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Showing papers by "Warren M. Zapol published in 1987"


Journal ArticleDOI
TL;DR: The authors' data indicate that the generation of high plasma levels of C5a anaphylatoxins and thromboxane is associated with pulmonary vaso- and broncho-constriction induced by protamine reversal of heparin in humans.
Abstract: The authors conducted a study in humans to determine the mediators associated with acute pulmonary vaso- and broncho-constriction occurring episodically with protamine reversal of heparin anticoagulation. Of 48 adult patients investigated prospectively after termination of cardiopulmonary bypass, two presented a sudden increase of airway pressure, acute pulmonary hypertension, and systemic hypotension 1-3 min after right atrial protamine injection. In these two subjects, plasma levels of C5a increased from 0.7 and 2.2 to 9.8 and 9.9 ng/ml, respectively, and thromboxane B2 increased from 0.26 and 0.34 to 7.5 and 16.2 ng/ml 1 minute after drug injection. A third subject not identified prospectively had an identical reaction and mediator profile (C5a, 10.2 ng/ml; TxB2, 18.6 ng/ml at 1 min). The plasma levels of these mediators were unchanged in the remaining patients (C5a, 0.7 +/- 1.1 [x +/- S.D.] to 0.6 +/- 0.9 ng/ml; TxB2, 0.16 +/- 0.12 to 0.15 +/- 0.07 ng/ml). Plasma histamine was not involved in this type of reaction, but increased from 0.7-10.4 ng/ml in a fourth patient who became hypotensive without acute pulmonary hypertension, bronchoconstriction, or elevation of C5a or TxB2. The authors' data indicate that the generation of high plasma levels of C5a anaphylatoxins and thromboxane is associated with pulmonary vaso- and broncho-constriction induced by protamine reversal of heparin in humans.

157 citations


Journal ArticleDOI
TL;DR: The first microprocessor-controlled monitors for collection of data on depth, heart rate, and body temperature of one fetal and five adult male freely swimming Weddell seals are developed and successfully used.
Abstract: We have developed and successfully used the first microprocessor-controlled monitors for collection of data on depth, heart rate, and body temperature of one fetal and five adult male freely swimming Weddell seals. Adult seals almost invariably experienced a prompt bradycardia at the start of each dive, and the mean heart rate during diving was significantly lower for dives greater than 20 min (P greater than 0.999). The heart rate was also significantly greater during the ascent portion of dives when compared with the descent portion (P greater than 0.95). The fetal seal experienced a slow onset of bradycardia when its mother dived; during diving the fetal heart rate decreased by an average of 1.1 beats/min for each minute of the dive. The fetal heart rate generally took approximately 10 min to recover to predive levels after its mother resurfaced to breathe. The body temperature of one adult male Weddell seal showed a decrease of greater than 1.5 degrees C from resting levels before dives of greater than 15 min were initiated and a drop of over 2 degrees C before dives of greater than 30 min duration.

142 citations


Journal ArticleDOI
TL;DR: In 19 patients with severe ARDS, 13 had vascular occlusions on balloon occlusion angiography, and these occlures correlated with increased post mortem counts of PA thrombi, suggesting diffuse vasoconstriction is present in early ARDS.
Abstract: Mild pulmonary artery hypertension (PAP, 29.6 +/- 10.6 mm Hg, mean +/- SD) due to a 3-fold elevation of pulmonary vascular resistance (PVR, 2.2 +/- 1.1 mm Hg X L/min) is a common finding in severe ARDS. A vasodilator such as nitroprusside (151 micrograms/kg X min) can be administered in early ARDS and will lower PAP and PAOP (capillary wedge pressure) while increasing cardiac output (CO) from 6.9 to 8.75 L/min X M2 and venous admixture from 23% to 31.6%. This suggests diffuse vasoconstriction is present in early ARDS. In 19 patients with severe ARDS, 13 had vascular occlusions on balloon occlusion angiography, and these occlusions correlated with increased post mortem counts of PA thrombi. At autopsy, there was a considerable increase of PA medial thickness and a reduction of lumen diameter. This hemodynamic and morphologic evidence suggests both vasoconstrictor and anatomic changes play major roles elevating the PVR in ARDS.

97 citations


Journal ArticleDOI
TL;DR: The results indicate that a discrete value for pulmonary capillary pressure can be reproducibly measured in paralyzed ventilated patients and suggest that there is unequal and variable partitioning of the increased PVR during acute respiratory failure.
Abstract: In this report, the authors present the results of 34 estimates of pulmonary capillary pressure (Pcap) in 15 adult patients receiving intensive care for acute respiratory failure (ARF). Within the pulmonary artery pressure profile during transient balloon occlusion, the authors identified two expone

69 citations


Journal ArticleDOI
TL;DR: It is concluded that fibrinolytic infusion can lyse thrombi and possibly improve hemodynamics and oxygenation in ARDS-associated pulmonary vascular thrombosis.
Abstract: IV streptokinase was infused to test the potential reversibility of adult respiratory distress syndrome (ARDS) associated pulmonary vascular thrombosis in five patients suffering from severe ARDS with elevated mean pulmonary artery pressure, increased pulmonary vascular resistance, and angiographically documented pulmonary vascular thrombosis. At 48 hr there was clearance of obstructions in arteries larger than 1 mm in diameter in all patients, increased filling of the microvasculature and small arteries less than 1 mm in diameter in four patients, a fall in pulmonary vascular resistance in all patients, a rise in cardiac output in four patients, improved oxygenation (PAO2/FlO2) in three patients, and variable changes in shunt fraction and ventilator pressures. Expressed as a mean fraction of the preinfusion controls, the postinfusion physiologic values were pulmonary artery pressure = 0.89 mm Hg, pulmonary vascular resistance = 0.68 mm Hg X min/L, cardiac output = 1.36 L/min, central venous pressure = 0.77 cm H2O, pulmonary capillary wedge pressure = 0.92 mm Hg, PAO2/FlO2 = 1.08, and shunt fraction = 0.95. Follow-up angiography showed no evidence of reocclusion. Postmortem studies of the three nonsurvivors confirmed recanalization of thrombosed pulmonary arteries. One documented bleeding episode occurred. We conclude that fibrinolytic infusion can lyse thrombi and possibly improve hemodynamics and oxygenation in ARDS-associated pulmonary vascular thrombosis.

61 citations



Journal ArticleDOI
TL;DR: The results suggest that in vivo platelet activation occurs in ARF, and ARF patients have quantitative and qualitative platelet defects that may contribute to thrombotic and hemorrhagic complications.
Abstract: To assess the role of platelets in thrombohemorrhagic complications of acute respiratory failure (ARF), we studied platelet function in 13 ARF patients admitted for intensive care, in six acutely ill intensive care patients without evidence of acute lung injury (non-ARF), and in 10 normal subjects Platelet counts in ARF and non-ARF patients were similar to the normal range The bleeding time of the ARF patients (85 +/- 09 min) was significantly longer (p less than 001) than the normal (48 +/- 02 min) but similar to non-ARF patients (54 +/- 08 min) The bleeding time prolongations in ARF patients were unrelated to platelet concentration Platelet aggregation induced by ADP and thrombin was normal in both ARF and non-ARF patient groups The epinephrine response was impaired in one non-ARF patient and in three ARF patients; collagen-induced aggregation was absent in two ARF patients, with a prolonged bleeding time Levels of VIII:C and vWF in both groups of patients were similar to the normal level, but VIIIR:Ag levels in ARF patients (407 +/- 45% of normal) were higher (p less than 001) than in both non-ARF patients (210% +/- 10%) and normal subjects (106% +/- 4) The electrophoretic mobility of VIIIR:Ag was abnormal in ARF patients The prolonged bleeding time in ARF patients appears to result from the qualitative and quantitative VIIIR:Ag defect beta-Thromboglobulin levels were greater (p less than 001) in ARF patients (876 +/- 69 ng/ml; p less than 0001) than in non-ARF patients (462 +/- 31 ng/ml) or in normal subjects (253 +/- 25 ng/ml p less than 00001) However, platelet factor 4 plasma levels in ARF patients (18 +/- 16 ng/ml) did not differ from those in non-ARF patients (150 +/- 30 ng/ml), but both were significantly different from normal (61 +/- 08 ng/ml) Plasma thromboxane B2 (T X B2) levels were not different from normal values in either ARF or non-ARF patients, but 6-keto-PGF1 alpha levels were significantly reduced (p less than 001) in ARF patients (215 +/- 43 pg/ml) compared to normal values (381 +/- 34 pg/ml) Non-ARF patients had 6-keto-PGF1 alpha levels (285 +/- 111 pg/ml) midway between the normal values and those of ARF patients Our results suggest that in vivo platelet activation occurs in ARF ARF patients have quantitative and qualitative platelet defects that may contribute to thrombotic and hemorrhagic complications

19 citations


Journal ArticleDOI
TL;DR: Fibrin is often seen occluding the lung vessels of patients dying from ARDS and is surrounded by regions of lung necrosis, and to learn if it could observe increased or focal fibrin deposition and assess the kinetics of plasmafibrinogen turnover during severe acute respiratory failure, technetium 99m-labeled human purified fibr inogen (Tc-HF) was injected and gamma camera scanning for as long as 12 h was used.
Abstract: Fibrin is often seen occluding the lung vessels of patients dying from ARDS and is surrounded by regions of lung necrosis. To learn if we could observe increased or focal fibrin deposition and assess the kinetics of plasma fibrinogen turnover during severe acute respiratory failure, we injected technetium 99m-labeled human purified fibrinogen (Tc-HF) and used gamma camera scanning for as long as 12 h in 13 sequential patients as soon as possible after ICU admission. The fibrinogen uptake rates were determined by calculating the lung:heart radioactivity ratios at each time point. Slopes of the lung:heart ratio versus time were compared between ARDS and mild acute respiratory failure (ARF). The slope of the lung:heart Tc-HF ratio of the 9 patients with ARDS (2.9 +/- 0.4 units) was markedly higher (p less than 0.02) than the slope of the 4 patients with mild ARF (1.1 +/- 0.4) and the 3 patients studied 5 to 9 months after recovery from respiratory failure (0.7 +/- 0.07). In the 1 patient with ARDS and the 2 patients with mild ARF studied both during acute lung injury and after recovery, the lung:heart Tc-HF ratio had decreased at recovery. To compare the pulmonary uptake of Tc-HF tomore » /sup 99m/Tc-labeled human serum albumin (Tc-HSA), 5 patients were injected with 10 mCi of Tc-HSA, and scanning of the thorax was performed with a similar sequential imaging protocol 24 h after conclusion of the Tc-HF study.« less

18 citations


Journal ArticleDOI
TL;DR: The cardiac output during acute pulmonary artery hypertension (PAH) may be compromised by right ventricular outflow obstruction, myocardial ischemia, or adverse ventricular interactions, and the relative contributions to impaired biventricular function are studied.

13 citations


Journal ArticleDOI
TL;DR: Investigation of the effects of a new pyridoquinazoline thromboxane synthetase inhibitor infused before administering Escherichia Coli endotoxin into 18 anesthetized sheep with lung lymph fistulas found plasma and lymph levels were increased several-fold, suggesting cyclooxygenase blockade at this dose.

10 citations



01 Jan 1987
TL;DR: The systemic blood contribution to the canine tracheobronchial tree is larger than the pulmonary one and that, in the presence of increased metabolic needs, it responds more promptly with increased blood flow.
Abstract: To investigate the quantity and pathophysiological relationship of pulmonary and bronchial artery supply to the tracheobronchial tree in dogs in absence and in presence of increased tissue metabolic requirements, pulmonary and bronchial blood flow to the trachea and bronchi was determined by the radioactive microsphere method in nine adult mongrel dogs Microspheres were injected into the right atrium of three dogs (pulmonary injection group) and into the left ventricle of four dogs (systemic injection group) just before and three, eight and fourteen days after resection and anastomosis of the right main bronchus The remaining two dogs served as controls without surgery After the fourth injection, the tracheobronchial tree was harvested, divided into segments, and the radioactivity counted in each segment At baseline the systemic flow to the tracheobronchial tree expressed as percentage of cardiac output was 0188% +/- 0121 and the pulmonary blood flow was 0007% +/- 0004 (mean +/- SD) Three, eight and fourteen days after transection and anastomosis of the right main stem bronchus, the systemic blood flow to the bronchial segments proximal and distal to the anastomosis increased significantly whereas pulmonary blood flow did not change Depending on the anatomical segment considered the systemic contribution was between 5 and 100 times larger than the pulmonary one, both at baseline and after transection and anastomosis of the right main stem bronchus, but the ratio diminished in more distal segments where pulmonary blood flow was larger It is concluded that the systemic blood contribution to the canine tracheobronchial tree is larger than the pulmonary one and that, in the presence of increased metabolic needs, it responds more promptly with increased blood flow