Leading through the first wave of COVID: a Canadian action research study.

PURPOSE: This first phase of a three-phase action research project aims to define leadership practices that should be used during and after the pandemic to re-imagine and rebuild the health and social care system. Specifically, the objectives were to determine what effective leadership practices Canadian health leaders have used through the first wave of the COVID-19 pandemic, to explore how these differ from pre-crisis practices; and to identify what leadership practices might be leveraged to create the desired health and care systems of the future. DESIGN/METHODOLOGY/APPROACH: The authors used an action research methodology. In the first phase, reported here, the authors conducted one-on-one, virtual interviews with 18 health leaders from across Canada and across leadership roles. Data were analyzed using grounded theory methodology. FINDINGS: Five key practices emerged from the data, within the core dimension of disrupting entrenched structures and leadership practices. These were, namely, responding to more complex emotions in self and others. Future practice identified to create more psychologically supportive workplaces. Agile and adaptive leadership. Future practice should allow leaders to move systemic change forward more quickly. Integrating diverse perspectives, within and across organizations, leveling hierarchies through bringing together a variety of perspectives in the decision-making process and engaging people more broadly in the co-creation of strategies. Applying existing leadership capabilities and experience. Future practice should develop and expand mentorship to support early career leadership. Communication was increased to build credibility and trust in response to changing and often contradictory emerging evidence and messaging. Future practice should increase communication. RESEARCH LIMITATIONS/IMPLICATIONS: The project was limited to health leaders in Canada and did not represent all provinces/territories. Participants were recruited through the leadership networks, while diverse, were not demographically representative. All interviews were conducted in English; in the second phase of the study, the authors will recruit a larger and more diverse sample and conduct interviews in both English and French. As the interviews took place during the early stages of the pandemic, it may be that health leaders' views of what may be required to re-define future health systems may change as the crisis shifts over time. PRACTICAL IMPLICATIONS: The sponsoring organization of this research - the Canadian Health Leadership Network and each of its individual member partners - will mobilize knowledge from this research, and subsequent phases, to inform processes for leadership development and, succession planning across, the Canadian health system, particularly those attributes unique to a context of crisis management but also necessary in post-crisis recovery. SOCIAL IMPLICATIONS: This research has shown that there is an immediate need to develop innovative and influential leadership action - commensurate with its findings - to supporting the evolution of the Canadian health system, the emotional well-being of the health-care workforce, the mental health of the population and challenges inherent in structural inequities across health and health care that discriminate against certain populations. ORIGINALITY/VALUE: An interdisciplinary group of health researchers and decision-makers from across Canada who came together rapidly to examine leadership practices during COVID-19's first wave using action research study design.

A tale of two frameworks: charting a path to lifelong learning for physician leaders through CanMEDS and LEADS.

PURPOSE: The purpose of this paper was to determine the complementarity between the Canadian Medical Education Directions for Specialists (CanMEDS) physician competency and LEADS leadership capability frameworks from three perspectives: epistemological, philosophical and pragmatic. Based on those findings, the authors propose how the frameworks collectively layout pathways of lifelong learning for physician leadership. DESIGN/METHODOLOGY/APPROACH: Using a qualitative approach combining critical discourse analysis with a modified Delphi, the authors examined "How complementary the CanMEDS and LEADS frameworks are in guiding physician leadership development and practice" with the following sub-questions: What are the similarities and differences between CanMEDS and LEADS from: An epistemological and philosophical perspective? The perspective of guiding physician leadership training and practice? How can CanMEDS and LEADS guide physician leadership development from medical school to retirement? FINDINGS: Similarities and differences exist between the two frameworks from philosophical and epistemological perspectives with significant complementarity. Both frameworks are founded on a caring ethos and value physician leadership - CanMEDS (for physicians) and LEADS (physicians as one of many professions) define leadership similarly. The frameworks share beliefs in the function of leadership, embrace a belief in distributed leadership, and although having some philosophical differences, have a shared purpose (preparing for changing health systems). Practically, the frameworks are mutually supportive, addressing leadership action in different contexts and where there is overlap, complement one another in intent and purpose. ORIGINALITY/VALUE: To the best of the authors' knowledge, this is the first paper to map the CanMEDS (physician competency) and LEADS (leadership capabilities) frameworks. By determining the complementarity between the two, synergies can be used to influence physician leadership capacity needed for today and the future.

The relevance of the LEADS framework during the COVID-19 pandemic.

COVID-19 has created a unique context for the practice of leadership in healthcare. Given the significant use of the LEADS in a Caring Environment capabilities framework (LEADS) in Canada's health system, it is important to document the relevancy of LEADS. The authors reviewed literature, conducted research, and reflected on their own experience to identify leadership practices during the pandemic and related them to LEADS. Findings are presented in three sections: Hindsight (before), Insight (during), and Foresight (post). We profile the issue of improving long-term Care to provide an example of how LEADS can be applied in crisis times. Our analysis suggests that while LEADS appears to specify the leadership capabilities needed, it requires adaptation to context. The vision Canada has for healthcare will dictate how LEADS will be used as a guide to leadership practice in the current context or to shape a bolder vision of healthcare's future.

Pathway to professionalizing health leadership in Canada: The two faces of Janus.

This article looks at the current state of health leadership in terms of expectations for professionalism: controlled entry, exit, and licensure/certification; a social contract to provide public services for the good of Canadians; and a unique body of knowledge and practice generally accepted. Looking to the future, and using the same three criteria, a compelling case for pursuing the professionalization of health leadership is made using LEADS as a roadmap. The article also outlines how to realize the professionalization of health leadership in Canada and why it is important to do so.

Enabling physicians to lead: Canada's LEADS framework.

Purpose The purpose of this paper is to provide a case study demonstrating that LEADS in a Caring Environment Capabilities Framework in Canada can assist physicians to be partners in leading health reform. Design/methodology/approach A descriptive case-based approach was followed, relying on existing documents, research papers and peer-reviewed articles, to substantiate the effect of LEADS on physician leadership in Canada. Findings The Canadian LEADS framework enables physicians to lead by providing them with access to best practices of leadership, acting as an antidote to fragmented leadership practice, setting standards for development and accountability and providing opportunities for efficient and effective system-wide leadership development and change. Research limitations/implications A formal systematic review of the literature was not conducted. Findings can only be generalized to other cases if the reader sees contextual similarities between the present study context and the other case's context. Practical implications This case demonstrates that national leadership frameworks have a role in facilitating physician leadership. Other national jurisdictions may wish to explore the Canadian case to determine how to use a common leadership language to engage physicians in health reform. Social implications Leadership is a key component of health reform. A common language and set of standards (LEADS) that can engage physicians will benefit patients and citizens in Canada. Originality/value This national case study shows how a nationally endorsed leadership framework such as LEADS can facilitate better physician leadership for health reform.

Return on investment in healthcare leadership development programs.

Purpose Strong leadership has been shown to foster change, including loyalty, improved performance and decreased error rates, but there is a dearth of evidence on effectiveness of leadership development programs. To ensure a return on the huge investments made, evidence-based approaches are needed to assess the impact of leadership on health-care establishments. As a part of a pan-Canadian initiative to design an effective evaluative instrument, the purpose of this paper was to identify and summarize evidence on health-care outcomes/return on investment (ROI) indicators and metrics associated with leadership quality, leadership development programs and existing evaluative instruments. Design/methodology/approach The authors performed a scoping review using the Arksey and O'Malley framework, searching eight databases from 2006 through June 2016. Findings Of 11,868 citations screened, the authors included 223 studies reporting on health-care outcomes/ROI indicators and metrics associated with leadership quality (73 studies), leadership development programs (138 studies) and existing evaluative instruments (12 studies). The extracted ROI indicators and metrics have been summarized in detail. Originality/value This review provides a snapshot in time of the current evidence on ROI indicators and metrics associated with leadership. Summarized ROI indicators and metrics can be used to design an effective evaluative instrument to assess the impact of leadership on health-care organizations.

Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.

BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

In their own words: describing Canadian physician leadership.

Purpose This is the first study to compile statistical data to describe the functions and responsibilities of physicians in formal and informal leadership roles in the Canadian health system. This mixed-methods research study offers baseline data relative to this purpose, and also describes physician leaders' views on fundamental aspects of their leadership responsibility. Design/methodology/approach A survey with both quantitative and qualitative fields yielded 689 valid responses from physician leaders. Data from the survey were utilized in the development of a semi-structured interview guide; 15 physician leaders were interviewed. Findings A profile of Canadian physician leadership has been compiled, including demographics; an outline of roles, responsibilities, time commitments and related compensation; and personal factors that support, engage and deter physicians when considering taking on leadership roles. The role of health-care organizations in encouraging and supporting physician leadership is explicated. Practical implications The baseline data on Canadian physician leaders create the opportunity to determine potential steps for improving the state of physician leadership in Canada; and health-care organizations are provided with a wealth of information on how to encourage and support physician leaders. Using the data as a benchmark, comparisons can also be made with physician leadership as practiced in other nations. Originality/value There are no other research studies available that provide the depth and breadth of detail on Canadian physician leadership, and the embedded recommendations to health-care organizations are informed by this in-depth knowledge.

Pretreatment with an intravenous lipid emulsion increases plasma eicosapentanoic acid and downregulates leukotriene b4, procalcitonin, and lymphocyte concentrations after open heart surgery in infants.

BACKGROUND: The effect of providing a lipid emulsion containing medium-chain triglyceride (MCT), soybean oil, and fish oil in critically ill infants is not widely studied. This study investigated lipid emulsion effects on plasma phospholipids and immune biomarkers. MATERIALS AND METHODS: Thirty-two infants undergoing cardiopulmonary bypass (CPB) and dependent on parenteral nutrition (PN) were randomized to receive either soybean oil (control, n = 16) or a 50:40:10 mixture of MCT, soybean oil, and fish oil (treatment, n = 16). PN was administered for 3 days preoperatively and 10 days postoperatively. Fatty acids, procalcitonin (PCT), leukotriene B4 (LTB4), and lymphocytes were quantified at baseline, before surgery, and days 1, 7 and 10 after surgery. RESULTS: PCT was significantly lower in the treatment vs control group 1 day postoperatively (P = .01). The treatment group exhibited a lower ω-6 to ω-3 ratio (P = .0001) and a higher ω-3 concentration at all postoperative study periods (P = .001). Treatment resulted in higher (P < .05) plasma phospholipid eicosapentaenoic acid (EPA) on days 7 and 10, while α-linolenic acid, arachidonic acid, and docosahexaenoic acid remained constant. An increase in plasma phospholipid EPA concentration was associated with a decrease in plasma phospholipid LTB4 concentration (P < .05). On postoperative day 10, treatment infants with high Pediatric Risk of Mortality III scores exhibited a 45% lower lymphocyte concentration (P < .05). CONCLUSION: These findings suggest that treating infants undergoing CPB with a lipid emulsion containing ω-3 improves fatty acid status and results in a lower inflammatory response after surgery. Overall, this alternative ω-3-enriched lipid emulsion may benefit clinical outcomes of critically ill infants after cardiac surgery.

Low energy intakes are associated with adverse outcomes in infants after open heart surgery.

BACKGROUND: Infants with congenital heart lesions who undergo open heart surgery may experience physiologic and metabolic stress in the postoperative period, leading to altered metabolism and hypercatabolism. The purpose of this study was to determine the relationship between energy intake and hospital outcomes during the first 10 days following neonatal open heart surgery. MATERIALS AND METHODS: A post hoc analysis of all patients in a prospective randomized controlled trial was performed. Nutrition intake and hospital outcomes were assessed in 32 infants (40 ± 2.2 weeks, 3.4 ± 0.5 kg) in the neonatal and pediatric intensive care units. Infants received parenteral nutrition (PN) for 1-4 days before and 10 days after open heart surgery. Infants were separated into those who received a cumulative energy intake of <689 kcal (average 63 kcal/kg/d) and those who received an intake ≥689 kcal during postoperative days 0-10. RESULTS: Lower energy intake was associated with a significantly increased duration of artificial ventilation (5 ± 1.2 days), time to chest closure (1.4 ± 0.5 days), time in intensive care (5 ± 1.8 days), and stay in the hospital (25 ± 6.4 days). Lower energy intake was also associated with a significant increase in the length of time infants required PN (8 ± 2.9 days) and longer time to achieve full enteral intake of 100 mL/kg/d (7 ± 2.2 days) and before enteral feeds could be initiated (5 ± 1.5 days). CONCLUSIONS: Providing <63 kcal/kg/d to infants after open heart surgery was associated with adverse pediatric intensive care outcomes.

Pre-treatment with an intravenous lipid emulsion containing fish oil (eicosapentaenoic and docosahexaenoic acid) decreases inflammatory markers after open-heart surgery in infants: a randomized, controlled trial.

BACKGROUND & AIMS: This study assessed the effects of administering a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid before and after open-heart surgery on cytokine production and length of hospital stay in infants. METHODS: Thirty-two infants (40 ± 2.3 weeks gestational age; 10.6 days at time of surgery) undergoing open-heart surgery with cardiopulmonary bypass were randomized to receive an intravenous lipid emulsion with (treatment) or without (control) eicosapentaenoic and docosahexaenoic acid in this prospective, randomized, double-blind, controlled trial. RESULTS: Mean plasma TNF-α concentration was significantly (p = 0.003) lower in the treatment (5.9 pg/mL) compared to the control group (14.8 pg/mL). In infants without sepsis, plasma TNF-α did not differ according to treatment, however when sepsis developed, mean plasma TNF-α was 21.1 pg/mL and 1.5 pg/mL (p = 0.0007) in control and treatment groups, respectively. Plasma TNF-α was positively correlated with length of hospital stay in the control group (p = 0.01), and negatively correlated with length of stay in the treatment group (p = 0.004), with a significant time by treatment interaction (p = 0.02). CONCLUSIONS: Providing a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid reduces TNF-α concentrations in infants undergoing open-heart surgery. Lipid emulsions containing eicosapentaenoic and docosahexaenoic acid may ameliorate the inflammatory response among critically ill infants.

Developing nurse/parent relationships in the NICU through negotiated partnership.

OBJECTIVE: To explore parents' experience and satisfaction with care in the Neonatal Intensive Care Unit (NICU). DESIGN: Qualitative design using an interpretive description method. SETTING: A tertiary-level care 69-bed NICU. PARTICIPANTS: Ten parents (nine mothers and one father) were interviewed. METHOD: Parents were interviewed in person or via telephone, either following or close to discharge. Interviews were recorded, transcribed, and then analyzed using an evolving coding guide. RESULTS: All parents indicated that the relationship they developed with the bedside nurse was the most significant factor affecting their satisfaction with their NICU experience. All parents described nursing actions of perceptive engagement, cautious guidance, and subtle presence, which facilitated the development of this relationship. Further analysis of the data revealed that parents portrayed nurses in ideal nurse/parent interactions as fulfilling the roles of teacher, guardian, and facilitator. CONCLUSION: Developing a collaborative and effective nurse/parent relationship is the most significant factor affecting parents' satisfaction with their NICU experience. Providing nursing care in a manner that optimizes consistency and continuity of care facilitates the ability of both parties to develop this relationship.

Effect of feeding a formula supplemented with long-chain polyunsaturated fatty acids for 14 weeks improves the ex vivo response to a mitogen and reduces the response to a soy protein in infants at low risk for allergy.

BACKGROUND AND OBJECTIVE: Feeding long-chain polyunsaturated fatty acids (LCP) influences immunity in adults; however, less is known about their effect during development. The aim of the study was to determine the effect of feeding LCP on immunity in healthy infants during the first 4 months of life. PATIENTS AND METHODS: Formula-fed infants were randomized at

Gangliosides protect bowel in an infant model of necrotizing enterocolitis by suppressing proinflammatory signals.

OBJECTIVES: Necrotizing enterocolitis (NEC) has high morbidity in premature infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors associated with NEC, whereas feeding human milk is protective. Vasoactive and inflammatory mediators in NEC remain elusive. Gangliosides are found in human milk and enterocyte membranes. An infant bowel model of NEC was developed to test the hypothesis that gangliosides modulate the inflammatory response to infection and hypoxia. PATIENTS AND METHODS: Viable, noninflamed bowel was obtained from 9 infants between 26 and 40 weeks' gestational age. Infant bowel was treated in culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the presence or absence of preexposure to gangliosides. Bowel necrosis and production of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and proinflammatory cytokines were measured. RESULTS: Ganglioside preexposure reduced bowel necrosis and endothelin-1 production in response to LPS. Gangliosides suppressed infant bowel production of nitric oxide, leukotriene B4, prostaglandin E2, hydrogen peroxide, interleukin-1beta, interleukin-6, and interleukin-8 in response to LPS exposure and hypoxia. CONCLUSIONS: A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression.

Effects of N-acetylcysteine on intestinal reoxygenation injury in hypoxic newborn piglets resuscitated with 100% oxygen.

BACKGROUND: Neonatal asphyxia may lead to the development of ischemia-reperfusion induced intestinal injury, which is related to oxygen-derived free radical production. N-Acetylcysteine (NAC) is a thiol-containing antioxidant which increases intracellular stores of glutathione. OBJECTIVES: Using a swine model of neonatal hypoxia-reoxygenation, we examined whether administration of NAC after resuscitation improved intestinal perfusion and reduced intestinal damage. METHODS: Twenty-four piglets (1-4 days old, 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of superior mesenteric arterial flow and oxygen delivery. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control and NAC treatment (150 mg/kg i.v. at 0 or 10 min of reoxygenation followed by infusion 100 mg/kg/h) groups. During hypoxia-reoxygenation, intestinal tissue glutathione content, caspase-3 activity and reoxygenation injury were examined. RESULTS: After 2 h of hypoxia, piglets were acidotic and hypotensive, with significantly depressed blood flow and oxygen delivery to the small intestine. Upon reoxygenation, hemodynamics recovered as did oxygen supply to the small intestine. After 4 h of reoxygenation, the NAC treatment improved mesenteric flow and oxygen delivery. Despite reducing the increase in caspase-3 activities after hypoxia-reoxygenation by NAC treatment, no significant differences in the glutathione content and histological grading of ileal injury were found among the experimental groups. CONCLUSIONS: In newborn piglets with hypoxia-reoxygenation, NAC may improve mesenteric blood flow and oxygen delivery without significant effect on tissue glutathione content. The protective role of NAC in the reoxygenated intestine after severe hypoxia warrants further investigation.

Feeding a formula supplemented with long chain polyunsaturated fatty acids modifies the "ex vivo" cytokine responses to food proteins in infants at low risk for allergy.

Long chain polyunsaturates (LCP) status during the early neonatal period is associated with a reduced risk of atopic symptoms and later allergies. In this study, we characterized the immune response of low-risk, term, formula-fed infants randomized at

Necrotizing enterocolitis: a multifactorial disease with no cure.

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Effect of providing a formula supplemented with long-chain polyunsaturated fatty acids on immunity in full-term neonates.

To determine the effect of feeding formula containing long-chain PUFA (LCP) on immune function, healthy term infants were randomised at age 2 weeks to either a standard term formula (Formula; n 14) or the same formula supplemented with the LCP 20 : 4n-6 and 22 : 6n-3 (Formula+LCP; n 16). Peripheral blood was collected at 2 and 6 weeks to measure immune cell response (the rate of [3H]thymidine uptake and cytokine production after stimulation with phytohaemagglutinin (PHA)). Compared with cells from infants receiving only human milk (HM), the rate of [3H]thymidine uptake in response to PHA, but not IL-2 production, was lower for Formula+LCP infants (P < 0.05). Compared with HM-fed infants, Formula-fed infants (but not Formula+LCP infants) produced more TNF-alpha (unstimulated) and had a fewer CD3+CD44+ cells before stimulation and fewer CD11c+ cells post-stimulation (P < 0.05). However, compared with Formula-fed infants, the Formula+LCP infants had an immune cell distribution (higher percentage CD3+CD44+ and CD4+CD28+ cells) and cytokine profile (lower production of TNF-alpha post-stimulation) that did not differ from HM infants. Additionally, it was found that feeding infants formula during the first 10 d of life influenced immune function. These infants had a higher percentage of CD3+, CD4+CD28+, and lower percentage of CD14+ cells and produced more TNF-alpha and interferon-gamma after PHA stimulation than HM-fed infants (P < 0.05). These results demonstrate that early diet influences both the presence of specific cell types and function of infant blood immune cells. Since many diseases have a strong immunological component, these immune changes may be of physiological importance to the developing infant.

N-acetylcysteine improves the hemodynamics and oxidative stress in hypoxic newborn pigs reoxygenated with 100% oxygen.

Neonatal asphyxia may lead to cardiac and renal complications perhaps mediated by oxygen free radicals. Using a model of neonatal hypoxia-reoxygenation, we tested the hypothesis that N-acetylcysteine (NAC) would improve cardiac function and renal blood flow. Eighteen piglets (aged 1-4 days old, weighing 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of pulmonary and renal artery flow (cardiac index [CI] and renal artery flow index [RAFI], respectively) and mean blood pressure. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control, and NAC treatment (i.v. bolus of 150 mg/kg given at 10 min of reoxygenation followed by 100 mg/kg per h infusion) groups. Myocardial and renal tissue glutathione content and lipid hydroperoxide levels were assayed, and histology was examined. After 2 h of hypoxia, all animals were acidotic (pH 6.96 +/- 0.04) and in cardiogenic shock with depressed renal blood flow. Upon reoxygenation, CI and RAFI increased but gradually deteriorated later. The NAC treatment prevented the decreased CI, stroke volume, mean blood pressure, systemic oxygen delivery, RAFI, and renal oxygen delivery at 2 to 4 h of reoxygenation observed in hypoxic controls (versus shams, all P < 0.05). The myocardial and renal tissue glutathione content was significantly higher in the NAC treatment group (versus controls). The CI and RAFI at 4 h of reoxygenation correlated with the tissue glutathione redox ratio (r = 0.5 and 0.6, respectively, P < 0.05). There were no significant differences in heart rate, pulmonary artery pressure, systemic oxygen uptake, and tissue lipid hydroperoxide levels between groups. No histologic injury was found in the heart or kidney. In this porcine model of neonatal hypoxia and 100% reoxygenation, NAC improved cardiac function and renal perfusion, with improved tissue glutathione content.