Effect of metabolic syndrome and aging on electrocardiographic responses to myocardial ischemia leading to sudden cardiac arrest in Ossabaw miniature swine

Background: Sudden cardiac arrest (SCA) is cessation of the heart beat due to electrical malfunction of the heart and can progress to sudden cardiac death (SCD) within minutes. Coronary artery disease (CAD), driven largely by atherosclerosis and aging, accounts for more than 75% of human SCD cases—with SCA mortality rates being 104-fold greater in old individuals compared to young. Ossabaw miniature swine are a well-established model of human cardiometabolic disease, developing metabolic syndrome (MetS) and CAD. Because CAD is closely linked to SCA, we hypothesized that young lean swine would tolerate ischemia longer and recover more quickly than young MetS and old lean swine. Methods: Female Ossabaw swine (n= 14) were assigned to young lean (~1-4 years; ~14-28 y human; n=5), old lean (~8.6-14 y; ~60-98 y human; n=6) groups, and young MetS (n=3). Animals underwent controlled myocardial ischemia via three sequential balloon occlusions primarily in the anterior descending (LAD) artery. Angiography was used to assess coronary anatomy and confirm occlusion and reperfusion. Occlusions were terminated if any of the following electrocardiographic (ECG) events occurred: ST-segment elevation >5 mm, QRS duration doubling, premature ventricular contraction (PVC), or if 15 minutes passed without meeting any of the criteria. These criteria for ischemia tolerance were based on our previous data showing that pigs meeting these criteria progressed rapidly to SCA and SCD. Results: Durations of occlusions 1, 2 and 3, respectively (mean±SE minutes): young lean (4.8±1.6, 5.0±2.5, and 3.3±0.4), old lean (4.2±0.6, 5.7±2.1, and 3.5±0.7), and young MetS (5.2±2.7, 6.6±4.2, and 2.1±0.9). There were no statistical differences within or between groups. ECG characteristics for ischemia termination differed among groups (ST elevation, QRS widening, PVC): young lean 60% ST, 40% QRS, 0% PVC; old lean 12% ST, 88% QRS, 0% PVC; and MetS 33% ST, 0% QRS, 67% PVC. Percentage of swine that experienced SCA: young lean (0%), old lean (20%), young MetS (67%). The recovery time between the occlusions: young lean (1.88±1.34), old lean (2.16±2.69), young MetS (2.43±1.97). Conclusion: While there was minimal risk of ischemia-induced SCA in the young lean group, aging increased the risk, and MetS substantially heightened that risk. Support: CorVus Foundation, Inc This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.