Investigating the cardiac pathology of SCO2-mediated hypertrophic cardiomyopathy using patients induced pluripotent stem cell-derived cardiomyocytes.

Mutations in SCO2 are among the most common causes of COX deficiency, resulting in reduced mitochondrial oxidative ATP production capacity, often leading to hypertrophic cardiomyopathy (HCM). To date, none of the recent pertaining reports provide deep understanding of the SCO2 disease pathophysiology. To investigate the cardiac pathology of the disease, we were the first to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) from SCO2-mutated patients. For iPSC generation, we reprogrammed skin fibroblasts from two SCO2 patients and healthy controls. The first patient was a compound heterozygote to the common E140K mutation, and the second was homozygote for the less common G193S mutation. iPSC were differentiated into cardiomyocytes through embryoid body (EB) formation. To test the hypothesis that the SCO2 mutation is associated with mitochondrial abnormalities, and intracellular Ca2+ -overload resulting in functional derangements and arrhythmias, we investigated in SCO2-mutated iPSC-CMs (compared to control cardiomyocytes): (i) the ultrastructural changes; (ii) the inotropic responsiveness to ß-adrenergic stimulation, increased [Ca2+ ]o and angiotensin-II (AT-II); and (iii) the Beat Rate Variability (BRV) characteristics. In support of the hypothesis, we found in the mutated iPSC-CMs major ultrastructural abnormalities and markedly attenuated response to the inotropic interventions and caffeine, as well as delayed afterdepolarizations (DADs) and increased BRV, suggesting impaired SR Ca2+ handling due to attenuated SERCA activity caused by ATP shortage. Our novel results show that iPSC-CMs are useful for investigating the pathophysiological mechanisms underlying the SCO2 mutation syndrome.

Comparison of the performance of battery-operated fluid warmers.

OBJECTIVES: Warming intravenous fluids is essential to prevent hypothermia in patients with trauma, especially when large volumes are administered. Prehospital and transport settings require fluid warmers to be small, energy efficient and independent of external power supply. We compared the warming properties and resistance to flow of currently available battery-operated fluid warmers. METHODS: Fluid warming was evaluated at 50, 100 and 200 mL/min at a constant input temperature of 20°C and 10°C using a cardiopulmonary bypass roller pump and cooler. Output temperature was continuously recorded. RESULTS: Performance of fluid warmers varied with flows and input temperatures. At an input temperature of 20°C and flow of 50 mL/min, the Buddy Lite, enFlow, Thermal Angel and Warrior warmed 3.4, 2.4, 1 and 3.6 L to over 35°C, respectively. However, at an input temperature of 10°C and flow of 200 mL/min, the Buddy Lite failed to warm, the enFlow warmed 3.3 L to 25.7°C, the Thermal Angel warmed 1.5 L to 20.9°C and the Warrior warmed 3.4 L to 34.4°C (p<0.0001). CONCLUSION: We found significant differences between the fluid warmers: the use of the Buddy Lite should be limited to moderate input temperature and low flow rates. The use of the Thermal Angel is limited to low volumes due to battery capacity and low output temperature at extreme conditions. The Warrior provides the best warming performance at high infusion rates, as well as low input temperatures, and was able to warm the largest volumes in these conditions.

One-minute heart rate variability - an adjunct for airway obstruction identification.

Heart rate variability (HRV) reflects cardiac and autonomic nervous system activity. It is usually measured over a relatively prolonged period and presented using multiple parameters. Here, we studied rapid HRV changes during airway obstruction using a short (1 min) sampling window. Forty healthy volunteers underwent a trial of obstructed breathing. Heart rate was recorded during three consecutive sets comprised of 1-min control followed by 1 min of obstructed breathing, with 1 min of rest between sets. Time and frequency domain analysis were used to compare HRV during control versus obstructed breathing. Compared with control, HRV intensely increased during obstructed breathing: R-R intervals (time between consecutive R waves) standard deviation increased from 65 to 108 msec (P < 0.0001), root mean square of successive R-R interval from 61 to 82 msec (P = 0.001), number of pairs of successive R-R intervals that differ by more than 50 msec (NN50) from 16.5 to 25.3 events (P < 0.0001), and proportion of NN50 divided by total number of R-R intervals from 26.6 to 35.1% (P = 0.001). Low frequency power increased by more than fourfold (P < 0.0001), allowing 90% sensitivity and 75% specificity for identifying airway obstruction (ROC area 0.88, P < 0.0001). We observed a rapid intense increase in HRV during obstructed breathing, significant enough to detect during a short 1-min sampling window. These findings suggest that HRV may be useful for rapid detection of airway obstruction, especially in situations where end-tidal CO2 monitoring is not optimal, such as during partial airway obstruction.

Comparison of Rhabdomyolysis Markers in Patients Undergoing Bariatric Surgery with Propofol and Inhalation-based Anesthesia.

BACKGROUND: Rhabdomyolysis is a relatively uncommon, severe complication of anesthesia and surgery in the morbidly obese. As the use of propofol-based anesthesia has been associated with an increased risk of rhabdomyolysis and metabolic acidosis, this pilot study was designed to assess the effect of propofol anesthesia on the incidence of rhabdomyolysis in morbidly obese patients undergoing bariatric surgery. METHODS: Thirty, morbidly obese patients (body mass index 43 ± 3 kg/m(2)) scheduled for bariatric laparoscopic sleeve gastrectomy were randomized to receive either propofol (P) or inhalational anesthetic (I)-based balanced general anesthesia. A sample of venous blood gas analysis including pH, bicarbonate concentrations, and calculated base excess was taken at the end of the operation. Creatine phosphokinase (CPK), troponin I, blood urea nitrogen, and creatinine plasma concentrations were measured at the end of the surgery and again 24 h later. RESULTS: All patients enrolled to the study completed it without significant complications. CPK, troponin I, blood urea nitrogen, and creatinine plasma concentrations at the end of the operation and at 24 h, as well as the bicarbonate concentration and the base excess at the end of the operation were not significantly different between the two study groups. A statistically significant mild respiratory acidosis was noted in the inhalational anesthetic group (pH 7.30 ± 0.04 vs. 7.36 ± 0.02 in the propofol group) CONCLUSIONS: This small-size pilot study may suggest that propofol-based anesthesia is not related to increased incidence of rhabdomyolysis in morbidly obese patients undergoing short, uncomplicated bariatric surgery.

A Call of Alert for the Ambu AuraStraight Disposable Laryngeal Mask.

One day after removal of an AuraStraight disposable laryngeal mask, a plastic laryngeal mask airway cuff shield was retrieved from the oropharynx of a 5-year-old child refusing to eat, drooling, and pointing to her throat. We discuss the reasons why this occurred and suggest how it can be prevented in the future.

Verification of intravenous catheter placement by auscultation--a simple, noninvasive technique.

BACKGROUND: Verification of proper placement of an intravenous catheter may not always be simple. We evaluated the auscultation technique for this purpose. METHODS: Twenty healthy volunteers were randomized for 18G catheter inserted intravenously either in the right (12) or left arm (8), and subcutaneously in the opposite arm. A standard stethoscope was placed over an area approximately 3 cm proximal to the tip of the catheter in the presumed direction of the vein to grade on a 0-6 scale the murmur heard by rapidly injecting 2 mL of NaCl 0.9% solution. The auscultation was evaluated by a blinded staff anesthesiologist. RESULTS: All 20 intravenous injection were evaluated as flow murmurs, and were graded an average 5.65 (±0.98), whereas all 20 subcutaneous injections were evaluated as either crackles or no sound, and were graded an average 2.00 (±1.38), without negative results. Sensitivity was calculated as 95%. Specificity and Kappa could not be calculated due to an empty false-positive group. CONCLUSIONS: Being simple, handy and noninvasive, we recommend to use the auscultation technique for verification of the proper placement of an intravenous catheter when uncertain of its position. Data obtained in our limited sample of healthy subjects need to be confirmed in the clinical setting.

Prolonged nerve blockade in a patient treated with lithium.

We report a case of a patient, chronically treated with oral lithium, who presented with an extremely prolonged (42-hour) duration of sensory and motor paralysis following an uneventful infraclavicular block for hand surgery that was performed under ultrasound guidance using bupivacaine and lidocaine. Due to its direct effect on nerve conduction of action potential, we propose that lithium may have had a role in the unusually prolonged duration of a peripheral nerve block.