Ruth E. Wachtel

Flow-Induced Dilation of Human Coronary Arterioles Important Role of Ca2+-Activated K+ Channels

BackgroundFlow-induced vasodilation (FID) is a physiological mechanism for regulating coronary flow and is mediated largely by nitric oxide (NO) in animals. Because hyperpolarizing mechanisms may play a greater role than NO in the microcirculation, we hypothesized that hyperpolarization contributes importantly to FID of human coronary arterioles. Methods and ResultsArterioles from atria or ventricles were cannulated for videomicroscopy. Membrane potential of vascular smooth muscle cells (VSMCs) was measured simultaneously. After constriction with endothelin-1, increases in flow induced an endothelium-dependent vasodilation. N&ohgr;-Nitro-l-arginine methyl ester 10−4 mol/L modestly impaired FID of arterioles from patients without coronary artery disease (CAD), whereas no inhibition was seen in arterioles from patients with CAD. Indomethacin 10−5 mol/L was without effect, but 40 mmol/L KCl attenuated maximal FID. Tetraethylammonium 10−3 mol/L but not glibenclamide 10−6 mol/L reduced FID. Charybdotoxin 10−8 mol/L impaired both FID (15±3% versus 75±12%, P <0.05) and hyperpolarization (−32±2 mV [from −28±2 mV after endothelin-1] versus −42±2 mV [−27±2 mV], P <0.05). Miconazole 10−6 mol/L or 17-octadecynoic acid 10−5 mol/L reduced FID. By multivariate analysis, age was an independent predictor for the reduced FID. ConclusionsWe conclude that shear stress induces endothelium-dependent vasodilation, hyperpolarizing VSMCs through opening Ca2+-activated K+ channels in human coronary arterioles. In subjects without CAD, NO contributes to FID. NO and prostaglandins play no role in patients with CAD; rather, cytochrome P450 metabolites are involved. This is consistent with a role for endothelium-derived hyperpolarizing factor in FID of the human coronary microcirculation.

Diabetes Mellitus Impairs Vasodilation to Hypoxia in Human Coronary Arterioles Reduced Activity of ATP-Sensitive Potassium Channels

Abstract— ATP-sensitive K+ channels (KATP) contribute to vasomotor regulation in some species. It is not fully understood the extent to which KATP participate in regulating vasomotor tone under physiological and pathophysiological conditions in the human heart. Arterioles dissected from right atrial appendage were studied with video microscopy, membrane potential recordings, reverse transcription–polymerase chain reaction, and immunohistochemistry. Hypoxia produced endothelium-independent vasodilation and membrane hyperpolarization of vascular smooth muscle cells, both of which were attenuated by glibenclamide. Aprikalim, a selective KATP opener, also induced a potent endothelium-independent and glibenclamide-sensitive vasodilation with membrane hyperpolarization. Reverse transcription–polymerase chain reaction detected mRNA expression for KATP subunits, and immunohistochemistry confirmed the localization of the inwardly rectifying Kir6.1 protein in the vasculature. In patients with type 1 or type 2 diabetes mellitus (DM), vasodilation was reduced to both aprikalim (maximum dilation, DM(+) 90±2% versus DM(−) 96±1%, P <0.05) and hypoxia (maximum dilation, DM(+) 56±8% versus DM(−) 85±5%, P <0.01) but was not altered to sodium nitroprusside or bradykinin. Baseline myogenic tone and resting membrane potential were not affected by DM. We conclude that DM impairs human coronary arteriolar dilation to KATP opening, leading to reduced dilation to hypoxia. This reduction in KATP function could contribute to the greater cardiovascular mortality and morbidity in DM.

Tactical Decision Making for Selective Expansion of Operating Room Resources Incorporating Financial Criteria and Uncertainty in Subspecialties' Future Workloads

We considered the allocation of operating room (OR) time at facilities where the strategic decision had been made to increase the number of ORs. Allocation occurs in two stages: a long-term tactical stage followed by short-term operational stage. Tactical decisions, approximately 1 yr in advance, determine what specialized equipment and expertise will be needed. Tactical decisions are based on estimates of future OR workload for each subspecialty or surgeon. We show that groups of surgeons can be excluded from consideration at this tactical stage (e.g., surgeons who need intensive care beds or those with below average contribution margins per OR hour). Lower and upper limits are estimated for the future demand of OR time by the remaining surgeons. Thus, initial OR allocations can be accomplished with only partial information on future OR workload. Once the new ORs open, operational decision-making based on OR efficiency is used to fill the OR time and adjust staffing. Surgeons who were not allocated additional time at the tactical stage are provided increased OR time through operational adjustments based on their actual workload. In a case study from a tertiary hospital, future demand estimates were needed for only 15% of surgeons, illustrating the practicality of these methods for use in tactical OR allocation decisions.

Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia

DiI-labeled colon sensory neurons were acutely dissociated from S1 rat dorsal root ganglia (DRG) and studied using perforated whole cell patch-clamp techniques. Forty-six percent (54/116) of labeled sensory neurons responded to capsaicin (10-8- 10-5M) with an increase in inward current, which was a nonspecific cation conductance. Responses to capsaicin applied by puffer ejection were dependent on dose, with a half-maximal response at 4.9 × 10-7 M; bath application was characterized by marked desensitization. Voltage-gated Na+currents in 23 of 30 DRG cells exhibited both TTX-sensitive and TTX-resistant components. In these cells, capsaicin induced an inward current in 11 of 17 cells tested. Of the cells containing only a TTX-sensitive component, none of six cells tested was sensitive to capsaicin. In all cells that responded to capsaicin with an increase in inward current, capsaicin abolished voltage-gated Na+currents ( n = 21). Capsazepine (10-6 M) significantly attenuated both the increase in inward current and the reduction in Na+currents. Na+ currents were not significantly altered by adenosine, bradykinin, histamine, PGE2, or serotonin at 10-6 M and 10-5 M. These findings may have important implications for understanding both the irritant and analgesic properties of capsaicin.

Tactical Increases in Operating Room Block Time for Capacity Planning Should Not Be Based on Utilization

When a decision has been made to expand operating room (OR) capacity, the choice of surgical subspecialties to receive additional block time and fill the additional OR capacity is a tactical decision. Such decisions are made approximately once a year. Afterwards, typically a few months before the day of surgery, a second stage occurs in which operational decisions allocate OR time and determine the hours of staffing for each specialty based on its expected workload. In practice, cases are not scheduled into block time that has been planned tactically, but instead are scheduled during the second stage into the staffed time that is allocated operationally. This article reviews the literature on tactical decision-making for expansion of OR capacity. When additional OR capacity is available, it should be planned for those subspecialties that have the greatest contribution margin per OR hour, that have the potential for growth, and that have minimal need for limited resources such as intensive care unit beds. Numerous reasons are presented to explain why tactical planning of additional block time should not be based on current or past utilization of block time.

Mechanical stimulation increases intracellular calcium concentration in nodose sensory neurons.

The cellular mechanisms involved in activation of mechanosensitive visceral sensory nerves are poorly understood. The major goal of this study was to determine the effect of mechanical stimulation on intracellular calcium concentration ([Ca2+]i) using nodose sensory neurons grown in culture. Primary cultures of nodose sensory neurons were prepared by enzymatic dispersion from nodose ganglia of 4-8 week old Sprague-Dawley rats. Whole cell [Ca2+]i was measured by a microscopic digital image analysis system in fura-2 loaded single neurons. Brief mechanical stimulation of individual nodose sensory neurons was achieved by deformation of the cell surface with a glass micropipette. In 31 of 50 neurons (62%), mechanical stimulation increased [Ca2+]i from 125 +/- 8 to 763 +/- 89 nM measured approximately 10 s after stimulation. [Ca2+]i then declined gradually, returning to near basal levels over a period of minutes. [Ca2+]i failed to increase after mechanical stimulation in the remaining 19 neurons. The mechanically-induced rise in [Ca2+]i was essentially abolished after the neurons were incubated for 5-10 min in zero Ca2+ buffer (n = 7) or after addition of gadolinium (10 microM), a blocker of stretch-activated ion channels (n = 5). The effect of gadolinium was reversed after removal of gadolinium. The results indicate that: (1) mechanical stretch increases [Ca2+]i in a subpopulation of nodose sensory neurons in culture, and (2) the stretch-induced increase in [Ca2+]i is dependent on influx of Ca2+ from extracellular fluid and is reversibly blocked by gadolinium. The findings suggest that opening of stretch-activated ion channels in response to mechanical deformation leads to an increase in Ca2+ concentration in visceral sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of the Operating Room Schedule on Tardiness from Scheduled Start Times

BACKGROUND: Tardiness from scheduled start times in a surgical suite is a common source of frustration for both operating room personnel and patients. METHODS: Data from two surgical suites were used to investigate the relative importance of various factors that contribute to tardiness, including average case duration, time of day, prolonged turnovers, whether a surgeon follows himself or another surgeon, the potential for starting cases early, concurrency (e.g., number of residents supervised simultaneously), expected under-utilized or over-utilized time, and case duration bias. RESULTS: Average tardiness per case did not depend on the individual durations of preceding cases or on the relative numbers of long and short cases. In contrast, the total duration of preceding cases was important in determining tardiness. Tardiness per case grew larger as the day progressed because the total duration of preceding cases increased, but began to decline for cases scheduled to commence 6 h after the start of the workday. Tardiness was not affected by prolonged turnovers, differences in average case duration among services, or whether a surgeon followed himself or another surgeon in the same operating room. Tardiness was affected by expected under-utilized or over-utilized time at the end of the workday and by case duration bias. CONCLUSIONS: Factors associated with the largest numbers of cases had the biggest influence on tardiness. Greater understanding of these factors aided in the development of several mathematical interventions to reduce tardiness in the two surgical suites. These interventions and their applicability for reducing tardiness are described in a companion article.

Reducing tardiness from scheduled start times by making adjustments to the operating room schedule.

BACKGROUND: Tardiness from scheduled start times is a common source of frustration for both operating room (OR) personnel and patients. Factors that influence tardiness were quantified in a companion paper and have been used to develop interventions that have the potential for reducing tardiness. METHODS: Data from two surgical suites were used to compare the effectiveness of several interventions to reduce tardiness, including i) moving cases to different ORs on the afternoon of surgery, ii) recalculating the OR schedule when it is published to correct for average lateness in first cases of the day, iii) recalculating the OR schedule when it is published to correct for average service-specific case duration bias, and iv) scheduling a gap (time buffer) before the cases of a “to follow” surgeon if the day is expected to end early. These last three interventions involve creation of a modified schedule with revised start times that are more accurate for both patient and “to follow” surgeon. The surgeon performing the first case of the day would not be affected. RESULTS: Moving cases to different ORs when a room was running late produced a 50%–70% reduction in the tardiness for those cases that were moved. However, overall tardiness in each suite was reduced by only 6%–9%, because few cases were moved. Scheduling a gap between surgeons if the day was expected to end early reduced tardiness by more than 50% for those cases that were preceded by gaps. However, overall tardiness in each suite was reduced by only 4%–8%, because few gaps could be scheduled. In contrast, correcting for the combination of lateness in first cases of the day and service-specific case duration bias reduced overall tardiness in each suite by 30%–35%. CONCLUSIONS: Interventions which involve small numbers of cases have little potential to reduce overall tardiness. Generating a modified or auxiliary OR schedule that compensates for known causes of tardiness can significantly reduce patient and “to follow” surgeon waiting times. Modifying the OR schedule to create revised start times for patients and “to follow” surgeons involves interventions that are simple to perform. The official schedule is not changed and case sequencing is not altered. Results do not depend on changing surgeon, anesthesia provider, or nursing behavior.

Strategies for net cost reductions with the expanded role and expertise of anesthesiologists in the perioperative surgical home.

The Perioperative Surgical Home is a model adopted by the American Society of Anesthesiologists to increase quality and patient safety and to decrease costs. This Special Article is about the latter topic. Using narrative review, we show that there are two principal opportunities for net cost reduction. One opportunity is to reduce unnecessary interventions that do not have potential to benefit patients (e.g., preoperative laboratory studies in healthy patients undergoing low-risk surgery and use of substantial fresh gas flows with volatile anesthetics). The other opportunity is to optimize staff scheduling, case scheduling, and staff assignment. These two are the same as the principal ways that a positive return on investment can be achieved from use of an anesthesia information management system. Three other opportunities are much less likely to achieve as large (if any) net cost reduction among all patients but may at some hospitals. These are to reduce cancellations, operating room times, and/or hospital postoperative lengths of stay.

Kinetics of nicotinic acetylcholine ion channels in the presence of intravenous anaesthetics and induction agents

1 Single channel currents activated by 250 nm acetylcholine were recorded from cell‐attached patches of BC3H1 mouse tumour cells grown in culture. Channels were recorded in the absence and presence of alphaxalone, diazepam, etomidate, fentanyl, ketamine, meperidine, or propofol. 2 All of the anaesthetics tested shortened channel open time but did not alter single channel current amplitude. Drug concentrations calculated to reduce the time constant of open‐time distributions by 50% were 99 μm alphaxalone, 66 μm diazepam, 57 μm etomidate, 26 μm fentanyl, 15 μm ketamine, 16 μm meperidine, or 81 μm propofol. 3 Ketamine, meperidine, and propofol reduced channel open time at concentrations comparable to plasma levels attained during therapeutic use of these agents, while alphaxalone, diazepam, etomidate, and fentanyl reduced channel open time only at levels higher than those encountered clinically. 4 The potency of these drugs in decreasing channel open time appears to be directly correlated with their octanol/buffer partition coefficients. In contrast to expectations, however, agents with higher partition coefficients were less potent in altering channel open time. 5 Ketamine and meperidine produced a prominent third component in closed‐time distributions, which were otherwise well described by the sum of two exponential components. Alphaxalone, diazepam, and etomidate also produced a small third component, while no additional component was seen with propofol or fentanyl. These additional components probably arise from creation of an additional closed state of the channel. 6 We conclude that these agents are not altering channel properties merely by exerting non‐specific effects via the lipid bilayer and that they are probably not all acting by similar mechanisms.