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Ischaemic preconditioning (IP) is a powerful mechanism for infarct reduction. Enhanced K+ conductance and shortening of action potential duration in the early phase of the sustained ischaemic episode have been proposed as important factors in the IP mechanism for infarct reduction. We have investigated whether the potassium channel-blocking class III anti-arrhythmic agent dofetilide could abolish IP in an in situ rabbit heart infarct model. Dofetilide is a specific blocker of the delayed rectifier potassium channel and thus lengthens the action potential duration by reducing potassium conductance during repolarization.Anaesthetized, open-chest rabbits were subjected to 30 min of regional ischaemia and 180 min of reperfusion. The ischaemic risk zone was determined by fluorescent particles, and infarct size was determined by TTC staining. Three groups were investigated: control, ischaemic preconditioned (IP) and IP plus dofetilide-treated (IPdof). The preconditioning protocol was 5 min regional ischaemia and 10 min reperfusion. The IPdof group underwent the same preconditioning protocol but additionally received dofetilide 20 ug kg-1 i.v. during the first 2 min of the first reperfusion period. Compared to pre-drug values dofetilide increased monophasic action potential duration from 149.2±11.5ms (n=4) to 215.8±12.4 ms, supporting blockade of the delayed rectifier potassium channel. At the same time heart rate was decreased from 255.5±12.5 to 230.3±8.2. The results expressed as percent infarction of the risk zone+SEM for the different groups were as follows: control (n=ll), 42.4+7.1; IP (n=6), 7.6±4.3*; IPdof (n=7), 12.3±4.1* (*p≤ 0.05 vs. control). These results show that the potassium channel-blocking agent dofetilide given after the preconditioning ischaemia but before the sustained ischaemia does not abolish ischaemic preconditioning.

Blocking of the KATP-channel with glibenclamide has been shown to abolish the infarct-reducing effect of ischemic preconditioning in dog and swine. In the rabbit the results have been divergent purportedly related to anaesthesia. The aim of this study was to investigate the importance of the KATP-channel in a rabbit model where anaesthesia was not a condounding factor. Isolated rabbit hearts perfused with a Krebs-Henseleit bicarbonate buffer were subjected to 30 min regional ischemia by ligating a coronary artery, followed by 120 min reperfusion. The preconditioning protocol was 5 min global ischemia and 10 min reperfusion. Glibenclamide (100µM) was added to the perfusion solution before the preconditioning ischemia and stopped after 5 min regional ischemia. Infarcts were measured with tetrazolium staining and risk zones with fluorescent microspheres. The main results expressed as percent infarction of the risk zone±SEM for the different groups are as follows: control (n=12) 26.8±3.2, ischemic preconditioning (IP) (n=9) 7.3+1.5 (p<0.05 vs. control), control+ glibenclamide (n=9) 46.9±7.3 (p<0.05 vs. control), IP+ glibenclamide (n=10). 38.3±6.9 (p<0.05 vs. IP). These results show that glibenclamide treatment aggravates ischemia. Also, under the influence of glibenclamide ischemic preconditioning was no longer effective in reducing infarct size in the isolated perfused rabbit heart.

Inhibition of Na+/H+ exchange with amiloride analogues has been shown to offer functional protection during ischemia and reperfusion and reduce infarct size in isolated rat hearts and intact pigs. The aim of the present study was to examine if pre- or postischemic treatment with ethylisopropylamiloride (EIPA), a selective Na+/H+ exchange inhibitor, could reduce infarct size in anin situ rabbit model of regional ischemia and reperfusion. Anesthetized, open-chest rabbits were subjected to 30 min of regional ischemia and 180 min of reperfusion. The risk zone was determined by fluorescent particles, and infarct size was determined by TTC staining. Preischemic treatment with EIPA (0.65 mg/kg) significantly reduced infarct size from 45.8±3.5% of the risk zone in the control group to 10.6±3.1% (p<0.01). EIPA-treatment during the first part of the reperfusion period did not reduced infarct size compared to controls (41.9±3.5%). We conclude that EIPA, when administered prior to ischemia, reduces infarct size in the rabbit heartin situ, a protection most likely due to inhibition of Na+/H+ exchange.

Locally least-cost error recovery is a technique for recovering from syntax errors by editing the input string at the point of error detection. An informal description of a parser generator which implements the technique is given. The generator takes as input an extended BNF description of a language together with a set of primitive edit costs and outputs a recursive descent syntax analyser including error recovery. Criteria for assessment of the technique are offered. Using these criteria the technique is assessed with respect to a database of over 100 example programs, and compared with an alternative local error recovery technique, that of follow set error recovery. The conclusion is that locally least-cost error recovery is more effective than follow set error recovery but much less economical in its use of storage space. The least-cost parser also runs between 15 and 20% slower than the follow set parser.