Cardiovascular Dysfunction Following Burn Injury: What We Have Learned from Rat and Mouse Models

Abstract

Abstract:Severe burn profoundly affects organs both proximal and distal to the actual burn site. Cardiovascular dysfunction is a well-documented phenomenon that increases morbidity and mortality following a massive thermal trauma. Beginning immediately post-burn, during the ebb phase, cardiac function is severely depressed. By 48 h post-injury, cardiac function rebounds and the post-burn myocardium becomes tachycardic and hyperinflammatory. While current clinical trials are investigating a variety of drugs targeted at reducing aspects of the post-burn hypermetabolic response such as heart rate and cardiac work, there is still a paucity of knowledge regarding the underlying mechanisms that induce cardiac dysfunction in the severely burned. There are many animal models of burn injury, from rodents, to sheep or swine, but the majority of burn related cardiovascular investigations have occurred in rat and mouse models. This literature review consolidates the data supporting the prevalent role that β-adrenergic receptors play in mediating post-burn cardiac dysfunction and the idea that pharmacological modulation of this receptor family is a viable therapeutic target for resolving burn-induced cardiac deficits.

Burn-Induced Cardiac Mitochondrial Dysfunction via Interruption of the PDE5A-cGMP-PKG Pathway

“…Cardiac damage is a well-documented event that increases mortality and morbidity after severe burns [9]. Research in in vivo and in vitro models has demonstrated that poor cardiac contractility starts immediately after thermal injury, continues for approximately 36 h after burn, and resolves by 72 h after burn [9,31].…”

“…Cardiac damage is a well-documented event that increases mortality and morbidity after severe burns [9]. Research in in vivo and in vitro models has demonstrated that poor cardiac contractility starts immediately after thermal injury, continues for approximately 36 h after burn, and resolves by 72 h after burn [9,31]. In this study, we found burn-induced cardiac mitochondrial damage evidenced by disruption of mitochondrial morphology and mitochondrial superstructures, altered activity of the electron transport chain, and decreased mitochondrial oxygen consumption resulting in ATP deficiency and decreased mitochondrial antioxidant enzyme activity (MnSOD).…”

“…Current investigations indicate that the molecular mechanisms underlying burn-induced cardiac dysfunction are associated with persistent β-Adrenergic Receptors (β-ARs) stimulation, leading to increase NO levels [9]. However, little is known of the role of the NOS-NO-cGMP-PKG pathway in burn-induced myocardial dysfunction.…”

“…Burn-induced cardiodynamic derangements contribute to multiple organ system failure, sepsis, and death [4,5]. Higher total body surface area (TBSA) results in higher mortality in both human patients [6] and animals [7] due to cardiac dysfunction post burn [8][9][10].…”

Improving Research Enrollment of Severe Burn Patients

“…Most of the evidence-based practices in burn care are from very successful single centers that have perfected the research enterprise with a defined patient population, standard treatment algorithms and a consistent surgical team. 11,12 Such centers have well-established basic science, animal, and translational science labs, 13,14 perform randomized-controlled trials to study treatment interventions, 15 and spearhead multi-centered trials. 16,17 These centers have established research protocols describing the risks, benefits, alternatives, and evidence, and have the staff to provide information and resources for patients and families with questions or concerns.…”