Beverly C. Morgan

Hemodynamic Effects of Intermittent Positive Pressure Respiration

The hemodynamic effects of intermittent positive pressure ventilation were studied in lightly anesthetized dogs following recovery from implantation of pulsed ultrasonic flow transducers on the aorta and vena cava. A partial rebreathing system was utilized to maintain constant PaCO. Data were obtained during spontaneous respiration and using a respirator, with peak airway pressures of 10, 20 and 30 cm. of water, inspiratory to expiratory ratios of 1:2, 1:1 and 2:1. Maximum values for stroke volume and cardiac output occurred during spontaneous breathing. Cardiac output and aortic stroke volume decreased with increasing airway pressure and increasing inspiratory to expiratory ratios. Venous return was inhibited by increasing pressure, and changes in vena caval flow were reflected in changes in aortic flow within the time of two heart beats. The circulatory effects of positive pressure breathing are related to the mean intrathoracic pressure and the effect on venous return.

Antenatal Sildenafil Treatment Attenuates Pulmonary Hypertension in Experimental Congenital Diaphragmatic Hernia

Background— Lung hypoplasia and persistent pulmonary hypertension of the newborn limit survival in congenital diaphragmatic hernia (CDH). Unlike other diseases resulting in persistent pulmonary hypertension of the newborn, infants with CDH are refractory to inhaled nitric oxide (NO). Nitric oxide mediates pulmonary vasodilatation at birth in part via cyclic GMP production. Phosphodiesterase type 5 (PDE5) limits the effects of NO by inactivation of cyclic GMP. Because of the limited success in postnatal management of CDH, we hypothesized that antenatal PDE5 inhibition would attenuate pulmonary artery remodeling in experimental nitrofen-induced CDH. Methods and Results— Nitrofen administered at embryonic day 9.5 to pregnant rats resulted in a 60% incidence of CDH in the offspring and recapitulated features seen in human CDH, including structural abnormalities (lung hypoplasia, decreased pulmonary vascular density, pulmonary artery remodeling, right ventricular hypertrophy), and functional abnormalities (decreased pulmonary artery relaxation in response to the NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide). Antenatal sildenafil administered to the pregnant rat from embryonic day 11.5 to embryonic day 20.5 crossed the placenta, increased fetal lung cyclic GMP and decreased active PDE5 expression. Antenatal sildenafil improved lung structure, increased pulmonary vessel density, reduced right ventricular hypertrophy, and improved postnatal NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide–induced pulmonary artery relaxation. This was associated with increased lung endothelial NO synthase and vascular endothelial growth factor protein expression. Antenatal sildenafil had no adverse effect on retinal structure/function and brain development. Conclusions— Antenatal sildenafil improves pathological features of persistent pulmonary hypertension of the newborn in experimental CDH and does not alter the development of other PDE5-expressing organs. Given the high mortality/morbidity of CDH, the potential benefit of prenatal PDE5 inhibition in improving the outcome for infants with CDH warrants further studies.

Relationship of Pericardial to Pleural Pressure During Quiet Respiration and Cardiac Tamponade

Pericardial pressure was studied in chronic experiments on dogs with relation to intrathoracic pressure in the normal state and in cardiac tamponade. In the normal resting animal, the two pressures were in good agreement throughout the respiratory cycle. The cardiac cycle produced superimposed pressure fluctuations amounting to 30% of the respiratory swings. Adding saline to the pericardial sac produced sigmoid pressure-volume curves; tamponade required 100 to 330 ml of fluid. Although during tamponade the pericardial pressure greatly exceeded the intrathoracic pressure, the pericardial pressure invariably fell with inspiration, generally by the same amount as the intrathoracic pressure. The cardiac cycle produced greater pressure fluctuations (50% of the respiratory pressure fluctuations). The superior vena caval pressure always fell with inspiration in the normal state and during tamponade. Hypovolemia did not change the resting pericardial pressure, but decreased the slope of the pressure-volume curve measured during cardiac tamponade. Hypervolemia increased the resting pericardial pressure considerably, and increased the slope of the pericardial pressure-volume curve. The results suggest that pleural pressure is a reasonable approximation of the pericardial pressure in normal dogs. There appears to be no substantial evidence that pulsus paradoxus is due to failure of the pericardial sac to transmit inspiratory reductions of pleural pressure.

The Hemodynamic Effects of Changes in Blood Volume during Intermittent Positive-pressure Ventilation

The hemodynamic effects of changes in blood volume during intermittent positive-pressure ventilation (IPPV) were studied in lightly anesthetized dogs following recovery from implantation of pulsed ultrasonic flow transducers on vena cava and aorta. Alveolar ventilation was maintained in excess of no

Effect of Respiration on Venous Return and Stroke Volume in Cardiac Tamponade

In 40 lightly anesthetized dogs, 5 to 30 days after surgical preparation, flow was measured simultaneously in the venae cavae, pulmonary artery, pulmonary vein, and aorta with ultrasonic flowmeters. Intrapleural and pericardial pressures were measured via silastic cannulas. Pulmonary vein diameter was monitored by miniature mutual inductance coils. In the resting animal with sinus arrhythmia, inspiration increased heart rate and flow in the vena cava, and to a lesser extent, in the pulmonary vein. Left ventricular stroke volume (LVSV) varied directly with the right ventricular stroke volume (RVSV) in dogs with slow heart rates. Cardiac tamponade invariably caused tachycardia and a marked decrease in cardiac output, arterial pressure, pulse pressure, and stroke volume; venous pressure and diameter increased. Pericardial pressure, although markedly elevated, fell with inspiration paralleling the fall in intrapleural pressure. Flow in the pulmonary vein rose or remained constant with inspiration. Pulmonary vein diameter frequently increased with inspiration during tamponade, but only after the pulmonary artery diameter increased with the inspiratory surge. LVSV did not decline sharply with inspiration, and actually increased within 2 beats of the increase in RVSV. The sum of LVSV plus RVSV increased markedly with inspiration, contradicting the concept of fixed intrapericardial volume. Almost all of the changes of pulsus paradoxus reflect the normal respiratory effects on the RVSV, delayed by transit through the pulmonary bed and exaggerated by the small LVSV in a vasoconstricted state.

Cardiac arrhythmias in premature infants: An indication of autonomic immaturity?

Sinus arrhythmia was demonstrated in all of 30 healthy infants whose birth weights were less than 1,500 grams, and in 90 per cent of them there were also more marked arrhythmias. The severity and frequency of arrhythmias decreased as the weight and development of the infant increased.

Hemodynamic Effects of Changes in Arterial Carbon Dioxide Tension During Intermittent Positive Pressure Ventilation

Hemodynamic effects of changes in arterial carbon dioxide tension during intermittent positive pressure ventilation (IPPV) were studied in lightly anesthetized dogs following recovery from implantation of pulsed ultrasonic flow transducers on aorta and vena cava. Alveolar ventilation was maintained in excess of normal, and arterial PCO2 was varied by alteration of inspired CO2 concentration. Data were obtained at PaCO2 20, 40 and 60 torr, and at each PaCO2 high (peak airway pressure 30 cm. of water, inspiratory to expiratory ratio of 2:1) and low (peak airway pressure 10 cm. of water, inspiratory to expiratory ratio of 1:2) levels of ventilation were employed. Two separate hemodynamic effects were observed, the effects of changes in intrathoracic pressure and those produced by alterations in PaCO2 At each PaCO2 high level of ventilation decreased stroke volume and cardiac output compared to low level of ventilation. At each level of ventilation, stroke volume and cardiac output were decreased during respiratory alkalosis and increased during respiratory acidosis.

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.

Correction of Total Anomalous Pulmonary Venous Drainage in Infancy Utilizing Deep Hypothermia with Total Circulatory Arrest

Four critically ill infants aged 3, 5, 5, and 13 months; weighing 3.7, 4.6, 5.3, and 6.5 kg, respectively; with total anomalous pulmonary venous drainage, underwent complete correction of their lesions with the utilization of surface-induced deep hypothermia. Although this series is small, we are not aware of any other consecutive series in this age group with a comparable mortality rate. Rectal temperatures of 17.5 to 20.2 C were utilized, with periods of cardiac arrest and total circulatory interruption of 32 to 41 minutes. Important aspects of the technique are surface cooling, deep ether anesthesia, intravenous low-molecular-weight dextran, induced respiratory alkalosis during cooling, and electrical pacing during resuscitation. This method works well in the infant, in contrast with perfusion techniques in which surgical mortality is excessively high.

Alternate deletion and potentiation as the cause of pulsus alternans.

Abstract We have tested the hypothesis that pulsus alternans could be explained by heterometric autoregulation. Dogs were aseptically prepared one week in advance with ultrasonic flow probes, pressure cannulae, dimension transducers (mutual inductance and sonar methods), and atrial stimulation electrodes. Under light morphine-nembutal anesthesia, rapid pacing usually produced alternation. The aortic back pressure had a consistently high negative correlation with left ventricular stroke volume (LVSV). The correlations of end-diastolic pressure and diameter with LVSV varied widely and were frequently negative. Modeling of the linear effects of ventricular diastolic volume and aortic back pressure on LVSV demonstrated prompt restoration of equilibrium after a transient disturbance rather than a sustained alternation. We agree with early theories of alternate deletion of contraction of some myocardial cells, but present evidence that potentiation is also inherent in pulsus alternans. All cells recover excitability in the interval available, but only a fraction may be restored to normal contractility. This population of cells are then excited but do not contract, allowing the energy from excitation to remain unutilized until the next beat, which will then have twice the amount of energy of excitation, and the alternate beat will be potentiated, similar to the mechanism of paired pulse stimulation.