Nonlinear isochrones in murine left ventricular pressure-volume loops: how well does the time-varying elastance concept hold?

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.

Technology and application of ultraminiature catheter pressure transducers.

After a brief historical account of the methods for pressure measurements in the cardiovascular system, the basic structural elements of a new generation of miniaturized catheter pressure transducers are described. These catheters have an outside diameter at the tip of 0.9 mm (3 French) and have been routinely applied in left and right heart catheterization in intact, anesthetized rats. Together with cardiac output measured by the thermodilution technique, a complete set of basal functional parameters can be obtained in vivo. The method of cardiac catheterization in rats is accurate, reliable and easy to perform. As to left heart function, changes occurring in several models of cardiac hypertrophy and heart failure have been recorded and correlated with morphological and metabolic alterations. In addition, the functional effects of catecholamines and thyroid hormones have been evaluated. In addition to the routine catheterization procedure, a double catheter method has been introduced recently, which allows measurement of left ventricular isovolumetric pressure in intact rats. Catheterization of the right ventricle requires a more refined catheter with a characteristic bend at the tip so that it can be comfortably slid from the right atrium into the right ventricle. With this method it was found that right ventricular systolic pressure was elevated markedly in rats with chronic myocardial infarction induced by ligation of the left anterior descending coronary artery, by pulmonary artery banding, by intermittent chronic hypoxia and by noradrenaline administration. The ultraminiature catheter pressure transducer has also been successfully applied in an isolated working rat heart preparation. Recent modifications of this kind of catheters also enabled the catheterization of the left ventricle in mice. Future applications of ultraminiature catheter pressure transducers may be directed to catheterization of the pulmonary artery in rats and to the in vivo and in vitro assessment of heart function of transgenic mice.

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

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. alpha-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/dtmax), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe (r2 = 0.98). This maneuver yielded end-systolic elastances of 79 +/- 21 mmHg/microliter, preload-recruitable stroke work of 82 +/- 5.6 mmHg, and slope of dP/dtmax-end-diastolic volume relation of 699 +/- 100 mmHg.s-1.microliter-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.

Subselective measurement of coronary blood flow velocity using a steerable Doppler catheter.

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.

Development of an improved multi-pressure-sensor probe for recording muscle contraction in human intestine.

We have developed an improved semiconductor recording probe for monitoring motility of the upper small intestine in humans. The probe consists of six ultraminiature silicon pressure sensors spaced 10 cm apart and encased in a flexible polyurethane sheath. The probe is small [2.67 mm (8F) diameter], is easily passed transnasally, and is tolerated by patients for prolonged recording periods (24-36 hr) with a minimum of discomfort. The initial semiconductor and catheter material were those designed for use in the cardiovascular system, but they proved to be easily damaged by gastric acid and enzymes. After improvement of this probe, we now have recordings from more than 100 patients for an approximate total of 6000 hr of recording time. The improved probe is a durable recording device that facilitates the investigation of motility of the small intestine in humans in health and disease.

Percutaneous left ventricular catheterisation with an ultraminiature catheter-tip pressure transducer.

Percutaneous left ventricular catheterisation with a 4F (O.D. 1.33 mm) catheter-tip pressure transducer is described. The transducer is small enough so that it can be introduced through a short 4F arterial insertion sheath or a Brockenbrough Trans-septal catheter. Experience in 35 patients suggests that this ultraminiature catheter mounted pressure transducer is a valuable addition to the cardiac catheterisation laboratory.