Experimental critical care in rats: gender differences in anesthesia, ventilation, and gas exchange.
OBJECTIVE
To compare normative ventilatory and gas-exchange data and anesthetic requirements in male and female rats subjected to critical care conditions.


METHODS
Prospective study.


METHODS
Critical care research laboratory in a hospital.


METHODS
Twenty-two age-matched young male and female rats (Sprague-Dawley, Long Evans strain).


METHODS
Anesthesia was induced with 65 and 45 mg/kg pentobarbital in male and female rats, respectively. The rats were then tracheostomized and cannulated in one femoral vein and artery. Anesthesia was maintained using 8-15 mg/kg/hr pentobarbital (iv) and controlled by continuous hemodynamic monitoring.


RESULTS
Normoxic baselines for breathing frequency, tidal volume, minute volume, inspiratory-to-expiratory ratio, inspiratory drive (tidal volume/inspiratory time), respiratory system compliance, peak airway pressure, and gas-exchange profiles were established. Ventilatory and gas-exchange responses to oxygen and CO2 were then determined by exposure to 10 mins of hyperoxia (100% oxygen), two levels of mild and severe hypercapnic hyperoxia (inspired Pco2 of 30 and 60 torr; 4 and 8 kPa), and two levels of mild and severe normocapnic hypoxia (inspired PO2 of 81 and 48 torr; 10.7 and 6.3 kPa). The average anesthetic requirement (during a 5- to 6-hr experiment) was 30% less in the female rats than in the male rats (p < .05). Female rats showed significantly lower breathing frequency, minute volume (mL/min/kg), and inspiratory drive (mL/kg/sec) during hyperoxia, mild and severe hypercapnia, and mild hypoxia. Pulmonary peak airway pressure was significantly lower in the female rats, consistent with a significantly higher weight-indexed compliance during all exposures. The female rats also had significantly higher inspiratory-to-expiratory ratio and higher PaCO2 with lower pH during normoxia, hyperoxia, and mild hypercapnia. These gender differences had no effect on PaO2, which was similar in all exposures.


CONCLUSIONS
There are significant gender differences in ventilation, gas exchange, and anesthetic requirements in rats subjected to critical care conditions. The gas-exchange values observed in these spontaneously breathing rats may represent the optimal levels attainable during pentobarbital anesthesia with normal lungs. They may serve as standards for ventilator settings in the rat models used for critical care studies.
Torbati
D
D
Division Critical Care Medicine, Miami Children's Hospital, FL 33155-3009, USA. dan.torbati@mch.com
Ramirez
J
J
Hon
E
E
Camacho
M T
MT
Sussmane
J B
JB
Raszynski
A
A
Wolfsdorf
J
J
D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D003422:Critical Care; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology; D018496:Hyperoxia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000187:drug effects; D012727:Sex Characteristics; D012737:Sex Factors
D000777:Anesthetics; D010424:Pentobarbital