ANOXIC DISTURBANCE OF THE ISOLATED RESPIRATORY NETWORK OF NEONATAL RATS

Tissue oxygen (PO2), K+ (aK(e)), pH (pH(e)) and Ca2+ ([Ca2+](e)) were measured in the region of the ventral respiratory group (VRG) in the i n vitro brainstem-spinal cord preparation of neonatal rats. During tis sue anoxia, elicited by superfusion of N-2-gassed solutions, an initia l increase in the frequency of respiratory activity, lasting between 2 and 12 min, turned into a frequency depression. During anoxia periods of up to 60 min, respiratory activity persisted in solutions containi ng CO2/bicarbonate, whereas a complete blockade was observed after 15- 25 min in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid- (Hepes) -buffered salines. After such anoxic apnea, respiratory rhythmicity co uld be reactivated by superfusion of hypoxic, CO2/bicarbonate-buffered solutions. In both types of hypoxic solutions, aK(e) increased by max imally 1.5 mM, whereas an initial increase of pH(e) by up to 0.05 pH u nits turned, after 2-4 min, into an acidification which could exceed 0 .5 pH units. In contrast, [Ca2+](e) remained unaffected by anoxia. Add ition of 2-5 mM cyanide (CN-) to oxygenated Hepes-buffered saline evok ed an increase in PO2 in the VRG from 100 to more than 300 mmHg. The e ffects of CN- on respiratory activity, aK(e) and pH(e) were almost ide ntical to those during anoxia. In oxygenated, CO2/bicarbonate-free sol utions of different pH, however, an increase in pH(e) in the VRG led t o a decrease in respiratory frequency, whereas a fall of pH(e) produce d a frequency acceleration. A rise of aK(e) in the VRG by more than 2 mM as induced by superfusion of a 7 mM K+ solution led to a sustained increase of respiratory frequency. The results indicate that blockade of aerobic metabolism does not severely perturb K+ and Ca2+ homeostasi s and that the biphasic response to anoxia is not directly related to the observed changes in PO2, aK(e), pH(e), or [Ca2+](e). In the respir atory network of neonatal mammals, CO2 might provide a stimulus for lo ng-term maintenance of respiratory activity under oxygen depletion.