Regional pulmonary blood flow in dogs under zone 3 conditions was measured in supine and prone postures to evaluate the linear gravitational model of perfusion distribution. Flow to regions of lung that were 1.9 cm3 in volume was determined by injection of radiolabeled microspheres in both postures. There was marked perfusion heterogeneity within isogravitational planes (coefficient of variation = 42.5%) as well as within gravitational planes (coefficient of variation = 44.2 and 39.2% in supine and prone postures, respectively; P = 0.02). On average, vertical height explained only 5.8 and 2.4% of the flow variability in the supine and prone postures, respectively. Whereas the gravitational model predicts that regional flows should be negatively correlated when measured in supine and prone postures, flows in the two postures were positively correlated, with an r2 of 0.708 +/- 0.050. Regional perfusion as a function of distance from the center of a lung explained 13.4 and 10.8% of the flow variability in the supine and prone postures, respectively. A linear combination of vertical height and radial distance from the centers of each lung provided a better-fitting model but still explained only 20.0 and 12.0% of the flow variability in the supine and prone postures, respectively. The entire lung was searched for a region of contiguous lung pieces (22.8 cm3) with high flow. Such a region was found in the dorsal area of the lower lobes in six of seven animals, and flow to this region was independent of posture. Under zone 3 conditions, neither gravity nor radial location is the principal determinant of regional perfusion distribution in supine and prone dogs.

Recent studies using microspheres in dogs, pigs and goats have demonstrated considerable heterogeneity of pulmonary perfusion within isogravitational planes. These studies demonstrate a minimal role of gravity in determining pulmonary blood flow distribution. To test whether a gravitational gradient would be more apparent in an animal with large vertical lung height, we measured perfusion heterogeneity in horses (vertical lung height = approximately 55 cm). Four unanesthetized Thoroughbred geldings (422-500 kg) were studied awake in the standing position with fluorescent microspheres injected into a central vein. Between 1,621 and 2,503 pieces (1.3 cm3 in volume) were obtained from the lungs of each horse with spatial coordinates, and blood flow was determined for each piece. The coefficient of variation of blood flow throughout the lungs ranged between 22 and 57% among the horses. Considerable heterogeneity was seen in each isogravitational plane. The relationship between blood flow and vertical height up the lung was characterized by the slope and correlation coefficient of a least squares regression analysis. The slopes within each horse ranged from -0.052 to +0.021 relative flow units/cm height up the lung, and the correlation coefficients varied from 0.12 to 0.75. A positive slope, indicating that flow increased with vertical distance up the lung (opposite to gravity), was observed in three of the four horses. In addition, blood flow was uniformly low in three of the four horses in the most cranial portions of the lungs. We conclude that in lungs of resting unanesthetized horses, animals with a large lung height, there is no consistent vertical gradient to pulmonary blood flow and there is a considerable degree of perfusion heterogeneity, indicating that gravity alone does not play the major role in determining blood flow distribution.

To investigate pulmonary gas exchange during exercise in athletes, 10 high aerobic capacity athletes (maximal aerobic capacity = 5.15 +/- 0.52 l/min) underwent testing on a cycle ergometer at rest, 150 W, 300 W, and maximal exercise (372 +/- 22 W) while trace amounts of six inert gases were infused intravenously. Arterial blood samples, mixed expired gas samples, and metabolic data were obtained. Indexes of ventilation-perfusion (VA/Q) mismatch were calculated by the multiple inert gas elimination technique. The alveolar-arterial difference for O2 (AaDO2) was predicted from the inert gas model on the basis of the calculated VA/Q mismatch. VA/Q heterogeneity increased significantly with exercise and was predicted to increase the AaDO2 by > 17 Torr during heavy and maximal exercise. The observed AaDO2 increased significantly more than that predicted by the inert gas technique during maximal exercise (10 +/- 10 Torr). These data suggest that this population develops diffusion limitation during maximal exercise, but VA/Q mismatch is the most important contributor (> 60%) to the wide AaDO2 observed.

Both in normal subjects exposed to hypergravity and in patients with acute respiratory distress syndrome, there are increased hydrostatic pressure gradients down the lung. Also, both conditions show an impaired arterial oxygenation, which is less severe in the prone than in the supine posture. The aim of this study was to use hypergravity to further investigate the mechanisms behind the differences in arterial oxygenation between the prone and the supine posture. Ten healthy subjects were studied in a human centrifuge while exposed to 1 and 5 times normal gravity (1 G, 5 G) in the anterioposterior (supine) and posterioanterior (prone) direction. They performed one rebreathing maneuver after approximately 5 min at each G level and posture. Lung diffusing capacity decreased in hypergravity compared with 1 G (ANOVA, P = 0.002); it decreased by 46% in the supine posture compared with 25% in the prone (P = 0.01 for supine vs. prone). At the same time, functional residual capacity decreased by 33 and 23%, respectively (P < 0.001 for supine vs. prone), and cardiac output by 40 and 31% (P = 0.007 for supine vs. prone), despite an increase in heart rate of 16 and 28% (P < 0.001 for supine vs. prone), respectively. The finding of a more impaired diffusing capacity in the supine posture compared with the prone at 5 G supports our previous observations of more severe arterial hypoxemia in the supine posture during hypergravity. A reduced pulmonary-capillary blood flow and a reduced estimated alveolar volume can explain most of the reduction in diffusing capacity when supine.

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Patients with acute respiratory distress syndrome have increased lung tissue weight and therefore an increased hydrostatic pressure gradient down the lung. Also, they have a better arterial oxygenation in prone (face down) than in supine (face up) posture. We hypothesized that this effect of the direction of gravity also existed in healthy humans, when increased hydrostatic gradients were induced by hypergravity. Ten healthy subjects were studied in a human centrifuge while exposed to 1 or 5 G in anterio-posterior (supine) or posterio-anterior (prone) direction. We measured blood gases using remote-controlled sampling and gas exchange by mass spectrometry. Hypergravity led to marked impairments of arterial oxygenation in both postures and more so in supine posture. At 5 G, the arterial oxygen saturation was 84.6 ± 1.2 % (mean ± S.E.M.) in supine and 89.7 ± 1.4 % in prone posture (P < 0.001 for supine vs. prone). Ventilation and alveolar PJ were increased at 5 G and did not differ between postures. The alveolar-to-arterial PJ difference increased at 5 G to 8.0 ± 0.2 kPa and 6.6 ± 0.3 kPa in supine and prone postures (P = 0.003). Arterial oxygenation was less impaired in prone during hypergravity due to a better-preserved alveolo-arterial oxygen transport. We speculate that mammals have developed a cardiopulmonary structure that favours function with the gravitational vector in the posterio-anterior direction.

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Background: Whole body hyperthermia induced by radiative systems has been used in therapy of malignant diseases for more than ten years. Von Ardenne and co-workers have developed the 'systemiche Krebs-Mehrschritt-Therapic' (sKMT), a combined regime including whole body hyperthermia of 42°C, induced hyperglycaemia and relative hyperoxaemia with additional application of chemotherapy. This concept has been employed in a phase I/II clinical study for patients with metastatic colorectal carcinoma at the Virchow-Klinikum since January 1997. Methods: The sKMT concept was performed eleven times under intravenous general anaesthesia, avoiding volatile anaesthetics. Core temperatures of up to 42°C were reached stepwise by warming with infrared-A-radiation (IRATHERM 2000®). During the whole procedure blood glucose levels of 380-450 mg/dl were maintained as well as PaO 2 levels above 200 mmHg. Extensive invasive monitoring was performed in all patients including measurements with the REF-Ox-Pulmonary artery catheter with continuous measuring of mixed venous saturation (Baxter Explorer®) and invasive monitoring of arterial blood pressure. Data for calculation of hemodynamic and gas exchange parameters were collected four times, at temperatures of 37°C, 40°C, 41.8-42°C and 39°C, during measurements FiO 2 was 1.0 at all times. Fluids were given in order to keep central-venous and Wedge pressure within normal range during the whole procedure. Statistics were performed using the Wilcoxon Test. Results: Statistically significant differences were found between heart rate, cardiac index and systemic vascular resistance comparing data at 37°C and 42°C. Heart rate and cardiac index increased to a maximum at 42°C (P < 0.0001) whereas systemic vascular resistance had its minimum at 42°C (P < 0.0001). Mean arterial pressure dropped with increasing temperature, differences were not significant. Calculation of stroke volume index and ventricular volumes showed only a slight decrease in endsystolic volumes with increasing temperature, the resulting differences in right ventricular ejection fraction were marginally significant (P = 0.038) comparing 42°C to baseline. Right ventricular stroke work index as well as mean pulmonary arterial pressure increased at 42°C (P = 0.0115 and P = 0.0037), pulmonary vascular resistance only dropped little compared to systemic vascular resistance, left ventricular stroke work index even dropped with increasing temperature, though showing no significant difference. Values for mixed venous oxygen saturation did not vary during therapy, pulmonary right-left shunt showed a temperature associated increase (P = 0.0323) to a maximum at 42°C. Conclusion: Under the procedure of sKMT cardiac function in patients, who do not have any pre-existing cardiac impairment, can be maintained almost unchanged, ie with normal right and left ventricular pressure, despite an increase in right ventricular stroke work Acknowledegment: Supported by Deutsche Krebshilfe.