A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular (LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury.

Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the ß-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.

Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture.

Decorin (DCN) is a small-leucine rich proteoglycan that mediates collagen fibrillogenesis, organization, and tensile strength. Adventitial DCN is reduced in abdominal aortic aneurysm (AAA) resulting in vessel wall instability thereby predisposing the vessel to rupture. Recombinant DCN fusion protein CAR-DCN was engineered with an extended C-terminus comprised of CAR homing peptide that recognizes inflamed blood vessels and penetrates deep into the vessel wall. In the present study, the role of systemically-administered CAR-DCN in AAA progression and rupture was assessed in a murine model. Apolipoprotein E knockout (ApoE-KO) mice were infused with angiotensin II (AngII) for 28 days to induce AAA formation. CAR-DCN or vehicle was administrated systemically until day 15. Mortality due to AAA rupture was significantly reduced in CAR-DCN-treated mice compared to controls. Although the prevalence of AAA was similar between vehicle and CAR-DCN groups, the severity of AAA in the CAR-DCN group was significantly reduced. Histological analysis revealed that CAR-DCN treatment significantly increased DCN and collagen levels within the aortic wall as compared to vehicle controls. Taken together, these results suggest that CAR-DCN treatment attenuates the formation and rupture of Ang II-induced AAA in mice by reinforcing the aortic wall.

Perioperative factors predicting poor outcome in elderly patients following emergency general surgery: a multivariate regression analysis.

BACKGROUND: Older adults (≥ 65 yr) are the fastest growing population and are presenting in increasing numbers for acute surgical care. Emergency surgery is frequently life threatening for older patients. Our objective was to identify predictors of mortality and poor outcome among elderly patients undergoing emergency general surgery. METHODS: We conducted a retrospective cohort study of patients aged 65-80 years undergoing emergency general surgery between 2009 and 2010 at a tertiary care centre. Demographics, comorbidities, in-hospital complications, mortality and disposition characteristics of patients were collected. Logistic regression analysis was used to identify covariate-adjusted predictors of in-hospital mortality and discharge of patients home. RESULTS: Our analysis included 257 patients with a mean age of 72 years; 52% were men. In-hospital mortality was 12%. Mortality was associated with patients who had higher American Society of Anesthesiologists (ASA) class (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.43-10.33, p = 0.008) and in-hospital complications (OR 1.93, 95% CI 1.32-2.83, p = 0.001). Nearly two-thirds of patients discharged home were younger (OR 0.92, 95% CI 0.85-0.99, p = 0.036), had lower ASA class (OR 0.45, 95% CI 0.27-0.74, p = 0.002) and fewer in-hospital complications (OR 0.69, 95% CI 0.53-0.90, p = 0.007). CONCLUSION: American Society of Anesthesiologists class and in-hospital complications are perioperative predictors of mortality and disposition in the older surgical population. Understanding the predictors of poor outcome and the importance of preventing in-hospital complications in older patients will have important clinical utility in terms of preoperative counselling, improving health care and discharging patients home.

CONTEXTE: La population qui connaît la croissance la plus rapide est celle des adultes âgés (≥ 65 ans). Ces personnes nécessitent un nombre croissant d'interventions chirurgicales urgentes. Or, la chirurgie d'urgence comporte souvent un risque de décès pour les patients âgés. Notre objectif était d'identifier les prédicteurs de la mortalité et d'une issue négative chez les patients âgés soumis à une chirurgie générale d'urgence. MÉTHODES: Nous avons procédé à une étude de cohorte rétrospective chez des patients de 65 à 80 ans soumis à une chirurgie générale d'urgence entre 2009 et 2010 dans un centre de soins tertiaires. Nous avons recueilli les données démographiques, les comorbidités, les complications perhospitalières, la mortalité et les détails sur l'état général de santé des patients. Nous avons utilisé l'analyse de régression logistique afin de dégager les prédicteurs ajustés en fonction des covariables pour la mortalité perhospitalière et les congés hospitaliers des patients vers leur domicile. RÉSULTANTS: Notre analyse a regroupé 257 patients âgés en moyenne de 72 ans; 52 % étaient des hommes. La mortalité perhospitalière a été de 12 %. La mortalité a été associée à des patients qui se classaient dans une catégorie ASA (American Society of Anesthesiologists) plus élevée (rapport des cotes [RC] 3,85, intervalle de confiance [IC] de 95 % 1,43­10,33, p = 0,008) et présentaient plus de complications perhospitalières (RC 1,93, IC de 95 % 1,32­2,83, p = 0,001). Près des deux tiers des patients qui ont reçu leur congé pour retourner à la maison étaient plus jeunes (RC 0,92, IC de 95 % 0,85­0,99, p = 0,036), se classaient dans une catégorie ASA moins élevée (RC 0,45, IC de 95 % 0,27­ 0,74, p = 0,002) et avaient connu moins de complications perhospitalières (RC 0,69, IC de 95 % 0,53­0,90, p = 0,007). CONCLUSION: La catégorie ASA et les complications perhospitalières sont des prédicteurs périopératoires de mortalité et d'état général de santé dans la population âgée soumise à la chirurgie. Comprendre les prédicteurs d'une issue négative et l'importance de prévenir les complications perhospitalières chez les patients âgés aura une importante utilité clinique pour les consultations préopératoires, l'amélioration des soins de santé et le retour des patients à la maison.