terminal-harvest-procedure-large-animal-model-chronic-myocardial

Terminal Harvest Procedure of a Large Animal Model of Chronic Myocardial Ischemia with Hemodynamic Characterization and Perfusion Analysis

Reproducibility and research integrity are foundational tenets to scientific discovery, which are produced utilizing well-established, proven principles ...

a-clinically-relevant-swine-model-chronic-myocardial-ischemia-ameroid

A Clinically Relevant Swine Model of Chronic Myocardial Ischemia by Ameroid Constrictor Placement with Simultaneous Perfusion Mapping

Despite breakthroughs in medical and procedural therapies for the treatment of cardiovascular disease, the need for translational large animal models has ...

Brown University

Rhode Island Hospital

There is a significant body of literature to suggest that coronary artery disease (CAD) is a highly sex-specific disease. The study of sex-specific therapeutics and sex-specific responses to treatment for CAD remains underreported in the literature. Sodium-glucose transporter 2 (SGLT2) inhibitors are of growing interest in the treatment of ischemic heart disease and heart failure; however, the sex-specific response to SGLT2 inhibitors is unknown. We studied an SGLT2 inhibitor, canagliflozin, in a swine model of metabolic syndrome (MS) and chronic myocardial ischemia with emphasis on the sex-specific outcomes. Yorkshire swine ( = 21) were obtained at 6 weeks of age and fed a high-fat diet to induce MS. Left thoracotomy was performed on all swine at 11 weeks of age for the placement of an ameroid constrictor to model chronic myocardial ischemia. Swine recovered for two weeks, then were assigned to either the drug group, CAN 300 mg daily group (M = 5, F = 5), or the control group (CON, M = 5, F = 6). Both groups received 5 weeks of therapy. After completion of therapy, swine underwent functional assessment and terminal harvest. The male animals treated with CAN (CAN-M) had significant increases in stroke volume and cardiac output ( = 0.047,  < 0.001) compared to control males (CON-M), which were not seen in females treated with CAN (CAN-F) compared to control females (CON-F). Effective arterial elastance was decreased in CAN-M compared to CON-M. The CAN-F group had a significant increase in ischemic myocardial capillary density compared to CON-F ( = 0.04). There was no difference in capillary density between the CAN-M and CON-M groups. CAN treatment resulted in sex-specific changes in angiogenesis and myocardial function. The CAN-M group had significant improvements in cardiac function based on afterload reduction, stroke volume, and increased cardiac output not seen in the CAN-F group. The CAN-F group had increased ischemic myocardial capillary density. These findings provide a foundation for further investigation of the sex-specific effects of SGLT-2 inhibitors in humans.

Sex-Specific Improvements in Myocardial Function and Angiogenesis with SGLT-2 Inhibitor Canagliflozin in a Swine Model of Metabolic Syndrome.

Ischemic heart disease (IHD) is the leading cause of mortality worldwide, underscoring the urgent need for innovative therapeutic strategies. The cardiac extracellular matrix (ECM) undergoes extreme transformations during IHD, adversely influencing the heart's structure, mechanics, and cellular signaling. Researchers investigating the regenerative capacity of the diseased heart have turned their attention to exploring the modulation of ECM to improve therapeutic outcomes. In this review, we thoroughly examine the current state of knowledge regarding the cardiac ECM and its therapeutic potential in the ischemic myocardium. We begin by providing an overview of the fundamentals of cardiac ECM, focusing on the structural, functional, and regulatory mechanisms that drive its modulation. Subsequently, we examine the ECM's interactions within both chronically ischemic and acutely infarcted myocardium, emphasizing key ECM components and their roles in modulating angiogenesis. Finally, we discuss recent ECM-based approaches in biomedical engineering, focusing on different types of scaffolds as delivery tools and their compositions, and conclude with future directions for therapeutic research. By harnessing the potential of these emerging ECM-based therapies, we aim to contribute to the development of novel therapeutic modalities for IHD.

Developments in Extracellular Matrix-Based Angiogenesis Therapy for Ischemic Heart Disease: A Review of Current Strategies, Methodologies and Future Directions.

Coronary artery disease (CAD) confers a continued challenge to healthcare necessitating innovative therapies. Linagliptin, a dipeptidyl peptidase 4 inhibitor, has been shown in preclinical and clinical studies to have cardioprotective effects independent of its glycemic control. An important pathway by which linagliptin has been described to induce these effects is due to its immune regulation. This study aims to evaluate the immune modulation by linagliptin treatment in a porcine model of chronic myocardial ischemia.

Linagliptin Modulation of Inflammation in Chronic Coronary Artery Disease.

There are striking sex disparities among cardiometabolic disorders; however, the understanding of its underlying disease pathology remains uncertain, creating insufficient preventative and therapeutic approaches. Our study investigates the sex-specific response to the dipeptidyl peptidase-4 inhibitor, linagliptin in a clinically meaningful model of metabolic syndrome and chronic myocardial ischemia.

Linagliptin exerts a sex-specific effect on cardiac function, collateralization, and metabolism in a swine model of cardiometabolic disease.

Vasoplegia is a well-established risk after cardiopulmonary bypass. Angiotensin II is a polypeptide integral to blood pressure and intravascular volume regulation, yet limited evidence explores angiotensin II in post-cardiopulmonary bypass vasoplegia. This study aims to investigate microvascular functional and mechanistic changes to angiotensin II response after cardiopulmonary bypass.

Impaired contractile response of human peripheral arterioles to angiotensin II after cardiopulmonary bypass.

Ischemic heart disease (IHD) is the leading cause of global mortality and is often complicated by metabolic syndrome (MetS), making its management challenging. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, such as canagliflozin (CAN), have demonstrated cardioprotective effects, but the precise molecular mechanisms underlying these benefits in the setting of IHD and MetS remain unclear.

ArticleTotal : 2	Year
Publication title	2025
Publication title Cited by 1	2025

Article	Year
Sex-Specific Improvements in Myocardial Function and Angiogenesis with SGLT-2 Inhibitor Canagliflozin in a Swine Model of Metabolic Syndrome. International journal of molecular sciences\| PubMed ID: 40076513	2025
Developments in Extracellular Matrix-Based Angiogenesis Therapy for Ischemic Heart Disease: A Review of Current Strategies, Methodologies and Future Directions. Biotech (Basel (Switzerland))\| PubMed ID: 40227326	2025
Linagliptin Modulation of Inflammation in Chronic Coronary Artery Disease. The Journal of surgical research\| PubMed ID: 40253935	2025
Linagliptin exerts a sex-specific effect on cardiac function, collateralization, and metabolism in a swine model of cardiometabolic disease. The Journal of thoracic and cardiovascular surgery\| PubMed ID: 40324745	2025
Impaired contractile response of human peripheral arterioles to angiotensin II after cardiopulmonary bypass. Surgery\| PubMed ID: 40651273	2025
Sodium-glucose Cotransporter-2 Canagliflozin's impact on cardiovascular disease in the setting of metabolic syndrome: A proteomic analysis. European journal of pharmacology\| PubMed ID: 40683440	2025

Kelsey C. Muir

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