New technique for measurement of left ventricular pressure in conscious mice

• Published in: American journal of physiology. Heart and circulatory physiology 2004-03, Vol.286 (3), p.H1208-H1215
• Main Authors: Ishizaka, Shinji, Sievers, Richard E, Zhu, Bo-Qing, Rodrigo, Manoj C, Joho, Shuji, Foster, Elyse, Simpson, Paul C, Grossman, William
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists; Anesthesia, Inhalation - methods; Anesthetics, Dissociative - pharmacology; Anesthetics, Inhalation - pharmacology; Animals; Aorta; Catheterization - methods; Consciousness; Echocardiography; Female; Isoflurane - pharmacology; Ketamine - pharmacology; Mice; Mice, Inbred C57BL; Models, Animal; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; Ventricular Pressure - drug effects; Ventricular Pressure - physiology; Xylazine - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00011.2003

1 Cardiology Division, Department of Medicine, and Cardiovascular Research Institute, University of California; and 2 Veterans Affairs Medical Center, San Francisco, California 94143-0124 Submitted 7 January 2003 ; accepted in final form 5 October 2003 Concern about the effects of anesthesia on physiological measurements led us to develop methodology to assess left ventricular (LV) pressure in conscious mice. Polyethylene-50 tubing filled with heparinized saline was implanted in the LV cavity through its apex via an abdominal approach and exteriorized to the back of the animal. This surgery was done under anesthesia with either an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (5 mg/kg) (K+X) in 11 mice or isoflurane (ISF; 1.5 vol%) by inhalation in 14 mice. Postoperatively, mice were trained daily to lie quietly head first in a plastic cone. LV pressure, the first derivative of LV pressure (dP/d t ), and heart rate (HR) in the conscious state were compared between the two groups at 3 days and 1 wk after recovery from surgery using a 1.4-Fr Millar catheter inserted into the LV through the tubing, with the mice lying quietly in the plastic cone. Acutely during anesthesia, K+X decreased HR (from 698 to 298 beats/min), LV systolic pressure (from 107 to 65 mmHg), and maximal dP/d t (dP/d t max ) (from 15,724 to 4,445 mmHg/s), all P < 0.01. Similar but less marked negative chronotropic and inotropic effects were seen with ISF. HR and dP/d t max were decreased significantly in K+X mice 3 days after surgery compared with those anesthetized with ISF (655 vs. 711 beats/min, P < 0.05; 14,448 vs. 18,048 mmHg/s, P < 0.001) but increased to the same level as in ISF mice 1 wk after surgery. In ISF mice, recovery of function occurred rapidly and there were no differences in LV variables between 3 days and 1 wk. LV pressure and dP/d t 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 wk postanesthesia. left ventricular hemodynamics; first derivative of left ventricular pressure; anesthesia; mouse physiology Address for reprint requests and other correspondence: W. Grossman, Cardiology Div., Dept. of Medicine, Univ. of California-San Francisco, 505 Parnassus Ave., Box 0124,