No abstract

We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i.v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PCO2, arterial PCO2, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75% increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the CO2 reactivities, given as delta CBF/delta PACO2 in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PACO2 level. The present dose of the drug caused no change in ventilation, alveolar and arterial PCO2 or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PCO2's. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.

The effect of moderate hypoxia on cerebral blood flow (CBF) in man has not been well described, and little is known about the interaction of changes in arterial PO2 and PCO2 as regards CBF. Using a non-invasive doppler ultrasound method we have measured the instantaneous mean blood velocity (which is proportional to CBF as long as the cross-section of the vessel is constant) in the carotid artery in four healthy unanaesthetized subjects. We found in all subjects that a reduction in alveolar PO2 from about 13 to about 8.7 kPa with maintained constant alveolar PCO2 (PA, CO2) caused CBF to increase gradually over 10 min (half-time about 4 min) to about 125% of control. The CBF decreased quickly (half-time about 45 s) towards control when alveolar PO2 was reset to 13 kPa. As measured 5 min after a step-change in PA, O2, the change in CBF was independent of PA, CO2 within the range 3.3-6.7 kPa. An increase in PA, O2 to about 33 kPa reduced CBF only if PA, CO2 was in the hypercapnic range. Unexpectedly we found that the CBF response showed 'adaptation' during both maintained increase and decrease in PA, CO2. The CBF started to return towards control level within 10 min after induction of hypo- or hypercapnia. We conclude that also moderate hypoxia causes increased CBF in unanaesthetized man within a wide range of PA, CO2.

Distribution of pulmonary blood flow has traditionally been regarded as determined by gravity. This view has been challenged recently by reports describing marked gravity-independent distribution of flow. These reports were based on experiments in which local blood flow was measured by methods that have not been thoroughly evaluated. In the present study, we showed that in the goat lung regional trapping of i.v. infused microspheres (O = 15 microns) correlated to endothelial uptake of a simultaneously i.v. infused diamine (r = 0.99, region size approximately 1.5 cm3, dry weight approximately 40 mg). This indicates that the deposition of microspheres reflects true regional pulmonary blood flow. Using the microsphere method, we found a marked gravity-independent heterogeneity in blood flow (coefficient of variation approximately 40%) in the awake goat. We could find no pattern related to anatomy that could account for this variability. We re-examined the influence of gravity by analysing the distribution of pulmonary blood flow in anaesthetized goats both in prone and supine positions. The dorsal to sternal distribution of flow appeared to be inverted when the animals were turned from prone to supine recumbency, indicating that gravity influenced the distribution of pulmonary blood flow along this axis. However, along the gravitational axis, distribution of blood flow varied considerably from lung to lung. It appears that in awake goats the distribution of pulmonary blood flow is the result of several different determinants.

Gravity has been regarded as the major determinant for local pulmonary perfusion and ventilation. Recent reports, describing major gravity independent heterogeneity in both variables, have questioned the importance of gravity. We asked to what extent ventilation and perfusion were related, and if they showed similar distributions along the vertical axis in the lung. We gave 99mTc-aerosols as tracers for ventilation and radioactive microspheres as blood flow tracers in five awake goats over 4 min. Ventilation and perfusion were determined in approximately 1.5 cm3 pieces of the lung. For both variables the vertical distribution could vary considerably from lung to lung, but within each lung the two distributions were similar. Both ventilation and perfusion were heterogeneously distributed (CV approximately 40% for both), they were highly correlated (r = 0.81) and the average 25-75-interpercentile interval for ventilation to perfusion ratio (0.84-1.13) was significantly less wide than for both ventilation (0.76-1.38) and perfusion (0.76-1.40). Some pieces were considerably overventilated while a few were correspondingly underventilated. This could indicate that perfusion is adjusted to ventilation in normoxic lungs with a low sensitivity to overventilation.