Effects of In Vivo Administration of an Endothelial KCa Channel Activator on Recovery of Cardiac Function Following Acute Myocardial Infarction in Mice
Bibliographic record
Abstract
Cessation of coronary blood flow, due to stenosis or acute blockage, produces prolonged ischemia that results in myocardial infarction (MI) and impaired cardiac function and blood pumping activity of heart. Increasing coronary blood flow to the ischemic area and/or reducing myocardial work are predicted to mitigate the damage typically associated with an acute MI injury. Recent studies from our group have demonstrated that pharmacological enhancement of endothelial KCa2.3 and KCa3.1 channels by the activator SKA‐31 improves agonist‐evoked vasodilation in small resistance arteries from multiple vascular beds and species. The goal of our present study is to investigate the potential cardio‐protective effects of SKA‐31 administration in male mice (12–15 weeks of age, C57B1/6 strain) following an acute myocardial infarct (MI) induced by permanent surgical ligation of the left‐anterior descending (LAD) coronary artery. Within 48 h post‐surgery, MI and sham surgery mice were treated orally with either vehicle or 10 mg/kg of SKA‐31 for 6–7 weeks. Myocardial damage in MI mice was confirmed by histological staining. Echocardiographic assessment of cardiac structure and function 2 weeks post‐surgery revealed that left ventricular (LV) wall thickness during systole and diastole was similar in sham animals treated with either vehicle or SKA‐31. In contrast, LV wall thickness during systole and diastole was ~30% greater in MI surgery mice receiving SKA‐31 treatment. At 4 weeks post‐surgery, sham animals exhibited LV wall thickness values during systole (1.00 mm ± 0.03, n=3) and diastole (0.82 mm ± 0.10, n=3) that were similar to those observed at 2 weeks, indicating that SKA‐31 treatment did not adversely affect these parameters. In MI surgery animals receiving SKA‐31 administration for 4 weeks, LV wall thickness during systole (0.97 mm ± 0.10, n=5) and diastole (0.80 mm ± 0.08, n =5) decreased to the values observed in sham surgery mice. At the end of the SKA‐31 treatment period, cardiac output (CO) and LV ejection fraction (EF) measured by pressure‐volume loop analysis were both higher in sham mice (CO = 6.49 mL/min, EF = 50.9%) compared with MI surgery animals (CO = 5.83 mL/min, EF = 40.7%). Following completion of ongoing measurements and analyses, we will present additional data describing changes in cardiac function in MI surgery mice treated with drug vehicle, and histological assessment of myocardial integrity in sham and MI surgery mice. Our preliminary findings thus far suggest that enhancement of endothelial KCa channel activity by SKA‐31 administration improves recovery of cardiac function following ischemic damage associated with blockade of the LAD coronary artery. Support or Funding Information This work was supported by research funding to APB from the Canadian Institutes of Health Research (MOP 142467) and the Natural Sciences and Engineering Research Council of Canada (RGPIN‐2017‐04116).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".