Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension

BACKGROUND: Monitoring left ventricular preload is critical to achieve adequate fluid resuscitation in patients with hypotension and sepsis. This prospective study tested the correlation of the pulmonary artery occlusion pressure, the left ventricular end-diastolic area index measured by transesophageal echocardiography, the arterial systolic pressure variation (the difference between maximal and minimal systolic blood pressure values during one mechanical breath), and its delta down (dDown) component (= apneic - minimum systolic blood pressure) with the response of cardiac output to volume expansion during sepsis. METHODS: Preload parameters were measured at baseline and during graded volume expansion (increments of 500 ml) in 15 patients with sepsis-induced hypotension who required mechanical ventilation. Each volume-loading step (VLS) was classified as a responder (increase in stroke volume index > or = 15%) or a nonresponder. Successive VLSs were performed until a nonresponder VLS was obtained. RESULTS: Thirty-five VLSs (21 responders) were performed. Fluid loading caused an overall significant increase in pulmonary artery occlusion pressure and end-diastolic area index, and a significant decrease in systolic pressure variation and delta down (P < 0.01). There was a significant difference between responder and nonresponder VLSs in end-diastolic area index, systolic pressure variation, and dDown, but not in pulmonary artery occlusion pressure. Receiver-operator curve analysis showed that dDown was a more accurate indicator of the response of stroke volume index to volume loading than end-diastolic area index and pulmonary artery occlusion pressure. A dDown component of more than 5 mmHg indicated that the stroke volume index would increase in response to a subsequent fluid challenge (positive and negative predictive values: 95% and 93%, respectively). CONCLUSION: The dDown component of the systolic pressure variation is a sensitive indicator of the response of cardiac output to volume infusion in patient with sepsis-induced hypotension who require mechanical ventilation.     

Right latissimus dorsi cardiomyoplasty augments left ventricular systolic performance

We hypothesized that the right latissimus dorsi cardiomyoplasty augments left ventricular performance. Five dogs underwent staged right latissimus dorsi cardiomyoplasty. Ventricular function was studied 1 to 3 weeks later. Left ventricular pressure was measured with a micromanometer and left ventricular dimensions with piezoelectric crystals. Inferior vena caval occlusion was used to vary preload. Pressure-volume data were collected with the muscle unstimulated and stimulated at 1:2 and 1:1 muscle/heart ratios. The end-systolic pressure-volume relation (mm Hg/mL), stroke work, preload recruitable stroke work, left ventricular end-diastolic volume, and the diastolic relaxation constant were calculated and expressed as mean +/- standard deviation. Stimulated beats at a 1:2 ratio showed an increase in stroke work of 42.1% (978 +/- 381 to 1,390 +/- 449 g.cm; p < 0.01) and preload recruitable stroke work of 28.8% (59.4 +/- 20.7 to 76.6 +/- 11.0 g.cm/cm3; p = 0.05) compared with the unstimulated beats. With the stimulator on at 1:1, smaller changes occurred: stroke work increased 9% (1,167 +/- 390 to 1,273 +/- 363 g.cm; not significant) and preload recruitable stroke work increased 27% (63.9 +/- 22.7 to 80.9 +/- 23.1 g.cm/cm3; p = 0.05). There were no significant changes in the end-systolic pressure-volume relation. The diastolic relaxation constant did not change at 1:1 (36 +/- 9.7 to 37 +/- 6.4 ms; not significant) or 1:2 (36 +/- 9.3 to 39 +/- 8.2 ms; not significant). Left ventricular end-diastolic volume was unchanged at 1:1 (34 +/- 10.7 to 32 +/- 10.3 mL) and at 1:2 (31 +/- 9.0 to 32 +/- 8.7 mL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Right ventricular end-diastolic volume as a predictor of the hemodynamic response to a fluid challenge

OBJECTIVE: To compare thermodilution right ventricular end-diastolic volume index (RVEDVI) and pulmonary artery occlusion pressure (Ppao) as predictors of the hemodynamic response to a fluid challenge. DESIGN: Prospective cohort study. SETTING: Medical ICU of a university-affiliated county hospital and medical-surgical ICU of a community hospital. PATIENTS: Twenty-five critically ill patients who had one or more clinical conditions that suggested the possibility of inadequate preload. INTERVENTIONS: Thirty-six fluid challenges. Fluid (saline or colloid) was administered rapidly until the Ppao rose by at least 3 mm Hg. When a patient underwent more than one fluid challenge, these were given on separate days and for different clinical indications. MEASUREMENTS AND RESULTS: Responders (n=20; > or = 10% increase in stroke volume [SV]) and nonresponders (n=16; <10% increase in SV) differed with respect to baseline Ppao (10.0+/-3.4 vs 14.2+/-3.6 mm Hg; p=0.001), but not with respect to baseline RVEDVI (105+/-31 vs 119+/-33 mL/m2; p=0.22). There was a moderate correlation between RVEDVI and fluid-induced change in SV (r=0.44); the relationship between Ppao and change in SV was stronger (r=0.58). A positive response to fluid was observed in 4 of 9 cases in which RVEDVI exceeded 138 mL/m2, a threshold value that has been suggested to reliably predict a poor response to fluid. CONCLUSION: RVEDVI was not a reliable predictor of the response to fluid. As a predictor of fluid responsiveness, Ppao was superior to RVEDVI. In an individual patient, adequacy of preload is best assessed by an empiric fluid challenge.     

P-selectin blockade is beneficial after uncontrolled hemorrhagic shock

OBJECTIVE: Increased intra-abdominal pressure (IAP) compromises cardiopulmonary function and visceral perfusion. Our goal was to characterize acute changes in these subsystems associated with operative abdominal decompression. PATIENT POPULATION: A series of 11 consecutive injured patients monitored with a pulmonary artery catheter and nasogastric tonometer in whom operative decompression was performed. Indications for decompression included oliguria or progressive acidosis despite aggressive resuscitation in the presence of elevated IAP (>25 mm Hg). MAIN OUTCOME MEASURES: Studied hemodynamic variables included pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic volume index (RVEDVI), and cardiac index (CI). Pulmonary variables included shunt fraction (Qs/Qt) and dynamic compliance (Cdyn). Visceral perfusion was assessed using hourly urine output 4 hours before and after decompression (UOP) and gastric intramucosal pH (pHi). Mean values before and after decompression were compared using the paired t test. Linear regression and Fisher's z transformation were used to evaluate the relationships between RVEDVI, PAOP, CI, and IAP. IAP was transduced via bladder pressures. Significance was defined as p < 0.05. Data are expressed as means+/-SD. RESULTS: IAP decreased with decompression (49+/-11 to 19+/-6.8 mm Hg; p < 0.0001). RVEDVI improved independent of CI and correlated better (p < 0.01) with CI (r =0.49, p=0.04) than PAOP did (r=-0.36, p=0.09). PAOP correlated significantly with IAP (r=0.45, p=0.04). Decompression resulted in significant improvements in Qs/Qt, Cdyn, UOP, and pHi. CONCLUSION: Abdominal decompression in patients with increased IAP improves preload, pulmonary function, and visceral perfusion. Elevated IAP has important effects on PAOP, which makes the PAOP an unreliable index of preload in these patients.     

Assessment of preload reserve in myocardial ischemia--the relation between preload reserve and ischemic size differs between anterior descending and circumflex coronary artery occlusions in a canine model

The role of changes in preload in maintaining stable hemodynamics during coronary obstruction was assessed in the presence of myocardial ischemia due to occlusions of the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. Changes in preload (mean left atrial pressure) to maintain a constant stroke volume after coronary occlusion were examined in 18 anesthetized dogs (LAD occlusion in 9 dogs, LCX occlusion in 9 dogs). The level of ischemia was assessed sonomicrometrically. Ventricular function curves relating left atrial pressure to stroke volume were assessed during a control state and after 1 min of coronary occlusion. The extent of preload reserve after coronary occlusion was examined on the ventricular function curves and was defined as the change in mean left atrial pressure required to maintain stroke volume at the level of the control state under conditions of regional ischemia. Ischemic size was determined by a stereo-angiogram after the animals were sacrificed. The extent of preload reserve (X) was linearly related to the ischemic size (Y) in both LAD (Y = 0.90 + 0.16X, r = 0.76, p < 0.001) and LCX (Y = -1.79 + 0.19X, r = 0.79, p < 0.001) occlusions. The slopes of the regression lines in LAD and LCX occlusions were the same. The X intercepts of these lines were -5.6% and 9.4% of the left ventricular weight in LAD and LCX ischemia (p < 0.001), respectively. Thus, the presence of systolic wall motion abnormalities due to coronary occlusion can be compensated for hemodynamically by changes in the preload reserve.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of ventricular volume reduction surgery in the dilated, poorly contractile left ventricle: a simple finite element analysis

OBJECTIVES: Ventricular volume reduction surgery has been proposed by Batista to improve cardiac function in patients with dilated cardiomyopathy. However, limited clinical data exist to determine the efficacy of this operation. A finite element simulation is therefore used to determine the effect of volume reduction surgery on left ventricular end-systolic elastance, diastolic compliance, stroke work/end-diastolic volume (preload recruitable stroke work), and stroke work/end-diastolic pressure (Starling) relationships. METHODS: End-diastole and end-systole were represented by elastic finite element models with different unloaded shapes and nonlinear material properties. End-systolic elastance, diastolic compliance, preload recruitable stroke work, and Starling relationships, as well as energy expenditure per gram of unresected myocardium, were calculated. Two different types of volume reduction surgery (apical and lateral) were simulated at 10% and 20% left ventricular mass reduction. RESULTS: Ventricular volume reduction surgery causes diastolic compliance to shift further to the left on the pressure-volume diagram than end-systolic elastance. Volume reduction surgery increases the slope of the preload recruitable stroke work relationship (dilated cardiomyopathy 0.006 J/mL; 20% lateral volume reduction surgery 0.009 J/mL) but decreases the slope of the Starling relationship (dilated cardiomyopathy 0.028 J/mm Hg; 20% lateral volume reduction 0.023 J/mm Hg). For a given amount of resection, lateral volume reduction has a greater effect than apical volume reduction. Ten-percent and 20% lateral volume reduction reduces energy expenditure by 7% and 17%, respectively. CONCLUSION: Ventricular volume reduction surgery shifts end-systolic elastance and diastolic compliance to the left on the pressure-volume diagram. The net effect on ventricular function is mixed. Volume reduction surgery increases the slope of preload recruitable stroke work, but increased diastolic compliance causes a small decrease in the Starling relationship (3 mm Hg difference between dilated cardiomyopathy and volume reduction surgery at stroke work = 0.5 J).     

Transesophageal echocardiography: an objective tool in defining maximum ventricular response to intravenous fluid therapy

Ventricular preload is an important determinant of cardiac function, which is indirectly measured in the clinical setting by the pulmonary capillary wedge pressure (PCWP). Transesophageal echocardiography (TEE) is rapidly gaining acceptance as a monitor of cardiac function. Although it provides high-resolution images of cardiac structures, clinical assessment of ventricular preload using TEE has been subjective, since quantitative measurements have been difficult to perform in a timely fashion. Automated border detection (ABD) is a new technology used in conjunction with TEE that allows quantitative real-time, two-dimensional measurement of cavity areas. To determine whether enddiastolic area (EDA) measured by ABD can be used to determine an appropriate end point for intravenous fluid administration, nine mongrel dogs were studied. Anesthetized animals were hemorrhaged to achieve a central venous pressure of 0-5 mm Hg. Each animal was then given intravenous fluid (autologous blood followed by hetastarch) until a peak in thermodilution cardiac output (CO) was achieved. Measures of PCWP, EDA, CO, and left ventricular stroke work (LVSW) were obtained after each fluid bolus. Bivariate plots displaying administered volume versus CO, LVSW, and EDA revealed parallel curves for each of these variables with peaks evident at cumulative volumes of 50-55 mL/kg. Multiple regression with mixed model analysis of covariance was performed to determine the significance of EDA in relation to changes in CO and LVSW. Analysis was likewise performed comparing the relationship between PCWP and changes in CO or LVSW. A significant relationship was demonstrated when comparing EDA to changes in CO and LVSW (P = 0.03 and P < 0.0001, respectively). Similar analysis comparing PCWP to changes in CO and LVSW failed to demonstrate a significant relationship (P = 0.54 and P = 0.36, respectively). These data suggest that changes in EDA measured using TEE with ABD are related to trends in cardiac function and can suggest an appropriate end point for intravenous fluid administration as defined by maximum CO and LVSW. PCWP did not demonstrate a significant relationship to changes in CO and LVSW.     

Fibroelastolytic papulosis of the neck: a report of 20 cases

BACKGROUND: Reports of pulmonary edema complicating inhaled nitric oxide therapy in patients with chronic heart failure and pulmonary hypertension have raised the concern that inhaled nitric oxide may have negative inotropic effects. METHODS AND RESULTS: We investigated the effect of multiple doses of inhaled nitric oxide (20, 40 and 80 ppm) on left ventricular contractile state in 10 open-chest pigs. Pressure-volume loops were generated during transient preload reduction to determine the end-systolic pressure-volume relationship and the stroke work-end-diastolic volume relation. Inhaled nitric oxide had no effect on systemic vascular resistance, cardiac output, end-systolic pressure volume relationship or stroke work-end-diastolic volume relation under normal conditions. After induction of pulmonary hypertension (intravenous thromboxane A2 analog), inhalation of nitric oxide (80 ppm) resulted in a reduction in pulmonary vascular resistance (mean +/- standard error of the mean) from 10.4 +/- 3 to 6.5 +/- 2 Wood units (p < 0.001) and in pulmonary artery pressure from 44 +/- 4 to 33 +/- 4 mm Hg (p < 0.05). Left ventricular end-diastolic volume rose from 53 +/- 9 ml to 57 +/- 10 ml (p = 0.02). No statistically significant change in cardiac output or systemic vascular resistance was observed. Inhaled nitric oxide had no effect on end-systolic pressure-volume relationship or stroke work-end-diastolic volume relation. CONCLUSIONS: In a porcine model of pulmonary hypertension, inhaled nitric oxide does not impair left ventricular contractile function. Therefore the cause of pulmonary edema observed in some patients receiving inhaled nitric oxide is not due to a negative inotropic action of this therapy.     

Effects of load manipulations, heart rate, and contractility on left ventricular apical rotation. An experimental study in anesthetized dogs

BACKGROUND: Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured. METHODS AND RESULTS: Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61 +/- 0.06 degrees/percent change; intercept, -60.1 +/- 6.2 degrees; n = 10) that differed from the end-systolic (ES) relation (slope, 1.36 +/- 0.27 degree/percent change; intercept, -132.5 +/- 24.9 degrees; P < .005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation-volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period. CONCLUSIONS: The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation.     

Central venous pressure, pulmonary capillary wedge pressure and intrathoracic blood volumes as preload indicators in cardiac surgery patients

OBJECTIVE: Monitoring of cardiac preload is mainly performed by measurement of central venous and pulmonary capillary wedge pressure in combination with assessment of cardiac output, applying the pulmonary arterial thermal dilution technique. However, the filling pressures are negatively influenced by mechanical ventilation and the pulmonary artery catheter is criticized because of its inherent risks. Measurement of right atria, right ventricular, global end diastolic and intrathoracic blood volume index by arterial thermal dye dilution utilizing the COLD-system may represent an alternative. METHODS: In 30 CABG patients with an uncomplicated postoperative course the mentioned parameters were measured 1, 3, 6, 12 and 24 h postoperatively to prove their qualification as preload indicators: As patients received no inotropic support, changes of cardiac index and stroke volume index must correlate to changes of presumably preload indicating parameters. RESULTS: When arterial and pulmonary arterial thermal dilution were compared, no differences were found; the correlation coefficient being 0.96, the bias 0.16 l/min per m2 (2.4%) and coefficients of variation did not exceed 7%. Changes of central venous pressure, capillary wedge pressure, right atrial end diastolic volume index and right ventricular end diastolic volume index did not correlate at all to changes of cardiac and stroke volume index (coefficients ranged from -0.01 to 0.28). In contrast, intrathoracic and global end diastolic blood volume indices with coefficients from 0.76 to 0.87, did show a good correlation to cardiac and stroke volume index. CONCLUSION: Central venous pressure, capillary wedge pressure, right atrial and right ventricular end diastolic volumes are no suitable preload parameters in cardiac surgery intensive care, compared to intrathoracic and global end diastolic blood volumes. The latter show a higher clinical value and can be obtained by less invasive methods, as no pulmonary artery catheter is required.     

Expanded blood volumes contribute to the increased cardiovascular performance of endurance-trained older men

To determine whether expanded intravascular volumes contribute to the older athlete's higher exercise stroke volume and maximal oxygen consumption (VO2 max), we measured peak upright cycle ergometry cardiac volumes (99mTc ventriculography) and plasma (125I-labeled albumin) and red cell (NaCr51) volumes in 7 endurance-trained and 12 age-matched lean sedentary men. The athletes had approximately 40% higher VO2 max values than did the sedentary men and larger relative plasma (46 vs. 38 ml/kg), red cell (30 vs. 26 ml/kg), and total blood volumes (76 vs. 64 ml/kg) (all P < 0.05). Athletes had larger peak cycle ergometer exercise stroke volume indexes (75 vs. 57 ml/m2, P < 0.05) and 17% larger end-diastolic volume indexes. In the total group, VO2 max correlated with plasma, red cell, and total blood volumes (r = 0.61-0.70, P < 0.01). Peak exercise stroke volume was correlated directly with the blood volume variables (r = 0.59-0.67, P < 0.01). Multiple regression analyses showed that fat-free mass and plasma or total blood volume, but not red cell volume, were independent determinants of VO2 max and peak exercise stroke volume. Plasma and total blood volumes correlated with the stroke volume and end-diastolic volume changes from rest to peak exercise. This suggests that expanded intravascular volumes, particularly plasma and total blood volumes, contribute to the higher peak exercise left ventricular end-diastolic volume, stroke volume, and cardiac output and hence the higher VO2 max in master athletes by eliciting both chronic volume overload and increased utilization of the Frank-Starling effect during exercise.     

Effects of intrapleural pressure changes on canine left ventricular function

Left ventricular diameter, pressure, and dP/dt, as well as aortic and intrapleural pressures, were recorded simultaneously from 10 acute anethetized mongrel dogs. Normal inspiration produced a significant decrease in end-diastolic diameter (46.9 +/- 1.2 to 43.1 +/- 1.0 mm) and end-systolic diameter (35.5 +/- 1.4 to 34.2 +/- 1.7 mm), reducing stroke diameter 2.5 mm. Airway occlusion (greater than or equal to 60%) produced a reduction in the decrease of end-diastolic diameter seen with normal inspiration and, to a lesser degree, in end-systolic diameter. Because only acute airway occlusion greater than or equal to 80% produced a significant increase in left ventricular afterload, the authors conclude that normal spontaneous inspiration results in a decrease in left ventricular preload due to pooling of blood in the pulmonary vasculature. The data suggest that this decrease in left ventricular preload is the predominant mechanism responsible for the inspiratory decrease in left ventricular stroke volume.     

Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure

OBJECTIVE: To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi). DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Seven mechanically ventilated flow-limited COPD patients (PEEPi = 9.7 +/- 1.3 cmH2O, mean +/- SD) with acute respiratory failure. INTERVENTION: Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH2O). MEASUREMENTS AND RESULTS: Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH2O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right end-diastolic ventricular volume index (RVEDVI) (r = 0.61; p < 0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r = -55; p < 0.001), but no with PEEPi,cw (r = -0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur. CONCLUSIONS: In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.     

Comparison of continuous left ventricular volumes by transthoracic two-dimensional digital echo quantification with simultaneous conductance catheter measurements in patients with cardiac diseases

Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 +/- 15 years, range 22 to 70; ejection fraction 63 +/- 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter = slope. DEQ + intercept, slope = 0.94 +/- 0.09, intercept = 5 +/- 8 ml, r2 = 0.86 +/- 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 +/- 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. End-diastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 +/- 0.31, mean intercept 14 +/- 37 ml, average r2 = 0.89 +/- 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 +/- 0.43, intercept = -20 +/- 26 ml, r2 = 0.67 +/- 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans.     

Determinants of myocardial performance after blunt chest trauma

OBJECTIVE: This study investigates whether factors that determine myocardial performance (preload, afterload, heart rate, and contractility) are altered after isolated unilateral pulmonary contusion. METHODS: Catheters were placed in the carotid arteries, left ventricles, and pulmonary arteries of anesthetized, ventilated (FiO2=0.5) pigs (31.2+/-0.6 kg; n=26). A unilateral, blunt injury to the right chest was delivered with a captive bolt gun (n=17) followed by tube thoracostomy. To control for anesthesia and instrumentation at FiO2 of 0.5, one group received tube thoracostomy only (sham injury; n=6). To control for effects of hypoxia without chest injury, an additional sham-injury group (n=3) was ventilated with FiO2 of 0.12. To generate cardiac function (i.e., Starling) curves, lactated Ringer's solution was administered in three bolus infusions at serial time points; the slope of stroke index versus ventricular filling pressure defines cardiac contractility. RESULTS: By 4 hours after pulmonary contusion, pulmonary vascular resistance, airway resistance, and dead space ventilation were increased, whereas PaO2 (72+/-6 mm Hg at FiO2=0.5) and dynamic compliance were decreased (all p < 0.05). Despite profound lung injury, arterial blood pressure, heart rate, cardiac filling pressures, and output remained within the normal range, which is inconsistent with direct myocardial contusion. The slope of pulmonary capillary wedge pressure versus left ventricular end-diastolic pressure (LVEDP) regression was reduced by more than 50% from baseline (p < 0.05), but there was no significant change in the slope of the central venous pressure versus LVEDP regression. By 4 hours after contusion, the slope of the stroke index versus LVEDP curve was reduced by more than 80% from baseline (p < 0.05). By the same time after sham injury with FiO2 of 0.12 (PaO2 < 50 mm Hg), the regression had decayed a similar amount, but there was no change in the slope after sham injury with FiO2 of 0.5 (PaO2 > 200 mm Hg). CONCLUSION: After right-side pulmonary contusion, the most often used estimate of cardiac preload (pulmonary capillary wedge pressure) does not accurately estimate LVEDP, probably because of changes in the pulmonary circulation or mechanics. Central venous pressure is a better estimate of filling pressure, at least in these conditions, probably because it is not directly influenced by the pulmonary dysfunction. Also, ventricular performance can be impaired by depressed myocardial contractility and increased right ventricular afterload even with normal left ventricular afterload and preload. It is thus conceivable that occult myocardial dysfunction after pulmonary contusion could have a role in the progression to cardiorespiratory failure even without direct cardiac contusion.     

Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans

BACKGROUND: Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS: Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.     

Straightening out the renal tubule: advances in the molecular basis of the inherited tubulopathies

OBJECTIVE: To assess the left ventricular determinants of cardiac output in 12 chronically instrumented fetal lambs, six of which where made anemic. METHODS: Twelve, singleton pregnant ewes were instrumented between 123-126 days gestation and chronic catheters placed in-situ. In six fetal lambs, isovolemic fetal anemia was induced (reducing the hematocrit from a mean of 35% to 20%). In a prospective study, absolute 'beat-to-beat' LV volumes and pressures were obtained (gestational age 131-134 days) using a conductance catheter method and a comparison made with non-anemic fetal lambs. RESULTS: The group of anemic fetuses (n = 6) had a significantly reduced hematocrit as compared to the control group (37% decrease: mean difference--13.4%; P < 0.001). The arterial blood gases of the two groups were not statistically different, with the exception of the pO2 and oxygen content which were significantly lower in the anemic group (P < 0.05). There was no significant change in fetal heart rate, LV preload (as assessed by venous pressure, end-diastolic volume and pressure) or mean arterial pressure between the anemic and control groups. However, a 75% increase in LV stroke volume was observed in the anemic fetal lambs (P < 0.05), secondary to a 61% fall in LV afterload (P < 0.05). There was no significant change in inherent myocardial contractility of the LV, although this did increase to approach statistical significance in the anemic group (P = 0.056). The diastolic time interval was increased by 22% in the anemic fetus, possibly allowing prolonged LV filling time. The indices measuring LV relaxation (Tau and dP/dtmin) were not significantly different in either group. CONCLUSIONS: This is the first study to report absolute left ventricular volumes in the anemic ovine fetus and the relationship of these data to LV pressure during the cardiac cycle. The model used produces a state of moderately severe, non-hydropic, isovolemic, fetal anemia consistent with those previously described. Although the anemic state was not prolonged, an observed increase in LV stroke volume (which is predominantly due to a decrease in afterload) has been described.     

Left atrial energy in normal subjects, in patients with symptomatic mitral stenosis, and in patients with advanced heart failure

In a population consisting of 45 subjects (15 patients with mitral stenosis, 15 patients with heart failure, and 15 normal subjects), the left atrial (LA) pressure-area relation was assessed and the correlations between LA stroke work, LA kinetic energy, and LA ejection force were studied. The area of the counterclockwise A loop expressing the LA external work was measured. LA kinetic energy was obtained from the formula: 1/2 x stroke volume x 1.06 x v2, where v = transmitral Doppler A velocity. An excellent correlation was found between LA stroke work index and LA kinetic energy when data from all patients were plotted together (r = 0.95, p <0.001). The Pearson's correlation similarity coefficient between LA ejection force and kinetic energy as well as between LA ejection force and stroke work index was r = 0.54 (p <0.001). The r value of 0.54 was significantly lower than r = 0.95 (p <0.03). LA kinetic energy extends the use of transmitral flow Doppler data to include assessment of LA work. LA work can be obtained noninvasively with a high degree of accuracy.     

Decisions about enteral tube feeding among the elderly

OBJECTIVE: To characterize the acute actions and physiologic dose profile of epinephrine, as a single inotrope, in patients with septic shock. DESIGN: Prospective clinical study. The relationship between epinephrine dose and cardiovascular variables was analyzed using repeated-measures analysis of variance. SETTING: ICU in a university teaching hospital. PATIENTS: Eighteen patients with septic shock, mean age 64 +/- 8 (SD) yrs, and with a mean admission Acute Physiology and Chronic Health Evaluation (APACHE II) score of 23 (range 14 to 35). INTERVENTIONS: Initial volume loading and the measurement of a baseline hemodynamic profile were followed by the administration of an epinephrine infusion at 3 microgram/min with subsequent increments of 3 micrograms/min and the determination of a hemodynamic profile after each dose increment. Therapy was titrated to clinical goals of perfusion and restoration of premorbid systolic arterial BP. MEASUREMENTS AND MAIN RESULTS: After volume loading, mean hemodynamic indices were as follows: mean arterial pressure (MAP) 62 +/- 7 mm Hg; cardiac index 3.8 +/- 1.1 L/min/m2; left ventricular stroke work index 25 +/- 11 g.m/m2; oxygen delivery (Do2) index 460 +/- 168 mL/min/m2; and oxygen consumption (VO2) index 165 +/- 64 mL/min/m2. In the dose range of 3 to 18 microgram/min, epinephrine produced linear increases in average heart rate, MAP, cardiac index, left ventricular stroke work index, stroke volume index, VO2, and DO2. No effect was noted on pulmonary artery occlusion pressure (PAOP), mean pulmonary arterial pressure, or systemic vascular resistance index. CONCLUSIONS: Epinephrine increases DO2 in septic shock by increasing cardiac index without an effect on systemic vascular resistance index or PAOP.     

Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans

OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.