Biomedical subjects
Publications and source records attributed to S G Shroff.
The introduction of new pharmacotherapies for long-term treatment of chronic cardiac failure has underscored the need for serial measurement of ventricular function in the ambulatory patient. Management strategies can best be guided by physiologic assessment of the heart's function as a muscular pump that must serve to propel gases to the metabolizing tissues on a moment-to-moment basis.
The right ventricle (RV) is responsible for accepting venous blood and propelling it to the lungs where it is oxygenated and its CO2 eliminated. Under normal conditions, at rest and during exercise, the pressure required by the RV to maintain the cardiac output (CO) is modest. The functional significance of the RV in sustaining circulatory homeostasis, therefore, appears to be minimal. However, whenever pulmonary vascular resistance (PVR) is elevated (e.g., left heart failure or pulmonary vascular disease) or whenever venous return is reduced (e.g., hypovolemia, increased pleural pressure), the necessity of this pulsatile pump is without question. As a muscular pump, the thin-walled RV is not unlike the left ventricle (LV) except that during diastole it is twice as distensible as the LV and during systole its stroke volume is twice as sensitive to the level of ejection pressure. However, under conditions of chronic pressure overload, the RV will hypertrophy and become capable of generating systemic levels of pressure. This is particularly necessary during physical activity in patients with pulmonary vascular disease. Thus, the RV is an integral component of the body's gas transport system and its contribution to sustaining circulatory homeostasis is without question.
To determine the mechanical properties of the left ventricle (LV) as a pump, a mathematical model of its systolic dynamics was developed. Initially the model consisted of three elements, i.e., elastance, resistance, and inertance. Results from three experiments, however, indicated that the inertial component was negligible compared with the other two components. The functional forms of elastance and resistance were determined by applying the flow-pulse response technique to an isovolumetrically beating, isolated canine heart. Results from three experiments indicated that the systolic elastance and resistance can be represented by a third-order polynomial in time and a linear function of instantaneous ventricular pressure (LVP), respectively. The simplified model was then tested by calculating the systolic elastance and resistance from LVP, volume, and flow data of an ejecting LV obtained over a single cardiac cycle. A total of 225 combinations (10 expts) of end-diastolic volume (EDV), ejection pressure (EP), heart rate (HR), and contractile state (CS) were evaluated. The results indicated that 1) the elastance function was insensitive to variations in EDV and EP but was a function of CS and HR; 2) the linear resistance-pressure relationship was insensitive to variations in EDV, EP, HR, and CS; and 3) the model could "prospectively" predict the LV isovolumetric pressure from the data of an ejecting beat. Thus a model of LV systolic dynamics has been established that can be used to calculate the intrinsic chamber mechanical properties, i.e., elastance and resistance, of an ejecting LV.
In recent years cardiologists and pulmonologists alike have taken a very narrow view of the heart and lungs. Each specialty has focused its respective attention on either the left ventricle or the alveoli. Ejection fraction and arterial O2 tension have become the order of the day. These narrowly focused viewpoints of the heart and lungs have distracted us from an equally compelling and more global perspective--the cardiopulmonary unit, in which the heart and lungs function as an integrated metabolic unit responsible for the body's gas transport and, as such, serving the metabolic needs of the tissues. A disease involving the cardiovascular or respiratory systems will disrupt the ability of the cardiopulmonary unit to deliver O2 to the tissues. In more subtle expressions of disease, this defect in O2 transport may require the heightened O2 requirements of exercising muscle to become apparent. The integration of the heart and lungs and the right and left sides of the heart is fostered by a variety of physiologic factors, including pleural and airway pressures, the pericardium, the interventricular septum and alignment of muscle fibers between the ventricles and septum, and the thoracic cage itself. Through its functional integration, the cardiopulmonary unit has been able to link the metabolizing cells to the atmosphere.
A transformation from the normal elliptical shape of the left ventricle that may accompany various disease states and that may be indicative of myocardial remodeling, has not been completely addressed in part because of the need for a descriptor of shape that is independent of chamber size. Accordingly, the goal of this study was twofold: to derive dimensionless echocardiographic descriptors of left ventricle chamber shape that are independent of chamber volume and to use these descriptors to quantitatively compare the shape of left ventricles that were either of normal size (81 +/- 17 ml, 19 patients) or were enlarged secondary to idiopathic cardiomyopathy (194 +/- 61 ml, 46 patients) or chronic aortic or mitral valve incompetence (196 +/- 67 ml, 14 patients). Two-dimensional and M-mode determined descriptors of left ventricle shape based on its width, length, and area were found to be independent of left ventricle volume. These descriptors were significantly greater in cardiomyopathy compared with the normal or dilated left ventricle secondary to valvular incompetence, indicating that the left ventricle had become nearly spherical. A spherical shape of the left ventricle was not observed with valvular incompetence. The ability to classify a patient as having either a normal or a cardiomyopathic left ventricle by discriminant function analysis was enhanced when both left ventricle size and shape were considered. In a prospective study using discriminant function and fractional shortening, we found that patients with valvular incompetence could be classified as having either a normal discriminant function and fractional shortening, an abnormal discriminant function and normal fractional shortening, or an abnormal discriminant function and fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantification of regional myocardial tissue blood flow (RMBF) based on contrast echocardiography has yet to be achieved. This study validated our recently proposed algorithm for quantification of RMBF with colored microspheres. Experiments were carried out in an isolated rabbit heart preparation (n = 11). Aortic root injections of perfluoropropane-filled albumin microsphere solution (FS069) and colored microspheres were performed at five levels of coronary flow achieved by altering perfusion pressure. During each injection of contrast material, consecutive end-diastolic images of the heart and an extracardiac reference chamber were acquired with a 7.5 MHz transducer and digitized. Time-intensity curves from the reference chamber and myocardial regions of interest, corresponding to the anatomic segments used for colored microsphere analysis, were analyzed for RMBF. Blood flow was calculated as the intravascular volume fraction (ratio of areas under myocardial and reference curves) divided by mean transit time (deconvolution of impulse response) and compared with those obtained with colored microspheres. Injections of FS069 resulted in highly reproducible enhancement of myocardial contrast. Analysis of time-intensity curves provided consistent measurements of RMBF (r = 0.91), which correlated highly with microsphere data (r = 0.84). The use of this new algorithm allows accurate quantification of RMBF in the isolated heart model. Further validation of this approach in an animal model with peripheral intravenous injections of contrast material will allow noninvasive clinical measurements of RMBF.
The effects of Albunex (Molecular Biosystems, Inc., San Diego, Calif.) and a second generation contrast agent, FS069, on left ventricular (LV) contractility were evaluated using an isolated rabbit heart model under constant loading conditions and heart rate. Contrast injections (2 ml total volume) were performed in two separate protocols (N1 = 6, N2 = 6). In protocol 1, various doses of Albunex (0.1 to 2.0 ml in saline solution) were used, and paired control injections of a matched dose of 5% solution of human albumin in saline solution were administered. In protocol 2, LV contractility was assessed during injections of the following solutions: (1) 1:250 suspension of FS069 in saline solution, which caused optimal myocardial contrast enhancement; (2) a 1:25 suspension of FS069; (3) a 1:25 suspension of FS069 prefiltered using an 8 microns pore filter; and (4) 2 ml saline solution as a control. Instantaneous LV pressure was analyzed for variations in peak systolic pressure (peak P) and maximum pressure derivative (peak P'), both indices of LV contractility under conditions of fixed heart rate and chamber volume. Albumin alone caused a transient, dose-dependent depression of LV contractility, reflected by decreases in both peak P and peak P' values. These decreases presumably were caused by the decreasing availability of ionized calcium as a result of calcium binding. No further decrease in contractility was noted when Albunex microspheres were present in the solution. Saline injections caused a transient minor increase in LV contractility, reflected by increases of 4.5% +/- 1.1% and 10.6% +/- 3.8% in peak P and peak P' values, respectively. These levels returned to baseline levels within 2 minutes. A similar response was observed when a 1:250 suspension of FS069 was used. The 1:25 suspension of FS069 caused a bimodal response, with initial rises in peak P and peak P' levels (5.2% +/- 3.6% and 12.8% +/- 6.5%, respectively), followed by minor reductions in contractility (2.0% +/- 2.4% and 1.7% +/- 2.1%, respectively). The latter decrease in contractility caused by the 1:25 suspension of FS069 was eliminated by filtering. The isolated rabbit heart model is a highly sensitive tool that allows accurate and direct assessment of possible adverse effects of intravascular contrast agents on LV contractility. Using this model, we showed that neither Albunex microspheres nor FS069 microspheres impaired myocardial contractility.
We have previously described the use of transesophageal echocardiography with automated border detection to quantify regional aortic elastic properties. The purpose of this study was to validate this technique further by measuring regional variations of aortic elastic properties and comparing them with previously published data acquired by invasive methods. In nine anesthetized, closed-chest dogs, aortic pressure and lumenal area (transesophageal echocardiography with automated border detection) signals were recorded simultaneously at two aortic sites: just distal to the branching site of the left subclavian artery (proximal) and at the level of the diaphragm (distal). Instantaneous wall thickness was estimated by combining M-mode measurement of aortic end-diastolic thickness with instantaneous lumenal area. Data were acquired over a wide range of loading conditions, generated by inferior vena caval balloon occlusion. Aortic compliance per unit length, midwall radius, midwall stress, and incremental elastic modulus were computed. Aortic midwall radius and incremental elastic modulus values for proximal and distal aortic sites were compared at a common level of midwall stress. Compliance per unit length was higher in the proximal compared with the distal descending thoracic aorta (0.013 +/- 0.003 versus 0.008 +/- 0.003 cm2/mm Hg; mean +/- SD; p = 0.0011). Midwall radius was larger at the proximal location (0.76 +/- 0.07 cm versus 0.64 +/- 0.07 cm; p = 0.0001), whereas incremental elastic modulus was greater distally (0.799 +/- 0.052 dynes x 10(6)/cm2 versus 0.912 +/- 0.130 dynes x 10(6)/cm2; p = 0.02). Lower compliance values at the distal site of the descending thoracic aorta resulted from greater wall stiffness and a smaller radius. Transesophageal echocardiography with automated border detection provides reliable measurements of instantaneous aortic areas necessary for quantifying regional elastic properties.
Transgenic and knock-out mice with cardiovascular phenotypes have created the need for methods to measure murine arterial and ventricular mechanics. The aims of this study were (1) to develop a method for the assessment of wall stress (sigma es)-rate corrected velocity of fiber shortening (Vcfc) relation and (2) to assess the feasibility of quantifying global arterial function in normal mice. This method can thus serve as a reference for future studies in genetically altered mice by establishing normal values for comparison. Ten anesthetized closed-chest mice were studied with targeted M-mode echocardiography of the left ventricle recorded simultaneously with high-fidelity aortic pressures. Data were acquired at baseline and during infusions of methoxamine and isoproterenol. Tracings were digitized to obtain end-systolic wall stress (sigma es) and rate-corrected velocity of fiber shortening (Vcfc) relationships and plots of systolic meridional wall stress. Instantaneous aortic pressures and continuous wave aortic Doppler velocities were digitized to study arterial hemodynamics. The Vcfc-sigma es relationship was inverse and linear in all mice studied with a median value of r2 = 0.94. Isoproterenol resulted in an upward shift from the baseline contractility line obtained with methoxamine (mean shift = 2.0 +/- 0.3 circ/sec). Relative to baseline the integral of wall stress decreased with isoproterenol and increased with methoxamine. Methoxamine increased mean arterial pressure and total vascular resistance and decreased heart rate, cardiac output, and arterial compliance. Isoproterenol decreased total vascular resistance and increased cardiac output. Stress-shortening relationships, systolic wall stress, and evaluation of vascular function can be obtained in a closed-chest mouse model.