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1 Cardiology Division, Department of Medicine, and the CVRI, UCSF, San Francisco, CA, USA
2 VA Medical Center, San Francisco, CA, USA
* To whom correspondence should be addressed. E-mail: grossman{at}medicine.ucsf.edu.
Concern about the effects of anesthesia on physiologic measurements led us to develop methodology to assess left ventricular (LV) pressure in conscious mice. PE-50 tubing filled with heparinized saline was implanted in the LV cavity through its apex via an abdominal approach, and exteriorized to the back. This surgery was done under anesthesia with either intraperitoneal injection of ketamine (80mg/kg) and xylazine (5mg/kg) (K+X) in 11 mice or isoflurane (ISF, 1.5 vol%) by inhalation in 14 mice. Post-operatively, mice were trained daily to lie quietly head first in a plastic cone. LV pressure, dP/dt and heart rate (HR) in conscious state were compared between the two groups at 3 days and 1 week following recovery from surgery using a 1.4 F Millar catheter inserted into the LV through the tubing with mice lying quietly in the plastic cone. Acutely during anesthesia, K+X decreased heart rate (HR) (698 to 298 bpm), LV systolic pressure (107 to 65 mmHg) and maximal dP/dt (dP/dtmax) (15,724 to 4,445 mmHg/sec), all p<0.01. Similar but less marked negative chronotropic and inotropic effects were seen with ISF. HR and dP/dtmax were decreased significantly in K+X mice 3 days after surgery compared to ISF (655 vs. 711 bpm; p<0.05, 14,448 vs. 18,048 mmHg/sec; p<0.001), but increased to the same level as in ISF mice 1 week after surgery. In ISF mice, recovery of function occurred rapidly and there were no differences in LV variables between 3 days and 1 week. LV pressure and its derivative can be measured in conscious mice with a micromanometer catheter inserted through tubing implanted permanently in the LV apex. Anesthesia with either K+X, or to a lesser extent ISF, depressed LV function acutely. This depression of function persisted for 3 days after surgery with K+X (but not ISF) and did not recover completely until 1 week post-anesthesia.
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