Acute in vivo studies of the Pittsburgh intravenous membrane oxygenator

The efficacy of an innovative intravenous membrane oxygenator (IMO) was tested acutely (6-8 hrs) in seven calves. The IMO prototypes consisted of a central polyurethane balloon within a bundle of hollow fibers with a membrane surface area of 0.14 m2. The IMO devices were inserted through the external jugular vein into the inferior vena cava of anesthetized calves (68.9 +/- 2.3 kg). Rhythmic balloon pulsation (60-120 bpm) was controlled with an intra-aortic balloon pump console. Oxygen sweep gas was delivered through the device at 3.0 L/min. Gas concentrations were monitored continuously by mass spectroscopy. The principal results were as follows: 1) oxygen and carbon dioxide exchange ranged from 125 to 150 ml/min/m2 and 150 to 200 ml/min/m2, respectively; 2) there was at least a 30-50% augmentation of gas exchange with balloon pulsation; 3) maximum exchange occurred with 60-90 bpm balloon pulsations; and 4) hemodynamic parameters remained unchanged. There were no device related complications, and the feasibility of insertion of the device by a cervical cut-down was established. These acute in vivo experiments show that the Pittsburgh IMO device can exchange oxygen and carbon dioxide gases in vivo at levels consistent with this current prototype design, and that intravenous balloon pulsation significantly enhances gas exchange without causing any end-organ damage.     

Rat hindlimb muscle blood flow during level and downhill locomotion

During eccentrically biased exercise (e.g., downhill locomotion), whole body oxygen consumption and blood lactate concentrations are lower than during level locomotion. These general systemic measurements indicate that muscle metabolism is lower during downhill exercise. This study was designed to test the hypothesis that hindlimb muscle blood flow is correspondingly lower during downhill vs. level exercise. Muscle blood flow (determined by using radioactive microspheres) was measured in rats after 15 min of treadmill exercise at 15 m/min on the level (L, 0 degrees) or downhill (D, -17 degrees). Blood flow to ankle extensor muscles was either lower (e.g., white gastrocnemius muscle: D, 9 +/- 2; L, 15 +/- 1 ml. min-1. 100 g-1) or not different (e.g., soleus muscle: D, 250 +/- 35; L, 230 +/- 21 ml. min-1. 100 g-1) in downhill vs. level exercise. In contrast, blood flow to ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 +/- 5; L, 31 +/- 6 ml. min-1. 100 g-1) during downhill vs. level exercise. When individual extensor and flexor muscle flows were summed, total flow to the leg was lower during downhill exercise (D, 3.24 +/- 0.08; L, 3.47 +/- 0. 05 ml/min). These data indicate that muscle blood flow and metabolism are lower during eccentrically biased exercise but are not uniformly reduced in all active muscles; i.e., flows are equivalent in several ankle extensor muscles and higher in ankle flexor muscles.     

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.     

Reusable tubular membrane oxygenator for isolated organ hemoperfusion

A reusable tubular membrane oxygenator is described for hypotraumatic hemoperfusion of isolated organs in physiological studies. The constructed oxygenator was of approximately 0.24-m2 effective surface area and contained 450 silicone rubber capillaries of 0.51-mm nominal ID, 34.9 cm long, fixed by conical-shaped, plastic blood headers at manifolds made from Dow-Corning MDX-4-4210 silicone elastomer. During ex vivo hemoperfusions in dogs at inlet hemoglobin saturations near 67%, oxygen transfer rates of the oxygenator increased serially, from 16.6 +/- 1.7 ml/min per m2 (mean +/- SD) at blood flows of 100 ml/min to 34.1 +/- 3.8 ml/min per m2 at flows of 500 ml/min. The oxygenator was thromboresistant and of much loss priming blood volume and wall compliance than the nonresuable Travenol membrane oxygenator of 0.26-m2 effective surface area. The tubular oxygenator was easily cleaned and reassembled, with reproducible oxygen transfer rates. It should prove useful for hemoperfusion studies in organs of moderate size, such as the isolated canine kidney, stomach, and pancreas.     

Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries

OBJECTIVES: Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET). BACKGROUND: In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern. METHODS: Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10+/-1 years after ASO. A subgroup of 15 children (9+/-1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13+/-3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26+/-6 years) served as the control group. RESULTS: Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102+/-29 vs. 77+/-6 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85+/-22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290+/-42 ml/100 g/min for group A, 240+/-28 for group B, 340+/-57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0+/-0.6 for group A, 2.9+/-0.6 for group B, 4.6+/-0.9 for normals; p < 0.01). CONCLUSIONS: Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.     

Clinical, biological, and immunophenotypical characteristics of B-cell chronic lymphocytic leukemia with trisomy 12 by fluorescence in situ hybridization

Intra-aortic balloon pumping is frequently used in patients with cardiogenic shock when oliguria persists despite maximal pharmacologic support. The objective of this study was to measure the effect of intra-aortic balloon pumping on renal blood flow, renal oxygen delivery, and renal oxygen consumption in such patients. Central hemodynamics, renal blood flow, and oxygen transport were measured in 10 patients in low cardiac output states. Measurements were made with and without intra-aortic balloon counterpulsation. Renal blood flow was measured by continuous renal vein thermodilution. Small improvements were observed in cardiac output (3.1 +/- 0.8 vs 3.5 +/- 0.8 L/min, P < .01) and pulmonary capillary wedge pressure (22 +/- 5.6 vs 19 +/- 5.3 mmHg, P < .05), but mean arterial blood pressure was unchanged (69 +/- 11 vs 69 +/- 5 mmHg, not significant). Baseline renal blood flow was reduced to approximately 37%, renal oxygen delivery to 31%, and renal oxygen consumption to 60% of normal values. No significant improvement was seen in single-kidney renal blood flow (184 +/- 108 vs 193 +/- 107 mL/min), renal oxygen delivery (28 +/- 16 vs 30 +/- 16 mL/min), or renal oxygen consumption (4.9 +/- 2.0 vs 4.7 +/- 2.5 mL/min) in response to 1:1 counterpulsation. In comparison with measurements made during short-term suspension of counterpulsation, 1:1 aortic balloon pumping failed to result in an increase in renal blood flow, oxygen delivery, or oxygen consumption from the low levels observed in these patients.     

Hemodynamic effects of the implantation of an intracaval oxygenator

Treatment of severe respiratory failure by extracorporeal membrane oxygenation (ECMO) is complex. However, there is now an intravascular gas exchanger (IVOX) available that provides extrapulmonary gas transfer without requiring an extracorporeal blood path. The present study was performed to determine the hemodynamic effects resulting from the intracaval placement of the intravascular device. A bovine model (n = 6; body-weight = 72 +/- 5 kg) was selected for temporary lung support with the intravascular device. The latter was placed in the caval axis under fluoroscopic control after full instrumentation of the animal for hemodynamic measurements including a pulmonary artery catheter for determination of cardiac output by thermodilution and continuous readout of mixed venous oxygen saturation. All measurements were taken after a stabilization period of 15 min. The heart rate moved from 65 +/- 8 before to 72 +/- 10 after implantation and 68 +/- 9 after onset of intravascular gas exchange (NS). Right atrial pressure was 13 +/- 3 mm Hg before, 12 +/- 3 mm Hg after implantation and 10 +/- 3 mm Hg after onset (NS) whereas femoral venous pressure moved from 14 +/- 3 mm Hg to 17 +/- 4 mm Hg (p < 0.05) and remained at 17 +/- 4 mm Hg after onset. Cardiac output was 5.3 +/- 0.7 l/min before, 5.4 +/- 0.7 l/min after implantation and 5.3 +/- 1.1 l/min after onset (NS) while mixed venous oxygen saturation dropped from 60 +/- 7% to 54 +/- 11% and moved to 57 +/- 11 after onset of the device (NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rat liver transport and biotransformation of a cytostatic complex of bis-cholylglycinate and platinum (II)

Dobutamine is used as an alternative to exercise in conjunction with 99mTc-sestamibi SPECT perfusion imaging for detection of coronary artery disease. However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for enhanced detection of coronary stenosis has not been established. The goal of this study is to examine the effects of dobutamine stress on regional myocardial blood flow and relative myocardial 99mTc-sestamibi activity in the presence of a single-vessel stenosis. METHODS: In six open-chest dogs with left circumflex artery stenosis, radiolabeled microspheres were injected during baseline, severe stenosis and peak dobutamine stress (10 microg/kg/min). Technetium-99m-sestamibi was injected intravenously at peak dobutamine. Hearts were excised 20 min after 99mTc-sestamibi injection for SPECT imaging and post-mortem gamma-well counting. RESULTS: Dobutamine significantly increased heart rate, rate-pressure product and the first derivative of left ventricular pressure. Ischemic zone (left circumflex) myocardial blood flows (in ml/min/g) were: baseline, 0.92 +/- 0.15; stenosis, 0.65 +/- 0.16; and dobutamine, 1.19 +/- 0.38. Nonischemic zone myocardial blood flows were: baseline, 0.99 +/- 0.18; stenosis, 1.01 +/- 0.12; and dobutamine, 1.94 +/- 0.32 (p < 0.01 versus stenosis). Ischemic flows, expressed as percentages of nonischemic flows, were: baseline, 94% +/- 2%; stenosis, 63% +/- 11% (p < 0.05 versus baseline) and dobutamine, 60% +/- 12% (p was not significant versus stenosis). Technetium-99m-sestamibi activity in the ischemic zone (75% +/- 6% nonischemic) underestimated the relative flow deficit produced during dobutamine stress (p = 0.056). Myocardial 99mTc-sestamibi activity correlated with flow when flow was less than 1.0 ml/min/g. At higher flow ranges (1.0 ml/min/g-3.5 ml/min/g), 99mTc-sestamibi did not track flow. CONCLUSION: In a canine model of flow-limiting, single-vessel stenosis, dobutamine (10 microg/kg/min) did not augment flow heterogeneity. In addition, relative myocardial 99mTc-sestamibi activity underestimated microsphere flow at higher flows induced by dobutamine, leading to underestimation of ischemia. These findings suggest that dobutamine stress 99mTc-sestamibi scintigraphy may underestimate the relative flow deficit.     

Development of a silicone hollow fiber membrane oxygenator for ECMO application

A new silicone hollow fiber membrane oxygenator for extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber, with a 300 microm outer diameter and a wall thickness of 50 microm. The hollow fibers were mechanically cross-wound on the flow distributor to achieve equal distribution of blood flow without changing the fiber shape. The housing, made of silicone coated acryl, was 236 mm long with an inner diameter of 60 mm. The surface area was 1.0 m2 for prototype 211, and 1.1 m2 for prototype 209. The silicone fiber length was 150 mm, and the silicone membrane packing density was 43% for prototype 211 and 36% for prototype 209. Prototype 211 has a priming volume of 208 ml, and prototype 209 has a priming volume of 228 ml. The prototype 211 oxygenator demonstrates a gas transfer rate of 120 +/- 5 ml/min (mean +/- SD) for O2 and 67 +/- 12 ml/min for CO2 under 2 L of blood flow and 4 L of O2 gas flow. Prototype 209 produced the same values. The blood side pressure drop was low compared with the silicone sheet oxygenator (Avecor, 1500ECMO). These results showed that this new oxygenator for ECMO had efficiency similar to the silicone sheet oxygenator that has a 50% larger surface area. These results suggest that the new generation oxygenator using an ultrathin silicone hollow fiber possesses sufficient gas transfer performance for long-term extracorporeal lung support.     

Defining the critical limit of oxygen extraction in the human small intestine

Although animal models have been used to characterize the relation between oxygen consumption and blood flow, reliable data have not been generated in the human small intestine. We perfused segments of human small intestine by using an ex vivo perfusion circuit that allowed precise manipulation of blood flow and perfusion pressure. Our goal was to define the critical level of intestinal blood flow necessary to maintain the metabolic needs of the tissue. Human small intestine (n = 5) tissue obtained at transplantation harvest was transported on ice to the laboratory. A 40-cm mid-jejunal segment was selected for perfusion, and appropriate inflow and outflow vessels were identified and cannulated. Perfusion with an autologous blood solution was initiated through an extracorporeal membrane oxygenation circuit. After a 30-minute equilibration period, arterial and venous blood gases were measured at varying flow rates while maintaining a constant hematocrit level. Arterial and venous oxygen content, arteriovenous oxygen difference (A-VO2 diff), and oxygen consumption (VO2) were then calculated. Our results demonstrated that at blood flows > 30 ml/min/100 g, VO2 is independent of blood flow (1.6 +/- 0.06 ml/min/100 g), and oxygen extraction is inversely related to flow. Below this blood flow rate of 30 ml/min/100 g, oxygen extraction does not increase further (6.3 +/- 0.3 vol%), and VO2 becomes flow dependent. This ex vivo preparation defines for the first time a threshold value of blood flow for small intestine below which oxygen consumption decreases (30 ml/min/100 g). Previous animal studies have correlated such a decrease in oxygen consumption with functional and histologic evidence of tissue injury. This "critical" flow rate in human intestine is similar to that found previously in canine and feline intestine, but lower than that of rodent species.     

Production and absorption of nitric oxide gas in the nose

Some nitric oxide gas (NO) produced in the sinuses and nasal cavity is absorbed before leaving the nose. To measure production and absorption, we introduced NO at different concentrations into one nostril while sampling the NO leaving the opposite nostril with the soft palate closed. The quantity of NO gas produced in six normal subjects (amount leaving plus the amount absorbed) averaged 352 nl/min and was the same at gas flows ranging from 8 to 347 ml/min and at 10 l/min. An absorption coefficient A was calculated by dividing the amount of NO absorbed by the concentration leaving the nose. A ranged from 17 ml/min at a nasal gas flow of 8 ml/min to an A of 24 ml/min at a nasal gas flow of 347 ml/min. The calculated rates of production and absorption did not change when gas flow rate was increased, suggesting diffusion equilibrium. The amount of uptake of NO in the nasal mucosa can be explained by its solubility coupled with tissue and blood reactivity.     

Improved oxygen utilization during mild exercise in heart failure

In heart failure with low cardiac output, exercise tolerance is reduced despite modulated regional blood distribution and oxygen extraction. However, low cardiac output does not necessarily lead to reduced exercise tolerance especially during mild exercise. In the present study, in order to understand the mechanisms regulating exercise tolerance in heart failure, we measured oxygen consumption (VO2) and cardiac output (CO) during both mild and intense exercise. Patients with heart failure were divided into 2 groups; group L (n = 8) consists of patients with low anaerobic threshold (AT) < 13 ml/min per kg and group H (n = 7) consisting of patients with AT > 13 ml/min per kg. At rest, VO2 was similar between groups L and H, whereas CO was lower in group L than in group H (3.5 + 0.3 vs 4.8 + 1.4 ml/min, p < 0.01). Increase in VO2 during warm-up exercise was not significant between the 2 groups (7.4 +/- 0.5 (group L) vs 6.2 +/- 0.3 ml/min per kg (group H), ns), but increase in CO was lower in group L than in group H (2.5 +/- 0.6 vs 3.4 +/- 0.4 ml/min, p < 0.01). After warm-up to the AT point, however, the increase in not only VO2 but also CO was markedly reduced in group L than in group H (VO2: 0.5 +/- 0.4 vs 3.7 +/- 0.8 ml/min per kg, p < 0.01, CO: 0.2 +/- 0.3 vs 1.1 +/- 0.3 L/min, p < 0.01). Based on these measurements, we calculated the arteriovenous oxygen difference (c(A-V)O2 difference) during exercise in individual patients using Fick's equation. The c(A-V)O2 difference was markedly increased in severe heart failure during the warm-up stage, but between the end of warm-up and the AT point, it remained at the same level as that of group H. These results suggest the presence of a unique mechanism regulating the c(A-V)O2 difference in severe heart failure patients, activation of which may, at least during mild exercise, contribute to efficient oxygen delivery to the peripheral tissues thus compensating for the jeopardized exercise tolerance in those patients.     

Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism

OBJECTIVE: The relation between the clinical manifestations of thyroid disease (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains uncertain. It has been suggested that tissue adrenergic responsiveness is decreased in hypothyroidism, but the reports have been conflicting and have invariably focused on a single physiological response. Therefore the aim of the present study was to determine in patients with moderate, short-term, symptomatic hypothyroidism the responses of heart rate, systolic and diastolic blood pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate known to achieve plasma concentrations in the middle of the physiological range. PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All were on thyroxine replacement for hypothyroidism following either thyroidectomy or radioactive iodine and had been biochemically euthyroid for at least 6 months. DESIGN: Studies were performed in random order. One study was undertaken on full replacement therapy and the other after 50 micrograms thyroxine daily for 2 weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose, metabolic rate and forearm blood flow were measured at rest and at 10-minute intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs 17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs 4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and full replacement therapy respectively, and increased to a similar level (2.36 +/- 0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48 +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs 0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic blood pressure, diastolic blood pressure and forearm blood flow were comparable on 50 micrograms thyroxine and full replacement therapy as were the changes in systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7 +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2 ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1 mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a normal response to adrenaline infusion despite reduced baseline heart rate and metabolic rate. Thus, under physiological and mild pathophysiological conditions there appears to be no evidence of any synergy between thyroid status and sensitivity to catecholamines.     

Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand

Impaired gut mucosal perfusion has been reported during cardiopulmonary bypass. To better define the adequacy of gut blood flow and oxygenation during cardiopulmonary bypass, we measured overall gut blood flow and ileal mucosal flow and their relationship to mucosal pH, mesenteric oxygen delivery and oxygen consumption in immature pigs (n = 8). Normothermic, noncross-clamped, right atrium-to-aorta cardiopulmonary bypass was maintained at 100 ml/kg per minute for 120 minutes. Animals were instrumented with an ultrasonic Doppler flow probe on the superior mesenteric artery, a mucosal laser Doppler flow probe in the ileum, and pH tonometers in the stomach, ileum, and rectum. Radioactive microspheres were injected before and at 5, 60, and 120 minutes of cardiopulmonary bypass for tissue blood flow measurements. Overall gut blood flow significantly increased during cardiopulmonary bypass as evidenced by increases in superior mesenteric arterial flow to 134.1% +/- 8.0%, 137.1% +/- 7.5%, 130.3% +/- 11.2%, and 130.2% +/- 12.7% of baseline values at 30, 60, 90, and 120 minutes of bypass, respectively. Conversely, ileal mucosal blood flow significantly decreased to 53.6% +/- 6.4%, 49.5% +/- 6.8%, 58.9% +/- 11.6%, and 47.8% +/- 10.0% of baseline values, respectively. Blood flow measured with microspheres was significantly increased to proximal portions of the gut, duodenum and jejunum, during cardiopulmonary bypass, whereas blood flow to distal portions, ileum and colon, was unchanged. Gut mucosal pH decreased progressively during cardiopulmonary bypass and paralleled the decrease in ileal mucosal blood flow. Mesenteric oxygen delivery decreased significantly from 67.0 +/- 10.0 ml/min per square meter at baseline to 42.4 +/- 4.6, 44.9 +/- 3.5, 46.0 +/- 3.6, and 42.9 +/- 3.9 ml/min per square meter at 30, 60, 90, and 120 minutes of bypass. Despite the decrease in mesenteric oxygen delivery, mesenteric oxygen consumption increased progressively from 10.8 +/- 1.4 ml/min per square meter at baseline to 13.4 +/- 1.2, 15.9 +/- 1.2, 16.7 +/- 1.4, and 16.6 +/- 1.54 ml/min per square meter, respectively. We conclude that gut mucosal ischemia during normothermic cardiopulmonary bypass results from a combination of redistribution of blood flow away from mucosa and an increased oxygen demand.     

Use of in vitro models of haemofiltration and haemodiafiltration to estimate dosage regimens for critically ill patients prescribed cefpirome

Membrane oxygenators have now gained wide acceptance. A new hollow-fibre membrane oxygenator, the Dideco D903 Avant 1.7, with an optimized membrane surface (1.7 m2) and a wavy blood flow pattern, was tested for gas transfer and blood path resistance in a standardized setting with surviving animals. Three calves (mean body weight 63.29 +/- 2.9 kg) were connected to cardiopulmonary bypass by jugular venous and carotid arterial cannulation, classic roller pump and the Dideco D903 oxygenator with a mean flow rate of 53 +/- 0.1 ml/kg/min for 6 h. After this time, the animals were weaned from the CPB and thereafter from the ventilator. After 7 days, the animals were killed electively. Blood gas analysis was performed before bypass, after mixing (10 min) and then hourly for the 6 h of perfusion. Further samples were taken 30 min (spontaneous breathing) and 60 min after bypass (extubated). Physiological blood gas values could be maintained throughout perfusion in all animals. Mean arterial oxygen saturation varied between 99.3% and 99.7% for the arterial side of the oxygenator compared to 64.6% and 71% for the venous side. The highest mean pressure drop through the oxygenator was 54 mmHg. Postbypass blood gas analysis showed physiological values and no evidence of major lung trauma or pulmonary oedema in relation to the 6 h perfusion. The hollow-fibre membrane oxygenator, Dideco D903, offers excellent gas exchange capabilities and a low pressure drop under experimental conditions, despite reduced membrane surface area. The post mortem examination did not show any deleterious lesion.     

Respiratory gas exchange. Anesthesia with enflurane or isoflurane in nitrous oxide during spontaneous and controlled ventilation

The estimation of oxygen consumption and carbon dioxide elimination is essential for predicting the metabolic activity and needs of any patient having anaesthesia. During anaesthesia oxygen consumption can be measured and compared to a predicted value. However, oxygen uptake is affected by anaesthetic agents, which complicates the interpretation of measured oxygen uptake rate. The purpose of this study was to investigate whether there are any differences in respiratory gas exchange during anaesthesia with enflurane and isoflurane and also to assess the effects of spontaneous versus controlled ventilation. METHODS. Forty orthopedic patients were randomized to enflurane or isoflurane anaesthesia in nitrous oxide with either spontaneous or controlled ventilation. A fresh low-gas-flow technique was used. Inspiratory oxygen and end-tidal carbon dioxide concentrations and expiratory minute ventilation were measured in a circle absorber system between the y-piece and the endotracheal tube with a sampling analyser. Between the mixing box and the absorption canister, carbon dioxide concentration was continuously measured. The carbon dioxide elimination was calculated from mixed expired concentration and expiratory minute ventilation. Excess gas was collected every 10 min in a non-permeable mylar plastic bag connected to the excess valve. The excess gas flow was calculated and the oxygen uptake rate was assumed to be the difference between the oxygen fresh gas flow and the oxygen excess gas flow. RESULTS. The grand mean oxygen uptake rate was 2.5 ml.kg-1 x min-1 or 100 ml.min-1 x m-2. There were no statistically significant differences in oxygen uptake between enflurane and isoflurane anaesthesia or between spontaneous and controlled ventilation. The mean oxygen uptake rate at 10 min was between 2.0 and 2.2 ml.kg-1 x min-1 in all groups. At 30 min the mean oxygen uptake rates were 2.6 to 2.8 ml.kg-1 x min-1. Carbon dioxide elimination was closely associated with expired minute ventilation, with a carbon dioxide excretion of about 30 ml per litre gas exhaled, irrespective of ventilatory mode employed.     

Influences of morphine on the ventilatory response to isocapnic hypoxia

BACKGROUND: The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. METHODS: The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). RESULTS: At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). CONCLUSIONS: Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.     

Forearm nitric oxide balance, vascular relaxation, and glucose metabolism in NIDDM patients

Endothelium-dependent and -independent vascular responses were assessed in 10 NIDDM patients and 6 normal subjects with no evidence of atherosclerotic disease. Changes in forearm blood flow and arteriovenous (AV) serum nitrite/nitrate (NO2-/NO3-) concentrations were measured in response to intra-arterial infusion of acetylcholine (ACh) (7.5, 15, 30 microg/min, endothelium-dependent response) and sodium nitroprusside (SNP) (0.3, 3, 10 microg/min, endothelium-independent response). Insulin sensitivity (determined by minimal model intravenous glucose tolerance test) was lower in NIDDM patients (0.82 +/- 0.20 vs. 2.97 +/- 0.29 10(4) min x microU(-1) x ml(-1); P < 0.01). Baseline forearm blood flow (4.8 +/- 0.3 vs. 4.4 +/- 0.3 ml x 100 ml(-1) tissue x min(-1); NS), mean blood pressure (100 +/- 4 vs. 92 +/- 4 mmHg; NS), and vascular resistance (21 +/- 1 vs. 21 +/- 1 units; NS), as well as their increments during ACh and SNP, infusion were similar in both groups. No difference existed in baseline NO2-/NO3- concentrations (4.09 +/- 0.33 [NIDDM patients] vs. 5.00 +/- 0.48 micromol/l [control subjects]; NS), their forearm net balance (0.31 +/- 0.08 [NIDDM patients] vs. 0.26 +/- 0.08 micromol/l x 100 ml(-1) tissue x min(-1); NS), and baseline forearm glucose uptake. During ACh infusion, both NO2- and NO3- concentrations and net balance significantly increased in both groups, whereas glucose uptake increased only in control subjects. When data from NIDDM and control groups were pooled together, a correlation was found between the forearm AV NO2- and NO3- differences and blood flow (r = 0.494, P = 0.024). On the contrary, no correlation was evident between NO2- and NO3- concentrations or net balance and insulin sensitivity. In summary, 1) no difference existed in basal and ACh-stimulated NO generation and endothelium-dependent relaxation between uncomplicated NIDDM patients and control subjects; 2) in both NIDDM and control groups, forearm NO2- and NO3- net balance following ACh stimulation was related to changes in the forearm blood flow; and 3) ACh-induced increase in forearm blood flow was associated with an increase in glucose uptake only in control subjects but not in NIDDM patients. In conclusion, our results argue against a role of impaired NO generation and blood flow regulation in determining the insulin resistance of uncomplicated NIDDM patients; rather, it supports an independent insulin regulation of hemodynamic and metabolic effects.     

Partial cardiopulmonary bypass in rats for evaluating ischemia-reperfusion injury

The authors developed a miniaturized partial cardiopulmonary bypass model in rats by using membrane oxygenators. Sprague-Dawley rats underwent general anesthesia and tracheostomy for ventilation. Partial cardiopulmonary bypass was carried out through the jugular cannula (18 gauge) for venous blood drainage and through the femoral arterial cannula (24 gauge) at a flow of 50 ml/kg/min. Membrane oxygenators used in this study maintained arterial oxygen tensions (PaO2) at 300-500 mmHg and carbon dioxide tensions (PaCO2) at 25-35 mmHg, with a gas mixture of 95% O2 + 5% CO2 (n = 7) for at least 2 hr of bypass circulation. To test the feasibility of this system for investigation of ischemia-reperfusion injury, hypoxic challenges with gas mixtures of different oxygen concentrations were examined. After equilibration of the bypass circulation for 1 hr, the following gases were tested for 15 min: Group I, 95% air + 5% CO2 (FiO2 = 0.21, n = 5); Group II, 10% O2 + 5% CO2 + 85% N2 (FiO2 = 0.1, n = 5); and Group III, 95% N2 + 5% CO2 (FiO2 = 0, n = 5). Equilibrated PaO2 values after challenge with these gases for 15 min were as follows: Group I: 89.6 +/- 3.7, Group II: 53.8 +/- 1.4, Group III: 25.6 +/- 2.0 mmHg (p < 0.01 between Groups I and II, I and III, II and III; p < 0.01 vs. prehypoxic PaO2 values in all groups). PaO2 values returned to the previous level within 15 min after return to the standard gas mixture (95% O2 + 5% CO2) supply. This system provided stable cardiopulmonary bypass in rats for at least 2 hr and may be useful for investigation of ischemia-reperfusion injury.     

The effect of hypoxia on the regional distribution of cardiac output in the dog

Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.