1. Change to when the primary outcome measure is assessed - final infarct size measured using MRI at six months (or slightly earlier for patients who may be scheduled for an implantable defibrillator/antiarrhythmic therapy). Oedema imaging (to correct for area at risk) will be added as a covariate to the analysis. The oedema imaging will be carried out during the first MRI scan that participants will have. Originally this was scheduled for 10-14 days after the MI, but we propose to carry this MRI out 6-8 days after the MI. The proposed changes to the timing of assessment of both final infarct size and oedema are based on the latest available evidence. 2. Change in the timing of the secondary endpoints, previously assessed at MRI at 10-14 days, to MRI at 6-8 days. This change fits in with the change in time of the first MRI scan (described in 1 above), and avoids the need to have a third MRI scan at 10-14 days. 3. Revision to inclusion criteria such that women aged <55 years who are not pregnant, sterilised, have had a hysterectomy or are using effective contraception, would be eligible to participate in the study. 4. To clarify that patients with new left bundle branch lock are suitable for inclusion in the study. 5. To add an exclusion criteria (left Main disease which after PCI of their culprit lesion (culprit lesions may be located in the LAD or LCx or RCA) are likely to require CABG within the time course of the study period (6 months)). 6. to reword the section on MRI imaging parameters. While the sequences will be standardised between centres as much as possible, bt the individual scan parameters will be optimised as appropriate according to the individual patient. The parameters that were previously given in the protocol are one example of how the MRI might be carried out. 7. To include three additional expected adverse events: pulmonary oedema, re-occlusion and respiratory arrest (REC only)

Inclusion of two additional exclusion criteria (prior coronary artery bypass grafting and prior thrombolysis for this event). Clarification that the prior revascularisation procedure is only an exclusion criteria if it was carried out in the same territory as the current infarct. Removal of atrial fibrillation at time of randomisation as an exclusion criterion. Restriction, unless absolutely indicated for the patient, the use of IV or oral nitrates within five minutes of PCI. Inclusion of additional outcome measure of LV end systolic volume index. Revision to the list of expected adverse events following administration of Investigational Medicinal Product or following PCI. Addition of information about storage conditions for IMP and placebo. Revision of dosing information such that the dose is given over 2.5 to 5 minutes. Revision of definition of PCI to include thrombus extraction. Confirmation that distilled water will be used for the preparation of IMP and placebo. Clarification of the timing of the injection in relation to the PCI. (REC only)

Removal of requirement to gain consent from a relative/legal representative following verbal agreement from a trial particiant who dies before giving informed consent. (REC only)

To add an recruitment site outwith the UK. To clarify that part of the NIAMI project will be written up as an educational project. (REC only)

Amendment to protocol and PIL to clarify where MRI images will be analysed. Amendment to publication policy. Amendment to protocol in relation to minor temperature deviations of study medication. Addition of sub-study to investigate blood plasma nitrite levels and methaemoglobin. Amendment to sample size. Clarification of inclusion criteria that patients with posterior infarcts with ST depression which meet the inclusion criteria can also be included. (REC and Regulatory Authority)

A change in the time-point at which the primary end-point is assessed. For scientific and logistical reasons, we propose to revert to measuring the primary end-point (infarct size) at the first MRI scan (6-8 days after infarct). This has been discussed with the Trial Steering Committee and they have ratified our proposal. Infarct size at 6 months will become a secondary endpoint. All MRI scans will be analysed in Aberdeen. We propose that there will be no transfer of images to Imperial College London. All scans will be assessed by a blinded observer. A second blinded observer will analyse a sample of images. We also propose to amend the patient information leaflet to take account of this change. Proposed sample size. To take account of our proposed change to the time-point at which the primary end-point is assessed, we have revised the section on proposed sample size. To account for loss of outcome measure due to death, those who decline MRI or are unsuitable for MRI due to renal dysfunction and those in whom the MRI scans are technically inadequate, we plan to recruit approximately 200-210 participants. (REC only)