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Biomedical subjects

J E Rinaldo

Publications and source records attributed to J E Rinaldo.

At least 37 records · Page 2Linked to original sources
PubMed1987

High-dose corticosteroids in patients with the adult respiratory distress syndrome.

Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.

Clinical Trials as Topic↗
PubMed1987

Shift in subfractions of rat alveolar macrophages in vivo during endotoxin-induced alveolitis.

To elucidate changes in alveolar macrophages that accompany sepsis-induced lung injury, this study analyzed the subfractions of alveolar macrophages (AM) recovered by lung lavage during the onset of endotoxin-induced acute neutrophilic alveolar inflammation in the rat model. Centrifugation on continuous self-generated density gradients of Percoll was used to fractionate AM into subpopulations between density limits 1.012 and 1.130. Two-thirds of AM recovered from pathogen-free control rats (group C) were in a fraction with a density range of 1.058-1.078 ["normal" density fraction, (ND)]. Only 6% were located in a very low density (VLD) fraction 1.037-1.048. Neutrophils accounted for less than 1% of recovered cells and usually were found in the fraction with density range of 1.079-1.130. By contrast, if rats underwent lung lavage 15 hours after the administration of endotoxin (group E), only 38% of macrophages were recovered in the "normal" density fraction, whereas 26% of the AM recovered were in the VLD fraction. This shift in the relative sizes of the density based subpopulations coincided with the onset of acute bronchoalveolar inflammation as indicated by the recovery of neutrophils by bronchoalveolar lavage (PMN = 7 X 10(4) in C, vs. 9.4 X 10(5) in E, p less than .001). The macrophages on the low density subfractions showed functional impairment: they were less viable in culture and migrated poorly in response to endotoxin-activated serum compared to macrophages in the "normal" density fraction from the endotoxin-treated animals. The rapid emergence of the low density population after endotoxin could represent an influx of new cells, but more likely indicates that injury to or previous activation of resident macrophages has caused their density to decrease. We speculate that the emergence of a population of AM in airspaces with low density and impaired function could weaken pulmonary host defence following endotoxemia.

Animals↗
PubMed1987

Neutrophil-endothelial interactions: modulation of neutrophil activation responses by endothelial cells.

There is controversy concerning whether intravascular activation of neutrophils during acute inflammation injuries contiguous endothelial cells in vivo. Several physiologic defense mechanisms tend to limit such injury. In this paper we have examined evidence for one of these putative protective mechanisms: endothelial cell modulation of the activation responses of neutrophils during adherence and diapedesis. In vitro, endothelial cells co-incubated with neutrophils inhibit the release of superoxide anion when stimulated by receptor-mediated activators. The possible mechanisms include contact-linked down-regulation of neutrophil activation, the release from endothelial cells of soluble mediators which attenuate neutrophil activation responses, and the presence of free radical scavengers in endothelial cells which are active at the interface between endothelial cells and adherent neutrophils. There may be a broad spectrum of mechanisms by which intercellular interactions protect the lining cells of the vascular lumen from 'inadvertent' destruction by phagocytes which become activated while in an intravascular location.

Animals↗
PubMed1986

Effects of ibuprofen on endotoxin-induced alveolitis: biphasic dose response and dissociation between inflammation and hypoxemia.

Ibuprofen is a cyclo-oxygenase inhibitor that is alleged to have additional direct effects on leukocyte function. These properties suggest that Ibuprofen may be of potential therapeutic value for neutrophil (PMN)-mediated acute lung injury in humans such as that resulting from septicemia by gram-negative organisms. This study quantitated the effect of pretreatment with Ibuprofen on the intensity of acute neutrophilic alveolitis following endotoxemia. The effect of Ibuprofen on neutrophilic alveolitis was biphasic: There was suppression of inflammation at a high dose (30 mg/kg), enhancement at a low dose (3 mg/kg), and intermediate doses (10-20 mg/kg) had no effect. In contrast, both 10 and 30 mg/kg of Ibuprofen prevented early hypoxemia following endotoxemia, suggesting that early hypoxemia and inflammation by neutrophils were not causally related. The dose of Ibuprofen required to suppress neutrophil alveolitis exceeds that required to inhibit cyclooxygenase in the model. Therefore, suppression of alveolitis by 30 mg/kg of Ibuprofen may depend on other pharmacologic properties of Ibuprofen such as its direct effect on neutrophil migration.

Animals↗
PubMed1986

Assessment of lung injury in the adult respiratory distress syndrome using multiple indicator dilution curves.

To assess its usefulness as an index of lung injury in critically ill patients with respiratory failure, the lung microvascular permeability surface area product for urea (14C-PSu) was measured using a multiple radioisotopic indicator dilution technique in 10 patients with the adult respiratory distress syndrome (ARDS) and in a control population of 5 patients without ARDS. The mean values for 14C-PSu and for extravascular lung water (EVLW) were both significantly elevated in patients with ARDS compared with those in control patients (14C-PSu: 18.7 +/- 4.4 versus 7.6 +/- 0.7, p less than 0.05; EVLW: 676 +/- 55 versus 269 +/- 53, p less than 0.001); 14C-PSu and EVLW were significantly correlated (R = 0.52, p less than 0.001). In the patients with ARDS, 14C-PSu and oxygenation, assessed as the alveolar-arterial oxygen difference, did not appear to be correlated. Repeated measurements of 14C-PSu were variable in the 3 control patients in whom 4 or more measurements were obtained (SD = 50, 57, and 54% of the mean values, respectively); 14C-PSu did not predict clinical outcome assessed by survival of individual patients with ARDS. These data suggest that measurement of 14C-PSu in critically ill patients is a clinically applicable parameter that reflects the degree of microvascular injury in groups of patients. However, our study did not indicate a clear advantage of 14C-PSu over EVLW in assessing lung injury in this patient population. The variability in 14C-PSu control patients also suggests that directional changes in 14C-PSu, as a measure of changes in the degree of lung microvascular dysfunction, should be interpreted with caution.

Adult↗
PubMed1985

Modulation of endotoxin-induced neutrophil alveolitis by captopril and by hyperoxia.

We compared survival and the intensity of bronchoalveolar inflammation reflected by lung lavage after the intraperitoneal injection of endotoxin from Escherichia coli serotype 055B5 in rats breathing air and those breathing 60% oxygen for six days after endotoxin injection. Survival following 7.5 mg/kg of endotoxin was comparable in air-breathing rats (50%) and in oxygen-breathing rats (63%). Endotoxin caused a dose-dependent increase in the recovery of polymorphonuclear leukocytes from the lung. Oxygen breathing reduced the percentage of neutrophils recovered by lavage 24 hr after endotoxin from 17% to 9% after 2.5 mg/kg of endotoxin and from 34% to 12% after 7.5 mg/kg of endotoxin. The absolute number of neutrophils recovered was also significantly decreased in oxygen-breathing rats. The activity of pulmonary angiotensin-converting enzyme (ACE) has been reported to be affected by oxygen tension, and ACE degrades bradykinin, a proinflammatory mediator. Therefore, we questioned whether the salutary effect of increased inspired oxygen tension on the magnitude of neutrophil influx into the airspaces could be related to changes in ACE activity. We found that after 48 hr of peroral pretreatment of the rats with captopril, a specific ACE inhibitor, there was increased recovery of neutrophils by lavage 24 hr after injection of endotoxin in air-breathing rats. Captopril pretreatment also increased the chemotactic activity of bronchoalveolar lavage fluid (BALF). There was no concomitant alteration in the accumulation of 125I albumin in the lung following captopril pretreatment either in endotoxin-treated rats or in controls. Thus, breathing 60% oxygen decreased the accumulation of neotrophils in airspaces after intraperitoneal endotoxin injection and pharmacologic inhibition of ACE had the opposite effect. Alterations in the activity of pulmonary angiotensin-converting enzyme related to alveolar oxygen tension is a potential speculative mechanism for modulation of alveolar inflammation by the inspired oxygen concentration in this model.

Animals↗
PubMed1985

Role of alveolar macrophages in endotoxin-induced neutrophilic alveolitis in rats.

Although bacterial endotoxins have potent effects on blood monocytes and tissue macrophages, the role of alveolar macrophages in regulating intrapulmonary neutrophil traffic following endotoxemia has not been studied previously. We have previously reported that a single intraperitoneal injection of endotoxin from Escherichia coli serotype 055B5 causes acute lung inflammation by neutrophils (PMN) in rats. The factors which influence the migration of PMN in the lung in this model are unknown. To determine whether macrophage-derived products could play a role in directing migration, we enumerated neutrophils in histologic sections and employed electron microscopy to document the location of neutrophils in the lung in vivo following endotoxin. We also cultured the alveolar macrophages recovered by lung lavage to measure the effect of their culture supernatants on neutrophil migration in vitro. In the first 6 hr following endotoxin, and also 24 hr later, there was an increase in the number of PMN enumerated in the lung parenchyma by light microscopy. Electron microscopy showed the location of the neutrophils to be exclusively intravascular at 6 hr. By contrast, neutrophils were observed in both interstitial and bronchoalveolar spaces at 24 hr, confirming that transvascular migration was active at that time. The pulmonary macrophages which were recovered by lung lavage from groups of rats sacrificed at 4 and at 15 hr following the administration of endotoxin were assayed for the release into culture media of migration-stimulatory activity for neutrophils. Macrophages from animals sacrificed 4 hr following endotoxin released less migration-stimulating activity into media than macrophages from controls. These macrophages could be stimulated to release migration-stimulating activity into culture media at levels comparable to macrophages from controls by the addition of opsonized Zymosan to the culture media. By contrast, macrophages from animals sacrificed 15 hr after endotoxin spontaneously released more migration-stimulating activity for neutrophils than did macrophages from controls. Thus, in this model, a specific increase in the synthesis or release by alveolar macrophages of factors which stimulate the migration of neutrophils in vitro coincided with a transition from intravascular to extravascular alveolar inflammation by neutrophils in vivo. These observations are consistent with the hypothesis that pulmonary alveolar macrophages may contribute to the regulation of alveolar inflammation following endotoxemia by releasing factors which influence the migration of neutrophils.

Animals↗
PubMed1985

Deterioration of oxygenation and abnormal lung microvascular permeability during resolution of leukopenia in patients with diffuse lung injury.

To determine whether circulating leukocytes contribute to gas exchange abnormalities in diffuse lung injury, we retrospectively examined oxygenation in 6 patients who met 3 criteria: leukopenia caused by marrow aplasia from remission-inducing chemotherapy for myelogenous leukemia, the eventual resolution of leukopenia, and concurrent acute respiratory failure diagnosed clinically as increased permeability pulmonary edema. Four of the 6 patients abruptly developed overt clinical evidence of pulmonary dysfunction within the 96 h preceding the resolution of the peripheral leukopenia. In all 6 patients, the alveolar to arterial oxygen tension difference increased between leukocyte counts. The mean value for the alveolar to arterial oxygen tension difference for the group doubled during this period (148 +/- 37 mmHg 3 days prior to resolution; 290 +/- 37 mmHg 1 day after resolution; p less than 0.05). As an index of lung capillary permeability, we measured the lung permeability-surface area product for urea (PSu) for an additional patient with oxygen toxicity and drug-induced leukopenia whose hypoxemia increased immediately before the resolution of leukopenia. The PSu in this patient was high, in the range previously reported as being highly specific for increased permeability pulmonary edema with a fatal outcome. We conclude that such diffuse lung injury resembling the adult respiratory distress syndrome can occur in leukopenic patients, but the resolution of leukopenia in such patients may be associated with worsening oxygenation and with abnormally high pulmonary microvascular permeability. These observations do not prove a causal relationship but provide a clinical parallel to several leukocyte-depletion studies reported in animal models of increased permeability pulmonary edema that implicate white blood cells in the pathogenesis of hypoxemia and lung edema.

Adult↗
PubMed1985

Modification by hyperoxia in vivo of endotoxin-induced neutrophil alveolitis in rats. Production of chemotactic factors by alveolar macrophages and ultrastructure.

We have previously shown that prior exposure to hyperoxia intensifies the influx of polymorphonuclear leukocytes into bronchoalveolar spaces after endotoxemia (E), but the mechanism is unknown. Because pulmonary alveolar macrophages (PAM) regulate the migration of polymorphonuclear leukocytes into the lung in several types of acute and chronic alveolitis, we studied the effect of pretreatment with hyperoxia in vivo on production of chemotactic factors by PAM after E. In this study, we cultured PAM recovered by lung lavage from oxygen- and air-pretreated rats 4, 15, and 48 h after E to determine whether a direct effect of hyperoxia on the release of chemotactic factors by PAM in response to E in vivo could contribute to the previous observations. We found that the chemotactic activity of the culture media supernatants from PAM recovered from oxygen-pretreated rats given E was 80% higher than that of media from PAM recovered from air-exposed rats given E. Neither PAM from air-exposed rats nor those from oxygen-exposed rats spontaneously released chemotaxins selective for other PAM. In contrast, when PAM were stimulated with zymosan in vitro, those from the oxygen-breathing group produced 50% more chemotactic activity for other PAM than did those from the air-breathing group. These differences in secretion of chemotactic factors were not associated with decreased viability of PAM either in vivo or in tissue culture, or with impaired adherence by PAM in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effect of mechanical ventilator mode on tendency towards respiratory alkalosis.

The question whether assist-control ventilation (A/C) results in more frequent or more severe respiratory alkalosis than intermittent mandatory ventilation (IMV) is often raised. We prospectively compared the respiratory rates and arterial blood tensions of 18 critically ill patients with respiratory failure of diverse causes who were mechanically ventilated for 1 h with each of these ventilatory modes. Each patient served as his own control. We found that after 1 h of IMV the average pH was 7.42 +/- 0.2 (mean +/- SEM), after 1 h of A/C the pH was 7.45 +/- 0.01 (p less than 0.005), the average PaCO2 during IMV was 40.7 +/- 1.8, the average PaCO2 during A/C was 37.9 +/- 1.6 (p less than 0.001), the average respiratory rate during IMV was 21 +/- 2.0, and the average respiratory rate during A/C was 15 +/- 2.0 (p less than 0.001). One patient became alkalemic (pH 7.55) during A/C. These pH and PaCO2 changes were not associated with any adverse clinical sequelae. We conclude that the responsible physician should be guided by factors other than control of pH in choosing the mode of mechanical ventilation for most patients.

Adult↗
PubMed1985

Effect of methylprednisolone and of ibuprofen, a nonsteroidal antiinflammatory agent, on bronchoalveolar inflammation following endotoxemia.

Septicemia by gram-negative organisms is a common cause of the adult respiratory distress syndrome (ARDS). The role of neutrophils in causing parenchymal lung damage in ARDS has recently been emphasized. A single intraperitoneal injection of Escherichia coli endotoxin in rats causes acute neutrophil alveolitis similar to that of ARDS. We studied the ability of pretreatment with either ibuprofen (IBU) or methylprednisolone (MP) to ablate directly the alveolar inflammatory response to endotoxin in the rat model. To compare the severity of inflammation, we quantified inflammatory cell recovery by whole lung lavage 24 hours after injection of endotoxin, the time point at which neutrophil alveolitis due to endotoxin is most intense. Pretreatment with a single dose of IBU 3.75 mg/kg prior to endotoxin injections was associated with a significant increase in the total number of inflammatory cells, and in both the percentage and the absolute number of neutrophils recovered from the lung, despite significantly decreasing the plasma level of thromboxane B2, which increased 10-fold after endotoxin. Paradoxically, IBU 30 mg/kg significantly decreased the intensity of neutrophil alveolitis. MP 30 mg/kg had no effect on recovery of inflammatory cells from the lung by bronchoalveolar lavage following endotoxin. Cyclooxygenase inhibitors such as ibuprofen may cause a dose-dependent biphasic effect on lung inflammation following endotoxin: enhancement of inflammation at a low dose and suppression of inflammation at a high dose.

Animals↗
PubMed1984

Local lung ventilation in critically ill patients using nonradioactive xenon-enhanced transmission computed tomography.

Nonradioactive xenon is sufficiently radiodense to increase the density of gas-containing lung as seen in a computed tomography (CT) scan. Subtraction of a baseline CT scan from the xenon-enhanced CT scan can accentuate gas space differences by subtracting fixed tissue densities. The baseline scan and the scan obtained during wash-in of xenon (before equilibration) allow circulation of local ventilation. The xenon CT scan, thus, provides more precise information about distribution of ventilation than planar radiogas techniques. The technical aspects of application to a critically ill patient and the mathematical basis of the technique are presented.

Humans↗
PubMed1984

Neutrophil alveolitis following endotoxemia. Enhancement by previous exposure to hyperoxia.

We injected Escherichia coli endotoxin, 2.5 mg/kg, intraperitoneally in rats, sequentially quantified alveolar inflammation during a 6-day period by several techniques, and observed the effect of previous exposure to hyperoxia on the intensity of alveolitis in this model. As noted in other models of endotoxemia, we found intravascular sequestration of leukocytes and an increase in the retention of 125I albumin in the lung 4 to 6 h after the injection of endotoxin. Bronchoalveolar lavage fluid (BALF) obtained at this time only slightly stimulated the migration of neutrophils in vitro, and the numbers and types of cells recovered by lavage were normal. Fifteen h after the injection of endotoxin, however, bronchoalveolar lavage fluid stimulated both random and directed migration of neutrophils in vitro, although recovery of neutrophils by lavage was increased only slightly. By 24 h, 125I albumin retention had returned to normal levels, but the chemotactic activity of BALF remained high, and the percentage and absolute number of neutrophils recovered by lung lavage were increased markedly. The recovery of neutrophils remained significantly elevated for 3 days but declined to control levels by 6 days, whereas the recovery of alveolar macrophages was increased at this time. Exposure to 100% O2 for 36 h prior to endotoxemia accelerated and intensified neutrophil influx into the lung and increased the stimulatory effect of BALF on neutrophil migration in vitro. We conclude that a single episode of endotoxemia in the rat causes a multi-phasic alveolar inflammatory response, and that this response is accelerated and intensified by prior, mild exposure to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗