Left atrial appendage: structure, function, and role in thromboembolism.

The left atrial appendage (LAA) is derived from the left wall of the primary atrium, which forms during the fourth week of embryonic development. It has developmental, ultrastructural, and physiological characteristics distinct from the left atrium proper. The LAA lies within the confines of the pericardium in close relation to the free wall of the left ventricle and thus its emptying and filling may be significantly affected by left ventricular function. The physiological properties and anatomical relations of the LAA render it ideally suited to function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high. These properties include the position of the LAA high in the body of the left atrium; the increased distensibility of the LAA compared with the left atrium proper; the high concentration of atrial natriuretic factor (ANF) granules contained within the LAA; and the neuronal configuration of the LAA. Thrombus has a predilection to form in the LAA in patients with atrial fibrillation, mitral valve disease, and other conditions. The pathogenesis has not been fully elucidated; however, relative stasis which occurs in the appendage owing to its shape and the trabeculations within it is thought to play a major role. Obliteration or amputation of the LAA may help to reduce the risk of thromboembolism, but this may result in undesirable physiological sequelae such as reduced atrial compliance and a reduced capacity for ANF secretion in response to pressure and volume overload.

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure.

OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects. BACKGROUND: Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes. METHODS: MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). CONCLUSION: This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.

External high frequency oscillation in normal subjects and in patients with acute respiratory failure.

External high frequency oscillation was performed on 20 healthy volunteers using a cuirass-based system, the Hayek Oscillator. Five-min periods of oscillation were carried out on each subject at frequencies of 1, 2, 3, 4 and 5 Hz. Effective ventilation was measured in terms of the fall in alveolar partial pressure of carbon dioxide immediately after oscillation. The optimum frequency for oscillation was 1-3 Hz but most of the subjects were adequately ventilated over a wide range of frequencies. Thus, the Hayek Oscillator is capable of adequately ventilating normal subjects by means of chest wall oscillation. We also compared external high frequency oscillation with intermittent positive pressure ventilation in five patients with respiratory failure. Using the same inspired oxygen fraction, the external high frequency oscillation replaced intermittent positive pressure ventilation for a 30-min period. External high frequency oscillation improved oxygenation by 16% and reduced the arterial carbon dioxide by 6%. These preliminary findings suggest that normal subjects and intensive care unit patients can be adequately ventilated by means of external high frequency oscillation.

The Hayek oscillator. Nomograms for tidal volume and minute ventilation using external high frequency oscillation.

The Hayek Oscillator is a recent development in external high frequency ventilation and is a useful mode of ventilatory support during anaesthesia, in chronic respiratory failure and weaning in intensive care. The Hayek Oscillator is new and its application is growing, as are the number of patients who have benefited from its use. However, there are no clear guidelines on how best to adjust the oscillator to achieve optimum ventilation. A simple method of predicting changes in tidal volume and minute ventilation following adjustment would make the oscillator more useful. We present nomograms for tidal volume, minute ventilation and effective alveolar ventilation when the three variables, oscillator frequency, mean chamber pressure and peak-to-trough pressure span were adjusted. The frequency-tidal volume relationship was unaffected by a mean chamber pressure of 0, -5, -10 cmH2O, but altered with changes in peak-to-trough pressure span. We have also determined the effect of increasing negative extrathoracic pressure on functional residual capacity. The relationship between tidal volume and frequency was non-linear and related to the peak-to-trough pressure span. Mean functional residual capacity significantly increased from 2.25 l (SEM 0.10) without the cuirass at rest to 2.61 l (SEM 0.14) at -10 cmH2O (p < 0.05; n = 5) and 2.47 (SEM 0.12) at -20 cmH2O of mean chamber pressure. Vital capacity was unchanged by increasing extrathoracic pressure as was total lung capacity.

Early results of intravascular oxygenation.

We have used the intravascular oxygenator (IVOX) in eight patients (14-76 years) with acute respiratory failure. At the time of referral for IVOX all patients were on inotropic support, five had pneumothoraces and two were on haemofiltration. Ventilatory data before IVOX were: ventilated for 2-14 days (median 6), PEEP 5-12 cm H2O (12), PIP 34-95 cm H2O (49), FiO2 0.7-1 (1), PaO2 5.4-26 KPa (8.5) and PaCO2 3.7-23 KPa (8). The intravascular oxygenator was used for 6 h-12 days (median 4), the oxygen transfer achieved was 68-140 ml/min (85) and the carbon dioxide removed was 40-106 ml/min (59). It was possible to decrease the ventilator settings with a significant increase in the PaO2 by 48 h (P < 0.05) but the fall in PaCO2 did not reach significance. As the IVOX was turned from "off" to "on" the mean PaO2 increase was 0.35 KPa +/- 0.14 SEM (P = 0.04) and the mean PaCO2 decrease 0.7 KPa +/- 0.2 SEM (P = 0.02) without any significant change in cardiac output. Two patients survived and six died from multisystem failure with three patients being hypoxic at the time of death. Postmortem examinations on five patients did not reveal any IVOX-related complications. We conclude that IVOX is safe but it is not as efficient in gas exchange as extracorporeal membrane oxygenation at present. Further improvement in the gas exchange efficiency of this prototype could render IVOX a very useful device.

Intravascular oxygenation with the IVOX.

Improvements in hollow fibre gas transfer membranes have enabled the development of an intravascular oxygenator which for the first time provides gas exchange without the need for an extracorporeal circuit. We describe all aspects of the clinical utilization of the intravascular oxygenator device.

High fat, low carbohydrate, enteral feeding lowers PaCO2 and reduces the period of ventilation in artificially ventilated patients.

The objective of this study was to compare the effect of a high fat, low carbohydrate enteral feed with a standard isocaloric, isonitrogenous enteral feed on PaCO2 and ventilation time in patients with acute respiratory failure requiring artificial ventilation. 20 clinically stable patients requiring enteral feeding were randomized to either feed in a double-blind fashion. Initial ventilator standard settings were adjusted according to clinical state. Measurements including minute volume and arterial blood gases were made twice daily. Weaning was carried out according to set criteria. During the feeding period, PaCO2 just prior to weaning fell by 16% in the high fat group but increased by 4% in the standard feed group (p = 0.003). The high fat group spent a mean of 62 h less time on the ventilator (p = 0.006). A high fat, low carbohydrate enteral feed appears to be beneficial in patients undergoing artificial ventilation.