Traube-Hering waves in the pulmonary circulation of the dog.

Although the pulmonary blood vessels receive an ample supply of nerves, it has been difficult to prove that these nerves operate in the regulation of the pulmonary circulation. In the present study, using the isolated lobe of the lung perfused in situ, waves in pulmonary arterial pressure were induced and were shown, as in the case of Traube-Hering waves in the systemic circulation, to be nervous in origin.

Hemoglobin as a tracer in hemodynamic pulmonary edema.

Stroma-free hemoglobin is an electron-opaque molecule useful as a tracer for the ultrastructural stuty of pulmonary capillary permeability. After this tracer was infused into the isolated pulmonary lobe of the dog, the endothelial junctions of the capillaries, as revealed by electron microscopy, act like distensible pores, thus allowing the tracer to escape when the pulmonary artery pressure was raised above 50 millimeters of mercury.

Hepatic dysfunction in the adult respiratory distress syndrome.

Multiple organ system failure is a major cause of mortality in the adult respiratory distress syndrome (ARDS). We serially evaluated parameters of multiple organ function in 24 patients during the first week after the diagnosis of ARDS and related them to outcome. The adult respiratory distress syndrome was associated with sepsis (n = 16), postoperation (n = 7), and trauma (n = 1). Fourteen of the 24 patients (58 percent) died. Although there were no significant differences in the indices of pulmonary or renal dysfunction between survivors and nonsurvivors, evidence of hepatic dysfunction was different in the two groups. On the day we identified ARDS, serum bilirubin was 1.2 mg/dl +/- 0.9 mg/dl in patients who survived, and was 2.3 mg/dl +/- 2.8 mg/dl (chi +/- SD) in those who died. Initial serum glutamic oxalacetic transaminase (SGOT) and alkaline phosphatase levels were lower in survivors than in those who died (71 +/- 44 IU/L vs 399 +/- 807 IU/L, and 121 +/- 53 IU/L vs 269 +/- 243 IU/L, respectively). These abnormalities persisted during the first week of respiratory failure, with significant differences in serum bilirubin and alkaline phosphatase between survivors and nonsurvivors (p less than 0.01). The degree of pulmonary and renal dysfunction was similar in both groups. These data suggest that liver function may be a major determinant of survival in patients with the adult respiratory distress syndrome.

Lung volume reduction surgery: an analysis of hospital costs.

OBJECTIVE: Lung volume reduction surgery (LVRS) represents a potential breakthrough in the management of advanced emphysema, although questions remain about clinical and economic implications of widespread application of LVRS. In this report, we describe hospital costs, excluding physicians' fees, for LVRS. DESIGN: Hospital charges were obtained from billing records and converted to costs by applying multiple cost-to-charge ratios. SETTING: A large, urban academic medical center. PATIENTS: Fifty-two consecutive patients who received bilateral LVRS through a median sternotomy between April 1995 and August 1996. RESULTS: Median hospital stay was 10 days (mean= 14.8+/-12.8 days; range=3 to 48 days), including 2 days (mean=6+/-9.2 days; range=1 to 35 days) in the ICU. One hospital death occurred. Hospital costs per case ranged from $11,712 to $121,829, with mean costs of $30,976 and median costs of $19,771. Costs were related significantly to duration of ICU stay and length of hospitalization. Patients who accrued the highest costs were significantly older than the remainder of the sample (69.3 years vs 62.4 years). CONCLUSIONS: Hospital costs of LVRS vary significantly but are related directly to hospital stay. Identification of factors associated with prolonged stays can be used in assessing benefits and risks of LVRS against utilization of health-care dollars.

Evaluation of pulmonary complications after bone marrow transplantation: the role of pretransplant pulmonary function tests.

To determine whether an association exists between abnormal pulmonary function tests (PFT) before bone marrow transplantation (BMT) and the rate of pulmonary complications after BMT, we retrospectively reviewed all transplants performed in our center between March 1984 and December 1990. A total of 163 patients, 15 years of age and older, with a hematologic malignancy or a solid tumor were treated with intensive therapy and autologous (118) or allogeneic (55) BMT. Sixty patients (37%) developed a pulmonary complication which contributed to patient death in 29 transplants (18%). Patients with pulmonary metastases, prior thoracotomy, or prior radiation to the chest had a higher frequency of abnormal PFT. By univariate analysis, patients with abnormal FVC, FEV1, or TLC before BMT had a significantly increased rate of pulmonary complications (p < 0.005). By multivariate analysis, the rate of pulmonary complications was significantly associated (p = 0.004) with abnormal FEV1 only: in the first 2 months after transplantation the rate was 65% in patients with FEV1 < 70% in contrast to 34% in patients with FEV1 > or = 70% (risk ratio = 1.9). There was no association, however, between abnormal pretransplant PFT and fatal pulmonary complications. We conclude that patients with pretransplant ventilatory defects have a higher risk of pulmonary complications after BMT, but the incidence of fatal complications was not significantly increased, although we cannot exclude a diminished study power due to the sample size. We believe that patients with abnormal PFT should not be excluded from transplantation if the anticipated anti-tumor effect is estimated to be substantial, but additional preventive measures may be necessary.

Pathophysiology of the congested lung.

The consequences of congestion, edema, and fibrosis on lung function of cardiac patients are reviewed. Special attention is paid to the physiologic alterations that may contrubute to the sensation of dyspnea.

The relationship of resting and exercise blood pressure in subjects with essential hypertension before and after drug treatment with propranolol.

OBJECTIVE: To investigate the relationship between clinic resting blood pressure (BP) and exercise BP in subjects with established essential hypertension during placebo and propranolol-treated phases. DESIGN: Prospective, placebo-controlled, cross-over trial. SETTING: University-affiliated medical center. PATIENTS: A convenience sample of 38 patients with essential hypertension, 34 men and four women, who ranged in age from 22 to 62 years (mean = 44 years, SD = 10.7). Subjects were diagnosed with mild to moderate diastolic or mixed systolic/diastolic essential hypertension at least 1 year before study entry. They had no clinical evidence of secondary hypertension, diabetes, heart, liver, pulmonary, or renal disease. OUTCOME MEASURES: Resting and exercise BP. INTERVENTION: Antihypertensive medication was tapered off and subjects were free of all prescription drug treatment for 2 weeks. They received placebo for an additional 2 weeks. Subjects then received treatment with propranolol at a dose necessary to control resting blood pressure for 4 to 6 weeks. At the end of both the untreated and treated phases, subjects were given a graded maximal exercise test on a bicycle ergometer. RESULTS: Propranolol effectively reduced mean resting and maximal exercise BP. The nonsignificant correlation between clinic resting and maximal exercise systolic BP was low in both phases. The correlation between clinic resting and maximal exercise diastolic BP was only moderate, but statistically significant (untreated, r = 0.43; p < 0.01; treated, r = 0.53; p < 0.001). For systolic BP or diastolic BP, there were no significant relationships between percent drop in BP because of propranolol at rest or maximal exercise. Clinic resting BP was not a valid predictor of maximal exercise BP. Degree of control of clinic resting BP was not a valid predictor of control observed at maximal exercise. CONCLUSIONS: Resting BP should not be used as a predictor of BP during maximal exercise in the untreated condition or with treatment with propranolol.

The role of catecholamines, age, and fitness on blood pressure reactivity to dynamic exercise in patients with essential hypertension.

OBJECTIVE: To determine the relationship between exercise blood pressure (BP) and catecholamine levels in hypertensive subjects and, secondarily, to evaluate the influence of age and fitness level. DESIGN: Descriptive correlational. SETTING: Midwestern, university-affiliated medical center. SUBJECTS: 27 hypertensive subjects, mean age 45 years, who were free of antihypertensive medications. OUTCOME MEASURES: BP and plasma catecholamines (norepinephrine and epinephrine). INTERVENTION: Subjects were given an incremental maximal exercise test on a cycle ergometer beginning at 25 watts with workloads increasing by 25 watts every 2 minutes until exhaustion. Plasma catecholamines were measured at rest, at 100 watts, and at maximal exercise. BP, heart rate, and oxygen consumption (VO2) were measured at rest and at the end of each workload. RESULTS: Systolic and diastolic BP were unrelated to catecholamines at rest and during exercise. When subjects were evaluated according to fitness level (VO2max), resting BP was not significantly different among groups (low fitness = VO2max < or = 25 ml/kg/min; moderate fitness = VO2max 26 to 39 ml/kg/min; high fitness = VO2max > or = 40 ml/kg/min). However, an inverse relationship was observed between fitness level and rate of rise of systolic and diastolic BP during submaximal work. Multiple regression showed that fitness predicted diastolic BP response (p = 0.02) at 100 watts. Age, however, predicted systolic BP response (p = 0.015). CONCLUSIONS: Neither the level of resting nor the magnitude of BP response to exercise in hypertensive subjects was directly related to level of plasma catecholamines. The magnitude of change in BP during exercise was modulated by age and fitness level.

Significance of sympathetic innervation of pulmonary vessels in response to acute hypoxia.

The role of the autonomic nervous system on the pulmonary vascular response to hypoxia was studied in anesthetized open-chest dogs. Acute hypoxia elicited reversible decreases in the slope of the instantaneous diameter-pressure relationship of the main pulmonary artery. These decrements in vascular compliance during hypoxia were prevented by either bilateral thoracic sympathectomy or by section of the cervical vagus and glossopharyngeal nerves and were reproduced by bolus injections of lobeline (0.1 mg) at the root of the aorta. Using separation of the airways with a tracheal divider, the effects of systemic and of alveolar hypoxia on vascular resistance of the left caudal lobe were compared. Systemic hypoxia in the absence of alveolar hypoxia had no effect on pulmonary vascular resistance. Alveolar hypoxia elicited reversible increases in vascular resistance that were not prevented by sympathectomy. It is concluded that at least two vascular sites of action and two mechanisms are involved in the pulmonary vascular response to hypoxia.

Hemodynamic pulmonary edema in dogs with acute and chronic lymphatic ligation.

The effect of lymphatic ligation on relative lung water (g H2O/g dry lung) was studied in dogs. Raising left atrial pressure to 20 mmHg for 2 h in chronically lymphatic-ligated dogs (4 days) caused a significantly greater increase in relative lung water than the same hemodynamic challenge did in sham-operated and acutely lymphatic-ligated dogs. There was no significant difference in relative lung water between the acutely lymphatic-ligated and sham-operated dogs. At normal left atrial pressures, there was no significant difference in relative lung water between the sham-operated and chronically lymphatic-ligated dogs. Since the combined effects of chronic lymphatic ligation and left atrial hypertension is greater than the sum of the individual effects, it appears that chronic lymphatic ligation increases the susceptibility of the lung to hemodynamic edema, we suggest that chronic lymphatic ligation may have produced increases in the interstitial volume and protein mass that are undetectable by our technique. These increases, in turn, could lead to a reduction in tissue safety factors against hemodynamic pulmonary edema.

Dynamic local distensibility of living arteries and its relation to wave transmission.

The dynamic local distensibility of the abdominal aorta was measured in 11 anesthetized dogs by recording simultaneously phasic pressure and instantaneous intravascular cross-sectional area, utilizing a special transducer. Axial motion of the vessel wall was recorded using a modification of the same transducer. A nonlinear relationship was found to exist between area and pressure in most cases studied. Fourier analysis was performed on data from eight experiments in order to obtain frequency characteristics of distensibility. In roughly half of the cases, Fourier analysis revealed that pressure variations displayed a phase lead over area variations for frequencies up to 10 Hz. This phenomenon was ascribed to viscoelastic properties of the vessel wall and the magnitude of the phase leads roughly matched those found in vitro by others. The behavior of the vessel wall in these instances was correctly predicted by the dynamic formula for distensibility, derived by others from wave transmission theory in which absence of axial wall motion is assumed. In these experiments, axial motion of the wall was found to be virtually absent. In the other half of the cases, the reverse situation was obtained: a phase lead of area variations over pressure variations for frequencies up to 15 Hz. In those cases a craniocaudal axial displacement of the vessel wall was observed with each systole, amounting to around 1 mm. The finding of the phase leads was partially explained by a dynamic formula for distensibility, developed by us from the theory of wave transmission in which free axial motion of the wall is a chosen boundary condition. The sign and order of magnitude of the phase leads were correctly predicted by the theoretical formula, but there was a disagreement on the frequency range in which they occurred. We concluded that additional forces, not yet considered in theoretical treatments, are operative on the aortic wall, which account for this lack of agreement. The frequency dependent properties of distensibility in vivo cannot be compared to those obtained in vitro in those cases in which there is axial displacement of the vessel wall of the same order of magnitude as the radial extensions.

Alveolar pressure in fluid-filled occluded lung segments during permeability edema.

In a model of increased hydrostatic pressure pulmonary edema Parker et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 267-276, 1978) demonstrated that alveolar pressure in occluded fluid-filled lung segments was determined primarily by interstitial fluid pressure. Alveolar pressure was subatmospheric at base line and rose with time as hydrostatic pressure was increased and pulmonary edema developed. To further test the hypothesis that fluid-filled alveolar pressure is determined by interstitial pressure we produced permeability pulmonary edema-constant hydrostatic pressure. After intravenous injection of oleic acid in dogs (0.01 mg/kg) the alveolar pressure rose from -6.85 +/- 0.8 to +4.60 +/- 2.28 Torr (P less than 0.001) after 1 h and +6.68 +/- 2.67 Torr (P less than 0.01) after 3 h. This rise in alveolar fluid pressure coincided with the onset of pulmonary edema. Our experiments demonstrate that during permeability pulmonary edema with constant capillary hydrostatic pressures, as with hemodynamic edema, alveolar pressure of fluid-filled segments seems to be determined by interstitial pressures.

Ventilatory dysfunction in palatal myoclonus.

A patient with palatal myoclonus and involvement of respiratory muscles is described. Partial characterization of the mechanism of ventilatory dysfunction was achieved using noninvasive tests. Ventilatory dysfunction in this disorder can be manifested in different patterns depending on which respiratory muscles are involved predominantly.

Reversible hypercapnic respiratory insufficiency in scleroderma caused by respiratory muscle weakness.

A patient with scleroderma presented with hypercapnic respiratory failure. Evaluation of pulmonary mechanics revealed severe restriction caused in part by respiratory muscle weakness. Treatment with prednisone corrected hypoventilation, improved symptoms, increased lung volumes, returned respiratory muscle strength to normal range, but did not change the degree of lung stiffness. This case demonstrates that restrictive patterns in scleroderma can be due to either lung or chest wall disease and that the latter may be reversible. If respiratory muscle weakness is present with restrictive ventilatory patterns in patients with scleroderma, a therapeutic trial of corticosteroid is warranted.

Hemodynamic consequences of delayed ventriculoconal conduction in the frog Rana catesbeiana.

We investigated the function of the conus arteriosus in the bullfrog Rana catesbeiana using a combination of anatomical and physiological techniques. Although there is a normal delay in ventriculoconal conduction and we could induce a spectrum of ventriculoconal conduction disturbances by manipulating the region of the ventriculoconal junction, we found no histological evidence of specialized conducting myocardial tissue in this region. The performance of the conus arteriosus was explored during various disturbances of ventriculoconal conduction and also during hemodynamic disturbances produced by hemorrhage and afterloading. The conus was found to contribute little to forward flow under ordinary circumstances, but its contribution increased greatly during bleeding or partial occlusion of the truncus. In contrast to the conclusion of others, no evidence could be adduced to support the idea that the conus serves as a depulsating chamber. Disparities in previous reports concerning the operation of the conus as a booster pump are attributed to special experimental circumstances.