Postmortem Pressure-volume Curves Research Articles

Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

Nitric oxide (NO) serves multiple functions in the developing lung, and pulmonary NO production is decreased in a baboon model of chronic lung disease (CLD) after premature birth at 125 days (d) gestation (term = 185d). To determine whether postnatal NO administration alters the genesis of CLD, the effects of inhaled NO (iNO, 5 ppm) were assessed in the baboon model over 14d. iNO caused a decrease in pulmonary artery pressure in the first 2d and a greater rate of spontaneous closure of the ductus arteriosus, and lung compliance was greater and expiratory resistance was improved during the first week. With iNO, postmortem pressure-volume curves were shifted upward, lung DNA content and cell proliferation were increased, and lung growth was preserved to equal that which occurs during the same period in utero. In addition, the excessive elastin deposition characteristic of CLD was normalized by iNO, and there was evidence of stimulation of secondary crest development. Thus, in the baboon model of CLD, iNO improves early pulmonary function and alters lung growth and extracellular matrix deposition. As such, NO biosynthetic pathway dysfunction may contribute to the pathogenesis of CLD.

DIMERIC SURFACTANT PROTEIN B PEPTIDE SP-B 1-25 IN NEONATAL AND ACUTE RESPIRATORY DISTRESS SYNDROME

Surfactant protein B (SP-B) is a constituent surfactant protein critical for normal lung function. Monomeric SP-B 1-25 (mSP-B 1-25) , a peptide based on the N-terminal domain of human SP-B, mixed in phospholipids partially restores lung function in surfactant-deficient animals. Because native SP-B is a homodimer, we synthesized and tested dimeric SP-B 1-25 (dSP-B 1-25) . Circular dichroism (CD) and Fourier Transform Infrared (FTIR) spectroscopy indicated that the secondary conformation of SP-B 1-25 was not significantly perturbed by dimerization. The effects on lung function were compared to phospholipids and Survanta in models of neonatal respiratory distress syndrome (RDS) and acute RDS (ARDS). Preterm rabbits born at 27 days of gestation received 100 mg surfactant / kg at birth and were ventilated for 1 hour with a tidal volume of 10 mL / kg. Dynamic compliance was monitored every 15 minutes and postmortem pressure-volume curves were measured. Adult rats were lavaged to induce surfactant deficiency, treated with 100 mg surfactant / kg, and ventilated for 2 hours. Lung function was assessed using arterial blood gases and dynamic compliance every 15 minutes and postmortem pressure-volume curves. Lung volumes in both models and oxygenation in the lavaged rats were consistently higher in the dSP-B 1-25 than in the Survanta and mSP-B 1-25 surfactant groups. The data suggest that dSP-B 1-25 is more efficient in restoring lung function in neonatal RDS and ARDS than mSP-B 1-25 surfactant.

Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1-25) in preterm rabbits

BACKGROUNDSurfactant protein B (SP-B) is an essential component of pulmonary surfactant, but shorter SP-B sequences may exert equivalent surface activity.METHODSWe synthesised a peptide based on the amino-terminal domain of SP-B...

Enhancement of Surfactant Effect by a Mechanical Volume Recruitment Maneuver Depends on the Lungs Preexisting Distension

‘Rescue’ surfactant treatment of premature infants with respiratory distress syndrome (RDS) results in two mechanisms: stabilization of alveoli already being ventilated and recruitment of alveoli collapsed before surfactant administration. Mechanical recruitment of alveoli from this collapsed compartment might enhance the immediate effects of surfactant treatment. To test this hypothesis 15 mechanically ventilated young rabbits underwent repeated airway lavage with normal saline at a constant, positive end-expiratory pressure (PEEP) of 3 cm H₂O until both the a/A ratio was <0.12 and a peak inspiratory pressure (PIP) >20 mbar was needed to keep the tidal volume (V_T) at 10 ml/kg. Surfactant (Survanta^®) was given over 4 min in conjunction with a mechanical volume recruitment maneuver (VRM) which consisted of an increased PIP by 33% of baseline values. The effects of surfactant were assessed using two indices of gas exchange (a/A ratio and PaCO₂), four indices of lung function (functional residual capacity, FRC, dynamic lung compliance, C_rs, V_T and the alveolar portion of V_T) and postmortem pressure-volume curves and were compared with two groups of rabbits receiving surfactant alone or no surfactant at all. VRM yielded an increase in C_rs by +22% whereas V_T increased by +58% suggesting overdistension of terminal airways to some extent. There were no differences between the surfactant and the VRM+surfactant groups for all indices assessed after an observational period of 2 h following surfactant administration. In a previous model using a PEEP of 1 cm H₂O [Krause et al., Am J Respir Crit Care Med 1997;156:862–866], significant differences have been disclosed for C_rs, V_T and FRC. In conclusion, the enhancement of surfactant effect by VRM largely depends on the preexisting distension of the lungs.

Compliance, mass, and shape of the canine left ventricle after global ischemia analyzed with two-dimensional echocardiography

End-diastolic pressure (EDP)-volume (EDV) curves were constructed for the left ventricle (LV) in 10 dogs on cardiopulmonary bypass before and after 45 min of normothermic ischemic arrest. LVEDV and mass were calculated from three perpendicular two-dimensional echocardiographic sections using a Simpson's rule algorithm. The echocardiographic method employed was specially developed in earlier work for physiologic studies in dogs. Postmortem pressure-volume curves were measured for comparison by direct saline infusion into sealed ventricles. LVEDV was plotted against LVEDP (0–20 mm Hg) and data were analyzed by two-way analysis of variance and also by exponential curve fitting to the relation EDP = αℓ βEDV, where β is the derived exponential constant reflecting slope and thereby ventricular stiffness. Postischemic EDP-EDV curves shifted to the left and the β constant increased (β = 0.02 ± 0.005 (SE) vs 0.05 ± 0.01, P < 0.05). LV eccentricity, the ratio between long- and short-axis measurements, was unchanged (1.43 ± 0.05 vs 1.46 ± 0.06 postischemia, NS), but LV mass increased (105 ± 7 vs 128 ± 9 g postischemia, P < 0.001). Postischemic LV mass by echo was not significantly different from measured postmortem LV mass ( r = 0.87). The nonparallel alteration in the EDP-EDV curves, lack of change in LV shape (eccentricity), and increase in LV mass in the postischemic ventricle suggest that increased ventricular stiffness rather than direct encroachment by the edematous endocardium on chamber volume is responsible for postischemic changes in LV diastolic properties.

Two-dimensional echocardiography in dogs: Variation of left ventricular mass, geometry, volume, and ejection fraction on cardiopulmonary bypass

Quantitative two-dimensional echocardiography was evaluated in 39 open-chest dogs placed on cardiopulmonary bypass. The correlation coefficient of left ventricular end-diastolic volume against postmortem pressure-volume curves was r = 0.89 to 0.93 (347 measurements in 15 dogs, 0 to 24 mm Hg). Ejection fraction was validated against roller pump flow and echo left ventricular end-diastolic volume (r = 0.83, n = 13). Left ventricular mass in vivo was compared with postmortem left ventricular mass (r = 0.81 in 21 early studies, r = 0.91 in 10 later studies with updated equipment) and was found to increase with ischemic injury as well as cardiopulmonary bypass with hemodilution. Left ventricular mass increased (p less than 0.001) from 119 +/- 5 (standard error of the mean) to 138 +/- 6 gm (n = 23) after 2 1/2 hours on cardiopulmonary bypass and moderate hemodilution. With the addition of ischemic arrest, left ventricular mass increased from 119 +/- 7 to 148 +/- 11 gm (p less than 0.01, n = 8), and myocardial water content increased by 2.0% +/- 0.4%, which accounted for at least 65% of the observed mass change. Mean left ventricular wall thickness increased from 13.8 to 15.5 mm (p = 0.02) after ischemia. Ventricular shape became more spherical with increasing left ventricular end-diastolic pressure. We conclude that two-dimensional echocardiography can be reliably used for accurate, serial measurements in physiological studies. The demonstrated variability in left ventricular mass is important, yet frequently ignored. Recognizing left ventricular mass changes may facilitate the detection of myocardial injury reflected as edema.

The absence of temperature effects on end-diastolic pressure-volume relations in the canine left ventricle determined by two-dimensional echocardiography

Because of divergent conclusions in the literature regarding the effects of temperature on end-diastolic compliance in the canine left ventricle (LV), pressure-volume relationships at normothermia and hypothermia (28 degrees C) were studied with two-dimensional ultrasound in nine dogs on cardiopulmonary bypass (open pericardium) over a range of left ventricular end-diastolic pressure (LVEDP) from 0 to 22 mm Hg. Three perpendicular echocardiographic sections were used with Simpson's rule to measure LV volume and mass at end-diastole for each level of LVEDP. Temperature was varied between 37 degrees and 28 degrees C by systemic cooling, and heart rate was allowed to slow spontaneously with temperature reduction. There was no change in left ventricular end-diastole pressure-volume (LVEDP-LVEDV) relationships at lower temperature provided that ventricular relaxation was complete at end-diastole. In addition, serial postmortem pressure-volume curves carried out by direct saline infusion into sealed ventricles at 38 degrees and 28 degrees C in three additional dogs demonstrated no temperature effects on postmortem LV compliance. Postmortem mass correlated well with echocardiographically determined LV mass, which showed a significant increase during the period of cardiopulmonary bypass, correlating with the development of myocardial edema. In summary, there appears to be no effect of moderate hypothermia on LVEDP-LVEDV relationships, provided the heart is in true diastasis at end-diastole. In addition, echocardiographic techniques can be used to study LV mass change on cardiopulmonary bypass.

Right and left ventricular compliance in the hereditary cardiomyopathy of the Syrian hamster.

Ventricular pressure-volume curves were examined in 10 pre-oedematous cardiomyopathic Syrian hamsters, aged 120 d, and 10 oedematous cardiomyopathic hamsters, aged 210 d, and compared with 10 and 8 age-matched controls, respectively. Previous studies had shown filling pressures and cardiac output to be normal in the pre-oedematous stage. In contrast, the oedematous stage was characterised by elevated filling pressures and increased cardiac output, raising the question whether this stage represents true myocardial failure or circulatory congestion associated with decreased ventricular compliance. Compliance, defined as dV/dP, was derived simulataneously for both ventricles from post-mortem pressure-volume curves from 0 to 2.66 kPa (0 to 20 mmHg). Left ventricular tissue elastic modulus, E, defined as dsigma/depsilon or the incremental stress (sigma) for an increment of strain (epsilon), was derived from the compliance curves and certain linear dimensions of the heart. At isobaric intervals, compliance did not differ between control and myopathic ventricles. At pressures corresponding to previously measured, naturally prevailing end-diastolic pressures, the myopathic ventricles were significantly dilated in both stages; end-diastolic compliance was normal in pre-oedematous hamsters, but was significantly decreased in the oedematous animals. Left ventricular elastic modulus was elevated at all values of sigma in both groups of myopathic animals.

Experimental myocardial infarction. IV. Reduction of left ventricular compliance in the healing phase.

Compliance of the infarcted left ventricle was studied in dogs 3-5 days after occlusion of the left anterior descending coronary artery. Compliance was assessed from postmortem pressure-volume curves and from pressure-length measurements (mercury-in-silastic segment length gauges) made both in vivo and postmortem. Postmortem pressure-volume curves showed reduced compliance compared to sham-operated animals. Postmortem pressure-length curves of infarcted and adjacent normal myocardium indicated that the diminished total compliance could be attributed to an increase in stiffness of the infarcted area. This was confirmed by in vivo end-diastolic pressure-length changes produced by transient aortic occlusion. The infarcted area was akinetic, showing neither contraction nor aneurysmal bulging. In addition, anesthetized dogs with infarcts, when compared with sham-operated animals, had similar left ventricular end-diastolic volumes (indicator dilution method), but higher left ventricular end-diastolic pressures. Taken with previous observations, which show that systolic aneurysmal bulging is uniformly present at the onset of ischemia, these results indicate that stiffening of the ischemic myocardium occurs during the first 5 days after infarction, and show that elevation of left ventricular filling pressure does not necessarily signify ventricular dilatation. The results also suggest a mechanism whereby ventricular performance may improve during recovery from acute myocardial infarction.