Ventricular function during exercise in mice and rats

Abstract

The mouse has many advantages over other experimental models for the molecular investigation of left ventricular (LV) function. Accordingly, there is a keen interest in, as well as an intense need for, a conscious, chronically instrumented, freely moving mouse model for the determination of cardiac function. To address this need, we used a telemetry device for repeated measurements of LV function in conscious mice at rest and during exercise. For reference, we compared the responses in mice to the responses in identically instrumented conscious rats. The transmitter body of the telemetry device (rat PA-C40; mouse PA-C10; Data Sciences International, St. Paul, MN) was placed in the intraperitoneal space through a ventral abdominal approach (rat) or subcutaneously on the left flank (mouse). The pressure sensor, located within the tip of a catheter, was inserted into the left ventricle through an apical stab wound (18 gauge for rat; 21 gauge for mouse) for continuous, nontethered, recordings of pulsatile LV pressure. A minimum of 1 wk was allowed for recovery and for the animals to regain their presurgical weight. During the recovery period, the animals were handled, weighed, and acclimatized to the laboratory, treadmill, and investigators. Subsequently, LV parameters were recorded at rest and during a graded exercise test. The results document, for the first time, serial assessment of ventricular function during exercise in conscious mice and rats. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research.

Fig. 1.

Second analog recordings of LV pressure and dP/dt at rest and during the 3rd min of a graded exercise protocol (5, 10, 15, and 20 m/min) in a mouse (A) and in a rat (B) are shown.

Fig. 2.

Heart rate (A) and the percent change in heart rate from rest (B) during graded treadmill exercise (5, 10, 15, and 20 m/min) for mice and rats are shown. *P < 0.05, mice vs. rats. #P < 0.05, exercise vs. rest.

Fig. 3.

LV systolic and diastolic pressures (A) and the percent change from rest in LV systolic (B) and diastolic (C) pressures during graded treadmill exercise (5, 10, 15, and 20 m/min) for mice and rats. *P < 0.05, mice vs. rats. #P < 0.05, exercise vs. rest.

Fig. 4.

LV dP/dt⁺ and dP/dt⁻ (A) and the percent change from rest for dP/dt⁺ (B) and dP/dt⁻ (C) during graded treadmill exercise (5, 10, 15, and 20 m/min) for mice and rats are presented. *P < 0.05, mice vs. rats. #P < 0.05, exercise vs. rest.

Fig. 5.

Force-frequency relationship, i.e., the relationship between the percent change from rest for LV pressure (A), dP/dt⁺ (B), and dP/dt⁻ (C) and heart rate, for mice and rats is presented.

Fig. 6.

Time for mice to recover night/day variations in heart rate and LV pressure is presented. Specifically, 12-h day and night averages for heart rate (A) and mean LV pressure (B), in mice, beginning the night following the procedures for implanting the telemetry device and continuing for 11 days are presented.

Fig. 7.

Effect of anesthesia on resting heart rate and LV hemodynamic parameters in mice is presented. Specifically, baseline values and the percent change from baseline following 30 min of anesthesia (pentobarbital sodium, 50 mg/kg ip) for heart rate, LV systolic pressure, dP/dt⁺ and dP/dt⁻, in mice, are presented.