Effects of Landiolol on Mechanical and Metabolic Changes in Rat Reperfused Ischaemic Hearts

Abstract

1. The aim of the present study was to clarify the effects of landiolol, a short-acting selective beta(1)-adrenoceptor blocking agent, on mechanical and metabolic changes in postischaemic perfused hearts. 2. Rat isolated hearts (n = 30) were randomly separated into non-ischaemic or ischaemic groups. The latter group was further divided into Krebs'-Henseleit solution (KHS)- and landiolol (30, 100 or 300 micromol/L)-treated groups. Ischaemic hearts were subjected to 25 min global ischaemia and 20 min reperfusion under atrial pacing. Time-course changes in left ventricular (LV) end-diastolic pressure (LVEDP), LV developed pressure (LVDP), peak positive velocity of change of LV pressure (LVdP/dt(max)) and coronary flow were observed along with tissue contents of adenosine triphosphate (ATP), creatine phosphate, inorganic phosphate (Pi), malondialdehyde (MDA) and lactate dehydrogenase (LDH) release in coronary effluent. The effects of landiolol on rat isolated aortic preparations under KCl contraction were also investigated. 3. Ischaemia-reperfusion significantly impaired cardiodynamics, such as LVEDP, LVDP and LVdP/dt(max), decreased myocardial ATP content and increased Pi and LDH release. In the 30 micromol/L landiolol-treated group, cardiovascular parameters impaired by ischaemia-reperfusion and increased LDH release were further exacerbated and myocardial MDA content was significantly increased. In the 300 micromol/L landiolol-treated group, cardiac contractile dysfunction was improved and myocardial MDA, ATP and Pi contents were preserved. All measurements in the 100 micromol/L landiolol-treated group were similar to those in the ischaemic KHS group. Furthermore, significant relaxations of isolated aortic preparations were obtained with landiolol 30-1000 micromol/L, suggesting a possible calcium antagonism with landiolol. 4. In conclusion, landiolol, at low concentrations, aggravated myocardial ischaemia-reperfusion injuries, whereas at high concentrations it ameliorated them. The former effect may be mediated by the production of reactive oxygen species, whereas the latter may involve calcium antagonist activity.

Landiolol does not enhance the effect of ischemic preconditioning in isolated rat hearts

“…Sakanashi et al [15] reported that landiolol at 300 lM ameliorated myocardial ischemiareperfusion injuries; in our study, the findings are similar to their reports.…”

“…Esmolol produced a dose-dependent decrease in mean arterial pressure that was not observed with landiolol [24]. Sakanashi et al [15] reported that, whereas 300 lM landiolol ameliorated myocardial dysfunction, LVEDP was similar to that in the ischemic KHS group. The effect of landiolol on postischemic cardiac parameters was said to be concentration dependent.…”

“…Efstathiou et al [26] reported differential LVEDP and LVDP recovery as a function of ischemic time (15,20,30, and 45 min). After 30 min of ischemia, there was no strong correlation between infarct size limitation and contractile function improvement.…”

“…L300 (preconditioning with landiolol 300 lM infused), and IPC ? L500 (preconditioning with landiolol 500 lM infused); the concentrations of landiolol were based on previous studies [14,15]. After 20 min of stabilization, in the IPC, IPC ?…”

Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

“…This is the key mechanism of cardioprotection by β-blockers. Other mechanisms of cardioprotection by β-blockers include the suppression of renin release [ 4 ], reduction of myocardial oxygen stress [ 5 ], and normalisation of calcium handling in the sarcoplasmic reticulum [ 6 ].…”