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Bradshaw et al. Vessel Plus 2023;7:35 https://dx.doi.org/10.20517/2574-1209.2023.121 Page 11 of 21

Figure 2. Summary of the benefits with use of K ATP channel opener diazoxide in a translational swine model of hypothermic cardioplegic
arrest and prolonged global ischemia similar to a prolonged global ischemia model for clinical cardiac surgery. Swine undergo
cardiopulmonary bypass and prolonged global ischemia of the heart via placement of aortic cross clamp (120 min) with one dose of
cardioplegia, similar to clinical cardiopulmonary bypass. Animals are randomized to one of two groups: cardioplegia alone or
cardioplegia plus diazoxide. Animals who underwent cardioplegia plus diazoxide in this model had preserved systolic and diastolic
function, suggesting that adding diazoxide to cardioplegia may result in improved outcomes [135] . This model simulates the clinical
situation of a patient presenting to the operating room for a prolonged global ischemic period for cardiac surgery protected with one
dose of cardioplegia [135] . This figure is used with permission from Elsevier (obtained September 4, 2023, license number
5621921258491) [135] . CPB: Cardiopulmonary bypass.

Figure 3. Photograph of porcine heart in the Lawton laboratory following cannulation for cardiopulmonary bypass, placement of left
ventricular pressure catheter, and placement of left anterior descending tourniquet for regional ischemia prior to a longer global
ischemia in a model simulating clinical cardiopulmonary bypass with an acutely injured heart. Regional ischemia is evident in this
porcine heart after occlusion of the left anterior descending coronary artery for 30 min for regional ischemia. Subsequently, the heart
will be exposed to two hours of global ischemia protected with cardioplegia with or without diazoxide, followed by reperfusion [136] . This
model simulates the clinical situation of a patient presenting to the operating room with ongoing ischemia prior to a coronary
revascularization procedure with prolonged global ischemia [136] . This figure is used with permission from Elsevier (obtained December
12, 2023, license number 5686380805849) [136] .