Cardiopulmonary Bypass In Man Research Articles

Cardiopulmonary bypass in man: role of the intestine in a self-limiting inflammatory response with demonstrable bacterial translocation

Background Cardiopulmonary bypass provokes a systemic inflammatory reaction that, in 1% to 2% of all cases, leads to multiorgan disfunction. The aim of this study was to evaluate the possible role of the intestine in the pathogenesis and development of this reaction. Methods Eleven selected patients scheduled for elective coronary artery bypass graft surgery were enrolled in a open, prospective clinical study. Gastric tonometry, chromium-labeled test and double sugar intestinal absorption tests, polymerase chain reaction microbial DNA test, and measurement of cytokines and transcriptional factor (nuclear factor κB) activation were performed. Results During the postoperative period, gastric pH remained stable (range,7.2 to 7.3). The partial pressure for carbon dioxide gradient between the gastric mucosa and arterial blood increased significantly (from 1 to 23 mm Hg), peaking in the sixth postoperative hour. Interleukin 6 increased significantly over basal levels, peaking 3 hours after cardiopulmonary bypass (96.3 versus 24 pg/mL). Nuclear factor κB never reached levels higher than those observed after lipopolysaccharide stimulation. Escherichia coli translocation was documented in 10 patients: in eight cases from removal of aortic cross-clamps and in two cases from the first postoperative hour. With respect to basal value (6.4%), the urine collection revealed a significant increase in excretion of the radioisotope during the first 24 hours after surgery (39.1%), although there were no significant variations with the double sugar test. Conclusions The results obtained showed a correlation between the damage of the gastrointestinal mucosa, subsequent increased permeability, E coli bacteremia, and the activation of a self-limited inflammatory response in the absence of significant macrocirculatory changes and postoperative complications.

Von Willebrand factor: a marker of endothelial damage?

von Willebrand factor: a marker of endothelial damage?

Impaired Platelet Aggregation after Cardiopulmonary Bypass in Man: Enhancement of Collagen-Induced Aggregation in whole Blood and Plasma by Adrenaline Ex Vivo

1. We tested the effect of intravenous adrenaline at 0.55-1.10 nmol min-1 kg-1 (for 3-8 min, at 7-10 min post bypass; n = 7) on both microaggregation in hirudinized whole blood, using platelet counting, and macroaggregation in platelet-rich plasma, using optical aggregometry. Control (n = 12) blood samples were taken before and at 10 and 20 min after bypass. 2. Post-bypass plasma adrenaline levels (nmol/l) increased slightly in controls (1.0 versus 0.7 at 10 min, medians; P = 0.05) and markedly with adrenaline infusion (36 versus 0.5 before infusion, P = 0.02). Microaggregation (percentage decrease in single platelets) in stirred blood, reflecting largely ADP-dependent 'spontaneous' aggregation, was not influenced by adrenaline infusion. In contrast, collagen (0.2 microgram/ml)-induced microaggregation in blood was enhanced by adrenaline (92% versus 41%, P = 0.02), with no change in controls (60% versus 53%, P = 0.61). 3. In controls, collagen (0.6 microgram/ml)-induced macroaggregation in platelet-rich plasma (extent of increase in light transmission, cm) was impaired at 10 min post bypass (5.3 versus 12.1 before bypass, P = 0.01), but was enhanced by adrenaline (7.0 versus 3.6 before infusion, P = 0.02). Platelet counts (x 10(9)/l) were decreased postbypass (155 versus 220, P = 0.02) and were not influenced by adrenaline infusion (167, P = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS)

Original Article: The Influence of Aspirin on the Proaggregatory Action of Adrenaline after Cardiopulmonary Bypass in Man

We recently showed that collagen-induced platelet aggregation (PA) is enhanced by adrenaline ex vivo following cardiopulmonary bypass in man. Collagen-induced PA is impaired following bypass and this may contribute to postoperative blood loss, and aspirin treatment may further aggravate bleeding. To determine the influence of aspirin on the proaggregatory action of adrenaline following bypass, we assessed the effect of aspirin on collagen-induced PA before and after bypass, and following adrenaline infusion after bypass. Using optical aggregometry and hirudinised platelet rich plasma, in non-aspirin-treated controls (n=6), collagen (1.0 pg/ml) induced PA (median amplitude; cm) was maximal before bypass (13.7) and impaired at 10 min after bypass (11.5, P=0.03). PA was inhibited by aspirin (1 mM) before bypass (7.2 vs 13.7, P=0.03), and following bypass in aspirin-treated controls (3.3 vs 11.5, P=0.03). In aspirin-treated patients given adrenaline after bypass (n = 6), PA before adrenaline was impaired to a similar extent as in aspirin-treated controls (2.4 vs 3.3), but was enhanced following intravenous adrenaline infusion (0.55-1.1 nmol kg(-1) min(-1)) for 3-10 min (5.2 vs 2.4, P=0.03), with no change in controls at 20 min post-bypass (4.1 vs 3.3). This study indicates that at normocalcaemia, adrenaline enhanced collagen-induced PA in aspirin-treated patients, despite impairment of PA, but only at a high concentration of collagen. These findings indicate that aspirin-treatment may further impair collagen-induced PA following bypass, by limiting the proaggregatory effect of adrenaline.

Prejunctional alpha-2 adrenoceptors and K + channel blockers in rat vas deferens

A parallel increase in systemic plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) was found during thoracotomy and surgery involving cardiopulmonary bypass in man. Thus, plasma levels of NPY-LI increased from 29 ± 4 pmol/l before anaesthesia to 59 ± 10 after thoracotomy and to 87 ± 8 pmol/l upon cardiopulmonary bypass. The corresponding NA levels increased from 1.3 ± 0.1 nmol/l before anaesthesia to 3.0 ± 0.6 and 4.2 ± 5 nmol/l after thoracotomy and cardiopulmonary bypass, respectively. A significant correlation was found between plasma levels of NPY-LI and NA during the operation but not between NPY-LI and adrenaline. The NPY-LI in human plasma was found to be similar to synthetic porcine NPY on reversed phase high performance liquid chromatography. Human submandibular arteries contained high levels of NPY-LI (24 ± 3 pmol/g). In in vitro experiments on isolated human submandibular arteries, NPY in low concentrations (1000 pmol/l) was found to potentiate the contractile effects of NA or transmural nerve stimulation and to exert vasoconstrictor activity per se in higher concentrations. The calcium-entry antagonist nifedipine abolished both the NPY-induced contractions and the enhancement of NA-evoked contractions. NPY depressed the nerve stimulation-evoked 3H-NA release from human submandibular arteries via a prejunctional mechanism which was resistant to nifedipine. NPY contracted human mesenteric veins and renal arteries, but not mesenteric arteries. In conclusion, NPY seems to be co-released with NA upon sympathetic activation in man. Furthermore, NPY exerts both pre- and postjunctional effects on sympathetic control of human blood vessels.

The effect of recombinant aprotinin on t-PA-induced bleeding in rats

High dose aprotinin administered during cardiopulmonary bypass (CPB) has been shown to reduce post-operative bleeding substantially. The exact mechanism of action is still debated. A reduction in fibrinolytic activity by inhibition of plasmin generated during CPB may be the primary mode of action. However, this hypothesis has been questioned as the apparent inhibitory constant of aprotinin for plasmin is orders of magnitude lower than the clinically effective plasma concentration of aprotinin. In the present study the effect of various plasma levels of aprotinin on a plasmin-induced bleeding in rats was investigated. The mean time of bleeding was 10 min in rats receiving only saline whereas a prolonged bleeding of up to > 45 min was seen in rats given t-PA and saline. The steady-state plasma concentration of recombinant aprotinin during infusion of 11 mg/kg/h was approximately 2 microM which roughly corresponds to the clinical use of aprotinin. This dose reduced the t-PA-induced bleeding to a mean value of 11 min, whereas no effects were observed with lower doses. The effect of aprotinin in clinical care of blood loss in CPB in man may therefore be caused by direct inhibition of plasmin.

Cardiopulmonary Bypass, Myocardial Management, and Support Techniques

Leukocyte adhesion to vascular endothelium is an early step in inflammatory damage to tissues. To investigate the expression of endothelial adhesion molecules in the inflammatory response associated with cardiopulmonary bypass, we measured messenger ribonucleic acid (mRNA) encoding the adhesion molecules E-selectin and intercellular adhesion molecule-1 in intraoperative samples of cardiac tissue and skeletal muscle from infants undergoing cardiopulmonary bypass. Atrial tissue samples were obtained before and after bypass from 11 children and paired samples of rectus abdominis muscle from 15. mRNA was analyzed by ribonuclease protection with the use of nonmuscle actin as an internal control. Atrial E-selectin mRNA levels increased from before to after bypass (median increase 3.5-fold, p = 0.0002) in each of nine patients tested, and atrial intercellular adhesion molecule-1 mRNA increased in seven of nine patients (median, 2.1-fold, p = 0.025). In skeletal muscle, E-selectin mRNA increased in 11 of 12 patients (median 4.3-fold, p = 0.0018), and intercellular adhesion molecule-1 mRNA levels increased in 13 of 13 patients (median 3.2-fold, p = 0.013). E-selectin and intercellular adhesion molecule-1 induction in skeletal muscle occurred with or without circulatory arrest. We conclude that adhesion molecule mRNA induction occurs in cardiac and noncardiac tissue during cardiopulmonary bypass in man.

Macroaggregation of Platelets in Plasma, as Distinct from Microaggregation in Whole Blood (and Plasma), as Determined Using Optical Aggregometry and Platelet Counting respectively, is Specifically Impaired following Cardiopulmonary Bypass in Man

We determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia. Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 micrograms/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0 micrograms/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7, 14.3], n = 10; p < 0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p < 0.001). Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p < 0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5, 10.9], n = 12), microaggregation was again near-maximal (96 [93, 97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelofusine) treated patients (5.6 [2.8, 8.6], n = 17; p < 0.005 v control), whereas the response to collagen was little different (9.3 v 9.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Action of Dopamine Infusion on Resistance and Capacitance Vessels During Cardiopulmonary Bypass in Man

Action of Dopamine Infusion on Resistance and Capacitance Vessels During Cardiopulmonary Bypass in Man

Action of Dopamine Infusion on Resistance and Capacitance Vessels During Cardiopulmonary Bypass in Man

Action of Dopamine Infusion on Resistance and Capacitance Vessels During Cardiopulmonary Bypass in Man

Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man

Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha-stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group.

Correlation of Whole-Body Oxygen Consumption with Mixed Venous Blood Temperature During Hypothermic Cardiopulmonary Bypass in Man

The correlation between whole-body oxygen consumption and mixed venous blood temperature was investigated in ten adult patients during hypothermic cardiopulmonary bypass. The perfusion flow was maintained constant at 2.4 L/min/m2 during cooling and rewarming. Mixed venous blood temperature was continuously monitored during bypass at the venous inlet of the oxygenator. The mixed venous blood temperature was decreased to 25-28°C. During rewarming, at every two degree increase in temperature, blood samples were withdrawn simultaneously from the arterial and venous ports of the oxygenator for blood gas analysis. Whole body oxygen consumption (arterial-venous oxygen content difference multiplied by the perfusion index) was calculated at the different mixed venous blood temperatures. The whole-body oxygen consumption showed a linear correlation with the venous blood temperature on a semi-logarithmic scale. The Q10 (the ratio of oxygen consumption at two temperatures separated by 10°C) was approximately 2.0, which is in agreement with Van’t Hoff’ s rule describing the effect of temperature on the equilibrium constant of a chemical reaction.

Effect of Hypothermia on Arterial Versus Venous Blood Gases During Cardiopulmonary Bypass in Man

The effect of moderate hypothermia on arterial versus venous blood gases was investigated in 11 patients during cardiopulmonary bypass. The pump and oxygen flows were maintained at a constant flow of 2.4 L/m2/min throughout bypass. After going on bypass, the central venous blood temperature was dropped to 27.8 ± 0.6°C, and after surgery was completed the patients were rewarmed to 37.0°C. Arterial and venous blood gases were sampled simultaneously from the arterial outlet and the venous inlet lines of the oxygenator every two degrees of temperature change until37°C was reached. The effect of temperature changes on pCO2 simulated the alpha-stat strategy of acid-base regulation; the temperature-corrected arterial and venous pCO2 varied directly and the corrected pH varied inversely with body temperature, while the uncorrected pCO2 and pH did not show a significant changE- with changes of body temperature. The arterial pO2 whether corrected or uncorrected, as well as the venous oxygen saturation and the uncorrected venous pO2, significantly increased with each increment decrease of body temperature. However, the corrected venous pO2 did not significantly change with changes of body temperature. The report suggests that maintenance of constant perfusion and oxygen flows at normothermic levels during hypothermic cardiopulmonay bypass will maintain a constant carbon dioxide content and a constant corrected venous pO2.

Systemic and Pulmonary Circulatory Effects of Protamine Following Cardiopulmonary Bypass in Man

The cardiovascular effects of protamine were studied in 19 men with normal left ventricular function undergoing primary myocardial revascularization. Protamine was given over 120 sec after termination of cardiopulmonary bypass. Arterial and pulmonary pressures, aortic blood flow, central venous pressure, heart rate and electrocardiogram were continuously registered. Pulmonary capillary wedge pressure was recorded at the times of maximal hemodynamic response. The systolic arterial pressure fell from 116 to 66 mmHg about 60 sec after the start of protamine infusion, but spontaneously began to rise after a few seconds, reaching 90% of pre-protamine levels at 126 sec. No inotropic drugs or volume infusion were given. At about 2 min, the mean pulmonary artery pressure rose from 16.3 to 26.2 mmHg and the central venous pressure from 7.0 to 11.4 mmHg. The heart rate and cardiac output were almost unchanged throughout. Systemic hypotension and pulmonary hypertension are suggested to represent true side effects of protamine or protamine/heparin complex. When left ventricular function is good, the hypotension reverses without treatment. Volume infusion may indeed precipitate right heart failure when the pre-load effect is added to the subsequent protamine-induced pulmonary hypertension.

Vasomotor waves of arterial blood pressure after cessation of cardiopulmonary bypass in man

The occurrence of vasomotor waves during cardiopulmonary bypass (CPB) is a recognized phenomenon. The lesser known oscillation of arterial pressure after cessation of CPB was observed in 18 open-heart patients. The duration of an oscillatory wave was 13.5±5.0 seconds, the amplitude 6.1 ±2.6mmNg and the mean arterial pressure 76.5± 10.7mmHg. Inter-and also intraindividual variations in frequency and amplitude of the oscillation, however, did occur. In 13 patients, this oscillation occurred during ventricular epicardial pacing. The oscillation continued until the end of the operation in eight patients; in others, the oscillation was of shorter duration. An oscillation of pulmonary arterial pressure (PAP) was simultaneously observed in nine patients (eight with pacemaker) and central venous pressure (CVP) oscillation in eight patients (all with pacemaker). The duration of a wave was the same as in systemic arterial pressure and the amplitudes were 1.5-3.0mmHg in PAP and 1.0-2.0mmHg in CVP. These arterial vasomotor waves, seen here after CPB, largely resemble those observed during perfusion in man and also the Mayerwaves explored in experimental animals. The pacing rhythm seems to favourthe appearance of those blood pressure oscillations.

Altered Hemodynamic Response To Epinephrine Before and During Cardiopulmonary Bypass in Man

The hemodynamic response to epinephrine was investigated in 10 patients undergoing aorto-coronary bypass surgery. Prior to bypass, the intravenous injections of epinephrine 10 μg increased the mean arterial pressure by 32.6 ± 5.1% associated, with a significant increase of the cardiac output, while the systemic vascular resistance did not show a significant change. In contrast, injection of the same dose of epinephrine during cardiopulmonary bypass and aortic cross-clamp only produced 17.9 ± 8.9% increase of mean arterial pressure associated with a corresponding increase of systemic vascular resistance. The results suggest that the pressor response to epinephrine is significantly lower during bypass as compared to the pre-bypass period.

Effect of Oxygen Flow on pCO2 and pO2 During Cardiopulmonary Bypass in Man

The effect of oxygen flow on arterial pO2 and pCO2 was investigated during cardiopulmonary bypass in three groups of patients undergoing open heart surgery. A Bentley-10 adult bubble oxygenator was used in all patients. The perfusion was maintained in the three groups at a constant flow of 2.31/m2/min throughout bypass. The oxygenator was bubbled in Group 1 by oxygen at an oxygen:perfusion ratio of 0.75:1.0 while 1.0:1.0 ratio was used in Group 2 and 1.5:1.0 ratio was used in Group 3. After going on bypass, moderate hypothermia was achieved, and the patients were rewarmed when surgery was completed. The report shows that the arterial pCO2, and pO2 may be determined during cardiopulmonary bypass by the bubbled oxygen flow. Increasing the oxygen:perfusion ratio from 0.5:1.0 to 1.0: 1.0 is associated with a significant decrease of pCO2 and increase of pO2. Further increase of the oxygen:perfusion ratio to 1.5:1.0 resulted in further decrease of pCO2 without a significant increase of pO2. The results suggest that optimal oxygenation and carbon dioxide elimination can be achieved by using an oxygen:perfusion ratio 1.0:1.0 during hypothermia and following rewarming.

The effect of arterial pH on whole body oxygen uptake during hypothermic cardiopulmonary bypass in man

To test the hypothesis of Rahn and Reeves that the optimal arterial pH during hypothermia follows the alpha-stat concept, we studied 50 patients during coronary artery bypass grafting or valve replacement (or both) and aortic occlusion. Intravenous anesthesia was produced by high-dose fentanyl. Thiopentone 3 mg.kg-1 body weight and pancuronium 0.1 mg.kg-1 body weight were given at the start of cardiopulmonary bypass to prevent shivering. When the temperature of venous blood reached 25 degrees C, pump flow was reduced to 1.8 L.m-2.min-1. In 17 patients (group I), arterial pH was changed in a randomized order either from high to low or from low to high by adjusting the carbon dioxide fraction of the gas flow to the bubble oxygenator. At the end of 10-minute periods with stable arterial pH, oxygen uptake was calculated by multiplying pump flow and the arteriovenous oxygen difference. In 33 other patients (group II), arterial pH was kept constant during the period of stable hypothermia at 25 degrees C, and two to five determinations of oxygen uptake were performed in each patient. The carbon dioxide fraction in the gas and arterial pH varied between the patients. In group I, oxygen uptake was 31.4 ml.m-2.min-1 at pH 7.31 and 40.3 ml.m-2.min-1 at pH 7.52-a significant difference (p less than 0.001). In group II, oxygen uptake was positively correlated to arterial pH (r = 0.52, p less than 0.01). Thus the results were in line with the alpha-stat concept of acid-base management during hypothermia.

The effect of pH a and whole body oxygen uptake on renal function during hypothermic cardiopulmonary bypass in man

The effect of pH a and whole body oxygen uptake on renal function during hypothermic cardiopulmonary bypass in man

Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man

We assessed the effects of the iron chelator deferoxamine in 24 adult patients (12 controls, 12 treated) undergoing cardiopulmonary bypass for various cardiac operations. Deferoxamine was given both intravenously (30 mg/kg of body weight, starting 30 minutes before and ending 30 minutes after bypass) and as an additive to the cardioplegic solution (250 mg/L). Right atrial blood samples were taken before, during, and after bypass, and isolated polymorphonuclear neutrophils were evaluated for their capacity to generate superoxide radicals after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FLMP, 10(-7) mol) and phorbol myristate acetate (100 ng/ml). At the same sampling times, measurement of the plasma levels of 6-keto-prostaglandin F1 alpha, the stable derivative of prostacyclin, was used as an index of membrane phospholipid breakdown. The two groups were not significantly different with regard to age, duration of bypass, and quantitative changes in polymorphonuclear neutrophil counts during the operation. Before bypass, the superoxide production of FMLP-stimulated polymorphonuclear neutrophils was comparable in the two groups. Conversely, after bypass, polymorphonuclear neutrophils harvested from deferoxamine-treated patients produced significantly fewer superoxide radicals than those of control patients (1.9 +/- 0.3 versus 3.7 +/- 0.2 nmol/10(6) polymorphonuclear neutrophils per minute, p less than 0.05). Stimulation of polymorphonuclear neutrophils by phorbol myristate acetate yielded similar changes, as the postbypass superoxide production was 12.6 +/- 2.5 nmol/10(6)/min in control patients and 7.1 +/- 0.9 nmol/10(6)/min in those receiving deferoxamine (p less than 0.05). In contrast, plasma levels of 6-keto-prostaglandin F1 alpha were not significantly different between the two groups. We conclude that deferoxamine-exposed polymorphonuclear neutrophils have a decreased oxidative responsiveness, compatible with the fact that they may have been less "primed" by secretagogues released during bypass, as compared with cells of untreated patients. Our results are consistent with the hypothesis that deferoxamine, by inhibiting iron-catalyzed free radical production, may limit the free radical-mediated amplification of the inflammatory response to bypass and as such could be effective in reducing the harmful effects of extracorporeal circulation.