endothelin-1 and urapidil

To evaluate the effect of urapidil on myocardial perfusion, and ventricular function in patients with ST-elevation acute coronary syndrome (ACS) treated with primary percutaneous coronary intervention (PCI).. Fifty-four patients were randomized into urapidil (12.5 mg, ic, n=27) or control group. Infarct related artery (IRA) was targeted with PCI following urapidil administration. TIMI blood flow, corrected TIMI frame count (cTFC), myocardial blush grade (MBG), ST resolution (STR) on ECG, creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) were measured before, and after PCI.. cTFC (18.38+/-3.30 vs 21.44+/-4.26, P=0.005), in the treatment group was lower than the placebo group, whereas MBG was higher (P=0.04). More patients in the urapidil group achieved significant STR following PCI (93% vs 70%, P=0.04). Left ventricular ejection fraction (LVEF), measured with echocardiography, in the urapidil group was higher than the control group 30 days after PCI (0.58+/-0.06 vs 0.54+/-0.06, P=0.04). Peak CK-MB and peak cTnT in the urapidil group was lower than the control group (P<0.01). Myocardial nitric oxide concentration in the urapidil group was higher than that of the control group (P<0.01). Following PCI, the endothelin-1 level did not change in the urapidil group (P>0.05) but it was increased in the control group (P<0.05).. Urapidil treatment improves coronary flow, myocardial perfusion and left ventricular function following PCI in patients with ST-elevation ACS. These beneficial effects are associated with an enhanced biosynthesis of nitric oxide.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Coronary Circulation; Echocardiography; Electrocardiography; Endothelin-1; Female; Humans; Male; Middle Aged; Nitric Oxide; Piperazines; Stroke Volume; Vasodilator Agents; Ventricular Function, Left

We investigated plasma endothelin (ET) levels in patients with congestive heart failure (CHF) during treatment for acute decompensation; we also measured imbalances in ET peptides across the pulmonary, coronary, and peripheral circulation. Methods and Results-In patients with severe CHF (n=21; cardiac index [CI], 1.9+/-0.2 L. min(-1). m(-2); pulmonary capillary wedge pressure [PCWP], 31+/-1 mm Hg), vasodilation was achieved with the nitric oxide donor sodium nitroprusside (n=11) or with the alpha(1)-antagonist urapidil (nitric oxide-independent, n=10). ET concentrations were determined from arterial blood and blood from the pulmonary artery, coronary sinus, and antecubital vein. Depending on sites of measurement, baseline big ET and ET-1 levels were, respectively, 12 to 16 times and 5 to 11 times higher than in controls (n=11), and 4 to 6 times and 2 to 3 times higher than in patients with moderate CHF (n=10; CI, 2.7+/-0.3 L. min(-1). m(-2); PCWP, 14+/-2 mm Hg). Patients with severe CHF demonstrated pulmonary net release and coronary and peripheral net consumption of both peptides (ie, arterial levels [big ET, 7.3+/-1.3 pmol/L; ET-1, 1.8+/-0.1 pmol/L] were higher than levels in the pulmonary artery [6.7+/-1.2 pmol/L; 1. 3+/-0.1 pmol/L], coronary sinus [6.4+/-1.0 pmol/L; 1.4+/-0.1 pmol/L], and antecubital vein [6.6+/-1.1 pmol/L; 1.3+/-0.1 pmol/L]). In these patients, sodium nitroprusside (SNP) and urapidil resulted in comparable hemodynamic improvement after 6 hours (CI: SNP, 63+/-2%; urapidil, 72+/-3%; PCWP: SNP, -50+/-2%; urapidil, -47+/-2%) and a maximum decrease in ET peptides by >50%. After 3 hours, pulmonary net release and coronary and peripheral net consumption were no longer detectable.. In patients with severe CHF, the lungs act as a producer and the heart and the periphery act as consumers of elevated circulating ETs. Short-term vasodilator therapy decreases ETs and restores their pulmonary, coronary, and peripheral balance.

Topics: Aged; Coronary Circulation; Endothelin-1; Endothelins; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Nitroprusside; Piperazines; Pulmonary Circulation; Stroke Volume; Vasodilator Agents