End-systolic Pressure-dimension Research Articles

Minor segmental wall motion abnormalities detected in patients with Chagas' disease have adverse prognostic implications

Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 +/- 6.9%) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4%) and in only 10 group 2 patients (22.2%; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.

Modulation of calcium transport improves myocardial contractility and enzyme profiles after prolonged ischemia-reperfusion

Background Ischemia-reperfusion (IR) injury causes myocardial dysfunction in part through intracellular calcium overload. A recently described pharmacologic compound, MCC-135 (5-methyl-2-[1-piperazinyl] benzenesulfonic acid monohydrate, Mitsubishi Pharma Corporation), alters intracellular calcium levels. This project tested the hypothesis that MCC-135 would influence regional myocardial contractility when administered at reperfusion and after a prolonged period of ischemia. Methods A circumflex snare and sonomicrometry crystals within remote and area-at-risk regions were placed in pigs (n = 18, 32 kg). Coronary occlusion was instituted for 120 minutes followed by 180 minutes of reperfusion. At 105 minutes of ischemia pigs were randomly assigned to IR only (n = 11) or MCC-135 (IR-MCC [300 μg · kg −1 · h −1, n = 7]) administered intravenously. Regional myocardial contractility was determined by calculation of the regional end-systolic pressure-dimension relation (RESPDR [mm Hg/cm]). Myocardial injury was determined by measurement of plasma levels of myocyte-specific enzymes. Results At 90 minutes ischemia, mean troponin-I was 35 ± 8 ng/mL with no significant difference between groups. At 180 minutes reperfusion, heart rate was increased by 18% ± 5% in the IR only group ( p < 0.05) and was reduced by 11% ± 4% with IR-MCC ( p < 0.05). At 90 minutes ischemia RESPDR was reduced from baseline by 51% ± 6% ( p < 0.05). By 30 minutes reperfusion, reductions in RESPDR were attenuated with IR-MCC compared with IR only values. The CK-MB levels were increased at 180 minutes reperfusion in the IR only group (52 ± 9 ng/mL) compared with baseline (6 ± 1 ng/mL, p < 0.05) but were attenuated with IR-MCC (24 ± 4 ng/mL, p < 0.05) compared with IR only values. Conclusions Despite similar degrees of injury at 90 minutes ischemia MCC-135 improved regional contractility and reduced the egress of CK-MB. Moreover MCC-135 was associated with decreased heart rate, a determinant of myocardial oxygen demand. Pharmacologic modulation of calcium transport ameliorates myocardial dysfunction in the acute IR period.

Direct inhibition of the sodium/hydrogen exchanger after prolonged regional ischemia improves contractility on reperfusion independent of myocardial viability

Background A mechanism for myocardial dysfunction after ischemia and reperfusion is Na +/H + exchanger activation. Although past in vivo models of limited ischemia and reperfusion intervals demonstrate that Na +/H + exchanger inhibition confers myocardial protection when administered at the onset of ischemia, the effect of Na +/H + exchanger inhibition on myocardial function after prolonged ischemia and reperfusion remains unknown. This investigation tested the hypothesis that Na +/H + exchanger inhibition instituted at reperfusion and after prolonged coronary occlusion in pigs would influence myocardial contractility independent of myocardial viability. Methods A coronary snare and sonomicrometry crystals were placed in pigs (n = 21, 32 kg). Coronary occlusion was instituted for 120 minutes followed by reperfusion for 180 minutes. At 105 minutes of ischemia, pigs were randomized to ischemia and reperfusion only (saline solution, n = 11) or Na +/H + exchanger inhibition (HOE-642, 3 mg/kg intravenously, n = 10). Myocardial injury was determined by tissue staining and measurement of plasma myocyte–specific enzymes. Myocardial contractility was determined by calculation of the regional end-systolic pressure-dimension relation (millimeters of mercury per centimeter) and by assessment of interregional shortening. Results Infarct size was not different between groups (39% ± 6%, P = .26). Moreover, at 180 minutes of reperfusion, plasma troponin-I and creatine kinase MB values had increased to identical levels in the ischemia and reperfusion–only and Na +/H + exchanger inhibition groups (300 ± 35 and 50 ± 6 ng/mL, respectively). At 90 minutes of ischemia, regional end-systolic pressure-dimension relation decreased from baseline (5.7 ± 0.5 versus 2.7 ± 0.3, P < .05) in the area at risk. By 30 minutes of reperfusion, regional end-systolic pressure-dimension relation decreased further in the ischemia and reperfusion–only group (1.6 ± 0.2, P < .05), but improved with Na +/H + exchanger inhibition (4.4 ± 0.7, P < .05). Conclusions Na +/H + exchanger inhibition instituted at reperfusion improved contractility independent of myocardial viability as assessed by absolute infarct size and myocyte-specific enzyme release. Thus, modulation of Na +/H + exchanger activity in the setting of prolonged ischemia and reperfusion may hold therapeutic potential.

Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker.

It is not known how the angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) attenuate heart failure (HF) in viable ischemic hearts. To assess HF in a rat coronary stenosis (CS) model, we administered vehicle and quinapril or candesartan (or both) orally for 12 wk. Compared with the sham group, the vehicle group showed impaired myocardial perfusion, impaired coronary endothelial nitric oxide (NO) function in vitro, exhausted myocardial mitochondrial respiration, larger left ventricular (LV) dimensions and lower ejection fraction, lower LV rate of pressure development over time (dP/dt), lower slopes of LV end-systolic pressure-dimension relations (ESPDRs), and increased myocardial fibrosis. Treatment with quinapril or candesartan ameliorated these parameters without modifying the epicardial CS severity. Moreover, their combination maintained similar myocardial perfusion, despite a trend toward lower blood pressure, and showed distinctive neurohumoral modulation, normalized mitochondrial respiration, and increased ESPDR slopes. Thus improved myocardial blood flow and coronary flow reserve by quinapril or candesartan are the key to alleviate CS-induced HF, and their combination may have a therapeutic significance partly through ameliorated mitochondrial respiration and improved LV systolic function.

Minor segmental dyssynergy reflects extensive myocardial damage and global left ventricle dysfunction in chronic Chagas disease

The majority of patients with Chagas disease (ChD) remain for 10 to 30 years or even for life in the indeterminate form (IF) of this disease. They have positive-specific serology tests for ChD, but no symptoms or physical signs, and normal findings for electrocardiograms (ECGs) and heart, esophagus, and colon radiographs. To investigate whether patients in this phase of disease have any impairment of left ventricular (LV) systolic performance, we assessed their contractility index by the slope of the LV end-systolic pressure-dimension (Pes-Des) relation. We studied 35 patients with ChD (14 IF, 11 digestive form [DF], 10 cardiac form [CF]) and 13 healthy subjects. Patients with the CF had only minor cardiac involvement (bundle-branch block, normal LV ejection fraction). All patients had normal baseline global LV systolic function on 2-dimensional echocardiography, but minor segmental wall motion abnormalities were observed in 3 DF, 3 IF, and 2 CF patients. At rest and during intravenous phenylephrine infusion, we measured LV dimensions by echocardiography, and LV end-systolic pressure was estimated by a calibrated carotid pulse tracing. We also measured percent fractional shortening (%ΔD) and the rate-corrected mean velocity of fiber shortening (Vcfc). Mean values (± SD) of %ΔD and Vcfc were not significantly different from those exhibited by healthy control subjects in any of the ChD groups at rest (except for CF) or at peak stress using phenylephrine. The Pes-Des slope was similarly and significantly reduced in all ChD patients (IF: 50.7 ± 25; DF: 52.3 ± 24; CF: 60.8 ± 22 mm Hg/cm) compared with normal subjects (89 ± 17 mm Hg/cm). The Pes-Des slope was even more depressed (39.6 ± 10 mm Hg/cm) in ChD patients who had minor segmental wall motion abnormalities (SWMAs) on the baseline 2-dimensional echocardiograph in comparison with the slightly reduced values found in patients with CF who had isolated conduction abnormalities on the ECG (71.8 ± 10 mm Hg/cm). Although %ΔD and Vcfc, even at peak afterload, do not differentiate ChD patients from normal controls, the Pes-Des slope is significantly impaired in IF, DF, and CF patients. The remarkably lower Pes-Des slope value documented in ChD patients exhibiting only minor LVWMAs suggests a more extensive myocardial damage in this group of patients, indicating that they should be considered as exhibiting symptoms of the CF version of the disease. (J Am Soc Echocardiogr 2002;15:610-16.)

End-systolic stress-velocity and pressure-dimension relationships by transthoracic echocardiography in mice.

The purposes of this study were to assess load-independent, end-systolic relationships in mice and compare these relationships to ejection phase indexes in assessing contractility. In 13 mice, ejection phase indexes (shortening fraction and velocity of fiber shortening) and end-systolic relationships [pressure-dimension relationship (ESPDR) and stress-velocity relationship (ESSVR)] were determined using M-mode echocardiography and simultaneous left ventricular pressure. Load was altered with phenylephrine and nitroprusside. Contractility was increased with dobutamine and decreased by induction of hypothyroidism. Ejection phase indexes increased with dobutamine infusion but were not significantly decreased with hypothyroidism. However, end-systolic relationships changed significantly with both dobutamine (gamma-intercepts: ESPDR from 22 to 48 mmHg, ESSVR from 3.7 to 6.6 circ/s, P < 0.05) and hypothyroidism (gamma-intercepts: ESPDR from 22 to 11 mmHg, ESSVR from 3.7 to 3.2 circ/s, P < 0.05). We conclude that end-systolic indexes can be accurately measured in the intact mouse by echocardiography with simultaneous left ventricular pressure recording and appear to be more sensitive to inotropic state than ejection phase indexes.

Left Ventricular Systolic and Diastolic Function Is Unaltered During Propofol Infusion in Newborn Swine

Propofol is a cardiac depressant with minimal diastolic effects in the adult myocardium. Cardiac effects of propofol in the newborn are unknown. We examined hemodynamic variables and systolic and diastolic left ventricular function in 12 newborn pigs exposed to propofol at three different infusion rates (7.5, 15, and 30 mg x kg(-1) x h(-1)) in random order with a background of fentanyl (100 microg x kg(-1) x h(-1)). Left ventricular (LV) pressure (Plv) and LV anterior-posterior dimension, determined by sonomicrometry, were continuously monitored. Mean arterial pressure (MAP), heart rate (HR), and LV end-diastolic pressure (LVEDP) were determined at every infusion. Systolic function was assessed by the maximal pressure-time derivative (dP/dt(max)), the slope of the end-systolic pressure-dimension relationship (ESP-D), and by the preload recruitable stroke work index (PRSWI). Diastolic function was assessed by relaxation indices, the minimal pressure-time derivative (dP/dt(min)) and the relaxation time constant (tau), and by a stiffness index, the slope of the EDP-D relationship. MAP decreased approximately 25%, from 75.9 +/- 15.6 to 56.3 +/- 14.8 mm Hg (P < 0.05) with propofol, with no dose effect. HR and LVEDP were unchanged from control. Both dP/dt(max) and dP/dt(min) decreased with propofol infusion, but load-independent indices of systolic function (ESP-D slope and PRSWI) and tau were unchanged. Diastolic stiffness was not affected with either 7.5- or 30-mg x kg(-1) x h(-1) infusions but decreased significantly from 0.27 +/- 0.18 mm Hg/mm at control to 0.18 +/- 0.18 mm Hg/mm (P < 0.05) with propofol 15 mg x kg(-1) x h(-1). With this profile, propofol may be useful for the newborn requiring anesthesia.Most anesthetics depress heart function in the newborn. We examined both heart contraction and relaxation during anesthesia with propofol in newborn pigs. Propofol had minimal influence on heart function in this model at the doses studied. This may therefore be a useful anesthetic to test in the newborn human.

Left ventricular systolic and diastolic function is unaltered during propofol infusion in newborn swine.

Propofol is a cardiac depressant with minimal diastolic effects in the adult myocardium. Cardiac effects of propofol in the newborn are unknown. We examined hemodynamic variables and systolic and diastolic left ventricular function in 12 newborn pigs exposed to propofol at three different infusion rates (7.5, 15, and 30 mg x kg(-1) x h(-1)) in random order with a background of fentanyl (100 microg x kg(-1) x h(-1)). Left ventricular (LV) pressure (Plv) and LV anterior-posterior dimension, determined by sonomicrometry, were continuously monitored. Mean arterial pressure (MAP), heart rate (HR), and LV end-diastolic pressure (LVEDP) were determined at every infusion. Systolic function was assessed by the maximal pressure-time derivative (dP/dt(max)), the slope of the end-systolic pressure-dimension relationship (ESP-D), and by the preload recruitable stroke work index (PRSWI). Diastolic function was assessed by relaxation indices, the minimal pressure-time derivative (dP/dt(min)) and the relaxation time constant (tau), and by a stiffness index, the slope of the EDP-D relationship. MAP decreased approximately 25%, from 75.9 +/- 15.6 to 56.3 +/- 14.8 mm Hg (P < 0.05) with propofol, with no dose effect. HR and LVEDP were unchanged from control. Both dP/dt(max) and dP/dt(min) decreased with propofol infusion, but load-independent indices of systolic function (ESP-D slope and PRSWI) and tau were unchanged. Diastolic stiffness was not affected with either 7.5- or 30-mg x kg(-1) x h(-1) infusions but decreased significantly from 0.27 +/- 0.18 mm Hg/mm at control to 0.18 +/- 0.18 mm Hg/mm (P < 0.05) with propofol 15 mg x kg(-1) x h(-1). With this profile, propofol may be useful for the newborn requiring anesthesia. Most anesthetics depress heart function in the newborn. We examined both heart contraction and relaxation during anesthesia with propofol in newborn pigs. Propofol had minimal influence on heart function in this model at the doses studied. This may therefore be a useful anesthetic to test in the newborn human.

Left ventricular spherical dilation and regional contractile dysfunction in dogs with heart failure.

Left ventricular (LV) short- and long-axis contractile function and LV structural changes were serially measured in eight instrumented dogs during the development of congestive heart failure (CHF) induced by rapid right ventricular (RV) pacing. After 10 days of pacing, LV end-diastolic volume (VED) had not increased; however, the slope of LV end-systolic pressure-volume relation had decreased from 7.4 +/- 2.6 to 4.9 +/- 1.1 mmHg/ml (P < 0.05), and the slope of LV stroke work-VED relation had fallen from 78.4 +/- 9.1 to 64.2 +/- 7.2 mmHg (P < 0.05). The slopes of end-systolic pressure-dimension relation and the stroke work area-end-diastolic dimension relation in the short axes (i.e., anteroposterior and septal-lateral) had decreased by 30% (P < 0.05), whereas the slopes of the long-axis (i.e., apical-basal) relations were unchanged (not significant). After 20 days of pacing, VED had significantly increased by 14% due to selective dilation of the short axes by 7%, and LV global contractility had further declined with a 40% contractile depression in the short axes and a 25% contractile depression in the long axis. After 30 days, the long-axis dimension at end diastole was also significantly increased with a further increase in the short-axis dimensions. In contrast to the spherical dilation occurring during CHF, acute volume loading of normal animals produced symmetrical LV dilation. These observations suggest that heterogeneous contractile depression initiates the spherical end-diastolic chamber dilation in pacing-induced CHF.

Isoflurane and halothane impair both systolic and diastolic function in the newborn pig.

Volatile anaesthetics have considerable effects on diastolic relaxation in the adult myocardium. We hypothesized that isoflurane (1) and halothane (H) may have even greater effects on diastolic function in the newborn, as the newborn heart has increased passive stiffness and altered calcium handling relative to the adult. Using a newborn pig model, we compared I and H at three clinically relevant concentrations with respect to both systolic and diastolic function. Sixteen newborn pigs were randomized for study at control (background fentanyl 100 micrograms.kg-1.hr-1 and 0.5, 1.0 and 1.5 MAC of I (n = 8) or H (n = 8). Temperature, arterial blood gases, and LVEDP were controlled. Left ventricular pressure (LVP) was monitored continuously and LV anterior-posterior dimension was determined by using sonomicrometry crystals. Systolic function was assessed by peak positive dP/dT (dP/dTmax) and the slope of the end-systolic pressure-dimension (ESP-D) relationship. Diastolic relaxation was given by peak negative dP/dT (-dP/dTmax) and the time constant for ventricular relaxation (tau). Left ventricular stiffness was calculated from the slope of the end-diastolic pressure-dimension (EDP-D) relationship. At equal MAC concentrations, I and H were identical in effect for every variable studied. Systolic function was depressed at all anaesthetic concentrations. Control dP/dTmax (I:1815 +/- 561 (SD) mmHg.sec-1, H:1841 +/- 509) decreased to 832 +/- 341 with 1.5 MAC I and 691 +/- 127 with 1.5 MAC H (P < 0.05 vs control). ESP-D slope decreased from 62 +/- 31 mmHg.mm-1 at control to 15 +/- 11 with 1.5 MAC I and from 79 +/- 16 to 37 +/- 15 with 1.5 MAC H (P < 0.05 vs control). Diastolic function was affected only at higher MAC anaesthesia. Control tau increased from 18.0 +/- 6 msec to 29.1 +/- 7.5 with 1.5 MAC I and from 20.8 +/- 5.9 to 30.0 +/- 11.3 with 1.5 MAC H (P < 0.05). EDP-D slope was increased at both 1 and 1.5 MAC anaesthesia. EDP-D slope increased from 0.16 +/- 0.24 mmHg.mm-1 at control to 0.58 +/- 0.46 with I MAC I and from 0.16 +/- 11 to 0.50 +/- 0.35 with 1 MAC H. The -dP/dTmax decreased at every MAC level of anaesthesia. These combined systolic and diastolic effects help to explain the increased sensitivity of the newborn myocardium to volatile anaesthetics.

Effect of Continuous Arteriovenous Hemofiltration Combined with Systemic Vasopressor Therapy on Depressed Left Ventricular Contractility and Tissue Oxygen Delivery in Canine Escherichia coli Sepsis

In a previous study, we showed that continuous arteriovenous hemofiltration (CAVH) reversed the depression in left ventricular (LV) contractility in canine Escherichia coli sepsis by the removal of a circulating substance the molecular weight of which is less than 30,000. Despite the normalization of LV contractility, however, we were unable to demonstrate an improvement in systemic arterial blood pressure (BP), presumably because the mechanisms underlying the depression in LV contractility and the decrease in BP are different in sepsis. In the current study, we examined the effect of combined treatment with CAVH and the alpha-adrenergic agonist phenylephrine on LV mechanics and tissue oxygen delivery in our canine E. coli model. Measurements were obtained at baseline (condition B), after 4 h of sepsis (condition S), and after 2 h of CAVH and phenylephrine (condition P) (total of 6 h of sepsis). During P, phenylephrine was infused to restore BP to that found at baseline. The slope of the end-systolic pressure-dimension relation was used as the index of LV contractility; LV anterior-posterior dimensions were measured by sonomicrometry. During combined CAVH and phenylephrine treatment, the decrease in the slope of the end-systolic pressure-dimension relation otherwise observed at S was reversed. The slope (mean +/- SD) was 57.5 +/- 32 mmHg/mm at B versus 22.2 +/- 8 mmHg/mm at S (P < 0.05, B vs. S) versus 62 +/- 37 mmHg at P (P < 0.05 S vs. P) (analysis of variance). Mean BP was restored to that found at B (123 +/- 19 mmHg versus 82 +/- 14 mmHg (P < 0.05 B vs. S) versus 116 +/- 27 mmHg (P < 0.05 S vs. P). Combination treatment with CAVH and phenylephrine also improved stroke volume (39.3 +/- 13.5 versus 32 +/- 8 versus 44 +/- 12 ml) and tissue oxygen delivery during P compared with results obtained when phenylephrine was given alone. Our study offers a rationale for the combined use of phenylephrine and CAVH in the reversal of cardiac depression and hypotension in sepsis.

Effects of cardioplegic arrest on left ventricular systolic and diastolic function of the intact neonatal heart

The effects of cardiopulmonary bypass and cardioplegic arrest on left ventricular systolic and diastolic function were studied in 20 intact neonatal lambs instrumented with ultrasonic dimension transducers and micromanometers for collection of left ventricular pressure-dimension data. Group I lambs underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) alone; group II lambs underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) with 1 hour of multidose, cold, crystalloid cardioplegic arrest (St. Thomas' Hospital No. 2 solution). The control neonatal lamb left ventricle was found to be relatively stiff, with the limit of diastolic filling reached at physiologic left ventricular filling pressures, resulting in apparent descending limbs of left ventricular function. After cardiopulmonary bypass, identical results were obtained in groups I and II. A significant loss of left ventricular compliance limited left ventricular performance via two mechanisms. First, left ventricular preload was significantly decreased, with a concomitant diminution in left ventricular stroke work; afterload (pressure work) was maintained at the expense of volume work (flow), which declined significantly. Second, preload behaved as though fixed, resulting in a loss of impedance matching (afterload mismatch). Although contractility as assessed by the end-systolic pressure-dimension relationship was significantly increased (because of increased levels of circulating catecholamines), global systolic performance as quantified by the stroke work/end-diastolic length relationship remained unchanged, reflecting the afterload sensitivity of the latter parameter in the face of fixed preload. We conclude that cardiopulmonary bypass in the intact neonate results in a loss of compliance and impedance matching rather than a loss of contractility; however, the addition of 1 hour of cold, crystalloid cardioplegic arrest results in no dysfunction beyond that attributable to cardiopulmonary bypass alone.

Histamine decreases left ventricular contractility in normal human subjects.

To determine whether histamine alters human left ventricular contractility we measured heart rate, calibrated carotid arterial pressure, and left ventricular dimensions (echocardiogram) in nine healthy volunteers. We assessed baseline contractility using the end-systolic pressure-dimension relationship and the end-systolic meridional wall stress-rate-corrected velocity of circumferential fiber shortening relationship determined over a wide range of afterloads using phenylephrine and nitroprusside infusions. We then infused histamine for 3-5 min at a dose predetermined to decrease mean arterial pressure by 20%, both before and after H1 receptor antagonist pretreatment (diphenhydramine 50 mg i.v.). Histamine decreased end-systolic pressure but, unlike an equally hypotensive infusion of nitroprusside, did not decrease end-systolic dimension or increase fractional shortening. Histamine also decreased velocity of circumferential fiber shortening at the same end-systolic meridional wall stress as controls (P < 0.05). These effects of histamine were inhibited by H1 antagonist pretreatment. We conclude that the dominant effect of histamine on the human heart is to decrease left ventricular contractility and that this decrease in contractility is dependent, at least partially, on H1-receptor activation.

Right heart function during prosthetic left ventricular assistance in a porcine model of congestive heart failure

A left ventricular assist device was used to produce a 90% reduction in peak systolic left ventricular pressure in pigs with congestive heart failure, and the resultant effects on right ventricular function were determined. Initially, eight farm pigs underwent rapid ventricular pacing at 230 beats/min for 7 days to produce congestive heart failure. When compared with an independent series of normal pigs, cardiac output in the paced animals was 33.3% less (2.2 +/- 0.2 versus 3.3 +/- 0.5 L/min; p less than 0.05), left ventricular end-diastolic pressure was elevated (13.8 +/- 3.5 versus 6.6 +/- 1.8 mm Hg; p less than 0.05), and the slope of the right ventricular global stroke work curve was significantly depressed (0.004 +/- 0.001 versus 0.033 +/- 0.003 joules/mm Hg; p less than 0.05). Next, the left ventricular assist device was connected between left ventricular apex and ascending aorta and left ventricular pressure was reduced from 92.0 +/- 3.8 to 10.5 +/- 2.2 mm Hg, while systemic arterial pressure was maintained constant. This led to a further impairment in cardiac output (-14%), mean arterial pressure (-15%), and the slope of the right ventricular global stroke work curve (-50%). Under each condition, right ventricular preload recruitable stroke work and end-systolic pressure-dimension relationships were studied in three different regions on the right ventricle during both steady-state and transient inferior vena caval occlusion. In the right ventricular septal-free wall dimension, left ventricular pressure unloading resulted in a 47.5% +/- 5.4% (p less than 0.05) reduction in the slope and 20.1% +/- 4.8% (p less than 0.05) increase in the dimension intercept of the preload recruitable stroke work relationship. There was also a 44.6% +/- 4.8% (p less than 0.05) reduction in the slope and 15.6% +/- 2.8% (p less than 0.05) increase in the dimension intercept of the end-systolic pressure-dimension relation. These slope changes plus reductions in cardiac output and in global stroke work, which are indicative of impaired right ventricular function during left ventricular pressure unloading in the congestive heart failure pigs, are not seen in normal hearts, whereas the intercept changes associated with leftward septal shift are present in both. These results suggest that anatomic ventricular interactions have a more significant role in heart failure than in the normal heart in determining overall right ventricular function during left ventricular assist device support.

Computer software for the on-line measurement of the left ventricular end-systolic pressure-dimension relationship

A microcomputer system was designed to measure the end-systolic pressure-dimension relationship (ESPDR), an index of cardiac contractility that is independent of preload, afterload, and heart rate. To test the system, pressure-dimension data were obtained from swine left ventricles and from a mathematical model of the heart. Algorithms for filtering, location of end-systole, selection of the measurement interval, and calculation of the ESPDR were evaluated on the basis of speed, precision, accuracy, and robustness. The resulting program runs on an IBM-AT and measures ESPDR on-line within 60 seconds of the start of data acquisition. By reducing the time spent in data analysis and providing rapid feedback of information, the on-line software has increased productivity and facilitated improvements in experimental technique. This is a US government work. There are no restrictions on on its use.

Slope of human left ventricular end-systolic force-length relation is independent of myocardial length

We have introduced a new contractility index (Ec), i.e., the slope of the left ventricular (LV) end-systolic force-length (Fes-Les) relation. To examine whether Ec was dependent on the LV wall myocardial length, 16 normal hearts of human subjects were evaluated to determine the LV end-systolic force-dimension (Fes-Des) and pressure-dimension (Pes-Des) relations (dimension denotes the distance between the LV septum and posterior wall). LV end-systolic pressures and dimensions were estimated simultaneously by intra-arterial cannulation and LV echocardiography. In seven subjects, the effect of a dobutamine infusion was also assessed. The Fes-Des relation was found to be nearly linear. Slopes and extrapolated dimension intercepts were obtained for the LV Fes-Des and Pes-Des relations [Ec, slope of LV Pes-Des relation (Es), and extrapolated dimension intercept of LV Fes-Des (Do), and of Pes-Des relation (D'o), respectively]. Es showed a hyperbolic relation to the baseline LV Des, whereas Ec was unrelated to it. The average variation for Ec (9.5%) was smaller than that for Es (22.5%). Dobutamine infusion increased Ec, Es, and D'o, whereas Do was not changed. Thus the assumption of linearity of the LV Fes-Les relation was found to be reasonable in normal human hearts. Do appears to provide a more accurate parameter than D'o for estimating the actual unstressed myocardial length, whereas Ec could possibly serve as an index of LV wall performance in the normal human heart that is independent of myocardial length and nearly constant between individuals.

Left ventricular systolic and diastolic function in term neonates after mild perinatal asphyxia

To assess possible changes in myocardial contractile function and relaxation occurring after mild perinatal asphyxia, maximal blood pressure and M-mode echocardiograms were registered simultaneously in 32 normal full-term neonates and in 22 full-term asphyxiated neonates. The slope of the end-systolic pressure-dimension relation (ESPDR) was used as a reliable index for evaluation of myocardial contractility. A nonpharmacological afterload increase was performed to calculate this relation. The following most prominent changes were observed in asphyxiated neonates: slope of ESPDR 5.9 vs. 14.4 mmHg/(cm/m 2); normalized peak rate of left ventricular (LV) filling 2.14 vs. 4.11 s −1; LV isovolumic relaxation period 63 vs 36 ms. These results suggest that ESPDR and parameters of LV relaxation and filling may serve as early and sensitive signs of hypoxic myocardial dysfunction.

Left ventricular contractility is depressed in IgE-mediated anaphylactic shock in dogs

To determine whether myocardial dysfunction contributes to vascular collapse in anaphylactic shock, we examined left ventricular (LV) contractility, coronary blood flow, and myocardial lactate metabolism during antigen challenge in eight dogs that were sensitized to ragweed pollen extract (anaphylaxis group). Findings in the anaphylaxis group were contrasted to those in another group of dogs in which mean blood pressure was decreased to the same extent by arteriolar vasodilation with nitroprusside. The animals were examined under nonhypoxic conditions while anesthetized and ventilated. LV mechanics were examined with subendocardial crystals placed primarily along the anterior-posterior minor axis of the LV. During antigen challenge, a depression in LV contractility was observed in the anaphylaxis group as assessed by fractional dimensional shortening, stroke volume, and the slope of the end-systolic pressure-dimension relationship. During anaphylaxis, moreover, coronary vasodilation rather than coronary vasoconstriction was observed, and evidence of myocardial ischemia as assessed by altered myocardial lactate metabolism was not found. Our results indicate that depressed LV contractility occurs in anaphylactic shock. The results further suggest that the mechanism may be due to a direct effect of mediators of anaphylaxis on the myocardium to produce systolic dysfunction.

Influence of adenosine on the stimulatory effect of isoprenaline and insulin on myocardial contractility in vivo

In vitro investigations have indicated that adenosine can inhibit beta adrenergic stimulated increases in cardiac contractility. The present study was designed to determine the ability of adenosine to inhibit isoprenaline induced increases in contractility in vivo. Adenosine has been reported to exert its inhibitory effects on contractility by inhibiting adenylate cyclase. Thus, adenosine should have no effect on positive inotropic agents that act independently of adenylate cyclase. We therefore assessed the ability of this nucleoside to inhibit the positive inotropic effect of insulin, a hormone that exerts a positive inotropic effect independently of alterations in cyclic AMP. Saline or adenosine (10 mumol.ml-1) was infused into the circumflex artery at 1 ml.min-1 as a background. Isoprenaline (20 or 200 pmol.min-1) was infused into the artery during saline or adenosine infusion. The response to insulin was determined during hyperinsulinaemic euglycaemic clamp. 16 adult mongrel dogs were anaesthetised with pentobarbitone. Five dogs were used in isoprenaline studies, and 11 dogs in insulin studies. Dogs were instrumented to obtain measurements of mean arterial blood pressure, heart rate, circumflex artery blood flow (Q), instantaneous left ventricular pressure, and posterior left ventricular wall thickness. We used the slope of the end systolic pressure-dimension relationship (Ees) as an index of myocardial contractility, previously shown to reflect changes in myocardial inotropic state independent of influence from afterload and preload. Left ventricular dP/dtmax was derived from left ventricular pressure with respect to time, and Ees was determined from left ventricular pressure and wall thickness. Neither adenosine, isoprenaline, nor insulin alone caused any significant changes in mean arterial pressure or heart rate. Adenosine caused a significant increase in Q. Both left ventricular dP/dtmax and Ees were significantly increased by either insulin or both doses of isoprenaline. Adenosine inhibited the increases in these indices caused by isoprenaline, but not those caused by insulin. Adenosine is capable of inhibiting the positive inotropic effect of isoprenaline in vivo. The results suggest that adenosine does not inhibit positive inotropic responses that act independently of the stimulation of adenylate cyclase.

Hemofiltration Reverses Left Ventricular Dysfunction during Sepsis in Dogs

Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis [FCS]); however, this finding is controversial. The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction. In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli. Left ventricular anterior-posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments. Left ventricular contractility was determined from the end-systolic pressure-dimension relationship. The slope of this relationship (Emax) is an index of contractility. After 4 h of sepsis, Emax was reduced by one half. Hemofiltration resulted in a return of Emax to control values. The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs. The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration. The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration.