The Contractile Response of the Thoracic Aorta to Vasoactive Substances

Summary

Hypertension affects 32-35% of the global adult population. Despite many drugs being available hypertension is not controlled in 50% of the over 500 million treated people leaving patients with an elevated blood pressure for life.

In the development of isolated systolic hypertension, the aorta plays a pivotal role. With each heartbeat, the heart empties its stroke volume into the large arteries. These arteries, particularly the thoracic part of the aorta, temporarily distend to buffer the stroke volume and thereby dampen the pressure fluctuation: they have a Windkessel function. When this function is reduced (and arterial stiffness is increased), the heart needs to contract more forcefully during ejection, leading to isolated systolic hypertension.

Likely, the aorta is not just a passive structure (the aorta as an elastic 'bicycle tube'). Rather, the smooth muscle cells in the aorta wall can presumably actively change the aorta's dimension through vasoconstriction/-dilation. If this is the case, such vasoconstriction/-dilation will have direct consequences for the aorta's Windkessel function and, since this Windkessel function directly influences the blood pressure flucturation, also for hypertension and its progression. Therefore, the aim of this study is to quantify the thoracic aorta's ability to vasoconstrict, and to assess whether this contractility is related to specific predictors.

During the study we will measure in the operating room the thoracic descending and ascending aortic diameter with transoesopahgeal echocardiography (part of standard clinical care), before and after administration of vasoactive drugs (phenylephrine and norepinephrine; also part of standard clinical care). During these measurements we will simultanesouly measure peripheral arterial blood pressure and an electrocardiogram (ECG, to monitor sympathetic activity as estimated using heart rate variability analysis). Measurements will be performed at Catharina Hospital Eindhoven, the Netherlands (NL), where patients undergo elective cardiac surgery. Using the data obtained, we will 1) establish and quantify the in vivo contractility of the human thoracic aorta, and 2) study whether and to which extent potential predictors (age, sex, smoking status, antihypertensive medication use/class, mean arterial pressure, pulse pressure as an indirect measure of arterial stiffness, diabetes, chronic kidney disease, total cholesterol, and sympathetic activity) influence contractility

Conditions

• Human Thoracic Aorta Contractility

Interventions

DRUG

Phenylephrine

At the OR, the patient will be sedated and have a transoesophageal echo (TEE) catether inserted, which is part of standard clinical care. When a patient becomes hypotensive and the attending anesthesiologist decides to infuse any of the following drugs (phenylephrine, ephedrine, norepinephrine, nitroprusside, or nicardipine), before infusion, the anesthesiolgist will acquire with TEE 10 beats of the thoracic ascending and descending aorta respectively. This is defined as one measurement. Five minutes after infusion the same measurement is repeated. A maximum of 10 measurements (5 before and 5 after infusion of a drug) per patient will be performed. We want to explicitly mention that for study purposes the surgery or anesthesia will never be prolonged or modified, nor will any drugs be give for study purposes.

Sponsors & Collaborators

• Maastricht University

  collaborator OTHER

• Catharina Ziekenhuis Eindhoven

  lead OTHER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-05-27

Primary Completion

2024-10-31

Completion

2024-10-31

Countries

• Netherlands

Study Locations