Adrenoceptor Polymorphisms and the Risk of Cardiac Injury and Dysfunction After Subarachnoid Hemorrhage

Abstract

Background and Purpose-Cardiac abnormalities occur commonly after subarachnoid hemorrhage (SAH) and may be caused by excessive release of catecholamines from the myocardial sympathetic nerves. We hypothesized that adrenoceptor polymorphisms resulting in greater catecholamine sensitivity would be associated with an increased risk of cardiac injury. Methods-This was a prospective cohort study. The primary outcome variables were the serum level of cardiac troponin I (cTi, abnormal if Ͼ1.0 g/L) and the left ventricular ejection fraction (LVEF, abnormal if Ͻ50%). Six adrenoceptor polymorphisms were genotyped: ␤1AR Arg389Gly, ␤1AR Ser49Gly, ␤2AR Gly16Arg, ␤2AR Gln27Glu, ␤2AR Thr164Ile, and ␣2AR del322-325. The effect of each polymorphism on the risk of developing cardiac abnormalities was quantified using multivariable logistic regression. Results-The study included 182 patients. The CC genotype (Arg/Arg) of ␤1AR Arg389Gly (odds ratio [OR] 3.4, Pϭ0.030) and the CC genotype (Gln/Gln) of ␤2AR Gln27Glu (OR 3.1, Pϭ0.032) were predictive of cTi release. The presence of the ␣2AR deletion was predictive of reduced LVEF (OR 4.2, Pϭ0.023). The combination of the ␤1AR 389 CC and the ␤2AR 27 CC genotypes resulted in a marked increase in the odds of cTi release (OR 15.5, Pϭ0.012). The combination of the ␤1AR 389 CC and the ␣2AR deletion genotypes resulted in a marked increase in the odds of developing a reduced LVEF (OR 10.3, Pϭ0.033). Conclusions-Genetic polymorphisms of the adrenoceptors are associated with an increased risk of cardiac abnormalities after SAH. These data support the hypothesis that cardiac dysfunction after SAH is a form of neurocardiogenic injury.

Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease

“…Genotyping was performed blinded to clinical status; positive and negative controls were included. Three polymorphisms were genotyped by the template-directed dye-terminator incorporation assay with fluorescence polarization detection 23,24 using the AcycloPrimeFP II kit (Perkin-Elmer) and read on the EnVision microplate reader (Perkin-Elmer). PCR conditions and primer sequences are shown in Supplemental Table 1.…”

Prognostic Implications of Left Ventricular Wall Motion Abnormalities Associated With Subarachnoid Hemorrhage

“…The pathophysiology of these abnormalities is related to increased sympathetic nervous activity 15) and to increased circulating and local myocardial tissue catecholamines. [16][17][18][19] In this context, neurological status has been reported to be related to cardiac abnormalities. 11) Cardiac dysfunction after SAH negatively influences mortality 11,20) and, more specifically, the sequelae of heart failure affect outcome after SAH.…”

Can Levosimendan Be a Treatment Option in Subarachnoid Hemorrhage?

“…Son zamanlarda miyokardiyal mikrovasküler disfonksiyon ve genetik yatkınlık, potansiyel patofizyolojik mekanizmalar olarak araştırılmıştır (4). NSK gelişen SAK'li hastalarda genetik polimorfizme bağlı olarak adrenoreseptörlerin daha yüksek katekolamin duyarlılığına sahip olduğu düşünülmektedir (16).…”