Functional In Vitro Myocardial Performance in Patients with Aortic Disease

Objectives: Diseases of the aortic valve are a common reason for heart surgery. Aortic stenosis (AS) is associated with pressure and aortic regurgitation (AR) with a volume overload of the left ventricle (LV). Over time both pathologies lead to systolic and diastolic heart failure, while progressive downregulation of β-adrenoceptors occurs. As recovery of the LV function is obvious in many patients after valve surgery, LV dysfunction sometimes persists or even proceeds. Therefore we aimed to evaluate in vitro protein kinase A dependent inotropic response in myocardial tissues obtained from patients undergoing aortic valve surgery.

Methods: Interventricular septal biopsy was performed in 58 consecutive patients who underwent aortic valve replacement or repair (AS [n = 22], AR [n = 36]). Preparations were set in an organ bath filled with Tyrode’s solution and paced with 1 Hz at 37°C. Force was measured isometrically. Isoprenaline (10 nmol to 10 µmol) was used for β-adrenoceptor activation and forskolin (10 µmol) to activate adenylyl cyclase directly. Preoperative blood drawing and echocardiography was done by routine.

Results: The mean basal myocardial force was 0.56 mN. The myocardial force in the presence of isoprenaline was 1.76 mN and of forskolin 2.13 mN. There were no differences between samples of patients with stenosis or regurgitation. We found a clear association between low sensitivity (high log EC50 values of isoprenaline) and small maximum effect size of isoprenaline, pointing out relevant β-adrenoceptor dysfunction. There was no significant context between in vitro response and preoperative echocardiography data or laboratory results. But cardiac tissue of patients with an increased pBNP level as well as female patients had a lower in-vitro response to catecholamines. Tissue of patients with β-blocker treatment had a higher sensitivity to isoprenaline.

Conclusions: We found a relevant β-adrenoceptor dysfunction in most of the patients with aortic valve disease with a major variability in the degree. There were no significant correlation between in vitro myocardial performance and clinical variables. But myocardial tissue of patients with increased pBNP level and female patients had a lower sensitivity to isoprenaline. Further work is needed to clarify whether impaired catecholamine response correlates to the long-time outcome after valve surgery.

No conflict of interest has been declared by the author(s).