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Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population. A multitude of age-related, medical, and lifestyle risk factors for HFpEF have been identified as potential causes for the sustained low-grade proinflammatory state that accelerates disease progression. Profound left ventricular (LV) systolic and diastolic stiffening, elevated LV filling pressures, reduced arterial compliance, left atrial hypertension, pulmonary venous congestion, and microvascular dysfunction characterize HFpEF, but pulmonary arterial hypertension, right ventricular dilation and dysfunction, and atrial fibrillation also frequently occur. These cardiovascular features make patients with HFpEF exquisitely sensitive to the development of hypotension in response to acute declines in LV preload or afterload that may occur during or after surgery. With the exception of symptom mitigation, lifestyle modifications, and rigorous control of comorbid conditions, few long-term treatment options exist for these unfortunate individuals. Patients with HFpEF present for surgery on a regular basis, and anesthesiologists need to be familiar with this heterogeneous and complex clinical syndrome to provide successful care. In this article, the authors review the diagnosis, pathophysiology, and treatment of HFpEF and also discuss its perioperative implications.

The heart, vascular system, and red blood cells play fundamental roles in O2 transport. The fascinating research history that led to the current understanding of the physiology of O2 transport began in ancient Egypt in 3000 BC, when it was postulated that the heart was a pump serving a system of distributing vessels. Over 4 millennia elapsed before William Harvey (1578-1657) made the revolutionary discovery of blood circulation, but it was not until the 20th century that a lucid and integrative picture of O2 transport finally emerged. This review describes major research achievements contributing to this evolution of knowledge. These achievements include the discovery of the systemic and pulmonary circulations, hemoglobin within red blood cells and its ability to bind O2, and diffusion of O2 from the capillary as the final step in its delivery to tissue. The authors also describe the classic studies that provided the initial description of the basic regulatory mechanisms governing heart function (Frank-Starling law) and the flow of blood through blood vessels (Poiseuille's law). The importance of technical advances, such as the pulmonary artery catheter, the blood gas analyzer and oximeter, and the radioactive microsphere technique to measure the regional blood flow in facilitating O2 transport-related research, is recognized. The authors describe how religious and cultural constraints, as well as superstition-based medical traditions, at times impeded experimentation and the acquisition of knowledge related to O2 transport.

Since cricoid pressure was introduced into clinical practice, controversial issues have arisen, including necessity, effectiveness in preventing aspiration, quantifying the cricoid force, and its reliability in certain clinical entities and in the presence of gastric tubes. Cricoid pressure–associated complications have also been alleged, such as airway obstruction leading to interference with manual ventilation, laryngeal visualization, tracheal intubation, placement of supraglottic devices, and relaxation of the lower esophageal sphincter. This review synthesizes available information to identify, address, and attempt to resolve the controversies related to cricoid pressure. The effective use of cricoid pressure requires that the applied force is sufficient to occlude the esophageal entrance while avoiding airway-related complications. Most of these complications are caused by excessive or inadequate force or by misapplication of cricoid pressure. Because a simple-to-use and reliable cricoid pressure device is not commercially available, regular training of personnel, using technology-enhanced cricoid pressure simulation, is required. The current status of cricoid pressure and objectives for future cricoid pressure–related research are also discussed.

Preoxygenation before anesthetic induction and tracheal intubation is a widely accepted maneuver, designed to increase the body oxygen stores and thereby delay the onset of arterial hemoglobin desaturation during apnea. Because difficulties with ventilation and intubation are unpredictable, the need for preoxygenation is desirable in all patients. During emergence from anesthesia, residual effects of anesthetics and inadequate reversal of neuromuscular blockade can lead to hypoventilation, hypoxemia, and loss of airway patency. In accordance, routine preoxygenation before the tracheal extubation has also been recommended. The objective of this article is to discuss the physiologic basis, clinical benefits, and potential concerns about the use of preoxygenation. The effectiveness of preoxygenation is assessed by its efficacy and efficiency. Indices of efficacy include increases in the fraction of alveolar oxygen, increases in arterial oxygen tension, and decreases in the fraction of alveolar nitrogen. End points of maximal preoxygenation (efficacy) are an end-tidal oxygen concentration of 90% or an end-tidal nitrogen concentration of 5%. Efficiency of preoxygenation is reflected in the rate of decline in oxyhemoglobin desaturation during apnea. All investigations have demonstrated that maximal preoxygenation markedly delays arterial hemoglobin desaturation during apnea. This advantage may be blunted in high-risk patients. Various maneuvers have been introduced to extend the effect of preoxygenation. These include elevation of the head, apneic diffusion oxygenation, continuous positive airway pressure (CPAP) and/or positive end-expiratory pressure (PEEP), bilevel positive airway pressure, and transnasal humidified rapid insufflation ventilatory exchange. The benefit of apneic diffusion oxygenation is dependent on achieving maximal preoxygenation, maintaining airway patency, and the existence of a high functional residual capacity to body weight ratio. Potential risks of preoxygenation include delayed detection of esophageal intubation, absorption atelectasis, production of reactive oxygen species, and undesirable hemodynamic effects. Because the duration of preoxygenation is short, the hemodynamic effects and the accumulation of reactive oxygen species are insufficient to negate its benefits. Absorption atelectasis is a consequence of preoxygenation. Two approaches have been proposed to reduce the absorption atelectasis during preoxygenation: a modest decrease in the fraction of inspired oxygen to 0.8, and the use of recruitment maneuvers, such as CPAP, PEEP, and/or a vital capacity maneuver (all of which are commonly performed during the administration of anesthesia). Although a slight decrease in the fraction of inspired oxygen reduces atelectasis, it does so at the expense of a reduction in the protection afforded during apnea.

A thorough understanding of cardiovascular physiology is a cornerstone of patient management in the perioperative period. The primary role of the cardiovascular system is to provide sufficient blood flow to satisfy the metabolic demands of the body tissues. This chapter presents the primary determinants of tissue blood flow (arterial pressure and local vascular resistance) and the factors that alter them. Because of its critical pumping role, the physiology of the heart is given particular emphasis. The major determinants of stroke volume, i.e., preload, contractility, and afterload, are discussed. Indices of cardiac function are reviewed, including cardiac output using thermodilution, ejection fraction from image-based measurements, and myocardial contractility assessed by cardiac function curves using a pulmonary artery catheter, and by end-systolic pressure-volume relations from pressure-volume loops. The determinants of coronary blood flow and myocardial oxygen demand are described, as well as how an imbalance between these variables may produce myocardial ischemia. Other topics covered include: 1) the principles of hemodynamics, and the mechanisms regulating function of the various vessel types, including the large arteries, arterioles, capillaries, and veins; 2) the transport of oxygen by blood and its delivery to the body tissues; 3) methods to measure tissue oxygen consumption, along with their advantages and limitations; 4) the role of the capillaries in tissue oxygen delivery, and in fluid filtration and absorption; 5) the responses elicited by activation of the major circulatory reflexes (the arterial baroreceptor, Bezold-Jarisch, and Bainbridge reflexes); 6) emerging developments in noninvasive perioperative cardiovascular monitoring.

Lower body negative pressure (LBNP) is a technique that redistributes blood from the upper body to the dependent regions of the pelvis and legs, thus reducing central venous pressure and venous return. The subject is placed in a cylindrical air-tight metal tank, which is sealed at the level of the iliac crests, and subatmospheric pressure is produced using a vacuum pump. This article reviews the historical background, physiological effects, research findings, and clinical applications of LBNP. LBNP is found in both the basic science and clinical literature, encompassing its diverse investigational and clinical applications. The first references to LBNP were in 1952 describing its effectiveness in inducing hypotensive anesthesia. Major interest in LBNP began in the mid 1960s when it was used to characterize the cardiovascular responses to hemorrhage and orthostatic stress, especially that associated with the weightlessness of space flight; these studies have continued to the present day. Advantages of LBNP for such experimental studies include the following: (1) The degree of central hypovolemia is easily controlled and has a rapid onset and reversal. (2) The technique is repeatable, reproducible, and noninvasive. (3) No exogenous pharmacologic agent is required to produce venous pooling. (4) The findings are independent of gravity. In recent years, a few institutions have applied LBNP clinically to diagnose abnormalities in cardiovascular autonomic function and, when combined with echocardiography, to uncover changes in cardiac performance through analysis of Starling curves.

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

Isoflurane was introduced for general clinical use in North America in 1981. Shortly thereafter, in 1983, a study suggested that the anesthetic was a potent coronary vasodilator that could cause coronary steal and myocardial ischemia in patients with coronary artery disease. Myocardial ischemia results from small-vessel dilation which leads to increased blood flow to well-perfused myocardium and decreased blood flow to myocardium with borderline perfusion. This action of isoflurane raised concerns and threatened its use. By the early 1990s, these concerns were resolved by carefully performed clinical and experimental studies demonstrating no evidence of adverse cardiac changes during isoflurane administration as long as hemodynamic variables were tightly controlled. Indeed, the controversy sparked by the 1983 study led to a chain of experimental studies that ultimately demonstrated ironically that isoflurane has a preconditioning, cardioprotective effect. This chapter in anesthesia history underscores the importance of allowing the passage of time before assessing the clinical and scientific impact of a research finding.

BACKGROUND Hemodilution is accompanied by an increase in cerebral blood flow, but whether this is due to vasodilation in response to reduced arterial oxygen content, reduced blood viscosity, or a combination of these mechanisms is a matter of debate. We performed the current study to gain insight into this question by evaluating the effect of hemodilution on (1) vasodilator reserve and (2) the level of blood flow during hypercapnia-induced vasodilation in regions of the brain and spinal cord. METHODS Sixteen mongrel dogs were anesthetized with halothane 0.9% (1 minimum alveolar concentration) while their lungs were mechanically ventilated. Radioactive microspheres (15 μm) were used to measure regional blood flow (RBF) in the cerebral cortex, cerebellum, pons, medulla, and spinal cord (cervical, thoracic, and lumbar segments). Arterial blood pressure was measured via an aortic catheter. Vasodilator reserve was assessed from the ratio of RBF during hypercapnia (PaCO2 approximately 65 mm Hg) to RBF before hypercapnia. PaCO2 was increased by the addition of dead-space tubing without changing the ventilator settings. The dilating effects of hypercapnia within the central nervous system (CNS) were assessed with hematocrit normal (group 1; n = 8) and after induction of isovolemic hemodilution to a hematocrit of 19 ± 4 (SD) with 5% dextran (group 2; n = 8). RESULTS Hemodilution increased RBF (P < 0.0001) and decreased the vasodilator reserve ratio (P < 0.05) in all regions of the brain and spinal cord; the ratios during hemodilution (group 2) were only 48% to 68% of those without hemodilution (group 1). The level of RBF during hypercapnia was not significantly different in the absence and presence of hemodilution (cerebral cortex: mean, 122 mL/min/100 g vs mean, 108 mL/min/100 g; 95% confidence interval of the difference (95% CID), -53 to 26; P = 0.46; cerebellum: mean, 117 mL/min/100 g vs mean, 100 mL/min/100 g; 95% CID, -52 to 18; P = 0.32; pons: mean, 83 mL/min/100 g vs mean, 73 mL/min/100 g; 95% CID, -12 to 31; P = 0.35; medulla: mean, 96 mL/min/100 g vs mean, 82 mL/min/100 g; 95% CID, -11 to 40; P = 0.25; cervical spinal cord: mean, 61 mL/min/100 g vs mean, 52 mL/min/100 g; 95% CID, -18 to 34; P = 0.51; thoracic spinal cord: mean, 35 mL/min/100 g vs mean, 46 mL/min/100 g; 95% CID, -30 to 8; P = 0.24; lumbar spinal cord: mean, 54 mL/min/100 g vs mean, 58 mL/min/100 g; 95% CID, -25 to 15; P = 0.61). Neither hypercapnia alone nor combined with hemodilution affected mean arterial blood pressure (P = 0.78 and P = 0.81, respectively). CONCLUSIONS Hemodilution caused recruitment of the vasodilator reserve, suggesting that vasodilation played a role in the increase in RBF throughout the CNS. Although the mean values for RBF during hypercapnia were similar with and without hemodilution, a large variation in the responses precluded a conclusive determination of whether or not reduced blood viscosity also contributed to the hemodilution-induced increases in RBF. A dependence on vasodilation would limit autoregulatory capability throughout the CNS during hemodilution, which would enhance the risk for ischemia if hypotension was superimposed.

Background We tested the hypothesis that an upregulation of antioxidant proteins [Cu-Zn superoxide dismutase (SOD), Mn SOD, catalase, glutathione peroxidase, and glutathione peroxidase] plays a role in the delayed protection against myocardial stunning produced by isoflurane preconditioning (ISOPC). Findings were compared with late ischemic PC (IPC). Methods Fourteen mongrel dogs were chronically instrumented to measure coronary blood flow and myocardial wall thickening (WT) in conscious state. In Group 1, dogs underwent IPC, induced by a 10-min coronary artery occlusion (CAO); after 24 h of reperfusion, they were subjected to a second 10-min ischemia CAO-reperfusion. In Group 2 (ISOPC), dogs inhaled one minimum alveolar concentration (MAC) ISO (1.4% in O2) for 60 min, allowed to recover for 24 h, and then subjected to CAO ischemia-reperfusion. Recovery of WT following the initial 10-min CAO in Group 1 served as control response for both ISOPC and IPC. Expression and activity of antioxidant proteins were measured using Western blotting and spectrophotometric techniques, respectively. Results Two to three hours of reperfusion were required for recovery of WT following either ISOPC or IPC; in contrast, without PC, WT remained markedly reduced (30% below baseline) at this time point and required more than 6 h of reperfusion for recovery. Neither IPC nor ISOPC affected expression of Cu-Zn SOD, Mn SOD, or catalase. However, ISOPC increased activity of Mn SOD (+40%), catalase (+39%), glutathione peroxidase (+37%), and glutathione reductase (+93%) (P

Our previous work has demonstrated that treatment with isoflurane has a preconditioning-like inhibitory effect on superoxide production (SOP) by polymorphonuclear neutrophils. The current objectives were to determine persistency of this effect and to clarify where in the signalling pathway this inhibition of SOP occurred. The latter was accomplished using two receptor-dependent neutrophil agonists, platelet activating factor (PAF) and formyl-methionyl-leucyl-phenylalanine (fMLP), and two receptor-independent neutrophil stimuli, the protein-kinase C stimulator, phorbol myristate acetate (PMA), and the calcium ionophore, A23187. Arterial blood samples were obtained from eight dogs under baseline condition (conscious state), during isoflurane (1 MAC) administration, and 24 and 48 hr post-isoflurane (also in conscious state). Neutrophils were isolated and stimulated with 1 μM concentrations of PAF, fMLP, PMA, and A23187. SOP was measured spectrophotometrically. Isoflurane administration caused (1) an approximate 50% decrease in SOP during PAF or fMLP (P 0.05 vs baseline). Isoflurane administration caused prolonged (from 24 to 48 hr) decreases in agonist-induced SOP by neutrophils. This effect involved inhibition at site(s) in the signalling pathway upstream from protein kinase C. The current findings suggest that the intraoperative use of isoflurane may result in an extended impairment to the antibacterial host defense mechanism and that neutrophil inhibition may play a role in the delayed tissue protection afforded by treatment with volatile anesthetics.

Chronic treatment with insulin-like growth factor I (IGF-I) improves contractile function in congestive heart failure and ischemic cardiomyopathy. The present study investigated the effect of chronic treatment with IGF-I on intrinsic myocyte function and the role of the phosphatidylinositol (PI)3-kinase-Akt-sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signaling cascade in these responses. Myocytes were isolated from 23 adult rats and cultured with and without IGF-I (10−6M). After 48 h of treatment, myocyte function was evaluated. IGF-I increased contractile function (percent contraction, 7.7 ± 0.3% vs. 4.5 ± 0.3%; P < 0.01) and accelerated relaxation time (time for 70% relengthening, 81 ± 4 vs. 106 ± 5 ms; P < 0.05) compared with untreated myocytes [control (Con)]. The enhanced function was associated with an increase in Ca2+transients assessed by fura-2 (340/380 nm; IGF-I, 0.42 ± 0.02 vs. Con, 0.25 ± 0.01; P < 0.01). The PI3-kinase inhibitor LY-249002 (10−9M) abolished the enhanced function caused by IGF-I. IGF-I increased both Akt and SERCA2a protein levels 2.5- and 4.8-fold, respectively, compared with those of Con ( P < 0.01); neither phospholamban nor calsequestrin was affected. To evaluate whether the SERCA2a protein was directly mediated by Akt-SERCA2a signaling, IGF-I-induced changes in the SERCA2a protein were compared in myocytes transfected with adenovirus harboring either constitutively active Akt [multiplicity of infection (MOI), 15] or dominant negative Akt (dnAkt; MOI, 15). The ability of IGF-I to upregulate the SERCA2a protein in myocytes transected with active Akt was absent in dnAkt myocytes. Taken together, our findings indicate that chronic treatment with IGF-I enhances intrinsic myocyte function and that this effect is due to an enhancement in intracellular Ca2+handling, secondary to the activation of the PI3-kinase-Akt-SERCA2a signaling cascade.

Increases in myocardial blood flow preserve myocardial oxygenation during moderate acute normovolemic hemodilution. Hypocapnic alkalosis (HA) is known to cause coronary vasoconstriction and increase hemoglobin-oxygen affinity. We evaluated whether these effects would compromise myocardial oxygenation during hemodilution.Eighteen anesthetized dogs were studied. Myocardial blood flow (MBF) was measured with radioactive microspheres. Arterial and coronary sinus samples were analyzed for oxygen content and plasma lactate. Myocardial oxygen supply, oxygen uptake, and lactate uptake were calculated. HA (PaCO2, 23 ± 2 (SD); pHa, 7.56 ± 0.03) was induced by removal of dead space tubing at baseline (n = 8) and during hemodilution (n = 10), with hematocrit at 43 ± 4% and 19 ± 2%, respectively.Hemodilution during normocapnia caused decreases in arterial oxygen content (19.9 ± 2.4 to 9.3 ± 1.2 ml/100; P0.05) and the coronary arteriovenous 02 difference (13.0 ± 3.0 to 6.4 ± 0.9 ml/100ml; P0.05). MBF increased (52 ± 12 to 111 ± 36 ml/min/100g; P0.05) to maintain myocardial oxygen supply and oxygen uptake. Myocardial lactate uptake increased (31 ± 19 to 68 ± 35 µeq/min/100g; P0.05). At normal hematocrit, HA decreased MBF (57 ± 18 to 45 ± 10 ml/min/100; P0.05), implying vasoconstriction, accompanied by decreased myocardial oxygen supply. These myocardial effects of HA were not apparent during hemodilution. HA did not alter myocardial lactate uptake during hemodilution.When HA was induced during hemodilution, its ability to cause coronary vasoconstriction was lost, and myocardial oxygenation remained well preserved.

Carbon dioxide (CO2) is an end product of aerobic cellular respiration. In healthy persons, PaCO2 is maintained by physiologic mechanisms within a narrow range (35-45 mm Hg). Both hypercapnia and hypocapnia are encountered in myriad clinical situations. In recent years, the number of hypercapnic patients has increased by the use of smaller tidal volumes to limit lung stretch and injury during mechanical ventilation, so-called permissive hypercapnia. A knowledge and appreciation of the effects of CO2 in the heart are necessary for optimal clinical management in the perioperative and critical care settings. This article reviews, from a historical perspective: (1) the effects of CO2 on coronary blood flow and the mechanisms underlying these effects; (2) the role of endogenously produced CO2 in metabolic control of coronary blood flow and the matching of myocardial oxygen supply to demand; and (3) the direct and reflexogenic actions of CO2 on myocardial contractile function. Clinically relevant issues are addressed, including the role of increased myocardial tissue PCO2 (PmCO2) in the decline in myocardial contractility during coronary hypoperfusion and the increased vulnerability to CO2-induced cardiac depression in patients receiving a β-adrenergic receptor antagonist or with otherwise compromised inotropic reserve. The potential use of real-time measurements of PmO2 to monitor the adequacy of myocardial perfusion in the perioperative period is discussed.

Background Caveolae mediated transendothelial transport of albumin has recently been shown to be the primary mechanism regulating microvascular endothelial albumin permeability. The authors investigated the effects of isoflurane and sevoflurane on pulmonary endothelial albumin permeability and assessed the potential role of the caveolae scaffold protein, caveolin-1, in these effects. Methods Isolated rat lungs and cultured rat lung microvessel endothelial cells (RLMVECs) were exposed to 1.0 or 2.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 30 min. I-albumin permeability-surface area product and capillary filtration coefficient were determined in the isolated lungs. In RLMVECs, uptake and transendothelial transport of I-albumin were measured in the absence and presence of pretreatment with 2 mm methyl-beta-cyclodextrin, a caveolae-disrupting agent. Uptake of fluorescent-labeled albumin, as well as phosphorylation of Src kinase and caveolin-1, was also determined. In Y14F-caveolin-1 mutant (nonphosphorylatable) expressing RLMVECs, uptake of I-albumin and phosphorylation of caveolin-1 were evaluated. Results In the isolated lungs, 2.0 MAC isoflurane increased I-albumin permeability-surface area product by 48% without affecting capillary filtration coefficient. In RLMVECs, isoflurane more than doubled the uptake of I-albumin and caused a 54% increase in the transendothelial transport of I-albumin. These effects were blocked by pretreatment with methyl-beta-cyclodextrin. The isoflurane-induced increase in uptake of I-albumin in wild-type RLMVECs was abolished in the Y14F-caveolin-1 mutant expressing cells. Isoflurane also caused a twofold increase in Src and caveolin-1 phosphorylation. Neither 1.0 MAC isoflurane nor 1.0 or 2.0 MAC sevoflurane affected any index of albumin transport or phosphorylation of caveolin-1. Conclusion Isoflurane, but not sevoflurane, increased lung transendothelial albumin permeability through enhancement of caveolae-mediated albumin uptake and transport in the isolated lung. This effect may involve an enhanced phosphorylation of caveolin-1.

Background The authors tested the hypothesis that pretreatment with isoflurane or sevoflurane can protect the heart against neutrophil-induced contractile dysfunction. Methods Studies were conducted in buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of contractility. Pretreatment consisted of administration of 1.0 minimum alveolar concentration isoflurane or sevoflurane for 15 min followed by a 10-min washout and was performed in the absence and presence of the adenosine triphosphate-sensitive potassium channel inhibitor glibenclamide (10 microM). Polymorphonuclear neutrophils and platelet-activating factor were then added to the perfusate for 10 min, followed by 30 min of recovery. Neutrophil retention was assessed from the difference between those administered and collected in coronary effluent and measurements of myeloperoxidase in myocardial samples. Isolated hearts were also used to assess the effect of volatile anesthetic pretreatment on cardiac dysfunction caused by enzymatically generated superoxide. In additional studies, the authors evaluated the effect of volatile anesthetic pretreatment on the adherence of neutrophils to isolated rat aortic segments. Results Platelet-activating factor-stimulated neutrophils caused marked and persistent reductions (> 50%) in left ventricular developed pressure. Pretreatment with either isoflurane or sevoflurane abolished these effects, as well as the associated increases in neutrophil retention. Glibenclamide did not alter these actions of the anesthetics. Pretreatment with either volatile anesthetic attenuated the reductions in left ventricular developed pressure caused by exogenous superoxide and abolished the increases in neutrophil adherence in the aortic segments. Conclusion Isoflurane and sevoflurane preconditioned the heart against neutrophil-induced contractile dysfunction. This action was associated with an inhibition to neutrophil adherence and likely involved an increased resistance of the myocardium to oxidant-induced injury; the adenosine triphosphate-sensitive potassium channels played no apparent role.

Background Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction. Methods Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent. Results Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure. Conclusion Neutrophils pretreated with 1.0 MAC isoflurane or sevoflurane lost their ability to cause cardiac dysfunction, while those pretreated with a concentration of isoflurane as low as 0.25 MAC were partially inhibited. This action of the volatile anesthetics was associated with reductions in superoxide production and neutrophil adherence to the coronary vascular endothelium. Our findings suggest that inhibitory actions on neutrophil activation and neutrophil-endothelium interaction may contribute to the preconditioning effects of volatile anesthetics observed in vivo during myocardial ischemia-reperfusion.

UNLABELLED Compensatory increases in oxygen extraction (EO(2)) during acute normovolemic hemodilution (ANH) have the effect of decreasing tissue oxygen tension values, thus increasing the threat of tissue hypoxia. We hypothesized that if the beta-adrenergic agonist isoproterenol (ISOP) could augment cardiac output (CO) during ANH, it could reverse the increases in EO(2) and restore the margin of safety for tissue oxygenation. Studies were performed in seven anesthetized (isoflurane) dogs. CO was measured by using thermodilution, and regional blood flow (RBF) was measured by using radioactive microspheres. Systemic oxygen delivery (DO(2)), oxygen consumption (OV0312;O(2)), and EO(2), as well as regional DO(2), were calculated. Measurements were obtained under the following conditions in each dog: 1) baseline-1, 2) ISOP (0.1 micro g. kg(-1). min(-1) IV), 3) baseline-2, 4) ANH, and 5) ISOP during ANH. Hematocrit was 45% +/- 3% under baseline conditions and 18% +/- 3% during ANH. Before ANH, ISOP caused parallel increases in CO and systemic DO(2), which, in the presence of an unchanged OV0312;O(2), reduced EO(2). RBF increased in myocardium and spleen, decreased in pancreas, and did not change in brain, spinal cord, or other tissues. ANH caused increases in CO, which were insufficient to offset the decrease in arterial oxygen content, and thus systemic DO(2) declined; systemic OV0312;O(2) was maintained by an increase in EO(2). ANH-related increases in RBF maintained DO(2) in myocardium, brain, duodenum, and pancreas, whereas DO(2) declined in kidney and spleen. ISOP during ANH increased CO and systemic DO(2), which returned systemic EO(2) to baseline, and it increased RBF in myocardium, kidney, duodenum, and spleen. We conclude that 1) beta-adrenergic stimulation with ISOP restored the systemic EO(2) reserve during ANH, without apparent adverse effects in the individual body tissues, and that 2) the use of inotropic drugs, such as ISOP, may extend the limit to which hematocrit can be reduced safely during ANH. IMPLICATIONS By restoring the oxygen extraction reserve, isoproterenol and other inotropic drugs can enhance the margin of safety and extend the limit to which hematocrit can be reduced safely during acute normovolemic hemodilution. The use of this approach will depend on the degree of hemodilution, the extent of mixed venous oxygen desaturation, and whether increases in cardiac output are possible or desirable.

We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L) obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald, Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen, Denmark). A total of 134 measurements per analyzer were obtained in arterial and venous blood samples from 10 patients undergoing cardiac surgery and 65 measurements per analyzer in venous blood samples from 2 healthy volunteers. The blood samples were equilibrated in a tonometer with gases of known composition (37 degrees C). Additional theoretical studies were performed to evaluate the relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using the formulas of the various analyzers. The standard deviations of repeated measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the other 4 analyzers. The maximal systematic difference between the average of all measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to differences in measuring pH, and, to a lesser extent, to differences in calculation and determination of PCO(2). Comparison of the results from samples with different oxygen saturation showed that the relative alkalinity of deoxygenated hemoglobin (Haldane effect) can also influence the determinations of BE(ecf).A clinically useful way to quantify nonrespiratory disturbances of the acid-base balance is calculation of the base excess of extracellular fluid by using blood gas analyzers. In this study, we found significant variability in estimates of base excess of extracellular fluid obtained with five analyzers from different manufacturers. This variability is attributable to multiple factors, including lack of correction for deoxygenated hemoglobin (Haldane effect).

Isoflurane protects myocardium during ischemia-reperfusion via a mechanism involving the adenosine triphosphate-sensitive potassium channels. We tested the hypothesis that an inhibition of the neutrophil-endothelium interactions by isoflurane contributes to this effect. Polymorphonuclear neutrophils and coronary artery segments were obtained from 35 healthy dogs. Superoxide production by neutrophils, stimulated with platelet-activating factor (PAF; 1.0 microM), was measured spectrophotometrically. Adherence of PAF-activated neutrophils to the endothelium of coronary segments was assessed by direct counting of neutrophils labeled with fluorescent dye. Coronary artery rings were exposed to PAF-activated neutrophils, and, after washing and preconstriction with U46619, they were evaluated for vasorelaxation responses to acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent). Measurements were performed in the absence and presence of isoflurane (1 and 2 minimum alveolar anesthetic concentration) both with and without glibenclamide (10 microM). Isoflurane inhibited superoxide production and adherence by neutrophils and abolished neutrophil-induced reductions in coronary vascular relaxation responses to acetylcholine. Glibenclamide did not alter the effects of isoflurane on neutrophils or coronary artery endothelium. In conclusion, isoflurane had an inhibitory action on neutrophil-endothelium interactions and neutrophil-mediated coronary endothelial dysfunction--effects that may be involved in its cardioprotective action in vivo. These inhibitory actions of isoflurane were not mediated by adenosine triphosphate-sensitive potassium channels.Isoflurane inhibited neutrophil-endothelium interactions and the inflammatory response in vitro via a pathway independent of the adenosine triphosphate-sensitive potassium channels. This action could be involved in the cardioprotection by isoflurane observed in vivo.

To evaluate the regional tolerance to acute normovolemic hemodilution (ANH).Prospective animal study.University research laboratory.Nine anesthetized (isoflurane) dogs.Hematocrit reduced in 10% decrements using dextran-for-blood exchange until cardiac insufficiency observed.Cardiac index (CI) was measured using thermodilution and regional blood flow (RBF) in myocardium, brain, spinal cord, kidney, liver, duodenum, pancreas, spleen, skeletal muscle, and skin with radioactive microspheres. Oxygen delivery (DO2) was calculated from the product of respective blood flow and arterial oxygen content. Systemic oxygen extraction (EO2) and oxygen consumption (VO2) were calculated. Increases in CI during ANH were inadequate to prevent decreases in systemic DO2; however, an increased systemic EO2 maintained VO2 during graded ANH to hematocrit10%. In the myocardium, brain, and spinal cord, increases in RBF were sufficient to maintain DO2 across the entire range of hematocrits, but this was not the case in the other organs studied. Of note, renal DO2 first decreased at a hematocrit of 30% and was only 25% of baseline at a hematocrit of 10%.During graded ANH, increases in RBF were sufficient to maintain DO2 in only the heart, brain, and spinal cord. The especially marked decrease in DO2 in the kidney, combined with previous physiologic studies demonstrating its inability to augment EO2, suggest that this organ may be the most at risk of hypoxic damage during ANH.

Despite intensive investigation, the role of nitric oxide (NO) in cholinergic modulation of myocardial contractility remains unresolved. The left anterior descending coronary artery of 34 anesthetized, open-chest dogs was perfused via an extracorporeal circuit. Segmental shortening (SS) was measured with ultrasonic crystals and coronary blood flow (CBF) was measured with an ultrasonic flow transducer. An intracoronary infusion of ACh (20 μg/min) was performed, with CBF held constant, under baseline and during dobutamine, CaCl2, or amrinone at doses increasing SS by ∼50% (10 μg/min, 15 mg/min, and 300 μg/min ic, respectively). ACh-induced responses during dobutamine were also assessed following treatment with the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 300 μg/min ic for 15 min). The effects of sodium nitroprusside (SNP; 80 μg/min ic), an exogenous NO donor, bradykinin (2.5 μg/min ic), a nonmuscarinic releaser of endothelial NO, and bilateral vagal stimulation (before and after l-NAME) were evaluated during dobutamine. ACh had no effect on SS under baseline or during CaCl2, but it decreased SS during dobutamine or amrinone (−23 ± 4% and −30 ± 5%, respectively). Vagal stimulation also reduced SS during dobutamine. l-NAME did not alter the ACh- or vagal-induced decreases in SS during dobutamine. Neither SNP nor bradykinin affected SS during dobutamine. In conclusion, ACh and vagal stimulation have a negative inotropic effect during stimulation of the β-adrenergic receptors that is independent of NO. The persistence of this effect during amrinone suggests that a mechanism downstream from adenylate cyclase is involved.

Various techniques of "preoxygenation" before anesthetic induction have been advocated, including tidal volume breathing (TVB) for 3-5 min, four deep breaths (DB) in 0.5 min, and eight DB in 1 min. However, no study has compared the effectiveness of these techniques, assessed extending deep breathing beyond 1 min, or investigated the influence of fresh gas flow (FGF) in the same subjects using a circle absorber system. In 24 healthy adult volunteers breathing oxygen from a circle absorber system by tight-fitting mask, we compared TVB/5 min and deep breathing at a rate of 4 DB/0.5 min for 2 min at 5, 7, and 10 L/min FGF. Inspired and end-tidal respiratory gases were measured at 0.5-min intervals. During TVB, end-tidal oxygen (ETO2) increased rapidly and plateaued by 2.5 min at 86%, 88%, and 88% with 5, 7 and 10 L/min FGF, respectively. ETO2 values ofor =90% were attained between 3 and 4 min. Four DB/0.5 min increased ETO2 to 75%, 77%, and 80% at 5, 7, and 10 L/min FGF. Eight DB/min resulted in ETO2 values of 82% and 87% at 7 and 10 L/min, respectively. Extending deep breathing to 1.5 and 2 min with 10 L/min FGF increased ETO2 byor =90%, although a decrease in ETCo(2) was noted. We concluded that TVB/3-5 min was effective in achieving maximal "preoxygenation" whereas 4 DB/0.5 min resulted in submaximal "preoxygenation," and thus should be used only when time is limited. Increasing FGF from 5 to 10 L/min does not enhance "preoxygenation" with either TVB or 4 DB/0.5 min. Deep breathing yields maximal "preoxygenation" when extended to 1.5 or 2 min, and only when high (10 L/min) FGF is used.Using a circle absorber system, normal breathing of oxygen for 3-5 min achieves optimal oxygenation of the lungs; whereas 4 deep breaths in 30 s does not. However, extending deep breathing to 1.5-2 min and using a high flow of oxygen improves oxygenation of the lungs to the same degree as normal breathing for 3-5 min. This may have important implications for patient safety.

Objective: To explore the possible use of recombinant hirudin (r-hirudin) as an alternative to heparin for anticoagulation during cardiovascular surgery. Design: Retrospective analysis. Setting: Two university hospitals. Participants: Fifty-seven patients with heparin-induced thrombocytopenia type II (HIT II) in whom r-hirudin was used during cardiovascular surgery with cardiopulmonary bypass (CPB). Interventions: None. Measurements and Main Results: The r-hirudin concentration was monitored on-line, at the point of the patient's care using the ecarin clotting time and maintained in the range of 3 to 4 μg/mL. The r-hirudin elimination at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. The duration of CPB was 63 to 246 minutes. The r-hirudin requirement per minute of CPB was 0.016 to 0.035 μg/kg/min, and the 24-hour blood drainage was 50 to 2,200 mL. Of the 57 patients, 54 fully recovered, including 9 patients who did not require any allogenic products. Four patients, all with impaired renal function, showed prolonged r-hirudin elimination and excessive bleeding and required surgical reexploration. Three patients died as a result of complications unrelated to the perioperative management. Conclusion: This study provides evidence that r-hirudin can be used safely and effectively for routine anticoagulation during CPB in patients diagnosed with HIT II. Almost 95% of the patients in whom it was used were discharged uneventfully. Patients with perioperative renal failure, however, showed increased bleeding. Copyright © 2000 by W.B. Saunders Company

HEPARIN-INDUCED THROMBOCYTOPENIA TYPE II (HIT II) is a potentially lethal complication, associated most frequently with unfractionated heparins. The incidence varies from approximately 1% to more than 30% of surgical patients, and 35% of these experience devastating outcomes.1,2 In cardiac surgery, the condition was associated with a complication rate of 51% and a mortality of 37%.3 If HIT II is either diagnosed or suspected, any form of heparin administration should be stopped immediately, and therapy with alternative anticoagulants should be instituted. In patients with HIT II, an immune response induces the formation of antibodies against heparin–platelet factor 4 complexes. The antigen-antibody complex stimulates platelet aggregation, which can result in arterial or venous thromboembolic events, often associated with a decrease in platelet count.1,4,5 Additional clinical signs may include stroke, myocardial infarction, or thromboembolism in the lungs, mesentery, or extremities. HIT II usually occurs after 2 to 14 days of exposure to heparin, but it can develop within hours in cases of reexposure to heparins.1,4 To date, HIT II has not been described to develop acutely under the condition of high-dose heparinization during cardiopulmonary bypass (CPB). Two cases in which HIT II developed immediately after institution of CPB are described.

Background The authors assessed the heparin management test in vitro in volunteers and in vivo during cardiopulmonary bypass. Methods In vitro, the heparin management test was analyzed for heparin levels between 0 and 6 IU/ml using variations in hematocrit, platelets, procoagulants, and storage time. The in vivostudies consisted of two groups: In group I (cardiopulmonary bypass /= 180 min, with aprotinin) included use (n = 10) and nonuse of coumadin (n = 10) and anticoagulation according to the automated heparin dose-response assay. Tests were performed in duplicate (whole blood, two heparin management test analyzers) and compared with anti-Xa activity (plasma). Results In vitro, the results of the heparin management test (n = 1,070) correlated well with heparin concentration (r2 = 0.98). Dilution and storage time did not affect the heparin management test; a hematocrit of 60% and reduced procoagulants (10%) prolonged clotting time. In vivo, the correlation (heparin management test vs. anti-Xa) was strong in group I (r2 = 0.97 [with aprotinin] and 0.96 [without aprotinin]; n = 960) and group II without coumadin (r2 = 0.89, n = 516). In group II with coumadin, the overall correlation was r2 = 0.87 and 0.79 (n = 484), although the range varied widely (0.57-0.94, between-analyzer differences 0-47%). Conclusions The results of the heparin management test were influenced by hematocrit, plasma coagulation factors, and the heparin level, but not by use of aprotinin. The heparin management test provided reliable values in vitro in group I, and in group II without coumadin but was less reliable in group II with coumadin.

Background An extracorporeal system was used to investigate the direct coronary vasomotor effects of sevoflurane and desflurane in vivo. The role of the adenosine triphosphate-sensitive potassium channels (KATP channels) in these effects was evaluated. Methods Twenty-one open-chest, anesthetized (fentanyl-midazolam) dogs were studied. The left anterior descending coronary artery was perfused at controlled pressure (80 mmHg) with normal arterial blood or arterial blood equilibrated with either sevoflurane or desflurane. Series 1 (n = 16) was divided into two groups of equal size on the basis of whether sevoflurane (1.2, 2.4, and 4.8%) or desflurane (3.6, 7.2, and 14.4%) was studied. The concentrations for the anesthetics corresponded to 0.5, 1.0, and 2.0 minimum alveolar concentration (MAC), respectively. Coronary blood flow (CBF) was measured with an ultrasonic, transit-time transducer. Local coronary venous samples were obtained and used to evaluate changes in myocardial oxygen extraction (EO2). In series 2 (n = 5), changes in CBF by 1 MAC sevoflurane and desflurane were assessed before and during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 microg/min). Results Intracoronary sevoflurane and desflurane caused concentration-dependent increases in CBF (and decreases in EO2) that were comparable. Glibenclamide blunted significantly the anesthetic-induced increases in CBF. Conclusions Sevoflurane and desflurane have comparable coronary vasodilative effects in in situ canine hearts. The KATP channels play a prominent role in these effects. When compared with data obtained previously in the same model, the coronary vasodilative effects of sevoflurane and desflurane are similar to those of enflurane and halothane but considerably smaller than that of isoflurane.

UNLABELLED The left anterior descending coronary arteries of 30 anesthetized, open-chest dogs were perfused via an extracorporeal circuit. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and segmental shortening (SS) were measured. Studies were performed with coronary perfusion pressure (CPP) or CBF constant. With CPP constant, effects of intracoronary (IC) infusions of dobutamine (2.5, 5.0, or 10.0 microg/min) were evaluated alone (control) and after inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine methyl ester (L-NAME). With CBF constant, a NO donor (sodium nitroprusside [SNP] 80 microg/min IC) or nitroglycerin [NTG] 40 microg/min IC) or a releaser of endogenous NO (acetylcholine [ACh]; 20 microg/ min IC) was infused along with dobutamine. Increases in CBF during dobutamine and isoproterenol were compared before and after blockade of beta1-adrenergic receptors with atenolol. Dobutamine caused proportional, dose-dependent increases in CBF, MVO2, and SS, which were not altered by L-NAME. Administration of the NO donors or ACh during dobutamine markedly decreased CPP, but only ACh also reduced SS and MVO2. These latter effects persisted after L-NAME. Atenolol blunted increases in CBF by dobutamine more than those by isoproterenol. We conclude that endogenous NO did not modulate the coronary vasodilation or the increases in myocardial contractility and MVO2 during dobutamine. In addition, neither SNP nor NTG altered myocardial contractility or MVO2 in dobutamine-stimulated myocardium, whereas ACh had a negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. IMPLICATIONS Endogenous nitric oxide (NO) did not modulate increases in coronary blood flow, myocardial contractility, or myocardial oxygen consumption during intracoronary infusions of dobutamine. The NO donors sodium nitroprusside and nitroglycerin had no effect on contractility or oxygen consumption in dobutamine-stimulated myocardium. Acetylcholine had negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO.

Background Halothane, isoflurane, and enflurane cause coronary vasodilation and cardiac depression. This study was performed to assess the role of adenosine triphosphate (ATP)-sensitive potassium channels (KATP channels) in these effects. Methods Twenty-five thoracotomized dogs were anesthetized with fentanyl and midazolam. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs. One reservoir was supplied with arterial blood free of a volatile anesthetic, and the second reservoir was supplied with arterial blood equilibrated in an oxygenator with a 1 minimum alveolar concentration of either halothane (0.9%, n = 10), isoflurane (1.4%, n = 8), or enflurane (2.2%, n = 7). Coronary blood flow (CBF) was measured using a Doppler flow transducer, and segmental shortening (SS) was measured with ultrasonic crystals. Responses to the volatile anesthetics were assessed under control conditions, during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 micrograms/min), and after cessation of glibenclamide (recovery). The effectiveness of glibenclamide was verified from inhibition of coronary vasodilator responses to the KATP channel opener cromakalim without effect on those to the KATP channel-independent vasodilators, sodium nitroprusside and acetylcholine. Results Under control conditions, the volatile anesthetics caused pronounced increases in CBF (isoflurane > halothane = enflurane), and decreases in SS (enflurane > halothane = isoflurane). Glibenclamide blunted significantly (and reversibly) the increases in CBF, but it had no effect on the decreases in SS. Conclusions The KATP channels play an important role in coronary vasodilation but apparently are not involved in cardiac depression caused by halothane, isoflurane, and enflurane in canine hearts in situ.

Rapid sequence induction and intubation (RSII) and awake tracheal intubation are commonly used anesthetic techniques in patients at risk of pulmonary aspiration of gastric or esophageal contents. Some of these patients may have a gastric tube (GT) placed preoperatively. Currently, there are no guidelines regarding which patient should have a GT placed before anesthetic induction. Furthermore, clinicians are not in agreement as to whether to keep a GT in situ, or to partially or completely withdraw it before anesthetic induction. In this review we provide a historical perspective of the use of GTs during anesthetic induction in patients at risk of pulmonary aspiration. Before the introduction of cricoid pressure (CP) in 1961, various techniques were used including RSII combined with a head-up tilt. Sellick initially recommended the withdrawal of the GT before anesthetic induction. He hypothesized that a GT increases the risk of regurgitation and interferes with the compression of the upper esophagus during CP. He later modified his view and emphasized the safety of CP in the presence of a GT. Despite subsequent studies supporting the effectiveness of CP in occluding the esophagus around a GT, Sellick's early view has been perpetuated by investigators who recommend partial or complete withdrawal of the GT. On the basis of available information, we have formulated an algorithm for airway management in patients at risk of aspiration of gastric or esophageal contents. The approach in an individual patient depends on: the procedure; type and severity of the underlying pathology; state of consciousness; likelihood of difficult airway; whether or not the GT is in place; contraindications to the use of RSII or CP. The algorithm calls for the preanesthetic use of a large-bore GT to remove undigested food particles and awake intubation in patients with achalasia, and emptying the pouch by external pressure and avoidance of a GT in patients with Zenker diverticulum. It also stipulates that in patients with gastric distension without predictable airway difficulties, a clinical and imaging assessment will determine the need for a GT and in severe cases an attempt to insert a GT should be made. In the latter cases, the success of placement will indicate whether to use RSII or awake intubation. The GT should not be withdrawn and should be connected to suction during induction. Airway management and the use of GTs in the surgical correction of certain gastrointestinal anomalies in infants and children are discussed.

Aims Few studies have investigated oxygen supply/demand relations in right ventricle (RV). The current study compared changes in myocardial oxygen uptake (MVO 2 ) and its determinants, myocardial blood flow (MBF) and oxygen extraction (EO 2 ), in RV and left ventricle (LV) during stimulation with inotropic drugs. Main methods Twenty-one anesthetized dogs were studied. MBF was measured with radioactive microspheres. A-VO 2 difference was determined separately for RV and LV, and used to calculate MVO 2 (Fick equation) and EO 2 . Responses to iv. infusions of isoproterenol (0.1 μg/kg/min), dobutamine (5 μg/kg/min), and amrinone (1 mg/kg + 10 μg/kg/min) were assessed. Key findings Baseline MVO 2 in RV was 50–60% of that in LV. The inotropes increased MVO 2 in both RV and LV (range 32–63%; P 2 in the RV was due to increases in both MBF and EO 2 , whereas in LV it was due only to increases in MBF. With dobutamine and amrinone, the increased MVO 2 in RV was due to increased MBF while EO 2 was constant (dobutamine) or decreased (amrinone), and that in the LV was due to increased MBF while EO 2 decreased. Significance RV possesses EO 2 reserve that contributed to increased MVO 2 during isoproterenol infusion, whereas LV depended on increased MBF alone. Because dobutamine and amrinone caused direct coronary vasodilation, i.e., “luxuriant perfusion,” it was not necessary to recruit the EO 2 reserve. Thus, it remained available to meet further increases in MVO 2 or to maintain MVO 2 in the face of reductions in MBF.