Joseph E. Pierce

Endothelial Nuclear Patterns in the Canine Arterial Tree with Particular Reference to Hemodynamic Events

The objective of the study was (1) to measure systematically the orientation, morphology, and population density of endothelial nuclei of the canine thoracic aorta and its major branches and (2) to obtain evidence in a chronic in vivo preparation that altered flow patterns do indeed change patterns of nuclear orientation. For this purpose, a segment of the descending thoracic aorta was removed, opened longitudinally, and reclosed to form a tube with a new longitudinal axis 90° from the original vessel axis. The new segment was then sutured back in place. The animals were killed at suitable postoperative periods. Endothelial nuclear patterns were studied from en face photomicrographs of preparations stained with Evans blue dye. Results indicated: (1) In uniform vessel segments, e.g., middle and lower descending thoracic aorta, the nuclei were oriented parallel to the axis of the blood vessel, and the ratio of major to minor axes of the nucleus was large. The flow in these regions is known to be stable. (2) Nonaxial, less-ordered nuclear orientation with smaller ratios of major to minor axes were found in entrance regions of many major arteries and in the ascending aorta. (3) In chronic studies in which the flow pattern was altered, the nuclear pattern realigned in the direction of flow within 10 days after surgery.

Control of Breathing Using an Extracorporeal Membrane Lung

Various amounts of carbon dioxide were removed through an extracorporeal membrane lung in spontaneously breathing lambs. The decrease in alveolar ventilation was proportional to the fraction of total carbon dioxide removed by the membrane lung. When extracorporeal CO2 removal approximated CO2 production (VCO2), alveolar ventilation almost ceased. Pulmonary ventilation can be controlled by extracorporeal carbon dioxide removal.

Effects of Chronic Right Ventricular Volume and Pressure Loading on Left Ventricular Performance

The effects of chronic right ventricular (RV) distension on left ventricular (LV) function were assessed in dogs 3 weeks after pressure and volume loading of the RV had been produced by the emplacement of a constricting band around the pulmonary artery and the creation of tricuspid insufficiency. This resulted in ascites, RV hypertrophy and dilatation, an increase in RV end-diastolic pressure (EDP), and a reduction of RV and LV norepinephrine concentrations. Peak LV pressure, wall stress, and dp/dt were measured during isovolumic beats at LVEDPs of 1 to 20 mm Hg, and comparisons at matched EDPs were made among the normal, sham-operated, and RV stressed dogs. Under these circumstances, LV function appeared to be depressed appreciably. The effects of RV volume loading on the pressure-volume curve of the LV in the potassium-arrested heart were assessed in a separate group of dogs. The pressure-volume curve of the LV was shifted so that any given LV volume was associated with a higher LV pressure. Thus, when peak pressure and wall stress were related to LV end-diastolic volume rather than to LVEDP, the relationship did not appear to differ from normal; peak dp/dt and peak VCE, however, remained depressed. This depression may represent a decrease in LV contractility consequent to the chronic RV stress or may reflect alterations in LV geometry. Thus, when the RV is subjected to a chronic flow and pressure load, assessment of LV function may be unreliable when indices of contractility are employed that require measurements of LVEDP.

Transcatheter embolization with a silicone rubber preparation. Experimental observations.

The concept of treating benign angiomatous malformations by filling them with an inert occluding silicone rubber cast is presented. Preliminary animal experiments with such a preparation are described. Kidneys were embolized in eight dogs; the absence of systemic toxicity or local tissue reaction is

Discrete subaortic stenosis in Newfoundland dogs: association of infective endocarditis.

Necropsy findings are described in eight Newfoundland dogs from the same colony with discrete subaortic stenosis. Infective endocarditis involving the aortic valve occurred in four dogs and in each it proved fatal. Damage to the aortic valve cusps by the jet of blood ejected through the discretely narrowed left ventricular outflow tract predisposes to the development of infective endocarditis in both dogs and human beings with discrete subaortic stenosis. Severe abnormality of the intramural coronary arteries in the ventricular septum, which also occurs in patients with hypertrophic cardiomyopathy, was present in all eight dogs. Myocardial fiber disorganization and asymmetric septal hypertrophy, two other findings observed in patients with hypertrophic cardiomyopathy, were absent in each of the eight Newfoundland dogs with discrete subaortic stenosis.

Prediction of gradients in fibrous subaortic stenosis by continuous wave two-dimensional Doppler echocardiography: Animal studies

The purpose of this study was to assess the accuracy of continuous wave, two-dimensional Doppler echocardiography for predicting pressure gradients across discrete subaortic stenoses. Twenty-three Newfoundland dogs with subaortic stenosis were studied by closed chest Doppler interrogation of aortic velocity from an apical view of the left ventricular outflow tract simultaneously with measurements of pressure gradient during cardiac catheterization. Continuous mode Doppler interrogation was used with two-dimensional echographic guidance (Irex model IIIB) to compare the Doppler-derived maximal velocity with the pressure gradient across the obstruction at rest and after provocation with amyl nitrite inhalation and isoproterenol infusion. The maximal velocities recorded by Doppler ranged from 98 to 539 cm/s and correlated with hemodynamic gradients ranging from 3 to 123 mm Hg (r = 0.92, SEE = 37 cm/s). Doppler velocities were converted to gradients using a simplification of the Bernoulli relation (gradient = 4 X maximal velocity2); the resulting Doppler-derived gradients also correlated closely with the catheterization-measured pressure gradients (r = 0.95, SEE = 7.1 mm Hg). The predictive capability of Doppler echocardiography for estimating the pressure gradient across fibromuscular subaortic obstructions in this group of dogs with a spectrum of disease similar to that found in human beings was validated. The results also indicate that Doppler methods may have clinical applications in patients with subaortic stenosis.

Management of the Antenatal Preterm Fetal Lung in the Prevention of Respiratory Distress Syndrome in Lambs

We have explored change in pulmonary compliance before, and after, repeated deep insufflation of the lungs to a pressure of 35 cm H2O, in 130-days gestation fetal lambs delivered by cesarean section, and while still connected to the intact umbilical cord and the ewe. As a group, all 15 out of 28 fetal lambs that had a rise in total compliance to above 0.2 ml (cm H2O)-1 kg-1 after the first inflation, tolerated 24 h of mechanical ventilation with excellent health and good lung function; only 3 animals out of 13 that showed no similar initial rise in compliance after the first inflation, ultimately survived. We believe the first deep insufflation is an important therapeutic intervention and a useful index to rapidly assess chance of survival in a high-risk fetal lamb population.

Enhancement of Lung Conditioning by Acetylcholine in the Prevention of Respiratory Distress Syndrome in the Preterm Fetal Lamb

We exposed 128- to 130-day-gestation fetal lambs by cesarean section leaving the umbilical cord and placenta undisturbed, and we then treated the lungs with pulmonary conditioning (i.e., repeated prolonged inflations to 35 cm H2O, followed by a continuous positive airway pressure of 15 cm H2O). To investigate the added effect of pulmonary vasodilation upon the increase of total compliance and pulmonary oxygen uptake, we also administered acetylcholine intravenously at a rate of 80 micrograms min-1. Eleven of 13 lambs met the endpoint criteria of either compliance (0.5 ml [cm H2O]-1 kg-1; 1 animal), or pulmonary oxygen uptake (6 ml kg-1 min-1; 6 animals), or both (4 animals), and were delivered within 0.6 +/- 0.3 h. This time was significantly (p less than 0.05) shorter than previously seen in similar studies without the infusion of a vasodilator; all animals so delivered survived 24 h of mechanical ventilation in excellent health. We suggest that pharmacologic pulmonary vasodilation, in addition to deep sustained pulmonary insufflation and distension, is an effective and rapid means of transforming stiff immature lungs into lungs that can sustain normal ventilation and gas exchange.

Angiocardiographic and Metabolic Studies in Immersed Lamb Fetuses Perfused Through an Artificial Placenta

Using angiocardiography we studied twelve premature lambs of 130–145 days gestation (2.3–4.0 kg) obtained at caesarian section and maintained in a filtered and thermoregulated bath of synthetic amniotic fluid. By selectively varying the oxygen concentration in the gas compartment of the membrane lung we were able to control the level of blood oxygen tension independent of pH, PCO2, and placental flow. Within 20 min after raising fetal umbilical pO2 from 13–20 to 40–60 mm Hg there was almost total conversion of the fetal circulatory pattern to that of the newborn. The I.D. of the ductus arteriosus constricted from 4.1 mm to less than 1.0 mm; pulmonary circulation time decreased from more than 18.4 to 2.4 sec. These findings were not affected by metabolic or respiratory acidosis. Inferior vena cava injections illustrated complete closure of the foramen ovale; no opacification of the left atrium occurring at pO2 from 40–60 mm Hg with a constricted ductus arteriosus. Oxygen consumption of fetuses paralyzed with succinylcholine measured continuously by spirometry averaged 6–7 ½ cm3/kg/min while carbon dioxide production was measured continuously by infrared analysis of effluent gas at 7–8.5 cm3/kg/min. Respiratory quotients consistently greater than one were observed with blood glucose levels above 100 mg%. Four fetuses were delivered following angiocordiographic study; two are long-term survivors.