In vivo murine left ventricular pressure-volume relations by miniaturized conductance micromanometry

Abstract

The mouse is the species of choice for creating genetically engineered models of human disease. To study detailed systolic and diastolic left ventricular (LV) chamber mechanics in mice in vivo, we developed a miniaturized conductance-manometer system. α-Chloralose-urethan-anesthetized animals were instrumented with a two-electrode pressure-volume catheter advanced via the LV apex to the aortic root. Custom electronics provided time-varying conductances related to cavity volume. Baseline hemodynamics were similar to values in conscious animals: 634 ± 14 beats/min, 112 ± 4 mmHg, 5.3 ± 0.8 mmHg, and 11,777 ± 732 mmHg/s for heart rate, end-systolic and end-diastolic pressures, and maximum first derivative of ventricular pressure with respect to time (dP/d t max), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe ( r 2 = 0.98). This maneuver yielded end-systolic elastances of 79 ± 21 mmHg/μl, preload-recruitable stroke work of 82 ± 5.6 mmHg, and slope of dP/d t max-end-diastolic volume relation of 699 ± 100 mmHg ⋅ s−1 ⋅ μl−1, and these relations varied predictably with acute inotropic interventions. The control normalized time-varying elastance curve was similar to human data, further supporting comparable chamber mechanics between species. This novel approach should greatly help assess cardiovascular function in the blood-perfused murine heart.

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

“…UcnII ( Fig. 1) (25). LV volume calibration for the impedance signal was accomplished by digital contrast biplane angiography with the catheter in the LV; the calculation of EDV and ESV used Simpson's rule (26)(27)(28)(29).…”

The effect of a myocardial infarction on the normalized time-varying elastance curve

“…In a later study by the same group, Georgakopoulos et al showed that the shape of the E n (t n ) is identical in different animal species, the similarity in E n (t n ) being attributed to small differences in myofibril protein isoforms and protein kinetics among species (10).…”

“…At the basis of the ESPVR stands the time-varying elastance [E(t)] concept, whereby the E(t) gives a time-domain description of the heart pump function (30). The shape of the normalized time-varying elastance curve [E n (t n )] has been shown to be similar in different animal species (10). It has been reported that, when E(t) is normalized with respect to peak value and peak time, the shape (wave form) of the E n (t n ) is independent of different cardiac pathologies, afterload, preload, and contractility (28).…”

Rodent models of heart failure: an updated review

“…Nevertheless, cardiac physiologic assessments have been made easier by recent technologies such as ultrahigh resolution ultrasound [169] and micromanometer conductance for pressure-volume analyses [80,218], but these techniques are quite expensive and pose a serious challenge to laboratories without an established expertise. The major advantage of mice compared to rats is the fact that pharmacologic studies become less expensive as the drug is usually administered proportionately to the animal weight.…”