Influence of myocardial ischemia and reperfusion on beta-adrenoceptor subtype expression.

The effects of ischemic injury and reperfusion on myocardial beta-adrenoceptor expression were examined in dogs after 30 min of left anterior descending coronary artery (LAD) ligation. Three sets of six dogs were allocated to either sham ligation (group I), 30 min ischemia without reperfusion (group II), or ischemia with 1 h of reperfusion (group III). The density of total beta-adrenoceptors along with beta1- and beta2-adrenoceptor subtypes were compared in tissue from the ischemic LAD and nonischemic left lateral zones by using radioligand binding with 125-labeled iodocyanopindolol (ICYP). In the control animals, there was no difference between total beta-adrenoceptors (43.8 +/- 7.2 vs. 40.7 +/- 8.0 fmol/mg protein +/- SEM) or percentage beta-adrenoceptor subtypes between the two zones. In group II, total beta-adrenoceptors increased 19.9% (p = 0.03) in the LAD compared with the lateral zone after 30 min of ischemia. Both beta-adrenoceptor subtypes increased, but only the increase in beta2-adrenoceptor was significant (39.8%; p = 0.02). Animals in group III revealed no difference in total beta-adrenoceptors density between LAD and lateral zones (48.3 +/- 13.4 vs. 55.2 +/- 8.5 fmol/mg protein). Brief myocardial ischemia is associated with an increase in total beta-adrenoceptors, attributed predominantly to increased beta2-adrenoceptors density. The increase in beta-adrenoceptor density is reversible after 1 h of reperfusion.

T lymphocyte beta 2-adrenergic receptor function and density after acute myocardial infarction.

The T lymphocyte beta 2-adrenergic receptor (beta 2AR) density and function were compared in 15 patients suffering acute myocardial infarction and 10 patients with stable coronary artery disease (CAD). Density was determined using radioligand binding with 125IPIN, and function by in vitro cyclic adenosine 3',5'-monophosphate (cAMP) production. In patients suffering acute myocardial infarction, T lymphocyte beta 2AR density (823.8 +/- 480 sites/cell) was slightly but not significantly different from that in patients with stable CAD (629 +/- 301 sites/cell). There was no difference in T lymphocyte cAMP production at baseline (1.11 +/- 0.70 vs 1.04 +/- 0.49 pM/10(6) cells) or after isoproterenol stimulation (2.53 +/- 1.63 vs 2.62 +/- 2.05 pM/10(6) cells), respectively. Further study is necessary to determine if beta 2AR numbers on T lymphocytes are significantly increased after acute myocardial infarction.

Nedocromil sodium (Tilade).

Nedocromil sodium is a well-tolerated antiasthmatic agent for initial therapy in patients with mild or moderate asthma not well controlled with inhaled beta-2 agonists and/or where methylxanthines are indicated. Like cromolyn sodium, nedocromil sodium offers a potential alternative to inhaled corticosteroids as maintenance therapy in patients with mild or moderate asthma not adequately controlled by bronchodilators. Furthermore, cromolyn sodium and nedocromil sodium may also reduce the usage of corticosteroids and provide some additional symptom control in patients whose asthma is not suitably controlled by optimal doses of inhaled corticosteroids. Both nedocromil sodium and cromolyn sodium are more efficacious than placebo for controlling of asthma, however, few studies have compared the effectiveness of cromolyn versus nedocromil at this time. Further experience and comparison studies of nedocromil sodium with cromolyn sodium in children are required before the role of nedocromil sodium as maintenance treatment in young asthmatic patients can be defined.