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Am J Physiol Heart Circ Physiol 292: H369-H377, 2007. First published August 11, 2006; doi:10.1152/ajpheart.00704.2006
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Left ventricular pressure-volume relationship in conscious mice

Shuji Joho,1 Shinji Ishizaka,1 Richard Sievers,1 Elyse Foster,1 Paul C. Simpson,2 and William Grossman1

1Cardiology Division, Department of Medicine, University of California; and 2Veterans Affairs Medical Center, San Francisco, California

Submitted 3 July 2006 ; accepted in final form 7 August 2006

With the availability of transgenic models, the mouse has become an increasingly important subject for genetic-hemodynamic studies. Recently, we developed a technique to measure left ventricular (LV) pressure in conscious mice with an implanted LV polyethylene tube. We extended our new method by evaluating the LV pressure-volume relationship and examined the feasibility of this method in this study. We studied 17 male mice (age, 11–20 wk) with a conductance catheter inserted into the LV through the polyethylene tube. Load-independent parameters of contractility derived from pressure-volume relationship [slope of the end-systolic pressure-volume relationship (Ees), slope of the maximum first derivative of LV pressure (dP/dtmax)-end-diastolic volume (EDV) relation, and preload-recruitable stroke work (PRSW)] were evaluated by inferior vena caval occlusion with an implanted snare. LV function assessed by this technique on two different days showed that the parameters were very similar, indicating reproducibility. Both linear and nonlinear regression analyses were performed for Ees. Contractility was enhanced by isoproterenol (Ees, 13.1 ± 6.6 to 20.8 ± 8.7 mmHg/µl; dP/dtmax-EDV, 496 ± 139 to 825 ± 178 mmHg·s–1·µl–1; and PRSW, 110 ± 23 to 127 ± 21 mmHg), depressed by atenolol (Ees, 14.5 ± 6.1 to 4.6 ± 2.0 mmHg/µl; dP/dtmax-EDV, 543 ± 188 to 185 ± 94 mmHg·s–1·µl–1; and PRSW, 117 ± 20 to 70 ± 15 mmHg) and isoflurane (Ees, 12.3 ± 6.0 to 5.7 ± 2.1 mmHg/µl; dP/dtmax-EDV, 528 ± 172 to 164 ± 68 mmHg/s·µl; and PRSW, 124 ± 19 to 48 ± 10 mmHg), significantly. In conclusion, this is the first description of the LV pressure-volume relationship in conscious mice. These findings suggest that this method is feasible to detect changes of contractility in the conscious state, allowing serial assessment of pressure-volume-derived cardiac function indexes over time without anesthesia or repeated surgery.

ventricular function; mouse physiology



Address for reprint requests and other correspondence: W. Grossman, Cardiology Division, Dept. of Medicine, Univ. of California, San Francisco, 505 Parnassus Ave., Box 0124, San Francisco, CA 94143–0124 (e-mail: grossman{at}medicine.ucsf.edu)




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