline V T with maintenance of a high Q, Q S/Q T remained increased, to 38 +/- 6% (p < 0.05), and Pa(O(2 ))remained decreased, to 93 +/- 4 mm Hg (p < 0. 05). These results agreed with effects of changes in VT and Q predicted by the mathematical lung model of the MIGET. We conclude that permissive hypercapnia increases pulmonary shunt, and that deterioration in gas exchange is explained by the combined effects of increased Q and decreased alveolar ventilation.

Adolescent↗
PubMed1996

Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome.

OBJECTIVE: To compare the effectiveness of perfluorocarbon-associated gas exchange to volume controlled positive pressure breathing in supporting gas exchange, lung mechanics, and survival in an acute lung injury model. DESIGN: A prospective, randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Eighteen piglets were randomized to receive perfluorcarbon-associated gas exchange with perflubron (n=10) or volume controlled continuous positive pressure breathing (n=8) after acute lung injury was induced by oleic acid infusion (0.15 mL/kg iv). MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and lung mechanics were measured every 15 mins during a 3-hr study period. All animals developed a metabolic and a respiratory acidosis during the infusion of oleic acid. Following randomization, the volume controlled positive pressure breathing group developed a profound acidosis (p<.05), while pH did not change in the perfluorocarbon-associated gas exchange group. Within 15 mins of initiating perfluorocarbon-associated gas exchange, oxygenation increased from a PaO2 of 52 +/- 12 torr (6.92 +/- 1.60 kPa) to 151 +/- 93 torr (20.0 +/- 12.4 kPa) and continued to improve throughout the study (p<.05). Animals that received volume controlled positive pressure breathing remained hypoxic with no appreciable change in PaO2. Although both groups developed hypercarbia during oleic acid infusion, PaCO2, steadily increased over time in the control group (p<.01). Static lung compliance significantly increased postrandomization (60 mins) in the animals supported by perflurocarbon-associated gas exchange (p<.05), whereas it remained unchanged over time in the volume controlled positive pressure breathing group. However, survival was significantly higher in the perfluorocarbon-associated gas exchange group with eight (80%) of ten animals surviving the entire study period. Only two (25%) of the eight animals in the volume controlled positive pressure breathing group were alive at the end of the study period (log-rank statistic, p=.013). CONCLUSIONS: Perflurocarbon-associated gas exchange enhanced gas exchange, pulmonary mechanics, and survival in this model of acute lung injury.

Animals↗
PubMed1995

[The effect of mechanical ventilation, thoracotomy, and one-lung respiration on intrapulmonary perfusion distribution. An animal experimental study].

The physiological pattern of regional pulmonary blood flow is mainly determined by the relationship of pulmonary arterial, venous, and alveolar pressures. Changes in alveolar pressure and pulmonary geometry may therefore be expected to influence regional perfusion, which is a key determinant of pulmonary gas exchange. Unilateral thoracotomy is usually performed with the patient in the lateral decubitus position. The present study examined the influence of mechanical factors on regional pulmonary blood flow distribution in rabbits in the lateral decubitus position during normoxia and unilateral hypoxia. METHODS. Anaesthetised white New Zealand rabbits (n = 8) weighing 2200-3900 g (mean = 2860 g) received central venous injections of radioactive microspheres while in the left lateral decubitus position during spontaneous breathing (SB) and during mechanical ventilation (two-lung ventilation, 2LV), under closed (2LVC) and open chest (2LVT) conditions, as well as during unilateral hypoxia of the nondependent lung induced by nitrogen inflation (1LVN) or atelectasis (1LVA). The method used for one-lung ventilation (1LV) has been previously described in detail. Arterial, central venous, and pulmonary arterial pressures were recorded continuously. Lungs were excised, dried in the inflated state, and cut into 16 sagittal slices, which were further divided into lobar components, the lower lobes into center and periphery. The radioactivity of each specimen was measured in a gamma-counter; perfusion of the individual tissue specimens was quantified using the software program MIC III. The Friedman test followed by paired comparisons according to Conover was used for statistical analysis of differences between the experimental phases. Perfusion of central and peripheral parts of isogravitational slices was compared by use of the Wilcoxon matched pairs test. Values are given as means +/- SE; the level of significance was P < 0.05 unless otherwise indicated. RESULTS AND DISCUSSION. Haemodynamic parameters did not differ significantly between the experimental phases (Table 1). Compared to 2LV, a significant increase in venous admixture (P < 0.05) and a corresponding decrease in PaO2 (P < 0.01) were observed during 1LV. This effect was significantly more pronounced during 1LVA as compared to 1LVN (P < 0.01). Since inspiratory pressure was kept constant throughout the experiments, moderate respiratory acidosis developed during both phases of 1LV. Regional perfusion (Qr) of the nondependent lung was slightly reduced during 2LVC compared to SB and 2LVT. One-lung ventilation induced a significant decrease in perfusion of the hypoxic lung (P < 0.001 1LVN, 1LVA vs. SB,2LVC,2LVT). In accordance with the data obtained from blood gas analysis and oximetry, this effect was more pronounced during N2 insufflation than during atelectasis (P < 0.01 1LVN vs. 1LVA). Among the factors that may account for this effect, PaCO2 did not differ significantly between both phases of 1LV. During N2 insufflation PO2 at the hypoxia-sensitive site is lower than during atelectasis, where it equals mixed-versus PO2 (PvO2). The difference in local PO2 is unlikely, however, to have caused the changes in regional perfusion between 1LVN and 1LVA, since PvO2 was as low as 40 mmHg during 1LVA and the pulmonary vascular response to hypoxia has been found to reach its maximum in this PO2 range [2, 11]. Enhanced redistribution of regional perfusion during 1LVN as compared to 1LVA is therefore most likely attributed to differences in alveolar pressure and pulmonary geometry. Apart from a radial perfusion gradient in the right lower lobe during 2LVC and 2LVT, no isogravitational Qr gradients were observed. CONCLUSION. We conclude that controlled mechanical ventilation in the lateral decubitus position causes only minor changes in vertical blood flow distribution.

Animals↗
PubMed2006

Is high-frequency ventilation more beneficial than low-tidal volume conventional ventilation?

The ventilator goals of the ICU clinician faced with caring for a critically ill child who has ALI/ARDS remain relatively simple: provide adequate ventilation and oxygenation without overdistending alveoli or furthering lung injury. How one obtains these goals is much less simple. The current use of CV calls for the use of relatively low V(T)s and limiting peak inspiratory pressure and plateau pressure while accepting a certain degree of respiratory acidosis. The ICU team can also often achieve these same goals with HFOV. How, then, does one use evidenced-based medicine to pick the best mode of mechanical ventilation for a particular patient? The answer is controversial, to say the least. Does one start with a gentle, open-lung mode of CV then switch to HFOV if the child deteriorates? Or does one use HFOV from the very early stages of ALI? Animal data appear to point to advantages of HFOV when used early in the course of ALI. Most of these studies report a beneficial effect of HFOV when applied on expanded lungs in the early stages of the disease process. These beneficial effects encompass improved gas exchange, oxygenation, lung tissue morphology and pulmonary mechanics. The studies by Arnold and colleagues in the pediatric population also help to answer our questions. In their work, the early initiation of HFOV was associated with improved gas exchange and a trend toward a lower mortality. In adults, Derdak and colleagues demonstrated the superiority of HFOV in terms of gas exchange and oxygenation; however, no statistical significant difference was found for mortality. So, where is the clinician left after a review of these data? It would appear that (1) low-V(T) CV remains a cornerstone of therapy for the pediatric patient who has ALI/ARDS; (2) HFOV is a safe and well-tolerated mode of mechanical ventilation; (3) early use of HFOV (as opposed to the rescue use of this mode) may be of benefit based on animal and human data; and (4) like so many areas of pediatric critical care, clinicians must await new data and trials that will help them continue to improve the care they provide.

Animals↗
PubMed2001

The relative roles of external and internal CO(2) versus H(+) in eliciting the cardiorespiratory responses of Salmo salar and Squalus acanthias to hypercarbia.

Fish breathing hypercarbic water encounter externally elevated P(CO(2)) and proton levels ([H(+)]) and experience an associated internal respiratory acidosis, an elevation of blood P(CO(2)) and [H(+)]. The objective of the present study was to assess the potential relative contributions of CO(2) versus H(+) in promoting the cardiorespiratory responses of dogfish (Squalus acanthias) and Atlantic salmon (Salmo salar) to hypercarbia and to evaluate the relative contributions of externally versus internally oriented receptors in dogfish. In dogfish, the preferential stimulation of externally oriented branchial chemoreceptors using bolus injections (50 ml kg(-1)) of CO(2)-enriched (4 % CO(2)) sea water into the buccal cavity caused marked cardiorespiratory responses including bradycardia (-4.1+/-0.9 min(-1)), a reduction in cardiac output (-3.2+/-0.6 ml min(-1) kg(-1)), an increase in systemic vascular resistance (+0.3+/-0.2 mmHg ml min(-1) kg(-1)), arterial hypotension (-1.6+/-0.2 mmHg) and an increase in breathing amplitude (+0.3+/-0.09 mmHg) (means +/- S.E.M., N=9-11). Similar injections of CO(2)-free sea water acidified to the corresponding pH of the hypercarbic water (pH 6.3) did not significantly affect any of the measured cardiorespiratory variables (when compared with control injections). To preferentially stimulate putative internal CO(2)/H(+) chemoreceptors, hypercarbic saline (4 % CO(2)) was injected (2 ml kg(-1)) into the caudal vein. Apart from an increase in arterial blood pressure caused by volume loading, internally injected CO(2) was without effect on any measured variable. In salmon, injection of hypercarbic water into the buccal cavity caused a bradycardia (-13.9+/-3.8 min(-1)), a decrease in cardiac output (-5.3+/-1.2 ml min(-1) kg(-1)), an increase in systemic resistance (0.33+/-0.08 mmHg ml min(-1) kg(-1)) and increases in breathing frequency (9.7+/-2.2 min(-1)) and amplitude (1.2+/-0.2 mmHg) (means +/- S.E.M., N=8-12). Apart from a small increase in breathing amplitude (0.4+/-0.1 mmHg), these cardiorespiratory responses were not observed after injection of acidified water. These results demonstrate that, in dogfish and salmon, the external chemoreceptors linked to the initiation of cardiorespiratory responses during hypercarbia are predominantly stimulated by the increase in water P(CO(2)) rather than by the accompanying decrease in water pH. Furthermore, in dogfish, the cardiorespiratory responses to hypercarbia are probably exclusively derived from the stimulation of external CO(2) chemoreceptors, with no apparent contribution from internally oriented receptors.

Animals↗
PubMed2001

Overview of current therapies.

The therapy of chronic obstructive pulmonary disease has been comprehensively reviewed in a number of international treatment guidelines. There is consensus about what elements should be included, but the purposes of therapy and the timing of its introduction remain poorly defined. Major factors limiting effective treatment beyond those associated with the biology of the condition itself are poor diagnostic methodology, failure to identify relevant co-morbidities and reluctance to devote appropriate resources to maximizing patient gain. Too many patients are identified at the end-stages of their illness when treatment is relatively limited. Most therapy is directed at reducing the impact of the disease in terms of symptoms, exercise performance and exacerbations on the individual and only smoking cessation modifies the evolution of the disease. Treatment of hypoxaemic patients with domiciliary oxygen improves mortality and slows the development of pulmonary hypertension. Effective smoking cessation is relevant at all stages of the disease. It depends on the willingness of the individual to participate, and quit rates can be improved by the use of nicotine replacement therapy and possibly bupropion. Inhaled bronchodilator drugs palliate symptoms and improve exercise performance in pharmacologically predictable ways. In patients with severe disease, reduction in operating lung volumes is more important than 'bronchodilitation' and is better sustained by long acting beta agonists and anticholinergics. Inhaled corticosteroids reduce exacerbation rates and improve health status in established disease but do not modify disease evolution. Pulmonary rehabilitation improves exercise performance and health status without changing underlying pulmonary mechanics. Whether hospitalizations and exacerbations can be modified is still to be established. Nutritional therapy is in its infancy but calorie supplementation alone is insufficient to improve patient well being. Selected individuals can undergo lung volume reduction surgery with benefits extending up to two years but the risks are dependent on the skill of the operators and the appropriateness of patient selection. Lung transplantation is symptomatically helpful but does not modify the natural history of the disease. Hospitalization due to exacerbations of disease is frequent and their treatment with bronchodilators, antibiotics and corticosteroids now have a basis in randomized trial data. Mortality reflects the incidence of respiratory acidosis and noninvasive ventilation has a role in safely managing patients outside of the intensive care unit. Effective prevention of exacerbation should be possible with newer antiviral agents but data are presently lacking.

Administration, Inhalation↗
PubMed1988

Effects of tromethamine and sodium bicarbonate buffers during cardiac resuscitation.

The effects on cardiac resuscitability of iso-osmolal solutions of tris-hydroxymethyl-aminomethane (tromethamine), sodium bicarbonate (NaHCO3) and sodium chloride placebo were compared in 30 domestic pigs using a well-established model of electrically induced cardiac arrest and resuscitation. We hypothesized that a carbon dioxide (CO2) consuming buffer like tromethamine would reduce and sodium bicarbonate would increase the respiratory acidosis of mixed venous blood, which had recently been demonstrated in our laboratory, Tromethamine did decrease and sodium bicarbonate did increase both arterial and mixed venous CO2 during cardiopulmonary resuscitation (CPR). Both concentrations of end-tidal CO2 and coronary venous PCO2 were significantly lower after tromethamine than after bicarbonate. However, tromethamine produced an unexpected vasodilator effect with reduction of mean aortic and coronary perfusion pressures to levels that are known to reduce resuscitability and survival independently of its buffer action. Neither resuscitability nor survival was altered by bicarbonate therapy in comparison with sodium chloride placebo.

Acid-Base Equilibrium↗
PubMed1994

Effects of medium acidification by alteration of carbon dioxide or bicarbonate concentrations on the resorptive activity of rat osteoclasts.

Little is known about the extracellular conditions or factors that stimulate mature osteoclasts to resorb mineralized tissues. Isolated mammalian osteoclasts are strongly stimulated by protons in HEPES-buffered culture media in the absence of CO2 and HCO3-, but it has been reported that cell-mediated Ca2+ release from bone organ cultures is increased only when media are acidified by reduction of HCO3- concentrations, and not by increasing PCO2 (considered models of metabolic and respiratory acidosis, respectively). We investigated this question using disaggregated rat osteoclasts cultured on dentin slices for 24 h. The number of pits resorbed per osteoclast was stimulated in media acidified by manipulation of either HCO3- or CO2 concentrations. In experiments in which incubator CO2 was varied, resorption was almost abolished in the presence of 2.5% CO2 at pH 7.61 but increased in a stepwise manner up to 1.3 pits per osteoclast when dentin slices were cultured with 10% CO2 at pH 6.97. The depths and widths of pits, measured using a confocal laser reflection microscope, also tended to increase with increasing CO2 and decreasing pH. However, in experiments where pH was lowered by reducing medium HCO3-, pit size decreased, partially offsetting the increased number of pits resorbed per osteoclast. These findings suggest that rat osteoclasts may be more sensitive to stimulation by CO2 acidosis than by HCO3- acidosis, at least in the short term, and may possibly reflect local regulatory processes in bone.

Acid Phosphatase↗
PubMed1994

Acid-base status of a pulmonate land snail (Helix aspersa) and a prosobranch amphibious snail (Pomacea bridgesi) during dormancy.

Changes in metabolism and acid-base status were compared during dormancy in the pulmonate land snail Helix aspersa and a prosobranch amphibious snail Pomacea bridgesi. The typical condition of higher blood PCO2 and bicarbonate levels for air-breathing versus water-breathing vertebrates was shown for the two snail species. When exposed to dry air for 24 hr, both species depressed oxygen uptake by about 65%. In Pomacea, hypercapnia (increase in hemolymph PCO2 from 5.5 to 18 torr) resulting from dormancy produced no significant change in pH due to large increases in bicarbonate (over 17 mmol/l). In Helix, on the other hand, hypercapnia (increase in hemolymph PCO2 from 13 to 18 torr) resulting from dormancy produced a significant decrease in pH and a less than 7 mmol/l increase in bicarbonate. Pre-existing high levels of bicarbonate in Helix may prevent compensation of hypercapnia resulting from dormancy, similar to the case described for air-breathing vertebrates. Complete compensation of respiratory acidosis during the first 24 hr of dormancy in Pomacea suggests that metabolic rate suppression is independent of pH.

Acid-Base Equilibrium↗
PubMed2003

Compensation for hypercapnia by a euryhaline elasmobranch: effect of salinity and roles of gills and kidneys in fresh water.

Specimens of the euryhaline elasmobranch, Dasyatis sabina were acclimated to seawater and fresh water, and exposed to normocapnic (air) and hypercapnic (1% CO2 in air) environmental water. Blood pH, PCO2, and [HCO3-], as well as whole-animal net-acid excretion, were measured for up to 24 h of hypercapnia. In a separate experimental series, urine was collected from freshwater acclimated stingrays during 8 h of normocapnia and hypercapnia. Stingrays in both salinities at least partially compensated for the respiratory acidosis by accumulating HCO3- in their extracellular spaces. The degree of compensation for blood pH was 88.5% in seawater, but only 31.0% in fresh water after 24 h of hypercapnia. Whole-animal net-acid excretion was also greater in seawater than in fresh water, as was the increase in extracellular fluid [HCO3-]. Mean urinary net-acid excretion rates were slightly negative, and never increased above normocapnic control rates during hypercapnia. Since whole-animal net-acid excretion rates increased with blood [HCO3-], and urinary excretion was always negative, the gills were probably the primary organ responsible for compensation from environmental hypercapnia. The faster, and more complete, compensation for hypercapnia in seawater than in fresh water for this euryhaline elasmobranch is consistent with data for euryhaline teleosts, and probably reflects Na+-dependent mechanisms of branchial acid excretion.

Animals↗
PubMed1990

Ultrastructure and organization of circumventricular organs and endolymphatic tubules in the treefrog, Hyla versicolor.

The morphology and anatomical relationship of the paraphysis, anterior choroid plexus, and endolymphatic tubules of Hyla versicolor suggest that these structures may act as a functional unit to regulate composition of the cerebrospinal fluid (CSF). Ependymal cells of both the paraphysis and the choroid plexus exhibit ultrastructural features (an extensive microvillar border, large intercellular spaces containing an amorphous material, and apically located mitochondria) which indicate active exchange between the blood and CSF. Mast cells (which may play a role in regulating vascular permeability) also occur on the brush border. The tubules of the endolymphatic sacs were found to lie in close relation with the dorsal portion of the paraphysis. The endolymphatic organ is known to play a role in systemic buffering during respiratory acidosis and may influence Na/K fluxes via calcium release. The association of the paraphysis with the endolymphatic tubules may therefore represent an important mechanism for ion regulation in the CSF of amphibians. The ultrastructure of the pineal organ agrees with descriptions for other species. No pineal stalk was present. Photoreceptor inner and outer segments project into a central lumen continuous with the third ventricle. Outer segments show signs of disorganization. Photoreceptor/neural dendrite contacts involve synaptic ribbons and conventional synapses.

Animals↗
PubMed1995

Inhaled nitric oxide improves oxygenation in piglets with meconium aspiration.

We hypothesized that nitric oxide (NO) inhalation in a model of meconium aspiration in newborn piglets would decrease pulmonary vascular resistance. Seven neonatal piglets were obtained at less than 48 hr of age and instrumented under fentanyl anesthesia. Inhaled NO (40 parts per million) was administered during normoxia and again after hypoxia was induced by reducing FiO2 to 0.13. During normoxia NO inhalation caused a fall in pulmonary artery pressure from a mean of 3.15 (SD 0.8) kPa to 2.84 (SD 0.7) kPa (P < 0.01). Hypoxia (mean arterial O2 saturation 35%) increased PA pressures to a mean of 5.4 (SD 1.6) kPa and NO administration during hypoxia decreased PA pressures to 3.6 (SD 1.2) kPa (P < 0.001). In order to determine the effects of NO in a model of meconium aspiration, 6 to 7 mL/kg of 20% human meconium in normal saline was instilled into the trachea. This procedure induced hypoxemia (mean SaO2 43.4%, SD 19), respiratory acidosis, (mean PaCO2 12.1 kPa, SD 0.5; mean pH 7.04, SD 0.03), and pulmonary arterial hypertension (mean pulmonary artery pressure 6.0 kPa, SD 1.3) despite ventilation with 90% oxygen. Inhaled NO was then administered in concentrations of 5, 10, 20, 30, 40, 60, and 80 parts per million in random order according to a Latin square design.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Modulation of synaptic transmission at low temperatures by hibernation-related changes in ionic microenvironment in hippocampal slices of golden hamsters.

In hamsters, the entrance into hibernation is associated with a respiratory acidosis and elevation of the blood plasma concentrations of potassium, calcium, and magnesium. To investigate the effects of presumed hibernation-related ionic changes in the brain interstitium on neuronal function, the transmission properties of hippocampal slices prepared from golden hamsters were studied at low temperatures in vitro. Slices were investigated at 15-20 degrees C in artificial cerebrospinal fluid (ACSF) of variable composition (K+, 3-5 mM; Ca2+, 2-4 mM; Mg2+, 2-4 mM; pH 7.0-7.7). Population action potentials (population spikes, PS) of CA1 pyramidal cells were continuously evoked with 100-microseconds stimulus pulses delivered to the Schaffer collaterals/commissural fibers in intervals of 30 s. The PS amplitude was measured as a function of extracellular ion concentrations at given temperatures or as a function of temperature at a given ACSF composition. Elevation of [K+]o, [Mg2+]o, or [H+]o all reduced the PS amplitude at low temperatures, whereas elevation of [Ca2+]o increased the PS amplitude. In conclusion, changes in the ionic microenvironment occurring during entrance into hibernation presumably result in depression of synaptic transmission at low temperatures in the hamster hippocampus. The modulatory effect of ionic changes may be an important factor supporting a general depression of the brain during entrance into hibernation.

Animals↗
PubMed1996

Early action potential shortening in hypoxic hearts: role of chloride current(s) mediated by catecholamine release.

We tested the hypothesis that the early action potential shortening induced by hypoxia in perfused hearts is attributable to chloride currents activated or modulated by endogenous catecholamine release. Rabbit hearts perfused at 33 degrees C and paced at 2.5-2.8 Hz were used for membrane potential recordings with microelectrodes. Catecholamine depletion was induced with reserpine treatment. The effects of nadolol (10 microM), the stilbenedisulfonic acid derivatives DIDS (10 microM) and SITS (1 mM), and diphenylamine-2 carboxylate (DPC, 100 microM) on action potential characteristics were determined at different times during hypoxia. The effect of chloride transport blockers on the outward currents induced by 200 nM carbonyl cyanide (CCCP) or by 1 microM isoproterenol in isolated cells was also tested. In control hearts, action potential duration (APD) at 25 and 95% repolarization decreased by 50 +/- 9% and 32 +/- 7% respectively after 5 min of hypoxia. This effect was fully antagonized by reserpine pretreatment, by respiratory acidosis, and by nadolol when present from the beginning of hypoxia. None of these agents affected action potential characteristics in normoxia and nadolol had no effect when added after 15 min of hypoxia. Lowering the chloride concentration to 17.5 mM reproduced the effects of nadolol and reserpine. DIDS and SITS lengthened APD in normoxia and attenuated the early APD shortening in hypoxia. DPC had no effect in normoxia but fully counteracted APD shortening produced by isoproterenol or early hypoxia. In isolated cells, DIDS did not affect the glibenclamide sensitive outward current induced by CCCP and DPC blocked the isoproterenol induced current. The data suggest that in whole hearts, chloride currents mediated by endogenous catecholamine release are involved in the early action potential shortening induced by hypoxia with preservation of glycolysis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Determination of cardiorespiratory function and the optimum anesthetic regimen during laparoscopic surgery in the rat model.

BACKGROUND: The rat is increasingly being used in laparoscopic research yet the hemodynamic and respiratory effects of CO2 pneumoperitoneum have not been studied in this model. METHODS: Five Lewis rats were anesthetized with inhaled isoflurane (1.4-2.0%) and a 50% O2/50% N2O mixture by mask (ISO). Another five rats were anesthetized with 1 ml/kg intraperitoneal sodium pentobarbital (PB) and given 100% O2 by mask. Catheters were placed in the femoral artery and the right jugular vein and a thermistor probe was placed in the aortic arch. Heart rate (HR), blood pressure (MAP), cardiac index (CI), arterial pH, and PCO2 were measured at baseline and following 10, 20, and 30 min of 2 mmHg CO2 pneumoperitoneum. RESULTS: CO2 pneumoperitoneum had no effect on HR, MAP, CI, pH, or PCO2 in either the ISO or PB anesthetic groups. Comparing the two anesthetic groups, PB demonstrated a significantly higher MAP at all time points, a significantly higher PCO2 at baseline, and 10 min of pneumoperitoneum, a significantly lower pH at baseline, 10, and 30 minutes of pneumoperitoneum, and a significantly longer induction time (31 vs. 6 min). There was no difference in HR or CI between the two anesthetics. CONCLUSION: Low-pressure CO2 pneumoperitoneum up to 30 min in the spontaneously breathing rat does not significantly affect HR, MAP, CI, pH, or PCO2. Inhalational isoflurance/N2O anesthesia produces less hypertension and respiratory acidosis than intraperitoneal pentobarbital during pneumoperitoneum in the rat.

Anesthesia, Inhalation↗
PubMed1995

Laparoscopy without pneumoperitoneum. Effects of abdominal wall retraction versus carbon dioxide insufflation on hemodynamics and gas exchange in pigs.

Laparoscopic surgery with CO2 insufflation is associated with adverse effects on hemodynamics and gas exchange. The abdominal wall retractor (AWR) is an alternative for pneumoperitoneum. Hemodynamics and gas exchange during the use of an AWR were compared to those of CO2 pneumoperitoneum. In eight pigs subjected to 1 h of CO2 pneumoperitoneum or abdominal wall retraction, hemodynamics, gas exchange, and oxygen transport were studied in a randomized cross-over study design. The only change observed during abdominal wall retraction was mild respiratory alkalosis. In contrast, during CO2 pneumoperitoneum mean arterial blood pressure increased 13%, central filling pressures doubled, and a small increase in cardiac output was observed. Peak airway pressures increased 50%, end-tidal CO2 increased 20%, and respiratory acidosis was induced (arterial pH from 7.46 +/- 0.07 to 7.31 +/- 0.06 and pCO2 from 33 +/- 3 mmHg to 53 +/- 4 mmHg). Arterial PO2 decreased but mixed venous oxygen saturation and oxygen consumption were unaffected. In contrast with CO2 pneumoperitoneum, laparoscopy using abdominal wall retraction was not associated with adverse effects on hemodynamics or gas exchange.

Abdominal Muscles↗
PubMed1990

Pitfalls in acid/base experiments with conscious dogs.

Arterial pH and blood gases were measured at intervals in conscious dogs after their first human contact of the day. Blood was sampled through an indwelling catheter in the aorta without disturbing the animals. It appeared that in the first 90 min arterial PO2, oxygen saturation and haemoglobin concentration significantly declined. PCO2 and pH changed less consistently when the acid/base status of the dogs was normal, but when a non-respiratory acidosis was present there was a significant decrease in pH and a significant increase in PCO2. Arterial pH and blood gases were also measured before and after feeding the animals. It appeared that an appreciable metabolic alkalosis developed within 2 h after a meal. The "alkaline tide" was accompanied by a trend to higher values for PCO2. It is concluded that, after a period of seclusion, renewed human contact causes behavioural changes in a dog, which may result in appreciable transitory changes in arterial pH and blood gas values. Blood sampling from conscious dogs should therefore take place after a proper period of habituation; preferably, a few samples should be taken at intervals to check that a steady state has been reached. If possible, blood should be collected before feeding; in any case the relationship in time of blood sampling to feeding should be constant throughout.

Acid-Base Equilibrium↗
PubMed1993

Comparison of acid/base status in conscious and anaesthetized rats during acute hypothermia.

Acute hypothermia was surface-induced in unrestrained conscious rats at two different levels, moderate (30 degrees C TB) and severe (20 degrees C TB). Data reflecting the acid/base status were determined. The values obtained for moderate hypothermia were compared with the acid/base pattern observed during hypothermia induced by two different anaesthetics, sodium pentobarbital and urethane, at room temperature. Conscious, hypothermic animals developed an apparent respiratory alkalosis, with an increase in pHa (from 7.476 to 7.546 in moderate hypothermia and from 7.484 to 7.563 in severe hypothermia) correlated with a decrease in arterial bicarbonate levels (from 22.9 to 16.8 mmol l-1 and from 20.7 to 14.9 mmol l-1 respectively). Lactate increased slightly in conscious, severely hypothermic rats (1.02 mmol l-1). This acid/base pattern was clearly different from that seen in sodium pentobarbital (mild respiratory acidosis) and urethane-induced hypothermia (metabolic acidosis). These results suggest that conscious rats follow a pattern closer to that underlying the relative alkalinity shown by many poikilotherms than to that underlying the constant pH shown in hibernating mammals. This latter pattern, nevertheless, approaches that observed during moderate pentobarbital hypothermia and the acid/base pattern during shallow hypothermia in birds. Anaesthesia may interfere with the development of the processes that lead to the acid/base pattern observed in conscious animals.

Acid-Base Equilibrium↗