deltibant and Hyperkalemia

Isolated rabbit hearts in a modified Langendorff preparation were used to study the role of bradykinin B2-receptor antagonism on recovery from cardiac ischemia. The experiments were performed to clarify a potential risk of administrating BK-receptor antagonists in patients with coronary heart disease and patients undergoing heart surgery. The hearts were perfused in an open system at a constant pressure of 70 mm Hg and at a constant temperature of 37 degrees C with Krebs-Henseleit-buffer solution containing 6.5% HAES (hydroxyethyl-amylopectin) and 10 mmol Na-pyruvate/l. The perfusate was equilibrated to a PO2 of about 500-600 mm Hg. After a steady state period of 30 min, coronary perfusion was stopped for 30 min and the hearts were subsequently reperfused for further 30 min. Pretreatment with the B2-receptor antagonist, CP-0127, significantly increased (p < 0.001) the coronary vascular resistance during reperfusion from 31.9 +/- 2.1 to 59.0 +/- 6.5 mm Hg/ml/min/10 g wt and decreased the left ventricular pressure amplitude to 44.0 +/- 15.2% (p < 0.005) of it's baseline. When ischemia was combined with hyperkalaemic cardioplegia, CP-0127 did not influence coronary vascular resistance, but depressed, only to a minor degree, left ventricular pressure amplitude to 65.1 +/- 15.4% (p < 0.005) during reperfusion. Arrhythmias during reperfusion with cardiac arrest occurred only in 2 hearts with B2-receptor inhibition when ischemia was not combined with cardioplegia. Dependent on the initial functional status of the heart B2-receptor inhibition impaired recovery from acute coronary ischemia by increasing the coronary vascular resistance and depressing the myocardial function and therefore may constitute a risk in patients undergoing heart surgery and extracorporeal circulation.

Topics: Analysis of Variance; Animals; Arrhythmias, Cardiac; Blood Pressure; Bradykinin Receptor Antagonists; Heart Arrest; Heart Arrest, Induced; Heart Rate; Hyperkalemia; In Vitro Techniques; Myocardial Ischemia; Myocardial Reperfusion Injury; Peptides; Rabbits; Receptor, Bradykinin B2; Temperature; Vascular Resistance; Ventricular Function, Left