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A simple and novel method to monitor breathing and heart rate in awake and urethane-anesthetized newborn rodents.

Zehendner CM, Luhmann HJ, Yang JW - PLoS ONE (2013)

Bottom Line: Rodents are most useful models to study physiological and pathophysiological processes in early development, because they are born in a relatively immature state.However, only few techniques are available to monitor non-invasively heart frequency and respiratory rate in neonatal rodents without restraining or hindering access to the animal.Here we describe experimental procedures that allow monitoring of heart frequency by electrocardiography (ECG) and breathing rate with a piezoelectric transducer (PZT) element without hindering access to the animal.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. Zehendner@uni-mainz.de

ABSTRACT
Rodents are most useful models to study physiological and pathophysiological processes in early development, because they are born in a relatively immature state. However, only few techniques are available to monitor non-invasively heart frequency and respiratory rate in neonatal rodents without restraining or hindering access to the animal. Here we describe experimental procedures that allow monitoring of heart frequency by electrocardiography (ECG) and breathing rate with a piezoelectric transducer (PZT) element without hindering access to the animal. These techniques can be easily installed and are used in the present study in unrestrained awake and anesthetized neonatal C57/Bl6 mice and Wistar rats between postnatal day 0 and 7. In line with previous reports from awake rodents we demonstrate that heart rate in rats and mice increases during the first postnatal week. Respiratory frequency did not differ between both species, but heart rate was significantly higher in mice than in rats. Further our data indicate that urethane, an agent that is widely used for anesthesia, induces a hypoventilation in neonates whilst heart rate remains unaffected at a dose of 1 g per kg body weight. Of note, hypoventilation induced by urethane was not detected in rats at postnatal 0/1. To verify the detected hypoventilation we performed blood gas analyses. We detected a respiratory acidosis reflected by a lower pH and elevated level in CO2 tension (pCO2) in both species upon urethane treatment. Furthermore we found that metabolism of urethane is different in P0/1 mice and rats and between P0/1 and P6/7 in both species. Our findings underline the usefulness of monitoring basic cardio-respiratory parameters in neonates during anesthesia. In addition our study gives information on developmental changes in heart and breathing frequency in newborn mice and rats and the effects of urethane in both species during the first postnatal week.

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Urethane anesthesia results in respiratory acidosis in P6/7 mice and rats.Blood gas analyses revealed a significant reduction in pH during urethane-anesthesia in P6/7 mice (A) and elevated pCO2 levels (B). Similar values were obtained in rats. Here, urethane administration resulted in a diminished pH (C) and was accompanied by an increased pCO2 (D). Box and whisker plots (displaying 75th percentile, median and 25th percentile) are shown, whiskers indicate minimum and maximum values. **P<0.01, ***P<0.001.
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pone-0062628-g004: Urethane anesthesia results in respiratory acidosis in P6/7 mice and rats.Blood gas analyses revealed a significant reduction in pH during urethane-anesthesia in P6/7 mice (A) and elevated pCO2 levels (B). Similar values were obtained in rats. Here, urethane administration resulted in a diminished pH (C) and was accompanied by an increased pCO2 (D). Box and whisker plots (displaying 75th percentile, median and 25th percentile) are shown, whiskers indicate minimum and maximum values. **P<0.01, ***P<0.001.

Mentions: In our study we measured thoracic or abdominal movements as parameters for breathing. It is known that excursions of the thorax and abdomen correlate to breathing frequency and activity of the phrenic nerve [15]. However, to strengthen the significance of our finding that RPM is reduced upon urethane administration we performed blood gas analyses. It is known that hypoventilation results in perturbances in acid-base status due to retention of CO2[16]. Urethane lowered RPM in both mice and rats at P6/7. Thus we analyzed blood gases in this age group to evaluate if the detected reduction on RPM by the piezoelectric technique relates to a reduction in lung ventilation. We found that urethane significantly lowered pH and increased CO2 partial pressure in both species (mice sham P6/7∶7.39±0.01 pH vs. mice urethane P6/7∶7.25±0.05 pH; mice sham P6/7∶49.1±0.78 mmHg pCO2 vs. mice urethane P6/7∶73.58±9.02 mmHg pCO2, n = 3–4 animals, P<0.01 in all groups, Figure 4 A, B, Table 1; rats sham P6/7∶7.44±0.03 pH vs. rats urethane P6/7∶7.34±0.02 pH, P<0.01; rats sham P6/7∶45.43±3.64 mmHg pCO2 vs. rats urethane P6/7∶60.58±3.39 mmHg pCO2, n = 4 animals, P<0.001, Figure 4C, D, Table 2). Base excess in extracellular fluid (BEECF) and standard bicarbonate (HCO3−standard) levels did not significantly differ between sham and urethane treated animals (Tables 1,2). We detected an increase of blood glucose levels in both species upon urethane treatment, however this increase was significantly elevated only in rats but not in mice (Tables 1,2). Additional data on levels of hemoglobin, blood glucose and bodyweight are displayed in tables 1 and 2.


A simple and novel method to monitor breathing and heart rate in awake and urethane-anesthetized newborn rodents.

Zehendner CM, Luhmann HJ, Yang JW - PLoS ONE (2013)

Urethane anesthesia results in respiratory acidosis in P6/7 mice and rats.Blood gas analyses revealed a significant reduction in pH during urethane-anesthesia in P6/7 mice (A) and elevated pCO2 levels (B). Similar values were obtained in rats. Here, urethane administration resulted in a diminished pH (C) and was accompanied by an increased pCO2 (D). Box and whisker plots (displaying 75th percentile, median and 25th percentile) are shown, whiskers indicate minimum and maximum values. **P<0.01, ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643944&req=5

pone-0062628-g004: Urethane anesthesia results in respiratory acidosis in P6/7 mice and rats.Blood gas analyses revealed a significant reduction in pH during urethane-anesthesia in P6/7 mice (A) and elevated pCO2 levels (B). Similar values were obtained in rats. Here, urethane administration resulted in a diminished pH (C) and was accompanied by an increased pCO2 (D). Box and whisker plots (displaying 75th percentile, median and 25th percentile) are shown, whiskers indicate minimum and maximum values. **P<0.01, ***P<0.001.
Mentions: In our study we measured thoracic or abdominal movements as parameters for breathing. It is known that excursions of the thorax and abdomen correlate to breathing frequency and activity of the phrenic nerve [15]. However, to strengthen the significance of our finding that RPM is reduced upon urethane administration we performed blood gas analyses. It is known that hypoventilation results in perturbances in acid-base status due to retention of CO2[16]. Urethane lowered RPM in both mice and rats at P6/7. Thus we analyzed blood gases in this age group to evaluate if the detected reduction on RPM by the piezoelectric technique relates to a reduction in lung ventilation. We found that urethane significantly lowered pH and increased CO2 partial pressure in both species (mice sham P6/7∶7.39±0.01 pH vs. mice urethane P6/7∶7.25±0.05 pH; mice sham P6/7∶49.1±0.78 mmHg pCO2 vs. mice urethane P6/7∶73.58±9.02 mmHg pCO2, n = 3–4 animals, P<0.01 in all groups, Figure 4 A, B, Table 1; rats sham P6/7∶7.44±0.03 pH vs. rats urethane P6/7∶7.34±0.02 pH, P<0.01; rats sham P6/7∶45.43±3.64 mmHg pCO2 vs. rats urethane P6/7∶60.58±3.39 mmHg pCO2, n = 4 animals, P<0.001, Figure 4C, D, Table 2). Base excess in extracellular fluid (BEECF) and standard bicarbonate (HCO3−standard) levels did not significantly differ between sham and urethane treated animals (Tables 1,2). We detected an increase of blood glucose levels in both species upon urethane treatment, however this increase was significantly elevated only in rats but not in mice (Tables 1,2). Additional data on levels of hemoglobin, blood glucose and bodyweight are displayed in tables 1 and 2.

Bottom Line: Rodents are most useful models to study physiological and pathophysiological processes in early development, because they are born in a relatively immature state.However, only few techniques are available to monitor non-invasively heart frequency and respiratory rate in neonatal rodents without restraining or hindering access to the animal.Here we describe experimental procedures that allow monitoring of heart frequency by electrocardiography (ECG) and breathing rate with a piezoelectric transducer (PZT) element without hindering access to the animal.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. Zehendner@uni-mainz.de

ABSTRACT
Rodents are most useful models to study physiological and pathophysiological processes in early development, because they are born in a relatively immature state. However, only few techniques are available to monitor non-invasively heart frequency and respiratory rate in neonatal rodents without restraining or hindering access to the animal. Here we describe experimental procedures that allow monitoring of heart frequency by electrocardiography (ECG) and breathing rate with a piezoelectric transducer (PZT) element without hindering access to the animal. These techniques can be easily installed and are used in the present study in unrestrained awake and anesthetized neonatal C57/Bl6 mice and Wistar rats between postnatal day 0 and 7. In line with previous reports from awake rodents we demonstrate that heart rate in rats and mice increases during the first postnatal week. Respiratory frequency did not differ between both species, but heart rate was significantly higher in mice than in rats. Further our data indicate that urethane, an agent that is widely used for anesthesia, induces a hypoventilation in neonates whilst heart rate remains unaffected at a dose of 1 g per kg body weight. Of note, hypoventilation induced by urethane was not detected in rats at postnatal 0/1. To verify the detected hypoventilation we performed blood gas analyses. We detected a respiratory acidosis reflected by a lower pH and elevated level in CO2 tension (pCO2) in both species upon urethane treatment. Furthermore we found that metabolism of urethane is different in P0/1 mice and rats and between P0/1 and P6/7 in both species. Our findings underline the usefulness of monitoring basic cardio-respiratory parameters in neonates during anesthesia. In addition our study gives information on developmental changes in heart and breathing frequency in newborn mice and rats and the effects of urethane in both species during the first postnatal week.

Show MeSH
Related in: MedlinePlus