No benefit of reduced heparinization in thoracic aortic operation with heparin-coated bypass circuits.

BACKGROUND: Heparin coating of the cardiopulmonary bypass circuit attenuates inflammatory response and confer clinical benefits in cardiac operations. The positive effects may be amplified with reduced systemic heparin dosage. We studied markers of inflammation and coagulation in thoracic aortic operations with heparin-coated circuits and standard vs reduced systemic heparinization. METHODS: Thirty patients were randomized to standard (group S; 300 IU/kg initially; activated clotting times [ACT] > 480 seconds; 5,000 IU in prime; n = 16) or reduced (group R; 100 IU/kg initially; ACT > 250 seconds; 2,500 IU in prime; n = 14) dose systemic heparin. The following markers were analyzed perioperatively: (a) inflammatory response; acute phase cytokine interleukin-6, and granulocytic proteins myeloperoxidase and lactoferrin; (b) complement activation; factor C3a and the C5a-9 terminal complement complex [TCC]; and (c) coagulation; thrombin-antithrombin III complex. RESULTS: The clinical outcome did not differ between groups. Four (29%) patients in group R had a perioperative thromboembolic event. All studied markers were significantly elevated during and throughout cardiopulmonary bypass in both groups. Maximal values were higher in group R for all variables except for TCC. There were no statistically significant intergroup differences regarding markers of inflammation, complement activation, or coagulation activation. CONCLUSIONS: The blood trauma in thoracic aortic operation is extensive, as reflected by the elevation of the studied biochemical markers, even when heparin-coated cardiopulmonary bypass circuits are used. In this study, we did not detect any benefits, either biochemical or clinical, of reducing the dose of systemic heparin.

Maintained cardiac output during positive end-expiratory pressure ventilation in open-chest pigs.

BACKGROUND: Does ventilation with positive end-expiratory pressure (PEEP) act to reduce cardiac output (CO) not only by impeding venous return but also by inducing myocardial depression? The present study was aimed to demonstrate the possible existence of this latter mechanism. METHODS: Eight pigs of Swedish native breed weighing 20-25 kg and 10-12 weeks old were anaesthetized, tracheotomized and connected to a volume-controlled ventilator. To prevent intrathoracic pressure from interfering with venous return, the heart and juxtacardiac vessels were exposed to atmospheric pressure by opening and retracting the chest and pericardium. Heart rate (HR), CO, stroke volume (SV), mean arterial (MAP), mean right (MRAP) and left (MLAP) atrial pressures were recorded before and after retransfusion of 500 ml of autologous blood. This procedure was carried out twice in each animal-during ventilation with zero and with 15 cm H2O of PEEP. RESULTS: Comparison of the two ventilation modes before volume load revealed negligible differences in HR, CO, SV, MAP, MRAP and MLAP. Moreover, the changes evoked by volume load were practically identical. CONCLUSIONS: Addition of PEEP to regular positive pressure ventilation does not induce any haemodynamically detectable myocardial depression in the piglet.

Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study.

OBJECTIVE: This study was carried out to: (a) compare complement and granulocyte activation during cardiac operations in patients operated with cardiopulmonary bypass coated with heparin by the Duraflo II method, with activation in patients operated with uncoated circuits; and (b) relate complement, and granulocyte activation to selected adverse effects. METHODS: In a multicentre study among Rikshospitalet, Ullevaal Hospital in Norway and Uppsala University Hospital in Sweden, plasma concentrations of the complement activation products C4b/iC4b/C4c (C4bc), C3b/iC3b/C3c (C3bc), the terminal SC5b-9 complement complex (TCC), and the granulocyte proteins myeloperoxidase and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass. Seventy-six patients underwent surgery operated with circuits coated by the Duraflo II heparin coating and 75 uncoated circuits. The same amount of systemic heparin was administered to all patients. RESULTS: In both groups a significant increase in C4bc was first seen by the end of operation, from 86.7 +/- 12.5 to 273.0 +/- 277.4 nM in controls and from 86.9 +/- 18.5 to 320.2 +/- 190.5 nM in the control group, confirming previous documentation that the classical pathway is not activated during CPB, but as a consequence of protamin administration. The formation of C4bc did not differ significantly between the two groups. In the uncoated group the C3bc concentration increased from 124.0 +/- 15.3 to a maximum of 1176.1 +/- 64.7 nM (P < 0.01) and in the coated group it increased from 129.8 +/- 16.1 to a maximum of 1019.4 +/- 54.9 nM (P < 0.01) during CPB. Summary values but not peak values differed significantly between the groups. In the uncoated group the TCC concentration increased from 0.52 +/- 0.03 to a maximum value of 8.09 +/- 0.57 AU/ml (P < 0.01) while in the coated group the TCC concentration increased from a baseline of 0.53 +/- 0.03 to a peak value of 5.2 +/- 0.24 AU/ml (P <0.01). The difference between the peak values was statistically significant (P = 0.00002). In both groups a significant increase in myeloperoxidase and lactoferrin release was observed by the end of operation. There was no difference in myeloperoxidase or lactoferrin release between the two groups. TCC levels were compared to the occurrence of perioperative infarction, development of lung or renal failure, postoperative bleeding, time on ventilator and days in hospital. Three patients developed perioperative infarction; the peak levels of TCC were significantly higher in these patients than in the 148 patients that did not develop infarction. The reduction in TCC formation in the heparin-coated group was not associated with differences in any of the other clinical parameters. Few adverse effects occurred in the study. The peak values of C3bc were higher in the patients needing inotropic support that in those who did not, the relevance of this finding remains uncertain. CONCLUSION: It is concluded that the Duraflo II heparin coating reduces complement activation, particularly TCC formation, during CPB, but not the release of specific neutrophil granule enzymes. No certain correlation was established between complement and granulocyte activation and clinical outcome.

Home use of a functional electrical stimulation system for standing and mobility in adolescents with spinal cord injury.

OBJECTIVE: Functional electrical stimulation (FES) is a technology that may allow some patients with spinal cord injury (SCI) to integrate standing and upright mobility with wheelchair mobility. The purpose of this study was to document the patterns of home and community use of a FES system for standing and mobility. DESIGN: A telephone questionnaire was administered every 1 to 4 weeks for a minimum of 1 year. An interview was given at the end of the study to probe the motivators and barriers to home use. SETTING: Training for use of the FES system was performed in an inpatient pediatric rehabilitation setting. Data collection began after the subjects were discharged to home. PARTICIPANTS: Five adolescents with complete, thoracic-level SCI. INTERVENTION: Subjects participated in a program of FES exercise followed by training in basic mobility skills such as standing transfers, maneuvering, level ambulation, one-handed and reaching activities, and stair ascent/descent. MAIN OUTCOME MEASURE: The frequency with which the FES system was used at home and the activities for which it was utilized were documented. Motivators and barriers to FES home use were examined. RESULTS: Subjects donned the FES system on the average once every 3 to 4 days. Between 51% and 84% of the times donned, the system was used for exercise. The remaining times it was used for standing activities, most commonly reaching, one-handed tasks, and standing for exercise. "Motivators" included being able to do things that would otherwise be difficult, perceiving a healthful benefit or a sense of well-being from standing and exercise, and feeling an obligation to stand as a participant in a research study. "Barriers" to FES use included not finding time to use the system, having difficulty seeing opportunities to stand, and being reluctant to wear the FES system all day.

Effects of stimulation intensity on the physiological responses of human motor units.

Quadriceps femoris muscles were studied in 50 healthy subjects to determine the physiological responses of the motor units recruited at different force levels during transcutaneous electrical stimulation. During one set of experiments force-frequency relationships were compared at stimulation intensities that produced tetanic contraction of 20%, 50%, or 80% of the maximum voluntary isometric contraction (MVC). No differences in the normalized force-frequency relationship were observed between the 20% and 50% of MVC conditions and only a slight shift to the left was observed at 80% of MVC. The other set of experiments measured the responses to electrically elicited fatigue tests using frequencies of 20, 40, or 60 pps and, at each frequency, intensities that produced 20% or 50% of MVC. Fatigue was greater for the 50% than 20% MVC force conditions. Within each force level fatigue increased with increasing frequency. However, though the differences in the level of recruitment needed to produce the two forces varied for each frequency, the differences in the amount of fatigue produced at each force did not vary between the three stimulation frequencies. This suggests that the fatigue characteristics of the recruited motor units were similar at all intensities tested. We posit, therefore, that the physiological recruitment order during transcutaneous electrical stimulation is less orderly than previously suggested.

Complement activation during cardiopulmonary bypass: effects of immobilized heparin.

The role of complement in biocompatibility reactions and the correlation between complement activation during cardiopulmonary bypass (CPB) and postperfusion syndrome have inspired attempts to improve the biocompatibility of extracorporeal blood oxygenation devices. Here we assessed the effect of immobilized heparin on the generation of C3a and terminal complement complexes during CPB. Thirty patients undergoing aortocoronary bypass were randomized to CPB with either heparin-coated (Duraflo II; Bentley, Irvine, CA) or noncoated control membrane oxygenators (Univox; Bentley). A standard dose of heparin (300 IU/kg) was given to the control group while the heparin dose was reduced to 30% (100 IU/kg) in the heparin-coated group. Significantly lower levels of terminal complement complexes were detected in the heparin-coated group by the end of CPB. From 28 +/- 5 AU/mL (heparin-coated group) and 26 +/- 3 AU/mL (control group, mean +/- standard error of the mean) the terminal complement complex levels increased to 391 +/- 35 AU/mL and 602 +/- 47 AU/mL, respectively (p < 0.002). This difference was still apparent 180 minutes after CPB. Although there was no difference in C3a levels between the two groups at the end of CPB, C3a levels were significantly lower in the heparin-coated group 30 minutes after CPB (194 +/- 18 ng/mL and 307 +/- 18 ng/mL in heparin-coated and control groups, respectively; p < 0.001). We conclude that the heparin-coated surface is more biocompatible with regard to complement activation than is the ordinary unmodified surface in extracorporeal circuits.

PEEP ventilation does not cause humorally mediated cardiac output depression in pigs.

OBJECTIVE: This study was designed to see if humorally mediated negative inotropism contributes to the cardiac output (CO) depression seen during positive end-expiratory pressure (PEEP) ventilation. DESIGN: 8 pairs of piglets were used and a combined blood circulation was established between the two animals in each pair. One animal was ventilated with a PEEP of 15 cmH20 (donor) and the other was ventilated without PEEP (recipient). MEASUREMENT AND RESULTS: CO and stroke volume deteriorated in the donors by 32% and 44%, respectively, while no change was seen in the recipients. CONCLUSION: As humorally mediated negative inotropism during PEEP ventilation has earlier been demonstrated in dogs, the results suggest that this mechanism might be species-dependent.

The effect of peep-ventilation on cardiac function in closed chest pigs.

OBJECTIVE: Does ventilation with positive end-expiratory pressure (PEEP) depress myocardial contractility? DESIGN: Ten piglets were anaesthetized and prepared for the measurement of cardiac output (SV) and right (MRAPtm) and left (MLAPtm) mean transmural atrial pressure, the latter serving as indices of preload. 500 ml of autologous blood was re-transfused during intermittent positive pressure ventilation without PEEP (IPPV) and continuous positive pressure ventilation with 15 cm H2O PEEP (CPPV). MEASUREMENTS AND RESULTS: Right and left ventricular function curves were drawn by plotting MRAPtm and MLAPtm respectively versus the corresponding strokevolumes before and after re-transfusion. Similar inclinations were obtained during IPPV and CPPV on either side of the heart. CONCLUSIONS: Although the ventricular function curves during IPPV and CPPV covered partially different preload levels, the results suggest that CPPV i.e. PEEP does not affect myocardial contractility.

Echocardiographic analysis of cardiac function during high PEEP ventilation.

OBJECTIVE: Does positive end-expiratory pressure ventilation (PEEP) deteriorate cardiac contractility? DESIGN: By means of echocardiography nine piglets were studies during ventilation with 0, 15 and 25 cmH2O (PEEP). Recordings were made before and after 500 ml of 6% dextran 70. MEASUREMENT AND RESULTS: Right and left ventricular end-diastolic diameters were plotted against the stroke volume determined by the thermodilution technique. By combining observations made before and after volume expansion during the different ventilation modes, a ventricular function curve was obtained. The slopes of the curves were similar during all three ventilation modes, both on the left and on the right side. CONCLUSION: This study indicates undisturbed myocardial contractility during PEEP ventilation. We infer that the cardiac output deterioration in the intact animal is caused entirely by impairment of venous return.

Biochemical and functional effects of creatine phosphate in cardioplegic solution during aortic valve surgery--a clinical study.

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.

Effects of positive end-expiratory pressure on cardiac output distribution in the pig.

Cardiac output (CO) and the blood flow to the heart, cerebellum, kidney, pancreas, spleen and skeletal muscle were studied in 20 pigs during spontaneous breathing (SB) and intermittent positive pressure ventilation (IPPV) with a positive end-expiratory pressure (PEEP) of 0, 8, 16 or 24 cmH2O. Microspheres (15 micrometers) labelled with either 85-sr or 141-Ce were used. Injection of microspheres labelled with one of the isotopes was given during SB (all pigs) and with the other isotope during IPPV with PEEP of 0, 8, 16 or 24 cmH2O (five pigs at each level). CO decreased by 11% during IPPV with PEEP of 0 and 31%, 53% and 66% during PEEP of 8, 16 or 24 cmH2O, respectively. Mean arterial blood pressure was fairly well maintained in all groups except the group with PEEP of 24 cmH2O. The perfusion of the six organs deteriorated, but when taken as fractions of CO measured at the same time, the blood flow to the heart, cerebellum and kidney increased with increasing airway pressure, while that to the pancreas, spleen and skeletal muscle decreased. The vascular resistance of the three former organs did not change, while in the latter it increased markedly. It is concluded that when CO decreases as a result of positive pressure ventilation, a redistribution takes place, mainly due to vascular constriction in skeletal muscle, which acts to preserve the blood flow to vital organs.

Monitoring of optimal oxygen Transport by the transcutaneous oxygen tension method in the pig.

The validity of the transcutaneous oxygen tension (PaO2) method as opposed to measurement of arterial oxygen tension (PaO2) and mixed venous oxygen saturation (SVO2), for monitoring optimal oxygen transport, was studied in six mechanically ventilated pigs with an oleic acid lung injury. With stepwise increments in positive end-expiratory pressure (PEEP) from zero to 20 cmH2O maximum oxygen flux was found at a PEEP of 8 cmH2O and named "optimal PEEP". With increasing PEEP, cardiac output (CO) was maintained up to a PEEP of 8 cmH2O, when it began to decline, while venous admixture decreased at all respiratory settings up to a PEEP of 16, when it was about one-fourth of the value (38.7%) at a PEEP of zero. PaO2 increased with rising PEEP and reached a steady level at a PEEP of 16 cmH2O. PtCO2 and SVO2 parallelled each other and rose steeply up to a PEEP of 8 cmH2O. They showed a further slight increase up to a PEEP of 12 and after that a tendency to decrease. It is concluded that PtCO2 and SVO2 both seem to distinguish the optimal PEEP and give more adequate information than does PaO2. The PtCO2 method has the advantage of being non-invasive.

Oleic acid lung damage in pigs.

With the purpose of producing a lung damage model simulating post-traumatic pulmonary insufficiency, oleic acid 0.1 ml . kg-1 body weight (b.w.) was infused intravenously into eight mechanically ventilated young pigs, and the effects were studied for 2 h. After the infusion, PaO2 during air breathing decreased to a fairly low and stable level of about 7 kPa. Venous admixture during air breathing and VD/VT showed a marked initial increase and then remained unchanged, while venous admixture during breathing of pure oxygen increased but less markedly. Haematocrit (EVF), arterial carbon dioxide tension (PaCO2) and base excess (BE) were unchanged. Mean pulmonary arterial pressure more than doubled and cardiac output decreased by 1/3, which was considered to reflect an insuperable increase in the resistance of the pulmonary blood flow. The lung model was found to resemble post-traumatic pulmonary insufficiency with respect both to the V/Q ratio displacement and to the macroscopic appearance of the lungs at autopsy.

The effect of positive end-expiratory pressure on central haemodynamics in the pig.

The effect on central haemodynamics of a stepwise increase in airways pressure from spontaneous breathing (SB) to intermittent positive pressure ventilation with a positive end-expiratory pressure (PEEP) of 0, 8, 16 and 24 cmH2O was studied in eight pigs under ketamine anaesthesia. Compared with SB, cardiac output (CO) was reduced by 12, 36, 50 and 64% at the respective ventilator settings. The transmural pressures of the right and left atrium, measured as the difference between atrial and pleural pressure, both decreased with increments in airway pressure. At a PEEP level of 24, there was a threefold increase in pulmonary vascular resistance. This increase was secondary to the decrease in CO and no signs of CO deterioration due to the increased right ventricular afterload were found. When 250 ml of dextran 70 was administered at a PEEP level of 24 and the airway pressure was then released stepwise, the left ventricular function curve improved, disclosing a relative myocardial failure at the highest PEEP levels. It is concluded that the principal causative mechanisms in CO reduction due to increased intrathoracic pressure is a decrease in preload to the right ventricle. At high PEEP levels there are also signs of myocardial depression.