Hypertension, Resistant to Conventional Therapy Clinical Trial
— ChemoBarOfficial title:
Peripheral Chemoreflex/Arterial Baroreflex Interaction in Patients With Electrical Carotid Sinus Stimulation
Verified date | January 2018 |
Source | Hannover Medical School |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Peripheral chemoreceptors and baroreceptors are located in close proximity in the carotid artery wall at the level of the carotid bifurcation. Baroreceptor stimulation lowers sympathetic activity and blood pressure. In contrast, chemoreceptor stimulation raises sympathetic activity and blood pressure. Thus, beneficial effects of electrical carotid sinus stimulation on blood pressure could be diminished by chemoreceptor overactivity and/or concomitant chemoreceptor activation through the device. Therefore, our study will assess baroreflex/chemoreflex interactions in patients with resistant hypertension equipped with carotid sinus stimulators. The study will inform us of potential additional anti-hypertensive benefits of simultaneous chemoreceptor denervation during electrode placement. Furthermore, the results may provide information about suitable electrode design to spare co-activation of peripheral chemoreceptors. Taken together, the study will help develop strategies for improving responder rate and efficacy of carotid sinus stimulators in patients with resistant hypertension.
Status | Completed |
Enrollment | 11 |
Est. completion date | December 2017 |
Est. primary completion date | December 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Implanted device for electrical baroreflex stimulation. - The patient is a 'responder', i. e. carotid-sinus stimulation causes a drop in systolic arterial pressure by at least 15 mmHg. - The patient gave informed consent. Exclusion Criteria: - The patient is an investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. - The mental condition renders the patient unable to understand the nature, scope, and possible consequences of the study. - The patient is unlikely to comply with the protocol. - The patient is pregnant or breast-feeding. - Hypoxic conditions for half an hour are considered harmful, e. g. in patients with shunts. - History of drug or alcohol abuse. - Discontinuation of diuretic medication for one day is considered harmful. (Reason: Bladder distension is a sympathoexcitatory stimulus and shortens experimental time. In order to prevent these shortcomings three measures are taken: Dispensation with beverages and diuretics as well as complete bladder voiding immediately before the experiment.) |
Country | Name | City | State |
---|---|---|---|
Germany | Hannover Medical School | Hannover | LSX |
Lead Sponsor | Collaborator |
---|---|
Hannover Medical School | Charite University, Berlin, Germany, Mayo Clinic, University of Bristol, Vanderbilt University School of Medicine |
Germany,
Abdala AP, McBryde FD, Marina N, Hendy EB, Engelman ZJ, Fudim M, Sobotka PA, Gourine AV, Paton JF. Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol. 2012 Sep 1;590(17):4269-77. doi: 10.1113/jphysiol.2012.237800. Epub 2012 Jun 11. — View Citation
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* Note: There are 20 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | End-tidal partial carbon dioxide pressure (etCO2) | Electrical carotid sinus stimulation may lead to co-activation of carotid body chemoreceptors which would result in increased ventilation and etCO2 reduction. According to our hypothesis, etCO2 is higher without than with electrical baroreflex stimulation. Hence, the endpoint is the difference etCO2,OFF - etCO2,ON. EtCO2 will be assessed during normoxia. Argument against hypoxia: The hypoxic challenge is expected to increase ventilation. The ensuing etCO2 drop would represent a confounder. Thus, we seek for normal etCO2 levels during hypoxia by adding variable tiny amounts of CO2 to the breathing gas. (Note: This is not an intervention but avoids an important confounder, namely etCO2 changes.) Argument against hyperoxia: Carotid body chemosensors may be desensitized to electrical stimulation during hyperoxia. |
Over 24 minutes of normoxia. | |
Other | Individual responses (MSNA, BP) without dopamine | MSNA and blood pressure responses to stimulation during normoxia and hyperoxia on an individual basis. | Over 24 minutes of stable de/oxygenation. | |
Other | Individual responses (MSNA, BP) with dopamine | Low-dose dopamine infusion is another means to simulate hyperoxic conditions. MSNA and blood pressure responses to stimulation with and without dopamine are to be compared. | Over 24 minutes of dopamine infusion. | |
Other | MSNA burst incidence | Changes in sympathetic activity measured as burst incidence (sympathetic bursts per 100 heart beats) and total activity (area under the sympathetic bursts). | Over 24 minutes of stable de/oxygenation +/- dopamine infusion. | |
Other | Diastolic and mean blood pressure (DBP, MBP) | Blood pressure responses to stimulation during normoxia, hyperoxia, and dopamine infusion. | Over 24 minutes of stable de/oxygenation +/- dopamine infusion. | |
Other | Sympathetic and cardiac baroreflex sensitivity. | Differences in the relationship between changes in sympathetic activity or heart interval and blood pressure. | Over 24 minutes of stable de/oxygenation +/- dopamine infusion. | |
Other | Ventilation | Air volume flow [L/min] | Over 24 minutes of stable de/oxygenation +/- dopamine infusion. | |
Primary | Muscle sympathetic nerve activity (MSNA) | Muscle sympathetic nerve activity (MSNA) will be determined as burst frequency, i. e. as the number of bursts per minute [bursts/min]. In responders, electrical carotid sinus stimulation will lead to a decline in MSNA: [-]MSNA. According to our primary hypothesis, [-]MSNA during hyperoxic conditions ([-]MSNA_hyperoxia) is larger than during hypoxia ([-]MSNA_hypoxia). Therefore, the primary endpoint of the study is the difference [-]MSNA_hyperoxia - [-]MSNA_hypoxia. The study is successful as soon as the difference between the reduction in the hyperoxic and the hypoxic condition is significantly different from zero. A positive value would confirm our primary hypothesis. In case of a negative difference, we would conclude that the potency of electrical baroreflex stimulation to lower sympathetic activity is larger under conditions of an activated chemoreflex. | Over 24 minutes of stable de/oxygenation +/- dopamine infusion. | |
Secondary | Systolic blood pressure (SBP) | In responders, electrical carotid sinus stimulation will lead to a decline in systolic blood pressure: [-]SBP. According to our primary hypothesis, [-]SBP during hyperoxic conditions ([-]SBP_hyperoxia) is larger than during hypoxia ([-]SBP_hypoxia). Therefore, the secondary endpoint of the study is the difference [-]SBP_hyperoxia - [-]SBP_hypoxia. A positive value would confirm our secondary hypothesis. If the difference turns out to be negative, we would conclude that the potency of electrical baroreflex stimulation to lower blood pressure is larger under conditions of an activated chemoreflex. However, such a finding would not necessarily imply that chemoreceptor activation is a prerequisite for optimal baroreflex activation therapy because SBP *level* could be lower with *inactive* chemoreceptors. | Over 24 minutes of stable de/oxygenation +/- dopamine infusion. |
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