Tissue hypoxia and hepatocellular insufficiency in patients with cirrhosis

To determine whether tissue hypoxia occurred in cirrhosis, oxygen contents, mixed venous and hepatic venous lactate concentrations as well as systemic hemodynamics were studied in 53 patients with cirrhosis. The influence of liver failure on tissue oxygenation was also studied. Cardiac index and mixed venous and hepatic venous lactate concentrations were significantly higher in patients with cirrhosis than in 20 control subjects. Oxygen consumption, oxygen extraction ratio and mixed venous and hepatic venous carbon dioxide tensions were significantly lower in the former than in the latter. Oxygen transport was not significantly different between the two groups. Cardiac index and oxygen transport were not significantly different between grade A (Pugh's classification) and grade C patients. Mixed venous as well as hepatic venous lactate concentrations were significantly higher while oxygen consumption, oxygen extraction ratio and carbon dioxide tensions were significantly lower in grade C than in grade A patients. We conclude that tissue hypoxia occurs in patients with cirrhosis and hepatic insufficiency. This tissue hypoxia might be due to arteriovenous shunting-related limitation of tissue oxygen extraction.     

Oxygen delivery and utilization during rapidly fatal septic shock in rats

Oxygen delivery and utilization were studied in a rapidly fatal model of rat peritonitis. Cecal ligation and perforation induced peritonitis and septic shock in five animals. Five animals served as sham-operated controls. Arterial pressure, central venous pressure, cardiac index, hemoglobin, plasma colloid osmotic pressure, arterial blood lactate concentration, and arterial and central venous oxygen saturation were sequentially measured over 5 hr. In septic animals, decreases in mean central venous pressure were associated with hemoconcentration and decreases in plasma colloid osmotic pressure from 16.3 +/- 0.8 to 12.2 +/- 0.1 mmHg (P less than 0.05). The cardiac index decreased from 359 +/- 35 to 166 +/- 25 ml/kg/min (P less than 0.001), and arterial lactate increased from 0.2 +/- 0.1 to 2.1 +/- 0.4 mmol (P less than 0.001). However, oxygen consumption was maintained secondary to increases in systemic oxygen extraction. Arterial lactate concentration was inversely correlated with systemic oxygen delivery and central venous oxygen saturation (r = -0.68, P less than 0.05 and r = -0.71, P less than 0.001, respectively). These observations during lethal peritonitis suggest that hypovolemia is associated with increases in microvascular permeability, although the concomitant influence of intravascular pooling cannot be excluded. Decreases in systemic perfusion appear to account for critical oxygen deficits and lactic acidosis. The increases in systemic oxygen extraction imply that cellular oxygen utilization is maintained during lethal septic shock.     

Effects of changes in arterial carbon dioxide tension on oxygen consumption during cardiopulmonary bypass.

The effects of changes in arterial carbon dioxide tension (PaCO2) on the oxygenation of tissues in 34 patients undergoing surgery for aortocoronary bypass were studied while temperature, systemic blood flow, and the delivery of oxygen to the peripheral tissues remained constant. Mixed venous and superior vena caval oxygen tensions (PvO2 and PsvcO2, respectively) and oxyhemoglobin saturations and the in vivo partial pressure of oxygen at which 50 percent of the hemoglobin is saturated (P50) increased with PaCO2, while peripheral vascular resistance, in vitro P50, the level of 2,3-diphosphoglyceric acid in the red blood cells, and the level of lactate in the blood remained constant. There was a close correlation between increases in PaCO2 and increases in PvO2 (r = 0.912; P less than 0.001) but not increases in PsvcO2 (r = 0.364; not significant). This indicated that the total-body consumption of oxygen diminished with increases in PaCO2 but that some regional redistribution of oxygen consumption occurred between the superior and inferior vena caval vascular beds. Since the level of lactate in the blood remained constant and since signs of metabolism acidosis did not develop, the reduced oxygen consumption due to increases in PaCO2 did not result in detectable increases in anaerobic metabolism.     

Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure

We studied the central hemodynamic, leg blood flow, and metabolic responses to maximal upright bicycle exercise in 30 patients with chronic heart failure attributable to severe left ventricular dysfunction (ejection fraction, 24 +/- 8%) and in 12 normal subjects. At peak exercise, patients demonstrated reduced oxygen consumption (15.1 +/- 4.8 vs. 32.1 +/- 9.9 ml/kg/min, p less than 0.001), cardiac output (8.7 +/- 3.2 vs. 18.6 +/- 4.4 l/min, p less than 0.001), and mean systemic arterial blood pressure (116 +/- 15 vs. 135 +/- 13 mm Hg, p less than 0.01) compared with normal subjects. Leg blood flow was decreased in patients versus normal subjects at rest and matched submaximal work rates and maximal exercise (2.1 +/- 1.9 vs. 6.4 +/- 1.4 l/min, all p less than 0.01). Mean systemic arterial blood pressure was no different in the two groups at rest or at matched submaximal work rates, whereas leg vascular resistance was higher in patients compared with normal subjects at rest, submaximal, and maximal exercise (all p less than 0.01). Although nonleg blood flow was decreased at rest in patients, it did not decrease significantly during exercise in either group. Peak exercise leg blood flow was related to peak exercise cardiac output in patients (r = 0.66, p less than 0.01) and normal subjects (r = 0.67, p less than 0.01). In patients, leg vascular resistance was not related to mean arterial blood pressure, pulmonary capillary wedge pressure, arterial catecholamines, arterial lactate, or femoral venous pH at rest or during exercise. Compared with normal subjects during submaximal exercise, patients demonstrated increased leg oxygen extraction and lactate production accompanied by decreased leg oxygen consumption. Thus, in patients with chronic heart failure compared with normal subjects, skeletal muscle perfusion is decreased at rest and during submaximal and maximal exercise, and local vascular resistance is increased. Our data indicate that nonleg blood flow and arterial blood pressure were preferentially maintained during exercise at the expense of leg hypoperfusion in our patients. This was associated with decreased leg oxygen utilization and increased leg oxygen extraction when compared to normal subjects, providing further evidence that reduced perfusion of skeletal muscle is important in causing early anaerobic skeletal muscle metabolism during exercise in subjects with this disorder.(ABSTRACT TRUNCATED AT 400 WORDS)     

Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure.

The effects of angiotensin converting enzyme inhibition on systemic and coronary hemodynamics and on myocardial lactate metabolism were investigated before and 2 and 6 hours after cilazapril at rest and during supine submaximal exercise in 10 patients with New York Heart Association class II or III chronic congestive heart failure. Angiotensin converting enzyme inhibition, indicated by a significant increase in plasma renin activity, resulted in significant reductions in blood pressure and systemic vascular resistance. Myocardial oxygen demand decreased (resting double product 10.9 +/- 3.7 vs 12.2 +/- 3.8 mm Hg beats/min 10(-3); p less than 0.05), but coronary sinus blood flow remained unchanged and calculated coronary resistance decreased (0.45 vs 0.5 units, rest 6 hours; p less than 0.05) suggesting coronary vasodilatation. Changes in coronary vascular resistance were directly related to changes in systemic vascular resistance (r = 0.75, p less than 0.5). Myocardial lactate extraction increased at rest (47 +/- 60 vs 134 +/- 132 mumol/min; p less than 0.5) and during exercise (27 +/- 54 vs 491 +/- 317 mumol/min; p less than 0.05) both in patients with coronary artery disease (n = 5) and idiopathic dilated cardiomyopathy (n = 5). Resting lactate production was converted to lactate extraction in two patients with coronary artery disease. Neither plasma catecholamine nor atrial natriuretic peptide concentrations changed significantly. The results suggest coronary vasodilation and improved aerobic myocardial metabolism by angiotensin converting enzyme inhibition in patients with congestive heart failure.     

Oxygen delivery in critically ill patients. Relationship to blood lactate and survival

Forty-four critically ill patients with or without adult respiratory distress syndrome (ARDS) were studied in an attempt to define critical levels of oxygen delivery. Blood lactate was used as the indicator of tissue hypoxia independent of cardiac output. Survival was good (55 percent) and blood lactate near normal for those with oxygen delivery more than 8 ml/kg/min. Below this level, survival was poor (14 percent) and blood lactate markedly increased. There were significant nonlinear correlations of lactate with O2 delivery (r = - .735, p less than .001) and cardiac output (r = - .602, p less than .001). Mixed venous oxygen was not a reliable indicator of blood lactate, survival, oxygen delivery, or oxygen consumption.     

Effects of isosorbide dinitrate on portal hypertension in alcoholic cirrhosis

It has recently been reported that vasodilators lower portal pressure in patients with cirrhosis. This effect, however, is not definitively proven. The effect of isosorbide dinitrate (5 mg sublingually) on splanchnic and systemic hemodynamics was investigated in 13 patients with alcoholic cirrhosis and portal hypertension. The administration of isosorbide dinitrate reduced hepatic venous pressure gradient by 34% (P less than 0.001), mean arterial pressure by 30% (P less than 0.001), cardiac index by 17% (P less than 0.001) and systemic vascular resistance by 11% (P = 0.05). Hepatic blood flow was not affected by the treatment. Significant correlations were found between the decrease in hepatic venous pressure gradient and that of cardiac index (P less than 0.05) and mean arterial pressure (P less than 0.05). These data indicate that isosorbide dinitrate lowers portal pressure in patients with cirrhosis. Decrease in cardiac output, rise in splanchnic arterial vascular resistance and decrease in porto-hepatic resistance seem to participate in determining the effect.     

Influence of upright exercise on pulmonary hemodynamics in left heart failure.

Studies in severe chronic stable heart failure (HF) indicate that pulmonary resistance might remain unchanged during exercise and could subsequently contribute to limitation in exercise capacity of these patients. We assessed the possible role of the exercise decreases in mixed venous oxygen tension on this phenomenon in fifteen patients with chronic congestive heart failure (N.Y.H.A. functional classes II to IV) who underwent a symptom-limited treadmill exercise test with hemodynamic monitoring as well as repeated arterial and mixed venous blood gas analysis. For all patients there was an increase in cardiac output (from 3.7 +/- 0.2 to 6.7 +/- 0.5 l/min, p less than 0.001) and pulmonary wedge pressure (from 16 +/- 2 to 31 +/- 3 mm Hg, p less than 0.001) along with exercise with highly significant decrease in total systemic resistance and no significant (from 25.6 +/- 1.5 to 15.8 +/- 1.0 U, p less than 0.001) changes in pulmonary vascular resistances. Arterial blood oxygen tension increased from 86 +/- 3 to 99 +/- 3 mm Hg (p less than 0.001) and mixed venous oxygen tension (PvO2) decreased from 33 +/- 1 to 22 +/- 1 mm Hg (p less than 0.001). Changes in pulmonary vascular resistance during exercise were inversely related to changes in PvO2 (r = -0.61; p less than 0.05). We conclude that the observed decrease in PvO2 might be a determinant of unchanged pulmonary vascular resistance during treadmill-exercise test in severe heart failure patients.     

Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization.

BACKGROUND: Supranormal mixed venous oxygen saturation (mixed venous hyperoxia), although reported, has never been characterized in humans resuscitated from cardiac arrest (postarrest cardiogenic shock). By contrast, cardiogenic shock without cardiopulmonary arrest (primary cardiogenic shock) is accompanied by mixed venous hypoxia under similar conditions of low oxygen delivery (DO2). The appearance of mixed venous hyperoxia indicates an excessive supply relative to demand in perfused tissue or cellular impairment of oxygen utilization, ie, low systemic oxygen consumption (VO2). Failure to improve VO2 has been associated with a poor outcome in other shock states. STUDY OBJECTIVE: This study evaluates the clinical significance of mixed venous hyperoxia and its implications for impaired systemic oxygen utilization. The oxygen transport patterns in surviving and nonsurviving cardiac arrest patients are compared for their prognostic and therapeutic implications. STUDY DESIGN: Consecutive, nonrandomized series. SETTING: Large urban emergency department (ED). PARTICIPANTS: Adult normothermic, nontraumatic out-of-hospital cardiac arrest patients presenting to the ED who develop a return of spontaneous circulation (ROSC). INTERVENTIONS: On arrival to the ED, a fiberoptic catheter was placed in the central venous position for continuous central venous oxygen saturation monitoring (ScvO2). A proximal aortic catheter was placed via the femoral artery for blood pressure monitoring. Upon ROSC, the fiberoptic catheter was advanced to the pulmonary artery. Mean arterial pressure (MAP), cardiac index (CI), VO2, DO2, systemic oxygen extraction ratio (OER), and systemic vascular resistance index (SVRI-dynes.s/cm5.m2) were measured immediately and every 30 min. The duration of cardiac arrest (DCA) in minutes and amount of epinephrine (milligrams) administered during ACLS was recorded. MEASUREMENTS AND RESULTS: Twenty-three patients were entered into the study. Survivors (living more than 24 h) and nonsurvivors (living less than 24 h) were compared. CONCLUSIONS: These findings indicate an impairment of systemic oxygen utilization in postarrest cardiogenic shock patients. In spite of a lower DO2 than survivors, the OER in nonsurvivors remained lower than expected. Venous hyperoxia is a clinical manifestation of this derangement. Epinephrine dose may have a causal relationship. The inability to attain a VO2 of greater than 90 ml/min.m2 after the first 6 h of aggressive therapy was associated with a 100 percent mortality in 24 h.     

Effect of oral propranolol on splanchnic oxygen uptake and haemodynamics in patients with cirrhosis

In order to elucidate the effect of beta-adrenergic blockade on liver metabolism and haemodynamics, splanchnic oxygen uptake, hepatic removal of indocyanine green (ICG) and splanchnic and systemic haemodynamics were studied in 13 patients with cirrhosis before and 1.5-2 h after an oral dose of 80 mg propranolol. All patients underwent hepatic vein catheterization and had a primed continuous intravenous infusion of ICG. Azygos vein catheterization was performed in six patients. Splanchnic (hepatic-intestinal) oxygen uptake (median control 68 ml/min vs. beta-blockade 56 ml/min, P less than 0.01), azygos venous oxygen saturation (76 vs. 67%, P less than 0.05), ICG clearance (263 vs. 226 ml/min, P less than 0.01), wedged-to-free hepatic vein pressure (16 vs. 13.5 mm Hg, P less than 0.01), hepatic blood flow (1.18 vs. 0.78 l/min, P less than 0.01), cardiac index (3.42 vs. 2.53 l/min . min 2, P less than 0.01), and heart rate (72 vs. 56 beats per min, P less than 0.01) decreased significantly after oral beta-blockade. The hepatic extraction ratio of ICG increased significantly (0.32 vs. 0.45, P less than 0.01), whereas estimated 'intrinsic' ICG clearance (289 vs. 300 ml/min, n.s.), arterial blood pressure, stroke volume, and systemic vascular resistance remained essentially unchanged. The results indicate that besides the well-known cardiovascular effects of propranolol, beta-adrenergic blockade may also reduce hepatic metabolic functions as evidenced by the significantly decreased splanchnic oxygen uptake. The raised hepatic extraction ratio of ICG may be caused by reduction in hepatic blood flow as well as in intrahepatic shunting.     

Mesenteric oxygen metabolism, ileal mucosal hydrogen ion concentration, and tissue edema after crystalloid or colloid resuscitation in porcine endotoxic shock: comparison of Ringer's lactate and 6% hetastarch.

We performed an experimental trial comparing crystalloid (Ringer's lactate) and colloid (hetastarch) resuscitation in pentobarbital-anesthetized pigs. Superior mesenteric arterial blood flow (Qsma) was measured using an ultrasonic flow probe, and ileal intramucosal hydrogen ion concentration [( H+]I) was estimated tonometrically. Beginning at t = 0 min, all animals were infused over 20 min with Escherichia coli (0111:B4) lipopolysaccharide (LPS; 150 micrograms/kg). Starting at t = 0 min and continuing for the duration of the experiment (3 hr), pigs in group I (N = 9) were resuscitated with Ringer's lactate (1.2 ml/kg min), whereas animals in group II (n = 9) were infused with 6% hetastarch in saline (0.4 ml/kg min). Systemic and mesenteric hemodynamic changes induced by LPS were similar in both groups; mean arterial pressure and systemic vascular resistance index decreased (P less than .05), but cardiac index was well preserved. Central venous pressure increased (P less than .05). Superior mesenteric O2 delivery decreased significantly (P less than .05) in both groups, although mesenteric O2 uptake was unchanged. Ileal [H+]I increased (P less than .05) in both groups. Gravimetrically determined extravascular water was greater in lung (P = .03) and ileum (P = .058) in group I as compared to group II. Although crystalloid infusion was associated with greater tissue edema, this effect did not translate into a difference in systemic or regional (i.e., mesenteric) O2 uptake or greater ileal tissue acidosis.     

Hemodynamic effects of experimental iron poisoning

The hemodynamic effects of severe iron poisoning were studied in five mongrel dogs. Anesthetized animals were instrumented with arterial, venous, and pulmonary artery thermodilution catheters. Iron intoxication was induced by orogastric administration of ferrous sulfate (600 mg/kg elemental iron). Pulmonary artery wedge pressure values were maintained near preintoxication values by saline infusion, and sodium bicarbonate (1.5 mEq/kg/dose) was given for pH less than 7.25. Hourly hemodynamic measurements were obtained for five hours. Cardiac output, mean arterial pressure, pH, and heart rate decreased significantly (P less than .05), whereas systemic vascular resistance, left ventricular stroke work, and oxygen consumption did not change. All animals developed metabolic acidosis despite saline (3.6 +/- 0.9 L, mean +/- SD) and bicarbonate administration (4.2 +/- 0.8 mEq/kg). These findings suggest that decreased cardiac output was partially due to decreased heart rate but not to decreased preload or abnormal left ventricular afterload. Alkali therapy and maintenance of oxygen consumption did not prevent development of metabolic acidosis.     

Assessment of peak oxygen consumption, lactate and ventilatory thresholds and correlation with resting and exercise hemodynamic data in chronic congestive heart failure

To determine the clinical value of respiratory gas analysis during exercise, oxygen consumption (VO2) at peak exercise and at lactate and ventilatory threshold was assessed in 34 patients with chronic heart failure who underwent maximal exercise testing with expiratory gas monitoring and serial determinations of mixed venous lactate and hemodynamics by Swan-Ganz catheterization. A lactate threshold, defined as the point of abrupt increment of blood lactate, could be identified in every patient; the ventilatory threshold, detected on the basis of the respiratory changes, was found in 26 patients (77%). Lactate and ventilatory thresholds were significantly related to each other (r = 0.94; p less than 0.001) and to peak VO2 (r = 0.89; p less than 0.001 in both). Among the resting hemodynamic measurements, peak VO2 was significantly related only to total pulmonary resistances (r = -0.35). Among the parameters at maximal exercise, it was positively related to cardiac index, stroke work, stroke volume index and mean arterial pressure (r = 0.89, 0.74, 0.74 and 0.56, respectively) and inversely related to systemic vascular and total pulmonary resistances (r = -0.74 and -0.63). Using multivariate stepwise regression analysis only maximal cardiac index and, to a lesser degree, total pulmonary resistance were related to peak VO2. Similar correlations were found between the hemodynamics and the lactate and ventilatory threshold. Thus, peak VO2, lactate and ventilatory thresholds can be detected in most patients with chronic heart failure. These parameters are highly correlated to each other and bear similar relations to the hemodynamic response to exercise. The cardiac index is the main central hemodynamic determinant of exercise capacity.     

Endogenous pancreatic polypeptide in different vascular beds: relationship to release and degradation in subjects with normal and decreased kidney function

The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had a significantly higher level of circulating PP than controls (n = 10): median PP = 52 (range 21 to 352) v 20 (6 to 143) pmol/L, respectively (P less than 0.02). Circulating PP was inversely correlated to 51Cr-EDTA plasma clearance (r = -0.57, P less than 0.02, n = 14) and directly correlated to serum creatinine concentration (r = 0.70, P less than 0.01). Hepatic venous PP was significantly higher than systemic PP in both controls and patients with kidney disease (P less than 0.001, n = 15). The values were positively correlated (r = 0.98, P less than 0.001; slope = 1.37 +/- 0.05, P less than 0.001), indicating a progressively increasing rate of PP secretion in subjects with raised circulating PP. No statistically significant difference could be detected between systemic and renal venous PP or across the lung, left adrenal gland, or lower limb. Assuming steady state between secretion and biodegradation, the metabolic clearance rate of the peptide was estimated to be approximately 600 to 800 mL/min in controls and slightly below this value in patients with nephropathy. These results suggest that the raised circulating PP found in patients with decreased kidney function is due to both increased secretion and decreased degradation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracellular and extracellular acid-base changes in hemorrhagic shock.

Each of 21 dogs was bled until mean arterial blood pressure fell to 50 torr; this hemorrhagic shock state was then maintained for two hours. During hemorrhagic shock, the blood lactate concentration increased sixfold. The severe metabolic acidosis in arterial blood was partially compensated by a decreased PCO2 caused by increased ventilation. However, in mixed venous blood, the metabolic acidosis was combined with a respiratory acidosis. This hypercapnia in venous blood was indicative of the increased PCO2 in tissues poorly perfused following hemorrhage. The increase in the PCO2 of the femoral venous blood was greater than that in mixed venous blood, suggesting that some tissue beds were better perfused than those of the hind limb during shock. The intracellular lactate concentration of hind limb skeletal muscle was greatly increased in the shock state, and tissue PCO2 rose. Intracellular pH of skeletal muscle was only slightly decreased and bicarbonate concentration was unchanged during this combined metabolic and respiratory acidosis. This capacity of skeletal muscle to maintain a high HCO-3 concentration in intracellular fluid during metabolic acidosis may be an enhanced response of the mechanism responsible for maintaining (HCO-3)i normally at a level approximately ten times that which would be expected if HCO-3 were distributed passively.     

Variability in coronary hemodynamics in response to ergonovine in patients with normal coronary arteries and atypical chest pain

Because an increase in coronary vascular resistance in response to ergonovine maleate has been suggested as a possible diagnostic aid for variant angina, changes were evaluated in coronary hemodynamics and serial myocardial thallium-201 perfusion scans in 15 patients without angina and with normal coronary arteries in response to ergonovine (0.05, 0.10 and 0.20 mg intravenously). For the group, heart rate-blood pressure product increased significantly (p less than 0.001) without any change in coronary sinus flow, coronary vascular resistance, myocardial oxygen extraction, arterial-coronary sinus oxygen difference and lactate extraction. In 7 of 15 patients, however, coronary vascular resistance increased (mean 39%, range 11 to 75%, probability [p] less than 0.001), and coronary sinus flow decreased (14%, p less than 0.001), despite an increase in heart rate-blood pressure product (36%, p less than 0.02). No electrocardiographic, metabolic or thallium-201 scan abnormalities occurred. Therefore, significant increases in coronary vascular resistance in response to ergonovine may occur in patients with normal coronary arteries and atypical chest pain.     

Pulmonary vascular extraction of circulating norepinephrine in infants with bronchopulmonary dysplasia

Although the pulmonary circulation in infants with advanced bronchopulmonary dysplasia (BPD) is characterized by abnormal structure and vasoreactivity, metabolic lung functions have not been studied in these infants. To test the hypothesis that patients with severe BPD may have abnormal metabolic lung function, we assessed the pulmonary vascular extraction of circulating norepinephrine in six children with BPD during cardiac catheterization. Plasma norepinephrine levels were measured from simultaneously drawn mixed venous (main pulmonary artery) and left atrium or femoral artery samples. In comparison with four infants with mild heart disease without pulmonary hypertension, we found that infants with BPD extract proportionately less norepinephrine than non-BPD infants [-7 +/- 50% (BPD) versus +27 +/- 6% (non-BPD); P less than 0.001, t test]. Three infants with BPD had higher arterial than mixed venous concentrations of plasma norepinephrine, suggesting net production across the lung. Plasma catecholamine levels and percent extraction correlated poorly with cardiac index and systemic and pulmonary vascular resistance indices. However, this study group was characterized by a high incidence of pulmonary (6/6) and systemic (4/6) hypertension, left ventricular hypertrophy (4/6), and subsequent death (3/6). We conclude that infants with severe BPD and pulmonary hypertension have decreased pulmonary vascular clearance or net production of circulating norepinephrine, but links between altered pulmonary catecholamine metabolism and pulmonary hypertension, or other cardiovascular abnormalities associated with BPD, remain speculative.     

Effects of removing oxygen from patients with chronic obstructive pulmonary disease

To determine the acute physiologic effects of removing oxygen from patients with chronic obstructive pulmonary disease (COPD) who are receiving long-term oxygen therapy, we made serial measurements in 20 patients during and after stopping low-flow oxygen therapy. Removing oxygen caused an increase in pulmonary vascular resistance, requiring 2 to 3 h to reach a new steady state. Removing oxygen therapy increased pulmonary vascular resistance index (PVRI) by 31% during rest (8.14 +/- 0.61 versus 6.23 +/- 0.51 units, p less than 0.001) and by 29% during exercise (8.11 +/- 0.9 versus 6.31 +/- 0.7, p less than 0.001). The increase in PVRI occurred because of an increase in pulmonary arterial pressure without a change in pulmonary capillary wedge pressure or cardiac index. At rest the increase in pulmonary arterial pressure caused by stopping oxygen correlated with the decrease in arterial oxygen saturation (r = 0.70, p less than 0.01). Removing oxygen decreased stroke volume index during rest and exercise. Although removing oxygen increased pulmonary vascular resistance, it did not affect systemic arterial pressure or vascular resistance. Stopping oxygen reduced arterial and mixed venous oxygen tension and oxygen delivery during rest and exercise. In patients who had a normal PaCO2 while breathing room air, removing oxygen therapy increased their oxygen consumption; conversely, in those patients who had an elevated PaCO2 while breathing room air, stopping oxygen therapy reduced oxygen delivery and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reciprocal relationship of synovial fluid volume and oxygen tension

To investigate the impact of synovial fluid volume on oxygen tension (PO2) and other metabolic correlates, 24 specimens of synovial fluid from the knees of 22 patients were analyzed for volume, number of leukocytes (WBC), pH, PO2, PCO2, glucose, protein, and complement (CH50) levels. Concurrent arterial blood samples were obtained in 21 instances. Synovial fluid PO2 values varied inversely with volumes of synovial fluid (r = -0.54, P less than 0.01), but when patients with rheumatoid arthritis were excluded, the correlation was more significant (r = -0.76, P less than 0.001). When synovial fluid PO2 dropped below 45 mm Hg, intraarticular acidosis resulted. The decrease in pH (r = 0.93, P less than 0.001), the lowering of glucose values (r = 0.89, P less than 0.001), and the rise in PCO2 (r = -0.79, P less than 0.01) can be explained by a shift toward anaerobic metabolism coupled with the impaired elimination of its products. Systemic acidosis and hypoxia were not found. Intraarticular hypoxia most likely represents circulatory imbalance at the level of the synovial membrane, although an inverse relationship of synovial fluid PO2 and WBC was also noted. Complement and protein levels had no correlation with volume, pH, or respiratory gas tensions of synovial fluids. Our data support the importance of the effective blood flow to the joint in maintaining homeostasis. The volume of synovial effusion and the compliance of the joint capsule appear to be important determinants of the articular blood supply.     

Study on risk factors of tissue hypoxia in patients with diabetic retinopathy]

Risk factors of tissue hypoxia was investigated in 26 patients with diabetic retinopathy (DMR), who compared with 62 patients without DMR. significant higher incidence of DMR was found in patients with poor diabetic control (HbA 1 greater than or equal to 10%), with orthostatic hypotension (OH), with peripheral neuropathy and with atherosclerosis respectively. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) was lower (P less than 0.05) and venous oxygen tension in pedal dorsum (PvO2) higher (P less than 0.05) in DMR patients than those in uncomplicated DMR patients and normal subjects. There was a rank correlation between DMR severity and PvO2 (r = 0.429, P less than 0.05), which imply that decreased blood oxygen utilization may be related to diabetic microangiopathy. These data suggested that abnormal changes of HbA 1 and 2,3-DPG, decrease of peripheral blood oxygen utilization, atherosclerosis, OH and neuropathy might be risk factors of tissue hypoxia in DMR patients.