We chronically implanted microtubules into the rostral pons of 6 goats to assess the response to hypoxia following irreversible damage to RPN. All goats recovered uneventfully after implantation. After breathing room air for 30 minutes (min), goats were subjected to 10.6% O2 for 30 min. PaO2 at min 6 and 26 of hypoxia was 28.41±0.57 and 26.87±0.58mmHg respectively. The normal response to hypoxia (Table) was a 1° (∼3 min) spike in pulmonary ventilation (VI) followed by a “roll‐off” in VI (∼6 min), and lastly a 2° increase in VI (within 20 min) associated with an increase in body temperature, shivering, VO2, and VCO2. Following irreversible damage to RPN, the 1° spike and “roll‐off” in VI were unchanged from pre‐damage conditions, but the 2° increase was attenuated (P<0.05). We conclude that damage to RPN does not alter the presumed peripheral chemoreceptor 1° response to hypoxia nor the VI “roll‐off”, but attenuates the 2° physiologic response. Comparison of physiologic variables in response to hypoxia, before and after RPN damage. VE(%) PaCO2(Δ mmHg) Temp(Δ °C) VO2 (l/min) VCO2 (l/min) 1° increase Roll‐off 2° increase 6 min hypoxia 26 min hypoxia Final 26 min hypoxia 26 min hypoxia Pre‐damage 174 130 251 −5.47 −8.18 0.96 158.1 197.1 Post‐damage 176 128 195* −5.31 −6.82 0.59* 8.9* 85.1* Significant difference between pre‐ and post‐damage by one‐way ANOVA (P<0.05). Supported s.

Controversies regarding the role of rostral pontine nuclei (RPN) in the control of breathing have prompted us to chronically implant microtubules into the rostral pons of 6 goats to assess the regulation of eupneic PaCO2 and the ventilatory response to hypercapnia following irreversible damage to RPN. All goats recovered uneventfully and 3 weeks after implantation PaCO2 and CO2 sensitivity were within normal limits. Whole body CO2 sensitivity was assessed by increasing inspired CO2 to 3, 5, and 7% at 5‐minute intervals, subsequent to breathing room air for 30 minutes. CO2 sensitivity was expressed as ΔVI/ΔPaCO2. Arterial blood was sampled during the control and min 4 of each hypercapnic level. As shown in the Table, CO2 sensitivity and resting PaCO2 were unaffected following sequential RPN damage (microtubule implantation, microdialysis probe insertion, and intra‐cranial ibotenic acid injection, respectively). We conclude that damage to RPN does not alter regulation of eupneic PaCO2 and the ventilatory response to hypercapnia. CO2 sensitivity and resting PaCO2 are not significantly changed subsequent to RPN damage. Pre‐implant Post‐implant Post‐microdialysis Post‐ibotenic acid CO2 sensitivity (l/min/mmHg) 2.24 2.25 2.08 2.30 Resting PaCO2 (mmHg) 40.24 39.57 38.67 40.00 No significant difference between variables by one‐way ANOVA (P<0.05). Supported by the Department of Veterans Affairs and NIH HL25739.

Both carotid and intracranial chemoreceptors are critical to a normal ventilatory CO2-H+ chemosensitivity. At low levels of hypercapnia, the carotid contribution is probably greater than the central contribution but, at high levels, the intracranial chemoreceptors are dominant. The carotid chemoreceptors are also critical to maintaining a stable and normal eupneic PaCO2, but lesion-induced attenuation of intracranial CO2-H+ chemosensitivity does not consistently alter eupneic PaCO2. A major unanswered question is why do intracranial chemoreceptors in carotid body denervation (CBD) animals tolerate an acidosis during eupnea which prior to CBD elicits a marked increase in breathing.