Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Abstract

Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 Ϯ 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 Ϯ 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 Ϯ 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 Ϯ 2.2 vs. 1.5 Ϯ 0.9 pmol/ml; P Ͻ 0.01) but similar to that seen in those with CHF (3.3 Ϯ 1.4; P ϭ NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure. pulmonary hypertension; norepinephrine; hemodynamics PULMONARY HYPERTENSION IS defined as a mean pulmonary artery pressure of more than 25 mmHg at rest and is classified into five groups based upon etiology (42, 43). Idiopathic pulmonary arterial hypertension (IPAH) and other forms of pulmonary hypertension due to abnormalities in the pulmonary vasculature [pulmonary arterial hypertension (PAH)] require the exclusion of other causes, particularly abnormalities of left heart function.

Association of Cardiac Troponin I With Disease Severity and Outcomes in Patients With Pulmonary Hypertension

“…Potential contributors based on other patient population studies include cellular injury related to excessive adrenergic signaling, chronic inflammation, or release due to increased myocardial apoptosis or autophagy. 3,17,18 In conclusion, low but detectable levels of cTnI are present in most patients with PH and are associated with increased risk of death. The exact mechanism(s) remain uncertain, but it seems plausible that cTn release may serve as a global measure of the adequacy of RV adaptation to increased afterload.…”

The Adrenergic System in Pulmonary Arterial Hypertension: Bench to Bedside (2013 Grover Conference Series)

“…13 As a consequence of this activation, RV β 1 -ARs in PAH are downregulated, to a similar degree as in failing LV or RV in HFrEF (Fig. 5).…”

“…[9][10][11] Most importantly, targeting the increased adrenergic activation with β-adrenergic receptor blocking agents has led to the development of arguably the single most effective drug therapy in HFrEF. 11 The pressure-overloaded and ultimately remodeled/failing RV in PAH is also adrenergically activated, 12,13 which raises the issue of whether an antiadrenergic strategy could be effectively employed in this setting. This review will state the case for an antiadrenergic approach to preventing or reversing RV dysfunction in PAH and will provide some thoughts on how such a treatment could be safely and effectively delivered.…”

Valsalva Maneuver in Pulmonary Arterial Hypertension

“…[16][17][18][19] Several studies dating back to 2004 have documented increased MSNA in patients with PAH at baseline. [16][17][18]20 However, because BRS-a was decreased in the PAH group, our findings suggest MSNA may actually be decreased during performance of the VM in PAH patients. One reason may be that MSNA is actually elevated during the VM, and vasodilators, such as pulmonary hypertension medications, are responsible for this apparent MSNA/BRS-a mismatch.…”