A Primer on Incorporating Sex as a Biological Variable into the Conduct and Reporting of Basic and Clinical Research Studies

The recent move to require sex as a biological variable (SABV), which includes gender, into the reporting of research published by the American Journal of Physiology - Heart and Circulatory Physiology follows a growing, and much-needed, trend by journals. Understandably, there is concern over how to do this without adding considerable work, especially if one's primary research focus is not on elucidating sex/gender differences. The purpose of this article is to provide additional guidance and examples on how to incorporate SABV into the conduct and reporting of basic and clinical research. Using examples from our research, which includes both studies focused and not focused on sex/gender differences, we offer suggestions for how to incorporate SABV into basic and clinical research studies.

Management of Metabolic Acidosis in the Post-Cardiac Surgical Patient

The base deficit is the best way to evaluate severity of Metabolic Acidosis (MA). It indicates a value corresponding to the number of mmol/L below 24 of the measured bicarbonate concentration. Base deficit between 0 and 5 mmol/L indicates that the patient is not at risk of immediate harm. Arterial blood gases are typically measured every 2-4 hours following cardiac surgery and there is always a trend in base deficit changes to consider. Where the base deficit is diminishing, this indicates that the patient is improving, whereas when it is worsening, the opposite is true. Base deficits between 5 and 10 indicate that a serious problem is present which requires urgent correction. Where the base deficit is greater than 10, cardiac arrest may occur, and such patients require constant supervision by a doctor if active management is being pursued. Where the base deficit is persistently greater than 15, survival is extremely unlikely. This degree of acidosis is associated with widespread disruption of mitochondria at cellular level. The mitochondria often do not recover even if the precipitating cause of the MA is corrected, in which case the patient develops fatal multisystem organ failure. The management of MA in post-cardiac surgical patients is indivisibly bound up in optimizing circulatory physiology. We have not expounded on how this foundational knowledge should be applied but without it the management of MA in this patient population will be severely hampered.

Using two-dimensional ultrasound imaging to examine venous pressure

Ultrasound imaging is being used increasingly to aid in the teaching of human physiology and anatomy. Here we describe how its use can be integrated into the teaching of concepts surrounding venous circulation, specifically 1) venous valves and the muscle pump, 2) the effects of hydrostatic pressure on venous pressure, and 3) central venous pressure. The imaging procedures described are relatively simple but add a dimension that helps deliver the teaching points clearly and is enjoyable for students. They also aid in the link of basic physiology to clinical aspects of venous circulatory physiology.

CORP: Assessing author compliance with data presentation guidelines for manuscript figures

The present study was undertaken to address the concern that author compliance with American Physiological Society (APS) journal instructions to authors for data presentation in manuscript figures is inadequate. Common instances of noncompliance are omitted molecular weight markers for immunoblots and bar graphs lacking individual data points. The American Journal of Physiology-Heart and Circulatory Physiology ( AJP-Heart and Circ) editorial team designed a program to assess figure data presentation in submitted manuscripts. The intended outcome was to improve author compliance with APS data presentation guidelines and to improve overall rigor and reproducibility in articles published in AJP-Heart and Circ. The AJP-Heart and Circ team invited 37 peer reviewers to participate in a figure reviewer project (FRp). Over a period of five months, 32 first-revision manuscripts were enrolled in the FRp. Each manuscript was reviewed by the original peer reviewers and an additional figure reviewer (FR). Post-peer review, corresponding authors and FRs were surveyed for insight into their experiences. Of the 32 corresponding authors invited, 20 (63%) responded to the survey. In response to the survey, 100% of respondents stated that peer review was performed in a timely fashion despite the additional FR. When asked whether the FR experience had any effect on how one would present data in manuscript figures in future submissions, 65% of authors and 83% of FRs said yes. In addition, 63% of authors responding agreed that the overall quality of their figures was improved after revising based on FR comments. This exercise resulted in improved compliance with APS data presentation guidelines and changed attitudes among both authors and reviewers as to the need for consistent and clear data presentation in manuscript figures. NEW & NOTEWORTHY The goal of the American Journal of Physiology-Heart and Circulatory Physiology figure reviewer program was to improve author compliance with existing APS data presentation instructions for manuscript figures. The result was an improvement in compliance with these guidelines. Time from submission to final decision did not significantly increase for papers with the additional figure reviewer, and both figure reviewers and corresponding authors reported positive feedback in post-program surveys.

Adaptive immunity-driven inflammation and cardiovascular disease

The adaptive immune response has recently emerged as an important factor in a wide variety of cardiovascular disorders including atherosclerosis, hypertension, cardiac remodeling, and heart failure; however, its role is not fully understood. Since an assortment of innate responsive cells, e.g., neutrophils and monocytes/macrophages, coordinate with adaptive immunity, e.g., T cells, dendritic cells, and B cells, the temporal response and descriptions pertinent to the cellular phenotype and inflammation processes, in general, need additional investigation, clarification, and consensus particularly in cardiovascular disease. This Perspectives article reviews the contributions of 15 articles (including 7 reviews) published in the American Journal of Physiology-Heart and Circulatory Physiology in response to the Call for Papers: Adaptive Immunity in Cardiovascular Disease. Here, we summarize the crucial reported findings at the cardiac, vascular, immune, and molecular levels and discuss the translational feasibility and benefits of future prospective research into the adaptive immune response. Readers are encouraged to evaluate the data and learn from this collection of novel studies.

Extracellular matrix in cardiovascular pathophysiology

The extracellular matrix (ECM) actively participates in diverse aspects of cardiovascular development and physiology as well as during disease development and progression. ECM roles are determined by its physical and mechanical properties and by its capacity to both release bioactive signals and activate cell signaling pathways. The ECM serves as a storage depot for a wide variety of molecules released in response to injury or with aging. Indeed, there is a plethora of examples describing how cells react to or modify ECM stiffness, how cells initiate intracellular signaling pathways, and how cells respond to the ECM. This Perspectives article reviews the contributions of 21 articles published in the American Journal of Physiology-Heart and Circulatory Physiology in response to a Call for Papers on this topic. Here, we summarize the contributions of these studies focused on the cardiac and vascular ECM. We highlight the translational importance of these studies and conclude that the ECM is a critical component of both the heart and vasculature. Readers are urged to examine and learn from this special Call for Papers.

Benefits of exercise training on cardiovascular dysfunction: molecular and integrative

Exercise training has been shown to ameliorate a wide variety of cardiovascular disorders. The mechanisms by which long-term benefits of exercise training are mediated remains incomplete, despite intense research in this area. Exactly how the act of chronic exercise improves function in every tissue is unknown, but many of the cellular, molecular, and genetic mechanisms are becoming progressively clearer. This “Perspectives” article reviews the contributions of 15 articles published in the American Journal of Physiology-Heart and Circulatory Physiology in response to a Call for Papers in this area. Here, we summarize the contributions of these studies at the cardiac, vascular, immune, and molecular levels. We discuss the translational benefit of these studies and conclude that the beneficial effects of exercise training in cardiovascular disease is due to a large interplay of cellular and molecular mediators in the heart and peripheral vasculature as well as changes in neural elements that regulate blood pressure and blood flow. Readers are encouraged to evaluate and learn from this collection of novel studies.