David S. Berger

Serial Assessment of the Cardiovascular System in Normal Pregnancy Role of Arterial Compliance and Pulsatile Arterial Load

BACKGROUND Temporal changes in systemic arterial compliance and wave propagation properties (pulsatile arterial load) and their role in ventricular-systemic arterial coupling during gestation have not been explored. Noninvasive methods combined with recently developed mathematical modeling techniques were used to characterize vascular and left ventricular (LV) mechanical adaptations during normal gestation. METHODS AND RESULTS Fourteen healthy women were studied at each trimester of pregnancy and again postpartum. Experimental measurements included instantaneous aortic pressure (subclavian pulse tracings) and flow (aortic Doppler velocities) and echocardiographic imaging of the LV. A small increase in LV muscle mass and end-diastolic chamber dimension occurred by late gestation, with no significant alterations in myocardial contractility. Cardiac output increased and the steady component of arterial load (total vascular resistance) decreased during pregnancy. Several changes in pulsatile arterial load were noted: Global arterial compliance increased (approximately 30%) during the first trimester and remained elevated thereafter. The magnitude of peripheral wave reflections at the aorta was reduced. The mathematical model-based analysis revealed that peripheral wave reflections at the aorta were delayed and that both conduit and peripheral vessels contributed to the increased arterial compliance. Finally, coordinated changes in the pulsatile arterial load and LV properties were responsible for maintaining the efficiency of LV-to-arterial system energy transfer. CONCLUSIONS The rapid time course of compliance changes and the involvement of both conduit and peripheral vessels are consistent with reduced vascular tone as being the main underlying mechanism. The pulsatile arterial load alterations during normal pregnancy are adaptive in that they help to accommodate the increased intravascular volume while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure.

Differential Effects of Chronic Oral Antihypertensive Therapies on Systemic Arterial Circulation and Ventricular Energetics in African-American Patients

BACKGROUND A comprehensive evaluation of arterial load characteristics and left ventricular energetics in systemic hypertension has been limited by the need for invasive techniques to access instantaneous aortic pressure and flow. As a consequence of this methodological limitation, no data exist on the effects of long-term antihypertensive therapy on global arterial impedance properties and indexes of myocardial oxygen consumption (MVO2). Using recently validated noninvasive techniques, we compared in hypertensive patients the effects of chronic oral treatment with ramipril, nifedipine, and atenolol on arterial impedance and mechanical power dissipation as well as indexes of MVO2. METHODS AND RESULTS Sixteen African-American subjects with systemic hypertension were studied with a randomized, double-blind, crossover protocol. Instantaneous central aortic pressure and flow, from which arterial load characteristics can be derived, were estimated from calibrated subclavian pulse tracings (SPTs) and continuous-wave aortic Doppler velocity in conjunction with two-dimensional (2D) echocardiographic measurements of the aortic annulus, respectively. To derive ventricular wall stress and indexes of MVO2, left ventricular short- (M-mode) and long-axis (2D echo) images were acquired simultaneously with SPTs. Data were collected at the end of a 2-week washout period (predrug control) and after 6 weeks of treatment with each agent. Although all three agents reduced diastolic blood pressure to the same extent, different effects on mean and systolic pressures and vascular impedance properties were noted. Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg). This improvement in arterial compliance was not entirely accounted for by the reduction in distending pressure. Ramipril also decreased TPR (1740 +/- 292 versus 1437 +/- 290 dyne-s/cm5) and increased ACL (1.214 +/- 0.190 versus 1.569 +/- 0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure. Atenolol, in contrast, did not affect either TPR or ACL. In agreement with the compliance results, nifedipine and ramipril significantly lowered the first two harmonics of the impedance spectrum, but atenolol did not. None of these agents resulted in a significant change in characteristic impedance or in the relative amplitude of the reflected pressure wave. Total vascular mechanical power and percent of oscillatory power remained unaltered with all antihypertensive treatments. Only ramipril and nifedipine reduced the integral of both meridional and circumferential systolic wall stresses, indicating that MVO2 per beat was reduced with these agents. Stress-time index, a measure of MVO2 per unit time, decreased significantly with ramipril but not with nifedipine because of an increase in heart rate noted in 10 of 16 patients (mean increase, 10 beats per minute). Thus, a reduction in MVO2 coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged. In contrast, there was no evidence of a reduction in wall stress, stress integral, or stress-time index with atenolol. CONCLUSIONS The noninvasive methodology used in this study constitutes a new tool for serial and simultaneous evaluation of arterial hemodynamics and left ventricular energetics in systemic hypertension. In this study, we demonstrate the differential effects of chronic antihypertensive therapies on systemic arterial circulation and indexes of MVO2 in African-American subjects. Consideration of drug-induced differential responses of arterial load and indexes of MVO2 with each drug may provide a more physiological approach to the treatment of systemic hypertension in indivi

True Arterial System Compliance Estimated From Apparent Arterial Compliance

AbstractA new method has been developed to estimate total arterial compliance from measured input pressure and flow. In contrast to other methods, this method does not rely on fitting the elements of a lumped model to measured data. Instead, it relies on measured input impedance and peripheral resistance to calculate the relationship of arterial blood volume to input pressure. Generally, this transfer function is a complex function of frequency and is called the apparent arterial compliance. At very low frequencies, the confounding effect of pulse wave reflection disappears, and apparent compliance becomes total arterial compliance. This study reveals that frequency components of pressure and flow below heart rate are generally necessary to obtain a valid estimate of compliance. Thus, the ubiquitous practice of estimating total arterial compliance from a single cardiac cycle is suspect under most circumstances, since a single cardiac cycle does not contain these frequencies.

Disparate effects of three types of extracellular acidosis on left ventricular function

Effects of acidosis on muscle contractile function have been studied extensively. However, the relative effects of different types of extracellular acidosis on left ventricular (LV) contractile function, especially the temporal features of contraction, have not been investigated in a single model. We constituted perfusion buffers of identical ionic composition, including Ca2+concentration ([Ca2+]), to mimic physiological control condition (pH 7.40) and three types of acidosis with pH of 7.03: inorganic (IA), respiratory (RA), and lactic (LA). Isolated rabbit hearts ( n = 9) were perfused with acidotic buffers chosen at random, each preceded by the control buffer. Under steady-state conditions, instantaneous LV pressure (Pv) and volume (Vv) were recorded for a range of Vv. The results were as follows. 1) LV passive (end-diastolic) elastance increased with IA and RA. However, this increase may not be a direct effect of acidosis; it can be explained on the basis of myocardial turgor. 2) Although LV inotropic state (peak active Pv and elastance) was depressed by all three acidotic buffers, the magnitude of inotropic depression was significantly less for LA. 3) Temporal features of Pv were altered differently. Whereas IA and RA reduced time to peak Pv( t max) and hastened isovolumic relaxation at a common level of LV wall stress, LA significantly increased t max and retarded relaxation. These results and a model-based interpretation suggest that cooperative feedback (i.e., force-activation interaction) plays an important role in acidosis-induced changes in LV contractile function. Furthermore, it is proposed that LA-induced responses comprise two components, one due to intracellular acidosis and the other due to pH-independent effects of lactate ions.Effects of acidosis on muscle contractile function have been studied extensively. However, the relative effects of different types of extracellular acidosis on left ventricular (LV) contractile function, especially the temporal features of contraction, have not been investigated in a single model. We constituted perfusion buffers of identical ionic composition, including Ca2+ concentration ([Ca2+]), to mimic physiological control condition (pH 7.40) and three types of acidosis with pH of 7.03: inorganic (IA), respiratory (RA), and lactic (LA). Isolated rabbit hearts (n = 9) were perfused with acidotic buffers chosen at random, each preceded by the control buffer. Under steady-state conditions, instantaneous LV pressure (Pv) and volume (Vv) were recorded for a range of Vv. The results were as follows. 1) LV passive (end-diastolic) elastance increased with IA and RA. However, this increase may not be a direct effect of acidosis; it can be explained on the basis of myocardial turgor. 2) Although LV inotropic state (peak active Pv and elastance) was depressed by all three acidotic buffers, the magnitude of inotropic depression was significantly less for LA. 3) Temporal features of Pv were altered differently. Whereas IA and RA reduced time to peak Pv (tmax) and hastened isovolumic relaxation at a common level of LV wall stress, LA significantly increased tmax and retarded relaxation. These results and a model-based interpretation suggest that cooperative feedback (i.e., force-activation interaction) plays an important role in acidosis-induced changes in LV contractile function. Furthermore, it is proposed that LA-induced responses comprise two components, one due to intracellular acidosis and the other due to pH-independent effects of lactate ions.

Wave Propagation in Coupled Left Ventricle–Arterial System Implications for Aortic Pressure

The objective of this study was to examine the effects of wave propagation properties (global reflection coefficient gamma IG; pulse wave velocity, c(ph); and characteristic impedance zeta(o) on the mechanical performance of the coupled left ventricle-arterial system. Specifically, we sought to quantify effects on aortic pressure (P(ao)) and flow Q(ao) while keeping constant other determinants of P(ao) and Q(ao) (left ventricular end-diastolic volume, V(ed), and contractility, heart rate, and peripheral resistance, R(s)). Isolated rabbit hearts were subjected to real-time, computer-controlled physiological loading. The arterial circulation was modeled with a lossless tube terminating in a complex load. The loading system allowed for precise and independent control of all arterial properties as evidenced by accurate reproduction of desired input impedances and computed left ventricular volume changes. While propagation phenomena affected P(ao) and Q(ao) morphologies as expected, their effects on absolute P(ao) values were often contrary to the current understanding. Diastolic (Pd) and mean (Pm) P(ao) and stroke volume decrease monotonically with increases in gamma G, c(ph), or zeta(o) over wide ranges. In contrast, these increase had variable effects on peak systolic P(ao) (Ps): decreasing with gamma G, biphasic with c(ph), and increasing with zeta(o). There was an interaction between gamma G and c(ph) such that gamma G effects on P(m) and P(d) were augmented a higher C(ph) and vice versa. Despite large changes in system parameters, effects on Pm and Ps were modest ( < 10% and < 5%, respectively); effects on Pd were always two to four times greater. Similar results were obtained when the single-tube model of the arterial system was replaced by an asymmetrical T-tube configuration. Our data do not support the prevailing hypothesis that P(s) (and therefore ventricular load) can be selectively and significantly altered by manipulating gamma G, c(ph), and/or zeta o.

Arterial wave propagation phenomena, ventricular work, and power dissipation

AbstractThe effects of wave propagation phenomena, namely global reflection coefficient (ΓG[ω]) and pulse wave velocity (cph), are studied in a model of the coupled left ventricle/arterial system. The left ventricle consists of a time-varying elastance, while the arterial system is modeled as a single, uniform, elastic tube terminating in a complex load. Manipulation of model parameters allowed for the precise control of (ΓG[ω]) andcphindependent of each other, peripheral resistance, and characteristic impedance. Reduction of ΓG(ω) andcph were achieved through increases in load compliance and tube compliance, respectively. The equations describing the system were solved for left ventricular and aortic pressures and aortic flow. From these, stroke volume (SV), left ventricular stroke work (SW), and steady

Ejection has both positive and negative effects on left ventricular isovolumic relaxation

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On descriptive and interpretive abilities of arterial system models

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