Vascular reactivity in patients with heart failure

Vasoplegia is a state defined by hypotension, a high cardiac index and the continuous need of vasopressors. It occurs in 5-25% of the patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) and is associated with an increased morbidity and mortality. Vasoplegia is a result of activation of several vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors, but the precise aetiology remains unclear. Important risk factors for the development of vasoplegia after cardiac surgery are a left ventricular ejection fraction <30%, CPB and CPB duration.

We hypothesize that in patients with chronic heart failure, the responsiveness of the vascular system is
permanently altered due to chronic endogenous adrenergic stimulation, resulting in down regulation and/or
desensitization of vascular a1-adrenoreceptors. The vascular system of patients with heart failure is easily pushed out
of balance by the systemic inflammatory reaction caused by the CPB and surgical trauma, making these patients more
prone for developing vasoplegia. Also activation of inducible nitric oxide synthase, activation of adenosine triphosphate
dependent potassium channels and deficiency of arginine vasopressin may play an important role.

The phenylephrine challenge will be performed:

1. Before induction, before start medication (dobutamine, milrinone, noradrenalin)

2. Before induction, after start medication

3. After induction

4. After CPB, before emergence

5. On day 1 postoperative

The vasodilation test will be performed at the beginning of the surgery after placement of the arterial catheter and 1 day post-operatively.

The biopsy (pericardial fat) will be collected at the beginning of the surgery and at from the same area as the surgical incision.

In phase 2 of the study (VASOR part 2) only a biopsy will be collected.

- Phenylephrine challenge

- Vasodilation test;
- Pericardial fat biopsy.