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 linear time-varying elastance theory is frequently used to describe the change in ventricular stiffness during the cardiac cycle. The concept assumes that all isochrones (i.e., curves that connect pressure-volume data occurring at the same time) are linear and have a common volume intercept. Of specific interest is the steepest isochrone, the end-systolic pressure-volume relationship (ESPVR), of which the slope serves as an index for cardiac contractile function. Pressure-volume measurements, achieved with a combined pressure-conductance catheter in the left ventricle of 13 open-chest anesthetized mice, showed a marked curvilinearity of the isochrones. We therefore analyzed the shape of the isochrones by using six regression algorithms (two linear, two quadratic, and two logarithmic, each with a fixed or time-varying intercept) and discussed the consequences for the elastance concept. Our main observations were 1) the volume intercept varies considerably with time; 2) isochrones are equally well described by using quadratic or logarithmic regression; 3) linear regression with a fixed intercept shows poor correlation (R(2) < 0.75) during isovolumic relaxation and early filling; and 4) logarithmic regression is superior in estimating the fixed volume intercept of the ESPVR. In conclusion, the linear time-varying elastance fails to provide a sufficiently robust model to account for changes in pressure and volume during the cardiac cycle in the mouse ventricle. A new framework accounting for the nonlinear shape of the isochrones needs to be developed.

The accuracy of coronary arteriography to predict obstruction to coronary blood flow has recently been questioned. Assessment of coronary hemodynamic variables and vasodilator reserve may provide more reliable information regarding the significance of coronary stenosis. To provide a clinically safe and reliable method of measuring coronary blood flow velocity and coronary flow reserve, a 3F steerable Doppler catheter capable of subselective placement in the coronary circulation was developed and validated in an animal model. Coronary blood flow velocity measured with the catheter correlated with simultaneous measurements by a previously validated external cuff type Doppler probe (r = 0.97), coronary sinus flow collections (r = 0.78) and femoral artery flow collections (r = 0.96). The extravascular Doppler cuff measurements of rest flow velocity and vasodilator reserve were not significantly different with or without the catheter in the artery, indicating that the Doppler catheter caused no obstruction to blood flow. The Doppler catheter has recorded stable and reproducible signals without complications in 28 patients, including 62 separate arterial cannulations. Thus: 1) the 3F Doppler coronary catheter is nonobstructing, steerable and safe; 2) there is an excellent correlation of blood flow velocity with volume collections; and 3) the catheter provides a reliable method of determining coronary blood flow velocity and coronary vasodilator reserve.

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. Catheterization of pulmonary artery in rats with an ultraminiature catheter pressure transducer. Am J Physiol Heart Circ Physiol 285: H2212-H2217, 2003. First published July 24, 2003 10.1152/ajpheart.00315.2003.-Utilizing new materials and miniaturization techniques, an ultraminiature catheter pressure transducer for catheterization of the pulmonary artery (PA) has been developed and applied in intact, spontaneously breathing, anesthetized rats. The catheter arrangement consists of three components: 1) an SPR-671 ultraminiature pressure transducer (measuring catheter), 2) a plastic introducer (sheath) that is slipped over the measuring catheter, and 3) an external wire mounted on the outside of the introducer for bending its tip. The measuring catheter is first inserted through the right jugular vein into the right ventricle. The introducer is then slipped over it. The tip of the introducer is bent so that there is an angle of ϳ90°or less to the shaft. The measuring catheter is advanced across the pulmonary valve into the PA. Measurements of pulmonary arterial pressure were made in five male Long Evans (364 Ϯ 7 g body wt) and five female Sprague-Dawley (244 Ϯ 7 g body wt) rats under control conditions. The effects of infusion of norepinephrine (0.1 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 iv for 20-min duration) were tested in Long Evans rats. Pulmonary arterial systolic pressure measurements were 34.0 Ϯ 0.8 and 29.5 Ϯ 0.4 mmHg, and diastolic pressure values were 23.6 Ϯ 0.8 and 18.1 Ϯ 0.6 mmHg in male Long Evans and female Sprague-Dawley rats, respectively. Norepinephrine induced an increase in pulmonary arterial systolic (40.8 Ϯ 0.1 mmHg) and diastolic (28.6 Ϯ 0.4 mmHg) pressures and an elevation in pulmonary vascular resistance from a control value of 0.093 Ϯ 0.003 to 0.103 Ϯ 0.004 mmHg ⅐ kg ⅐ min ⅐ ml Ϫ1 .cardiac output; contractility; norepinephrine; right heart IN BASIC CARDIOVASCULAR RESEARCH, the right heart and pulmonary circulation have been studied less frequently than the left heart and peripheral circulation. Also, the method for catheterization of the left ventricle in rats using ultraminiature catheter pressure transducers was established earlier (21) than that for catheterization of the right ventricle (24). Recently, catheterization of both heart chambers with microtip catheters has become feasible also in mice (3). For the characterization of experimental animal models with alterations in pulmonary circulation and right ventricular (RV) function such as pulmonary hypertension and RV hypertrophy and failure, the measurement of pulmonary arterial pressure is needed to better understand the underlying pathophysiological processes. Some attempts have been made over the past 30 years to obtain this important parameter in small laboratory animals. However, no microtip catheter method is presently available that can be applied for measurements of pulmonary arterial pressure and pulmonary vascular resistance. In a one-step approach, a 3.5-Fr umbilical vessel catheter prefilled with heparinized saline had a 90°a ngle to the...