History and purpose In drug research using the rat Langendorff heart preparation it is possible to study left ventricular (LV) using an intraventricular balloon (IVB) and during coronary ligation‐induced regional ischaemia. an inflated IVB reduced ischaemia‐induced ventricular fibrillation (VF) incidence as a trend. Repeating studies in hearts with large IZs revealed the effect to be significant. There were no changes in QT interval or other variables that might explain the effect. Insertion of an IVB that was minimally inflated had no effect on any variable compared with ‘no IVB’ controls. The antiarrhythmic effect of verapamil (a positive Rabbit polyclonal to SEPT4. control drug) was unaffected by IVB inflation. Removal of an inflated (but not a non‐inflated) IVB caused a release of lactate commensurate with reperfusion of an endocardial/subendocardial layer of IVB‐induced ischaemia. This was confirmed by intracellular 31phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy. Conclusions and implications IVB inflation does not inhibit VF suppression by a standard drug but it has profound antiarrhythmic effects of its own likely to be due to inflation‐induced localized ischaemia. This means rhythm and contractility cannot be assessed concurrently by this approach with implications for drug discovery and safety assessment. Aliskiren hemifumarate AbbreviationsBGbigeminyIVBintraventricular balloonIZischaemic zoneLVleft ventricularNMRnuclear magnetic resonanceNOnitric oxidePCrphosphocreatinePiinorganic phosphateTVWtotal ventricular weightUZuninvolved zoneVFventricular fibrillationVPBventricular premature beatVTventricular tachycardia Tables of Links LV contractility Aliskiren hemifumarate simultaneously in a single experiment is a strategy that would give a more comprehensive assessment of drug effects with reduced animal usage. Indeed the growing interest in the rat Langendorff preparation with an IVB for cardiac safety assessment (Henderson be measured (impossible if none were added). This gave an LV created pressure at baseline of ~30?mmHg. A third group of hearts with no IVB was included in the study. Hereafter we refer to the three groups as ‘IVB inflated’ (~0.12?mL) ‘IVB’ (<0.01?mL) and ‘no IVB’ respectively. The IVB technique together with some caveats concerning IVB manufacture and troubleshooting is discussed in Clements‐Jewery and Curtis (2014). Figure 1 One of the IVBs used in the present study shown uninflated (for insertion into the left ventricle) minimally inflated (0.01?mL) and inflated (0.12?mL) according to the definitions provided in the text. Experimental protocols The study was divided into a sequence of experiments designed to address separate questions. Within each experiment hearts were randomized to groups and analysis of variables was undertaken blind. After 5?min of perfusion all hearts were subjected to regional ischaemia Aliskiren hemifumarate for 120?min (initial set of experiments) or 30 followed by reperfusion. The 120?min duration was Aliskiren hemifumarate chosen to capture the full spectrum of phase 1 ischaemia‐induced ventricular arrhythmias in rat isolated hearts (Ravingerova tests if was significant and there was no variance inhomogeneity in accordance with journal guidance (Curtis the incidence of VF (as a non‐significant trend). To test whether the effect was robust the study was repeated in hearts with large IZs (more scope to detect VF suppression) and a substantial and significant effect was detected (Figure?4E). IVB inflation also significantly reduced the incidence of VT (30-60?min ischaemia; Figure?4D) and a five‐point arrhythmia score (Figure?4F) in these hearts. Figure 3 Occurrence (% incidence per group) of increasingly severe ventricular arrhythmias (VPB to VF) and five‐point summary arrhythmia score (mean?±?SEM) during 120?min ischaemia in hearts with IZs. There were … Figure 4 Occurrence (% incidence per group) of increasingly severe ventricular arrhythmias (VPB to VF) and five‐point summary arrhythmia score (mean?±?SEM) during 120?min ischaemia in hearts with IZs. There were … Nevertheless in hearts with small IZs the IVB and IVB inflation significantly the incidence of less severe phase 1A (0-10?min; Figure?5A) and early phase 2 arrhythmias (>30?min; Figure?3B-D) and a five‐point arrhythmia score (Figure?3F?+?5B). There was also a non‐significant trend Aliskiren hemifumarate to an increase in susceptibility to phase 1A arrhythmias in hearts with large IZs where there is much less range to detect a rise due to the high baseline susceptibility (data not really shown). Body 5 Incident (% occurrence per group) of significantly serious ventricular arrhythmias (VPB to VF) (component A) and Aliskiren hemifumarate five‐stage.