Johnson, Maja

Activation or inhibition of the carotid body chemoreceptors (CBCs) may impact cardiac baroreflex sensitivity (cBRS). The purpose of this study was to test the hypothesis that inhibition of the CBCs will elicit a change in cBRS when compared to normal resting conditions. Young, healthy subjects (n=16, 31±2, 6 women) were given IV saline and a range of IV dopamine (DA) (1‐4 µg/kg/min) for 15 minutes prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects were initially infused with IV saline. After each HVR, the DA infusion rate was increased by 1 µg/kg/min. A 3‐lead EKG and beat‐by‐beat blood pressure (NexFin) were used to determine cBRS. Data were analyzed from the 5 minutes prior to the HVR associated with the DA dose that elicited the greatest attenuation of the HVR when compared to saline. Heart rate was not significantly different during saline vs. DA (62±3 vs. 65±3, p=0.25). Diastolic blood pressure (77±2 vs. 72±1 mmHg), mean arterial pressure (98±2 vs. 92±2 mmHg), and cBRS “up” sequence (38±7 vs. 21±3 ms/mmHg) were significantly lower during saline vs. DA (p<0.05 for all). cBRS values from the RRI spectrum were not statistically distinguishable between saline and DA (26±4 vs. 21.1±3, p=0.06). In summary, inhibiting the CBCs via DA infusion in young, healthy subjects results in a fall in blood pressure and a reduction in cBRS in response to a rise in blood pressure. These data suggest the CBCs contribute to cBRS and play an important role in modulating parasympathetic control of blood pressure. Funding: NIH R01DK090541

Cerebral blood flow velocity responses to hypercapnia are blunted by the cyclooxygenase inhibitor indomethacin (INDO). We hypothesized that INDO would also attenuate middle cerebral artery blood flow velocity (MCAv) responses to an acute cognitive challenge. We evaluated the MCAv responses to an acute cognitive challenge in 20 healthy young (20‐35 yrs) and older (56‐76 yrs) healthy adults, including 10 men and 10 women before and 90 minutes after INDO administration. The cognitive challenge consisted of 2 blocks of the Stroop color word test: easy (3 colors) and difficult (8 colors). Mean arterial pressure (MAP), end‐tidal CO 2 , and MCAv were monitored throughout the protocol. There were no differences in MAP or end tidal CO 2 between trials. Indeed, MCAv was lower during INDO than baseline for both the easy (50±4 vs. 68±4 cm/s; p<0.01) and difficult (49±3 vs. 66±3 cm/s; p<0.001) cognitive challenges. Additionally, there was an Age x Sex interaction for the increase in MCAv during the easy cognitive task, with older men having a greater increase than older women (15±5 vs. ‐1±5%, respectively; p<0.05). This interaction was not statistically significant for the difficult cognitive task or during the INDO trial. In conclusion, similar to hypercapnia, the cyclooxygenase inhibitor INDO blunts cerebral blood flow velocity responses to an acute cognitive challenge. Funded by NIH grant HL 118154

We tested the hypothesis that administering low‐dose dopamine (2 mcg/kg/min) to desensitize the carotid body chemoreceptors would alter metrics of heart rate variability (HRV). Electrocardiogram (ECG) recordings were obtained from 18 healthy adults (age = 31 ± 2 years; BMI = 24.6 ± 0.6 kg/m 2 ) during two randomized study days where they received an IV infusion of saline (S) or dopamine (DA). HRV was analyzed during five minute segments at baseline and during infusions of S and DA. Time‐domain analysis of the root mean square of the successive differences (RMSSD) along with spectral domain analysis of low (LF) and high frequency (HF) were obtained. There were no differences (P > 0.05) in respiration rate or blood pressure at any time point. Heart rate increased from baseline during DA (60 ± 2 vs. 63 ± 2 bpm; P < 0.01) and during infusion it was greater in DA vs. S (63 ± 2 vs. 58 ± 2 bpm; P < 0.01). RMSSD decreased from baseline to infusion during DA (68.2 ± 7.6 vs. 51.6 ± 6.0 ms; P < 0.01) and during infusion it was lower in DA vs. S (78.3 ± 10.3 vs. 51.6 ± 6.0 ms; P < 0.01). HF was reduced during DA vs. baseline (1733± 301 vs. 870 ± 171 ms 2 ; P < 0.01), and during infusion DA was also lower than S (1936 ± 471 vs. 870 ± 171 ms 2 ; P = 0.02). There were no changes (P > 0.05) in LF, LF/HF or normalized HF and LF values. These data indicate that during resting conditions the carotid body chemoreceptors likely modulate parasympathetic components of HRV in healthy adults. Grant Funding Source : Supported by NIH R01DK090541 and RO1HL61388