Objective: Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia / reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. Methods: Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 mmol / kg / min), BQ788 (3 mmol / kg / min), ET-1 (8 pmol / kg / min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n512 each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after 1 and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. Results: Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups ( p,0.05). Conclusions: These results suggest that endogenous ET release is involved in the pathogenesis of reperfusion injury after heart transplantation. ET-A and ET-B receptor antagonists may be useful to reduce ischemia / reperfusion injury.

Background: This stu dy was designed to invest igate the ef· feet s of th e select ive endothelin-Areceptor antagonist BQ123 on myocardial and endothe lial funct ion after rever sible deep hypot hermic ischem ia and reperfusion . Methods: Isogenic intra-abdomina l het erotopic hea rt transplantati on was perfo rmed in l ew is rat s. Afte r one hour of cold ischemic preservation reperfusia n was sta rte d afte r a pplicatio n of either saline vehicle or BQ l23 (l !lmol/l).left-ventricular pressure-volum e relat ions and myocardial blood flow were asse sse d aft er one and 24 hour s of reperfu sion . Responses to endothelium-de pende nt vasodilator acetylcholine and endot helium-inde pende nt vaso dilato r sodium nitropru sside we re also det ermin ed. Results: BQ123 significant ly improved myocardial co ntract ility. as indicated by the leftward shift of the systolic pressure-volume relation and significantly increased myocardial blood flow during ea rly reperfu sion (p < 0.05). Although myocardial functi on and baseline myocardial blood flow were similar in both gro ups after 24 hour s of reperfuslon, endothelium-depende nt vasod ilatation was st ill sig nificantly higher in the BQ 123 group (p < 0.05). Conclusions: These results suggest that endot helin-A receptor antagonists may be useful in reducing ischemia/ reperfusion injury after heart transplanta tion by preservat ion of myocardial and endothelial function.

1. The actions of pronethalol and propranolol have been studied to see if there was any relationship between the reduction in coronary flow and any other cardiovascular action they have. 2. The experiments were carried out in anaesthetized open chest dogs. Measurements included central arterial, left and right venous or atrial pressures, heart rate, ventricular size and stroke volume, intra-ventricular pressures, total left coronary flow, arterial and coronary sinus blood p02. The pressure-time index (PTI) and maximum rate of isovolumetric contraction (dp/dt) were obtained from these records. 3. It was concluded that, in these experiments, the reduction in coronary flow produced by pronethalol and propranolol was not directly related to a decrease in perfusion pressure, a raised venous pressure, the increase in ventricular volume and hence wall tension, the decrease in heart rate, or to the increased duration of systole. 4. The PTI and dp/dt were always reduced at the same time as the coronary flow. These findings are discussed. 5. Studies of the effects of sympathetic stimulation, of phentolamine, of reduced arterial oxygen tension and electrical pacing of the heart, all after ,/-blockade, did not support the suggestion that the reduction in coronary flow after 8-blockade was due to the unmasking of an active vasoconstriction.

No abstract

No abstract