Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.     

The pharmacokinetics of repetitive benzene exposures at 300 and 100 ppm in AKR Mice and Sprague-Dawley rats

Groups of AKR Mice and Sprague-Dawley rats were exposed to either 300 or 100 ppm benzene for 6 hr/day × 5 days/week for 20 days. The uptake and clearance of benzene was followed in blood during and after the 1st, 6th and 20th exposures. In rats, the maximum concentrations of benzene in blood (C_max) were proportional to the exposure concentrations, that is the C_max values at 300 ppm were three times the C_max values at 100 ppm. This was not the case with the mice which showed C_max values at 300 ppm equal to five to eight times the C_max values at 100 ppm. At both exposure levels mice exhibited larger elimination rate constants than rats. Both rats and mice showed larger elimination rate constants at 100 ppm than at 300 ppm. At 300 ppm, the mice showed progressive increases in elimination rate constants, progressive decreases in C_max and an unusual shift from monoexponential clearance to biexponential clearance between the 6th and 20th exposures. It is postulated that the induction of benzene-metabolizing enzymes and/or an increase in lipid tissue mass are responsible for the progressive changes of the kinetic parameters of the mice.     

The effect of static tympanic pressure gradients on hearing sensitivity in normal subjects

The effects of static tympanic air pressure gradients on hearing sensitivity was studied by introducing overpressures of 100 mm H₂O to 400 mm H₂O into the ear canals of 22 normal subjects. Sweep frequency threshold measures were obtained using a pressure-tight probe transducer driven by a Bekesy automatic audiometer. These gradients of tympanic pressure disequilibrium produced threshold losses through 4000 Hz, most prominently for the region of 500 to 1000 Hz, that increased systematically with the degree of overpressure. The data may be useful in estimating the degree of conductive loss associated with middle ears presenting retraction without effusion and normally compliant though negatively skewed tympanograms.