Diosgenin-induced protection against myocardial ischaemia-reperfusion injury is mediated by mitochondrial KATP channels in a rat model.

OBJECTIVE: This study was aimed to evaluate the effects of diosgenin on myocardial ischaemia-reperfusion injury and the potential involvement of mitochondrial KATP (mitoKATP) channel and nitric oxide (NO) system blockades in this field. MATERIALS AND METHODS: After isolation of hearts of male Wister rats, the study was conducted on control and diosgenin- receiving hearts in the presence or absence of 5-HD and L-NAME (as antagonists of mitoKATP channel and NO system, respectively) in an isolated buffer-perfused heart model. Global ischaemia was induced by 30-min occlusion of aortic flow followed by 90-min reperfusion. Cardiac haemodynamics were recorded throughout the experiment using a PowerLab data acquisition system. RESULTS: The levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) in the coronary effluents were estimated colourimetrically. Diosgenin pre-administration significantly decreased the release of LDH and CK-MD into the coronary effluent as compared the with the control group (P < 0.05). The left ventricular developed pressure (LVDP) and contractility (± dP/dt) were significantly improved and restored to pre-ischaemic values in the diosgenin-receiving group (P < 0.05). There were no significant differences in left ventricular end-diastolic pressure, coronary flow and heart rate between the control and diosgenin-treated groups during the pre-ischaemic and reperfusion periods. Blocking the mitoKATP channels by 5-HD completely eliminated the positive effect of the diosgenin on the LVDP and ± dP/dt (P < 0.05). However, blocking the NO system by L-NAME slightly reduced the diosgenin effects and the inhibitory effect of L-NAME was less than 5-HD. CONCLUSION: The results showed that diosgenin may have cardioprotective effects against myocardial reperfusion injury through activating the mitoKATP channels.

Effect of hydration on lung interstitial permeability response to albumin and hyaluronidase.

Previous studies showed that the flows of albumin and hyaluronidase solutions increased relative to that of saline in isolated segments of rabbit lung interstitium (Lai-Fook et al. J. Appl. Physiol. 67:606-613, 1989). We questioned whether these effects were hydration dependent. In interstitial segments the flows of lactated Ringer, albumin (5 and 10 g/dl), and hyaluronidase (0.02%) solutions were measured at mean interstitial pressures (Pm) between -5 and 15 cmH2O with a constant driving pressure of 5 cmH2O. The albumin-to-Ringer flow ratio increased monotonically from near the viscosity-dependent value (0.75-0.77) at -5 cmH2O Pm to values of 1.6-2.1 at 15 cmH2O Pm. A similar behavior was observed for the flow of the hyaluronidase solution relative to that of Ringer solution. The increased permeability response to albumin was independent of the albumin concentration used. By contrast, the response to hyaluronidase was lower when the interstitium was perfused with the higher concentration albumin solution (10 g/dl) before the flow of hyaluronidase, indicating an inhibitory effect of albumin on the hyaluronidase response. Estimates of interstitial hydration from Pm indicated an increased interstitial permeability (conductivity) to the flows of albumin and hyaluronidase solutions only after interstitial volume had doubled, whereas interstitial permeability was viscosity dependent at normal interstitial hydration.