Changes In Ventricular Contractility Research Articles

Novel Neuromodulation Approach to Improve Left Ventricular Contractility in Heart Failure: A First-in-Human Proof-of-Concept Study.

Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. Fifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dtMax) indicated changes in ventricular contractility. Of 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dtMin), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.

Intraoperative Transesophageal Echocardiography in Tricuspid Valve Surgery

Imaging the tricuspid valve (TV) using transesophageal echocardiography (TEE) seems more difficult than imaging other cardiac valves due to not only the complex valvular structure but also the anterior, far-field distance from the probe. The focus of the TEE during the surgery would not be much different from that of preoperative TEE. However, the anesthesia-induced changes of ventricular contractility, filling status, and vascular resistance should be considered when interpreting the images. Here, we thoroughly reviewed the major issues in the preand post-cardiopulmonary bypass intraoperative TEE in the TV surgery. Ultimately, a real-time intraoperative TEE monitoring should involve a simple or less time-consuming analysis which gives quick on-site information regarding the cardiac or hemodynamic status, communicating with the surgeon to lead to an optimal process. Keywords: Intraoperative; Echocardiography, Transesophageal; Tricuspid valve

Assessment of single beat end-systolic elastance methods for quantifying ventricular contractility.

Multi-beat end-systolic elastance (EMB) is considered a gold-standard index of ventricular contractility. However, it is difficult to measure clinically due to the need for transient manipulation of ventricular preload or afterload. We compared the performance of 5 'single-beat' methods that do not require loading interventions, for estimating the equivalent of EMB. In 7 sheep instrumented with a micromanometer/conductance catheter, single-beat methods were compared with EMB, obtained after transiently decreasing preload or increasing afterload under a broad range of heart rates and inotropic conditions. The single-beat elastance (ESB) method described by Shishido et al. (Circulation 102(16):1983-1989, 2000) had the highest correlation (R = 0.69, y = 0.52x + 0.43) with EMB, although the absolute accuracy was poor. Interestingly, for all methods tested, a higher correlation was observed when EMB was obtained with an afterload increase (R = 0.47 - 0.78) rather than a preload reduction (R = 0.07-0.57). Within-animal regression coefficients were higher than those obtained from pooled data, with excellent within-animal correlation observed for Shishido et al. method (0.73 ≤ R ≤ 0.96) when using afterload increase as the loading intervention. We conclude that (1) current methods perform better when using an afterload increase to obtain reference EMB, (2) intra-individual ESB comparisons may be more reliable than inter-individual comparisons and (3) Shishido et al.'s method demonstrated the strongest correlation with EMB. Current ESB methods have limited and variable accuracy, but may hold promise for tracking relative changes in ventricular contractility in individuals.

Ventricular-vascular dynamics in pediatric patients with heart failure and preserved ejection fraction

ObjectiveThe details of the ventricular-vascular dynamics of heart failure with preserved ejection fraction (HFpEF) in children remain poorly understood. We tested the hypothesis that pediatric HFpEF patients have ventricular systolic, diastolic, and arterial stiffening at rest as well as impaired reserve function associated with coronary supply/demand imbalance. MethodsWe studied the ventricular pressure-area relationship in 22 pediatric HFpEF patients and 22 control subjects before and after dobutamine infusion and during abdominal compression. Coronary supply/demand balance was assessed by subendocardial viability ratio (SEVR) calculated from the aortic pressure waveform. ResultsCompared with controls, the HFpEF patients had significantly higher end-systolic (Ees) and arterial (Ea) elastance. Increased ventricular diastolic stiffness also occurred in the HFpEF patients, resulting in modest elevation of end-diastolic pressure (EDP) at rest (13.6±4.3 vs. 7.3±2.3mmHg, P<0.0001). The difference in EDP became more evident with a preload increase through abdominal compression, indicating a limited diastolic reserve in HFpEF patients (EDP changes; 11.3±6.2 for HFpEF vs. 3.4±0.6mmHg for controls, P=0.016). The HFpEF patients exhibited impaired beta-adrenergic reserve in ventricular contractility and ventricular-arterial coupling in response to dobutamine infusion. SEVR was significantly lower in the HFpEF (0.64±0.11) than in the control (0.79±0.07, P<0.0001) and was significantly correlated with LV diastolic stiffness and dobutamine-induced changes in ventricular contractility. ConclusionsHFpEF in children involves higher ventricular-arterial stiffness at rest as well as impaired systolic and diastolic reserve, which closely correlate with impaired coronary supply/demand balance.

Abstract 19128: Acute Changes in Left Ventricular Contractility Following Mitraclip Implantation Depend on Left Atrial Volume

Background: The acute hemodynamic changes following elimination of mitral regurgitation is a much discussed issue, particularly in patients with severely compromised left ventricular function where the incompetent mitral valve was regarded as a pop-off valve. Herein, we investigated the acute changes of ventricular contractility in relation to left atrial volume. Methods and results: Echocardiographic left atrial and left ventricular longitudinal strain measurements before and 3 days after the procedure were performed in 19 patients (mean age: 77.9±7.9, 47% female, 73,7% functional mitral valve regurgitation, 26,3% degenerative mitral valve regurgitation) undergoing MitraClip implantation at our institution. Procedural success with reduction in MR to grade 2+ or less was achieved in all patients. Overall there was no significant change in left atrial or ventricular global or regional longitudinal strain after the procedure. However, a strong correlation was observed between worsening in left ventricular strain and left atrial volume (r: -0.72, p&lt;0.01), i.e. there was a greater reduction in left ventricular contractility after clip implantation in patients with larger left atrial volumes. Multivariate, linear regression analyses revealed that left atrial volume predicted the change of left ventricular longitudinal strain following MitraClip implantation (r2: -0.07, p&lt;0.01) independently of left ventricular ejection fraction (r2: -0.05, p=0.40), mitral regurgitant volume (r2: -0.09, p=0.09) and left atrial strain (r2: -0.03, p=0.85). Discussion: Our data suggest that enlarged left atria act as a low-resistance reservoir in mitral regurgitation. As a consequence elimination of mitral regurgitation in these patients leads to worsening of left ventricular contractility whereas in smaller atria left ventricular contractility is not negatively affected by elimination of MR.

Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs

Increased sympathetic activation during acute ventricular ischemia is involved in the occurrence of life-threatening arrhythmias. To test the effect of sympathetic inhibition by renal denervation (RDN) on ventricular ischemia/reperfusion arrhythmias. Anesthetized pigs, randomized to RDN or SHAM treatment, were subjected to 20 minutes of left anterior descending coronary artery (LAD) occlusion followed by reperfusion. Infarct size, hemodynamics, premature ventricular contractions, and spontaneous ventricular tachyarrhythmias were analyzed. Monophasic action potentials were recorded with an epicardial probe at the ischemic area. Ventricular ischemia resulted in an acute reduction of blood pressure (-29%) and peak left ventricular pressure rise (-40%), which were not significantly affected by RDN. However, elevation of left ventricular end-diastolic pressure (LVEDP) during LAD ligation was attenuated by RDN (ΔLVEDP: +1.8 ± 0.6 mm Hg vs +9.7 ± 1 mm Hg in the SHAM group; P = .046). Infarct size was not affected by RDN compared to SHAM. RDN significantly reduced spontaneous ventricular extrabeats (160 ± 15/10 min in the RDN group vs 422 ± 36/10 min in the SHAM group; P = .021) without affecting coupling intervals. In 5 of 6 SHAM-treated animals, ventricular fibrillation (VF) occurred during LAD occlusion. By contrast, only 1 of 7 RDN-treated animals experienced VF (P = .029). Beta-receptor blockade by atenolol showed comparable effects. Neither VF nor transient shortening of monophasic action potential duration during reperfusion was inhibited by RDN. RDN reduced the occurrence of ventricular arrhythmias/fibrillation and attenuated the rise in LVEDP during left ventricular ischemia without affecting infarct size, changes in ventricular contractility, blood pressure, and reperfusion arrhythmias. Therefore, RDN may protect from ventricular arrhythmias during ischemic events.

Development of a Pump Flow Estimator for Rotary Blood Pumps to Enhance Monitoring of Ventricular Function

Estimation of instantaneous flow in rotary blood pumps (RBPs) is important for monitoring the interaction between heart and pump and eventually the ventricular function. Our group has reported an algorithm to derive ventricular contractility based on the maximum time derivative (dQ/dt(max) as a substitute for ventricular dP/dt(max) ) and pulsatility of measured flow signals. However, in RBPs used clinically, flow is estimated with a bandwidth too low to determine dQ/dt(max) in the case of improving heart function. The aim of this study was to develop a flow estimator for a centrifugal pump with bandwidth sufficient to provide noninvasive cardiac diagnostics. The new estimator is based on both static and dynamic properties of the brushless DC motor. An in vitro setup was employed to identify the performance of pump and motor up to 20 Hz. The algorithm was validated using physiological ventricular and arterial pressure waveforms in a mock loop which simulated different contractilities (dP/dt(max) 600 to 2300 mm Hg/s), pump speeds (2 to 4 krpm), and fluid viscosities (2 to 4 mPa·s). The mathematically estimated pump flow data were then compared to the datasets measured in the mock loop for different variable combinations (flow ranging from 2.5 to 7 L/min, pulsatility from 3.5 to 6 L/min, dQ/dt(max) from 15 to 60 L/min/s). Transfer function analysis showed that the developed algorithm could estimate the flow waveform with a bandwidth up to 15 Hz (±2 dB). The mean difference between the estimated and measured average flows was +0.06 ± 0.31 L/min and for the flow pulsatilities -0.27 ± 0.2 L/min. Detection of dQ/dt(max) was possible up to a dP/dt(max) level of 2300 mm Hg/s. In conclusion, a flow estimator with sufficient frequency bandwidth and accuracy to allow determination of changes in ventricular contractility even in the case of improving heart function was developed.

EARLY CHANGES IN ELECTRICAL PROPERTIES OF ISCHEMIC HEART WITH AND WITHOUT ECE INHIBITION: THREE-DIMENSIONAL ELECTROCARDIOGRAPHY STUDY: PP.13.488

Little is known about the significance of ECE inhibition for modulation of electrical heart activity. The study aim was to assess three-dimensional electrocardiogram (ECG) changes during development of acute heart ischemia (AHI) due to global coronary arteries microembolization using 15 um microsphere with and without ECE inhibition. ECE inhibitor PP36 was used in current study. Two days before coronary embolization, male Wistar rats were randomized for treatment with PP36 (3.5 × 10–5 M/kg, AHI + PP36 group, n = 29) or with a vehicle (AHI group, n = 31 and sham control group, n = 15). Application of PP36 continued for two days post-embolization in AHI + PP36 group. Under anesthesia (sodium pentobarbital, 40 mg/kg), ECG were recorded with an orthogonal three-lead system before and after coronary vessels microembolization, and two days after global AHI induction. Data were analyzed with dedicated computer software. Invasively measured maximal left ventricular systolic pressure (LVSP) developed in response to aorta occlusion was similar between PP36 treated (261 + 5 mmHg) and untreated (261 + 4 mmHg) rats. Measured before induction of global heart ischemia magnitude of Q-wave and area under STT segment of controls and PP36 treated for two days rats were similar. ECG parameters of controls did not significantly change over time. However PP36 significantly reduced QRS-T angle after two days application. Immediately after induction of heart ischemia, LVSP was decreased by 26–27% and STT area was increased three-fold in AHI and AHI + PP36 groups. Differences between AHI and AHI + PP36 groups were reflected by depolarization changes in QRS-vector magnitude and repolarization changes in QRS- and T-axis orientation. In conclusion, three-dimensional ECG analysis appears to be very sensitive to early changes in ECE activity modulation. Induction of AHI with PP36 application is characterized by early ECG changes preceding left ventricular contractility changes compared to AHI group.

Augmentation Index, Left Ventricular Contractility, and Wave Reflection

Augmentation index (AIx), a correlate of mortality, is thought to be influenced by left ventricular contractility and wave reflections. However, the relationship of AIx with left ventricular contractility changes has never been assessed, and the wave reflection theory has recently been questioned. This study sought to examine arterial waveform changes in response to reduced "wave reflection" and increased left ventricular contractility induced by dobutamine. Simultaneous radial tonometry (for AIx) and tissue Doppler echocardiography (for peak longitudinal systolic strain rate [SR] as an analogue of left ventricular contractility) were recorded at rest and peak dobutamine-induced stress in 50 patients (41 men; aged 62+/-10 years). From baseline to peak stress there was an increase in heart rate (70+/-11 to 127+/-17 bpm; P<0.001) and SR (-0.88+/-0.23 to -1.81+/-0.43 1/s; P<0.001), whereas AIx decreased (27+/-9% to -7+/-15%; P<0.001). There was also a greater increase in the systolic (compared with diastolic) pressure-time integral relative to cardiac cycle length (3.2+/-1.9 versus 1.8+/-1.1 mm Hg; P<0.001), indicating that wave reflection was not shifted into diastole as per the current belief. AIx was significantly associated with ejection duration (r=0.88), heart rate (r=-0.81), and SR (r=0.72; P<0.001 for all). However, when SR was heart rate corrected, there was no significant association with AIx (r=0.18; P=0.11). The strongest independent correlate of AIx was ejection duration, accounting for 78% variance (beta=0.88; model R2=0.77; P<0.001). Neither SR (beta=0.12; P=0.18) nor heart rate-corrected SR (beta=0.02; P=0.72) was associated with AIx. We conclude that AIx is determined by chronotropic rather than inotropic effects, as well as factors other than wave reflection.

Assessment of cardiovascular dynamics by pressure-area relations in pediatric patients with congenital heart disease

Objectives: It is particularly useful to separately quantify the ventricular contractility and loading conditions for a better understanding of the cardiovascular dynamics in congenital heart disease, where abnormalities in chamber and loading properties may coexist. Furthermore, ventricular contractility and loading conditions may alter independently or simultaneously with disease progression and therapeutic intervention. The objectives of the present study were (1) to test whether ventricular pressure-area analysis can provide such quantitation among patients with various forms of congenital heart disease, (2) to reveal basal cardiovascular interaction in congenital heart disease by means of pressure-area analysis, and (3) to test the feasibility of this method in a simplified and less invasive form to further enhance its clinical value. Methods: We constructed pressure-area loops during caval occlusion by using transthoracic echocardiographic automated border detection combined with ventricular pressure recordings in 59 pediatric patients with congenital heart disease and in 7 normal control subjects. Results: Area measurements obtained by automated border detection were highly reproducible, and area changes reflected volume changes. The pressure-area data provided load-independent measures of contractility, which were consistently increased by use of dobutamine ( P < .05). End-systolic and arterial elastance individually quantified simultaneous changes in ventricular contractility and loading with milrinone infusion and predicted net cardiac performance. The pressure-area analysis better characterized the ventricular contractile states under a variety of loading conditions in congenital heart disease, whereas predominant load dependence of conventional indices confounded them. Furthermore, pressure-area relations were reasonably estimated from a single beat and from aortic pressure data during abdominal compression. Conclusions: Pressure-area analysis should provide a useful modality with which to assess cardiovascular dynamics in pediatric patients with congenital heart disease in more detail and should thus help improve the management of patients with this disease.

EFFECTS OF CARDIOTROPHIN-1 ON HAEMODYNAMICS AND CARDIAC FUNCTION IN CONSCIOUS RATS

Cardiotrophin-1 (CT-1), a newly discovered cytokine, has been shown to induce cardiac hypertrophy in vitro and in vivo. The present study examined the effects of CT-1 on haemodynamics and cardiac function. The measurements of haemodynamic parameters were made using in-dwelling catheters and flow probes in conscious, unrestrained rats. Intravenous administration of CT-1 caused a dose-dependent decrease in mean arterial pressure (MAP), and an increase in heart rate (HR). CT-1 (100 μg/kg) significantly elevated cardiac output and HR, and decreased MAP and systemic vascular resistance. Stroke volume was unaltered, suggesting that the CT-1 induced increase in cardiac output was secondary to increased HR. There was no significant difference in left ventricular maximal dP/dtbetween the CT-1-treated and vehicle-treated groups, suggesting that CT-1 might not induce a meaningful change in ventricular contractility. Pretreatment with intravenous Nω-nitro-l-arginine methyl ester, a specific inhibitor of nitric oxide synthase, significantly attenuated the depressor and tachycardic responses to CT-1. These results indicate that nitric oxide plays an important role in mediating the haemodynamic effects of CT-1.

Evaluation of Ventricular dP/dt Before and After Open Heart Surgery Using Transesophageal Echocardiography.

The mean dP/dt during isovolumetric contraction (mean dP/dt(ic)) is a new echocardiographic index of ventricular function that has been shown to approximate and closely correlate with invasively measured peak dP/dt. It is amenable to rapid measurement via transesophageal echocardiography (TEE) and is theoretically independent of variations in ventricular anatomy and wall motion. It is therefore well suited for the assessment of ventricular function during surgery. The purpose of this study was to assess the clinical value of TEE determinations of mean dP/dt(ic) before and after cardiopulmonary bypass (CPB). The mean dP/dt(ic) of 50 patients undergoing open heart surgery for a variety of congenital and acquired heart defects was measured before and 15-30 minutes after CPB. Mean dP/dt(ic) averaged 1147 +/- 492 before and 1428 +/- 702 mmHg/sec after CPB (P < 0.01). Mean dP/dt(ic) was unchanged or increased in 45 patients and fell in only 5 patients. It increased significantly even among patients who did not receive supplemental inotropic agents. Mean dP/dt(ic) correlated well with the shortening fraction, especially among patients without segmental left ventricular wall-motion abnormalities. The general patterns observed for mean dP/dt(ic) were also seen when the data was corrected for variations in heart rate. A preoperative mean dP/dt(ic) < 765 mmHg/sec or a heart rate corrected mean dP/dt(ic) < 620 mmHg/sec indicated a high likelihood that inotropic support would be needed to facilitate weaning from CPB. Mean dP/dt(ic) may be a clinically useful, quantitative TEE index of perioperative changes in ventricular contractility.

Parasympathetic denervation supersensitivity of the transplanted human ventricle in vivo.

Sympathetic inotropic supersensitivity after transplantation-associated denervation of the cardiac autonomic nervous system has been described in humans previously. Potential changes of the parasympathetic regulation of the human ventricular contractility have not been investigated yet. We studied the antiadrenergic, negative inotropic effect of carbachol (3.6 micrograms/kg) during continuous beta-adrenergic stimulation (with isoproterenol, 20 ng.kg-1.min-1) in seven heart transplant recipients and seven healthy controls. Changes in ventricular contractility were calculated as increase of the systolic pressure-to-dimension ratio (delta P/D) and the rate-corrected velocity of circumferential fiber shortening (delta Vcfc), using M-mode echocardiography. In the control group, the isoproterenol-induced increase in contractility was attenuated only insignificantly by carbachol [delta P/D from 1.53 +/- 0.53 to 0.81 +/- 0.55 mmHg/mm, delta Vcfc from 0.77 +/- 0.20 to 0.63 +/- 0.22% x square root of beats/min (bpm)/ms]. In contrast, the transplant group exhibited a significant reduction of the isoproterenol-induced increase in contractility [delta P/D from 1.27 +/- 0.71 to -0.81 +/- 0.51 mmHg/mm (P < 0.01), delta Vcfc from 1.04 +/- 0.84 to 0.04 +/- 0.43% x square root of bpm/ms (P < 0.01)]. These data are consistent with parasympathetic indirect negative inotropic supersensitivity of the transplanted human heart in vivo.

Short- and long-term variability of echocardiographic stress-velocity indexes of cardiac function in a pediatric population

This study determined the short- and long-term variability of stress-velocity relationships at end systole and peak systole. A prospective study during the short term (0 to 15 and 0 to 30 minutes) and long term (0 to 1 and 0 to 12 months) was performed calculating variability by the limits of agreement method. The study was performed in a tertiary-care pediatric echocardiographic laboratory. Twenty-five normal children underwent repeat testing as described. Standard blood pressure, carotid pulse tracing, and M-echocardiography of the left ventricle was performed at the intervals described. The rate-corrected mean velocity of fiber shortening (MVCF C), echocardiographic stress at end systole (SES), and echocardiographic stress at peak systole (SPS) were calculated for all recordings. The slopes of MVCF C-SES and MVCF C-SPS were determined by regression and plotted. With these slopes, the second and third stress values were normalized to the first stress value for the short and long term. The differences in normalized MVCF C and MVCF C (ΔMVCF C) for 15 to 0 minutes, 30 to 0 months, 1 to 0 month, and 12 to 1 month were obtained for both SES and SPS, and 95% limits of agreement were estimated. The mean ΔMVCF C for SES and SPS for the short and long term were not different from 0 or each other, indicating no bias. The 95% limits of agreement of ΔMVCF Cs (i.e., variability for SES at 15 to 0 minutes, 30 to 0 minutes, 1 to 0 months, and 12 to 0 month) were ±0.18, ±0.24, ±0.34, and ±0.27, respectively, and for SPS ±0.18, ±0.24, ±0.33, and ±0.28. Variability showed an increasing trend with time but was significant only from 15 to 0 minutes and 1 to 0 month ( p = 0.006). This study has established short- and long-term variability in the stress-velocity relationship that is essential for monitoring acute and chronic changes in ventricular contractility in an individual patient.

Mechanical matching of the left ventricle with the arterial system in exercising dogs.

We investigated how changes in ventricular contractility and arterial properties associated with exercise influence the energy transmission from the left ventricle to the arterial system. On six chronically instrumented dogs preconditioned to run on a treadmill, we imposed exercise loads of various degrees by altering the speed and slope of the treadmill (up to 7 km/hr and 20% slope). We evaluated ventricular contractility by end-systolic elastance (Ees) and arterial properties in terms of the effective arterial elastance (Ea). Ea was estimated by the ratio of mean aortic pressure to stroke volume. With exercise, Ees significantly increased from 7.6 +/- 1.7 to 10.9 +/- 2.6 mm Hg/ml (p less than 0.005), and Ea tended to increase from 4.9 +/- 1.4 to 6.7 +/- 1.8 mm Hg/ml (p = 0.068), whereas the ratio of Ea to Ees remained fairly constant (from 0.69 +/- 0.26 to 0.63 +/- 0.21, NS). The mechanical optimality index, defined as the ratio of stroke work to its theoretically derived maximal value, was 0.93 +/- 0.07 at rest and 0.92 +/- 0.08 at peak exercise. Similarly, the metabolic optimality index, defined as the ratio of cardiac oxygen consumption to stroke work conversion efficiency and its theoretical maximal value, was 0.98 +/- 0.02 at rest and 0.99 +/- 0.01 at peak exercise (NS). We conclude that external work of the left ventricle of these dogs was at a near maximal level for a given preload during exercise as well as at rest without compromising the conversion efficiency of metabolic energy to stroke work.

Effects of portal vein occlusion on myocardial contractility.

We studied canine left ventricular contractile performance following 15 min of portal vein occlusion by analyzing the end-systolic pressure diameter relationship (ESPDR) which many investigators have reported as being independent of changes in preload and afterload but sensitive to changes in ventricular contractility. Portal vein occlusion for 15 min decreased the mean arterial pressure, left ventricular peak systolic pressure, and cardiac index, while the release of the occlusion gradually increased these values, although it did not restore them to the control values. The systemic vascular resistance index increased during portal vein occlusion and returned to the control values after release. Left ventricular end diastolic diameter decreased during portal clamping and returned to the control values after release. ESPDR and percent shortening were not significantly changed during or after portal clamping. These results indicate that the decrease in blood pressure during portal vein occlusion was not due to a reduction in myocardial contractility but rather was due to a reduction in preload.

The Effect of Sodium Intake on Ventricular Performance in Healthy Men

We analyzed the effects of acute sodium intake on left ventricular performance in 11 healthy normotensive men using Doppler echocardiography. For 2 weeks, they took 2,700-kcal diets containing 6 g and 24 g sodium chloride per day in the low sodium phase (5 days) and in the high sodium phase (5 days), respectively. Blood pressure, urine, hematocrit, and echocardiographic values were measured every day throughout this study. Although a decrease in the serum norepinephrine concentration and an increase in the ejection fraction were noticed in the low sodium phase, there was no significant change in the relation between end-systolic stress and mean velocity of circumference shortening. All subjects also performed a cold pressor test in both phases, and we analyzed the end-systolic stress-volume relation (modified Emax). Modified Emax of the high sodium phase was significantly larger than that of the low sodium phase. As published in previous research on dogs, we consider that this discrepancy at rest may be caused by a dysfunction at the cardiac adrenergic neuroeffector junction in humans, too, and that sodium intake may enhance the change in ventricular contractility by a cold pressor test.

Late systolic indices of ventricular function: Noninvasive derivation in congestive heart failure

The slopes of end-systolic pressure/end-systolic dimension and volume relations have been found to be relatively load-independent indices of left ventricular contractility. Noninvasive determination of these relationships has been performed in normal subjects and has been found to reflect baseline and drug-induced changes in ventricular contractility. Three late systolic indices of ventricular contractility were noninvasively determined in subjects with chronic congestive heart failure to determine the feasibility of the method and to assess the linearity and slopes of the relationships in this population. All relations were linear with individual correlation coefficients ranging from 0.86 to 0.99. The mean ± SD slope was 42.8 ± 26.4 mm Hg/cm for the end-systolic pressure-dimension relation, 0.59 ± .42 mm Hg/ml for the end-systolic pressure-volume relation, and 48.7 ± 32.2 mm Hg/cm for the peak systolic pressure-end-systolic dimension relation. All slopes were markedly reduced compared to those reported in normal individuals. The relative degree of depression was greater for the pressure-volume slope than for the pressure-dimension slope, which is explained by the relationship between volume and dimension in dilated ventricles. These data indicate that measurement of late systolic indices of ventricular contractility by this noninvasive technique is feasible in subjects with congestive heart failure and yields reduced slopes consistent with the diminished contractile state of this population. Pressure-volume rather than pressure-dimension relations may more accurately reflect inotropic state in dilated ventricles.

Effect of positive end-expiratory pressure on right and left ventricular function in patients with the adult respiratory distress syndrome.

The predominant mechanism of the cardiac output reduction associated with positive end-expiratory pressure (PEEP) is unclear. Reported possibilities include decreased systemic venous return, increased pulmonary vascular resistance, or change in ventricular contractility. We investigated this question by studying 9 patients with the adult respiratory distress syndrome (ARDS) during PEEP application. We used an equilibrium radionuclide angiography method modified for improved right ventricular imaging to evaluate changes in left and right ventricular volume and contractility. Thermodilution cardiac output and stroke volume progressively declined (27 and 33% mean decrease, respectively) with increasing increments of PEEP. Right and left ventricular end diastolic counts, reflecting volume, also progressively diminished as PEEP increased (38 and 27% mean decrease in RV and LV counts, respectively; p less than 0.001 for both ventricles). A slight upward trend in ejection fraction was found for both ventricles. These findings support the concept that during PEEP application the reduction in cardiac output is due to biventricular reduction in blood volume. This biventricular volume reduction is compatible with either preload reduction to both ventricles because of impeded venous return or to change in ventricular configuration caused by external compression of both ventricles.

Canine left ventricular function during experimental pancreatitis

Left ventricular contractility following induction of experimental pancreatitis (EP) was studied. Contractility was evaluated by analyzing the left ventricular end systolic pressure-diameter relationship ( Σ ES). Σ ES is independent of large changes in preload, afterload, and heart rate, but sensitive to changes in ventricular contractility. Following injection of 100,000 IU trypsin in 4% taurocholate into the pancreas to induce EP, seven of eight dogs survived 5 hr. These dogs exhibited an initial significant reduction in mean arterial pressure (MABP) which stabilized at 90% of control at 3–5 hr post-EP. Cardiac output (CO) dropped slowly after EP induction (from 3.08 ± 0.43 to 2.22 ± 0.22 liters/min) associated with no significant change in peripheral resistance. Stroke work and stroke volume were markedly depressed reflecting the changes in MABP and CO. No consistent changes in + dP/dt or − dP/dt were observed. The ratio of endo/epicardial blood flow was unchanged as was blood Ca 2+ levels throughout the experiment. Ventricular contractility as reflected by Σ ES tended to improve (from 49.7 to 69.6 mm Hg/mm at 4 hr following EP). Therefore, it was concluded that these animals exhibited no loss of ventricular contractility during EP.