Mechanisms of Volatile Anesthetic-Induced Myocardial Protection

Volatile anesthetics protect myocardium against reversible and irreversible ischemic injury. Experimental evidence from several in vitro and in vivo animal models demonstrates that volatile agents enhance the recovery of stunned myocardium and reduce the size of myocardial infarction after brief or prolonged coronary artery occlusion and reperfusion, respectively. This protective effect persists after the anesthetic has been discontinued, a phenomenon known as anesthetic-induced preconditioning (APC). Recent clinical data also demonstrates evidence of APC in patients during cardiac surgery. Thus, administration of volatile anesthetics may represent a novel therapeutic approach that reduces morbidity and mortality associated with perioperative myocardial ischemia and infarction. The mechanisms responsible for APC appear to be similar to those implicated in ischemic preconditioning, but nonetheless have subtle differences. Accumulating evidence indicates that APC is characterized by complex signal transduction pathways that may include adenosine receptors, G proteins, protein kinase C, reactive oxygen species, and sarcolemmal or mitochondrial KATP channels. Opioid analgesics may further enhance APC as well. This article will review recent advances in the understanding of mechanisms responsible for volatile anesthetic-induced myocardial protection

Zatebradine, a specific bradycardic agent, enhances the positive inotropic actions of dobutamine in ischemic myocardium

AbstractObjectives. This investigation determined whether attenuation of the tachycardia produced by dobutamine administration would improve perfusion and function distal to a severe coronary artery stenosis.Background. Tachycardia adversely affects perfusion and function distal to a coronary artery stenosis. It is not known whether a specific bradycardic agent can improve blood flow and function in an ischemic zone during administration of dobutamine.Methods. The effects of dobutamine (2, 5 and 10 μg/kg body weight per min) alone and in combination with zatebradine (0.5 mg/kg), a specific bradycardic agent, on hemodynamic status, segment shortening (ultrasound length transducers) and myocardial perfusion (microspheres) were studied in anesthetized dogs with severe left circumflex coronary artery stenosis.Results. A 50% reduction in left circumflex coronary artery blood flow (58 ± 4 to 29 ± 2 ml/min [mean value ± SEM]) produced a decrease in systolic shortening in the ischemic zone. Only a dose of dobutamine that did not elevate heart rate (2 μg/kg per min) produced an increase in segment shortening in the ischemic zone. High doses of dobutamine (10 μ/kg per min) caused an increase in heart rate without improvement in function and a reduction in the subendocardial/subepicardial flow ratio (0.74 ± 0.06 to 0.48 ± 0.05). Zatebradine administered in the presence of dobutamine caused a decrease in heart rate, an increase in subendocardial/subepicardial blood flow ratio (0.48 ± 0.05 to 0.78 ± 0.09) and allowed an increase in ischemic zone segment shortening. When normalized for changes in heart rate, ischemic zone subendocardial flow increased by 123 ± 41% (0.39 ± 0.09 to 0.71 ± 0.12 ml/100 g per beat). Atrial pacing abolished the effects of zatebradine.Conclusions. The present data suggest that the perfusion-contraction matching that accompanies a decrease in heart rate results in enhancement of inotropic stimulation of an ischemic zone. The actions of zatebradine are related to an increase in subendocardial blood flow per beat that allows improvement of regional contractile function

Valuation of Country Food in Nunavut Based on Energy and Protein Replacement

Communicating value across the pluralities of Indigenous Peoples’ food systems requires attention to economy and environment, food and wildlife, and the health of the people and that of the land. Valuation of distinct entities is always difficult but often essential to describe collective wealth and well-being, to quantify trade-offs, and to consider compensation when one is compromised for another. Here we estimate the replacement value of Nunavut country food by combining information on the amount and nutritional composition of harvested country food with the nutritional content and local price of store-bought food. Comparing the five-year average of energy and protein available in reported harvest to recommended dietary allowances indicates that 17 of 21 Nunavut communities harvest enough country food to satisfy the protein requirements of all community members. Nunavut’s country food system annually harvests five million kg of protein-rich food from across the territory, which would cost $198 million to purchase as store-bought protein, with a replacement value between$13.19 and $39.67 per kg depending on energy versus protein replacement and the inclusion versus exclusion of store-bought food subsidies. These valuations are higher than most previous estimates of local food value because they are more reflective of the energy and nutrient richness of country food and the high price of store-bought food in northern communities. The country food system is priceless in many, profound ways; better awareness of its energy and protein cost of replacement, together with the breadth of its nutritional and cultural value, may help to ensure local food systems are prioritized in northern food security and economic development initiatives. La communication de la valeur à travers les pluralités des systèmes alimentaires des peuples autochtones doit tenir compte de l’économie et de l’environnement, de l’alimentation et de la faune, de la santé des gens et de celle de la terre. L’évaluation d’entités distinctes est toujours difficile, mais souvent essentielle pour décrire la richesse et le bien-être collectifs, pour quantifier les concessions et pour considérer une compensation lorsqu’un système est compromis en raison d’un autre. Dans cet article, nous estimons la valeur de remplacement de la nourriture traditionnelle du Nunavut en combinant des données sur la quantité et la composition nutritionnelle des aliments récoltés sur le terroir, ainsi que sur le contenu nutritionnel et le prix local de la nourriture achetée en magasin. La comparaison de la moyenne quinquennale des données en valeur énergétique et protéique provenant des récoltes déclarées aux apports nutritionnels recommandés permet de constater que 17 des 21 collectivités du Nunavut récoltent suffisamment de nourriture traditionnelle pour satisfaire aux besoins en protéines de tous les membres des collectivités. Annuellement, le système alimentaire traditionnel du Nunavut donne lieu à des récoltes de cinq millions de kilogrammes de nourriture riche en protéines à l’échelle du territoire, ce qui représenterait des achats d’aliments protéinés en magasin d’une valeur de 198 millions de dollars, moyennant une valeur de remplacement s’échelonnant entre 13,19$ et 39,67 $ le kilogramme, selon que le remplacement est calculé en fonction de la valeur énergétique ou protéique, et avec inclusion ou exclusion des subventions au titre de la nourriture achetée en magasin. Ces évaluations sont plus élevées que la plupart des estimations antérieures de la valeur de la nourriture locale parce qu’elles tiennent davantage compte de la valeur énergétique et de la richesse en nutriments de la nourriture traditionnelle ainsi que du prix élevé de la nourriture achetée en magasin dans les collectivités nordiques. À bien des égards importants, le système alimentaire traditionnel a une valeur inestimable. Le fait de prendre davantage conscience du coût de remplacement de la valeur énergétique et protéique des aliments, en plus de l’ampleur de la valeur culturelle et nutritionnelle du système, pourrait aider à faire en sorte que les systèmes alimentaires locaux soient priorisés par les initiatives de sécurité alimentaire et de développement économique dans le Nord.

Microfocal X-Ray Computed Tomography Post-Processing Operations for Optimizing Reconstruction Volumes of Stented Arteries During 3D Computational Fluid Dynamics Modeling

Restenosis caused by neointimal hyperplasia (NH) remains an important clinical problem after stent implantation. Restenosis varies with stent geometry, and idealized computational fluid dynamics (CFD) models have indicated that geometric properties of the implanted stent may differentially influence NH. However, 3D studies capturing the in vivo flow domain within stented vessels have not been conducted at a resolution sufficient to detect subtle alterations in vascular geometry caused by the stent and the subsequent temporal development of NH. We present the details and limitations of a series of post-processing operations used in conjunction with microfocal X-ray CT imaging and reconstruction to generate geometrically accurate flow domains within the localized region of a stent several weeks after implantation. Microfocal X-ray CT reconstruction volumes were subjected to an automated program to perform arterial thresholding, spatial orientation, and surface smoothing of stented and unstented rabbit iliac arteries several weeks after antegrade implantation. A transfer function was obtained for the current post-processing methodology containing reconstructed 16 mm stents implanted into rabbit iliac arteries for up to 21 days after implantation and resolved at circumferential and axial resolutions of 32 and 50 μm, respectively. The results indicate that the techniques presented are sufficient to resolve distributions of WSS with 80% accuracy in segments containing 16 surface perturbations over a 16 mm stented region. These methods will be used to test the hypothesis that reductions in normalized wall shear stress (WSS) and increases in the spatial disparity of WSS immediately after stent implantation may spatially correlate with the temporal development of NH within the stented region

Cash Economy and Store-Bought Food Biases in Food Security Assessments of Inuit Nunangat

Researchers, community organisations, and Inuit leaders increasingly question the suitability of methods to assess the prevalence of food insecurity in Inuit Nunangat (the Inuit homeland in Canada). Of particular contention is the United States Department of Agriculture’s (USDA) Household Food Security Survey Module (HFSSM), applied in modified form as part of Health Canada’s nationwide Canadian Community Health (CCHS) and Aboriginal Peoples Surveys. The 18-question HFSSM is the primary survey tool used by the Government of Canada to assess food security prevalence, yet the Module asks only about the affordability of store-bought foods (also termed ‘market foods’ elsewhere in literature) when collecting data to designate food security status. This is despite communities in Inuit Nunangat having complex ‘dual’ or ‘mixed’ food systems and foodways: relying on foods harvested from ancestral lands (country foods) in combination with store-bought foods to sustain mixed cash-subsistence economies and diets. Sourcing country foods requires money for the purchase of equipment and machinery. However, they also have numerous access and availability criteria dictated by non-financial factors. In this paper, we explore the problem of the monetary bias (the focus on an individual or household’s ability to purchase foods) in the HFSSM and discuss the knock-on effects of using monetary metrics as the sole means of measuring and monitoring food security in dual food environments. We contend that relying on monetary access as a measure presents an incomplete picture of the reality of food insecurity in Inuit Nunangat. Presently, there is little consideration of the nuance of social norms and cultural values that govern dual food systems or the importance of less tangible non-financial factors that might affect food access (e.g. knowledge of where and how to harvest and maintain machinery, suitable environmental conditions for travel, conducive harvest regulations, social relationships, and ecological stability). Ultimately, this contributes to restricted policy-level understandings of what it means to ensure stable, culturally adequate, and just food systems, and limits self-determination in northern food environments

Cardioprotection by Glucose-Insulin-Potassium: Dependence on K\u3csub\u3eATP\u3c/sub\u3e Channel Opening and Blood Glucose Concentration Before Ischemia

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent K+ (KATP) channel activation and is abolished by hyperglycemia before the ischemia. Dogs were subjected to a 60-min coronary artery occlusion and 3-h reperfusion in the absence or presence of GIK (25% dextrose; 50 IU insulin/l; 80 mM/l KCl infused at 1.5 ml·kg−1·h−1) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of KATP channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood glucose (BG) concentrations to 300 or 600 mg/dl or experimental diabetes (alloxan/streptozotocin). Infarct size (IS) was 29 ± 2% of the area at risk in control experiments. GIK decreased (P \u3c 0.05) IS when administered beginning 5 min before reperfusion. This protective action was independent of BG (13 ± 2 and 12 ± 2% of area at risk; BG = 80 or 600 mg/dl, respectively) but was abolished in dogs receiving glyburide (30 ± 4%), hyperglycemia before ischemia (27 ± 4%), or diabetes (25 ± 3%). IS was unchanged by GIK when administered before ischemia independent of BG (31 ± 3, 27 ± 2, and 35 ± 3%; BG = 80, 300, and 600 mg/dl, respectively). The insulin component of GIK promotes cardioprotection by KATP channel activation. However, glucose decreases KATP channel activity, and this effect predominates when hyperglycemia is present before ischemia

Adenosine Type 1 (A ) Receptors Mediate Protection Against Myocardial 1 Infarction Produced by Chronic, Intermittent Ingestion of Ethanol in Dogs

Background: Chronic consumption of small amounts of ethanol protects myocardium from ischemic injury. We tested the hypothesis that adenosine type 1 (A1) receptors mediate these beneficial effects. Methods: Dogs (n=37) were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 weeks, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intravenous drug vehicle (50% polyethylene glycol in 0.1 N sodium hydroxide and 0.9% saline over 15 min) or the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.8 mg/kg over 15 min) and were subjected to a 60 min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and transmural coronary collateral blood flow were measured with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Results: The area at risk (AAR) for infarction was similar between groups. Pretreatment with ethanol significantly reduced infarct size to 13±2% (n=7) of the AAR as compared to control experiments (26±2%; n=7). DPCPX abolished the protective effects of ethanol pretreatment (30±3%; n=7) but had no effect in dogs that did not receive ethanol (25±2%; n=7). No differences in transmural coronary collateral blood flow were observed between groups. Conclusions: The present findings indicate that chronic ingestion of small amounts of ethanol produces myocardial protection that persists after the discontinuation of ethanol. The results indicate that A1 receptors mediate ethanol-induced preconditioning in dogs independent of alterations in systemic hemodynamics or coronary collateral blood flow

Influence of Isoflurane on Left Atrial Function in Dogs With Pacing-Induced Cardiomyopathy: Evaluation With Pressure-Volume Relationships

Objective The actions of volatile anesthetics on left ventricular (LV) function in normal and failing hearts have been previously evaluated, but the effects of these agents on left atrial (LA) function in the presence of LV dysfunction are unknown. The hypothesis was tested that isoflurane alters LA mechanics evaluated with pressure-volume relations. Design Prospective. Setting Laboratory. Participants Barbiturate-anesthetized dogs (n = 8) were instrumented for measurement of aortic, LA, and LV pressures (micromanometers), and LA volume (epicardial orthogonal sonomicrometers) after 3 weeks of rapid ventricular pacing (220 beats/min). Interventions LA myocardial contractility (Ees) was assessed with end-systolic pressure-volume relations. LA stroke work and reservoir function were assessed by A and V loop area, respectively, from the steady-state pressure-volume diagram. LA-LV coupling was determined by the ratio of Ees to LV elastance (ELV). Dogs received 0.6, 0.9, and 1.2 minimum alveolar concentration isoflurane in a random manner, and LA function was determined after a 20-minute equilibration at each dose. Measurements and main results Isoflurane significantly (p \u3c 0.05) decreased heart rate, mean arterial pressure, LV end-systolic pressure, and LV +dP/dtmax. Isoflurane produced dose-related reductions in Ees and Ees/ELV. Declines in LA stroke work, emptying fraction, reservoir volume, V loop area, and the active LA contribution to LV filling also occurred. Conclusions The results indicate that isoflurane depresses LA myocardial contractility, impairs LA-LV coupling, and reduces active LA contribution to LV filling in dogs with pacing-induced cardiomyopathy. The impact of isoflurane on LA function in the presence of LV dysfunction has profound effects on cardiac performance

Antegrade Iliac Artery Stent Implantation for the Temporal and Spatial Examination of Stent-Induced Neointimal Hyperplasia and Alterations in Regional Fluid Dynamics

Neointimal hyperplasia remains an important problem after stent implantation. Previous investigations examining vascular responses to stent implantation and effects of drugs have used a retrograde deployment approach that may inadvertently alter the local fluid dynamics surrounding the stent. We present a model of antegrade iliac artery stent implantation that facilitates the analysis of stent-induced alterations in neointimal hyperplasia and wall shear stress in vivo.Methods: Stent delivery catheters were inserted through the left carotid artery in anesthetized rabbits (n=37). Catheters were advanced under fluoroscopic guidance to the distal iliac arteries, where the stent was deployed. Hemotoxylin and eosin (H&E) staining of unstented and stented vascular sections was performed 21 days after implantation. Results: Selective unilateral stent implantation was successful in 32 of 37 rabbits. No histological abnormalities were observed in the aorta, contralateral unstented iliac, or distal femoral arteries. Neointimal hyperplasia was localized to the stented region.Discussion: The model of stent implantation was relatively easy to perform and produced selective neointimal hyperplasia within the stented region without evidence of damage, cellular proliferation, or flow disruption in the surrounding normal arterial vessels. The model will allow detailed examination of the influence of stent implantation on indices of wall shear stress, neointimal hyperplasia, the mechanisms of cellular proliferation in vivo, and their modification by drugs