The Myocardial Lesions Produced by the Potassium Channel Opener Aprikalim in Monkeys and Rats Are Prevented by Blockade of Cardiac {beta}-Adrenoceptors

Aprikalim is a potent, specific, and selective opener of ATP-sensitiveK⁺ (K_ATP) channels. By virtue of this pharmacological property,aprikalim affords cardioprotection in experimental models ofischemia/reperfusion injury, and, at higher doses, also causesperipheral or coronary vasodilatation. Direct-acting peripheralvasodilators can cause myocardial lesions, particularly in ratsand dogs. However, unexpectedly, aprikalim produced this effectalso in monkeys. Thus, the primary aim of this investigationwas to assess whether in monkeys these myocardial lesions werethe direct or indirect consequence of the vascular effects ofaprikalim. Cyno-mologus monkeys were given the ß-adrenoceptorantagonist nado-lol (2 mg/kg po, twice daily) for 4 consecutivedays. On the third and fourth day of the experiment, they receivedaprikalim (1 mg/kg po). In another series, two monkeys carryingtelemetry transmitters for blood pressure and heart rate measurementswere also given aprikalim or its vehicle. Finally, aprikalim(1 mg/kg po for 2 days) or its vehicle was administered to ratswhich were concurrently treated with the ß-adrenoceptorantagonist atenolol (5 mg/ kg sc) or its vehicle. In cynomologusmonkeys, aprikalim produced focal and multifocal myocardialnecrosis of minimal to moderate intensity in or near the papillarymuscles of the left ventricle. These effects were abrogatedby nadolol. Similarly, necrotic lesions were caused by aprikalimonly in those rats which had not been pretreated with atenolol.In monkeys, aprikalim produced a marked and long-lasting decreasein aortic blood pressure, accompanied by an even more prolongedtachycardia. These results demonstrate that aprikalim can producemyocardial necrosis not only in rats but also in monkeys. Toour knowledge, this is the first time that such adverse effectsare reported for a vasodilator in monkeys. More importantly,these effects were prevented by blocking cardiac ß-adrenoceptors.Thus, the myocardial lesions produced by aprikalim may be attributedto its profound and prolonged hemodynamic effects.     

A comparison of bonfils fiberscope‐assisted laryngoscopy and standard direct laryngoscopy in simulated difficult pediatric intubation: a manikin study

Introduction: Difficult airway management in children is challenging. One alternative device to the gold standard of direct laryngoscopy is the STORZ Bonfils fiberscope (Karl Storz Endoscopy, Tuttlingen, Germany), a rigid fiberoptic stylette‐like scope with a curved tip. Although results in adults have been encouraging, reports regarding its use in children have been conflicting. We compared the effectiveness of a standard laryngoscope to the Bonfils fiberscope in a simulated difficult infant airway. Methods: Ten pediatric anesthesiologists were recruited for this study and asked to perform three sets of tasks. For the first task, each participant intubated an unaltered manikin (SimBaby ^TM, Laerdal, Puchheim, Germany) five times using a styletted 3.5 endotracheal tube (ETT) and a Miller 1 blade (group DL‐Normal). For the second task, a difficult airway configuration simulating a Cormack‐Lehane grade 3B view was created by fixing a Miller‐1 blade into position in the manikin using a laboratory stand. Each participant then intubated the manikin five times with a styletted 3.5 ETT using conventional technique but without touching the laryngoscope (group DL‐Difficult). In the third task, the manikin was kept in the same difficult airway configuration, and each participant intubated the manikin five times using a 3.5‐mm ETT mounted on the Bonfils fiberscope as an adjunct to direct laryngoscopy with the Miller‐1 blade (group BF‐Difficult). Primary outcomes were time to intubate and success rate. Results: A total of 150 intubations were performed. Correct ETT placement was achieved in 100% of attempts in group DL‐Normal, 90% of attempts in group DL‐Difficult and 98% of attempts in BF‐Difficult. Time to intubate averaged 14 s (interquartile range 12–16) in group DL‐Normal; 12 s (10–15) in group DL‐Difficult; and 11 s (10–18) in group BF‐Difficult. The percentage of glottic opening seen (POGO score) was 70% (70–80) in group DL‐Normal; 0% (0–0) in group DL‐Difficult; and 100% (100–100) in group BF‐Difficult. Discussion: The Bonfils fiberscope‐assisted laryngoscopy was easier to use and provided a better view of the larynx than simple direct laryngoscopy in the simulated difficult pediatric airway, but intubation success rate and time to intubate were not improved. Further studies of the Bonfils fibrescope as a pediatric airway adjunct are needed.     

Reduction of plasma and urinary vasopressin during treatment of severe hypertension by captopril

Abstract. Plasma concentrations and urinary excretion rate of vasopressin (VP) were examined in ten cases of severe hypertension before and during short-term treatment by Captopril (SQ 14 225). Before Captopril, plasma and urinary VP were high (respectively 5.24 pmol/1 and 68 pmol/day) and positively correlated to plasma renin activity (PRA) and plasma aldosterone (PA). The decline in blood pressure (mean —15%) after Captopril was correlated not only to initial PRA and PA values, but also to plasma ( r = 0.89; P < 0.001) and urinary ( r = 0.78; P < 0.01) VP values. The initial dose of Captopril (1 mg/kg) induced a rapid decrease in blood pressure whereas plasma VP did not rise and aldosterone decreased. At the eighth day of Captopril treatment (mean daily dose 6±1.5 mg/kg) the drop in blood pressure (— 12%) and in aldosterone persisted together with a significant reduction in plasma (1.18 pmol/1; P <0.01) and urinary (25 pmol/day; P <0.01) VP. It is suggested that these sustained simultaneous reductions in the rates of secretion of vasopressin and aldosterone are both elements of the antihypertensive effect of Captopril.     

Abnormal maturation pathway of keratinocytes in psoriatic skin

We compared the maturation pathway of normal and psoriatic epidermis using three different markers: (1) Involucrin, which is normally detected in the stratum granulosum in normal skin, was detected in all but the basal layer of involved psoriatic skin; (2) an antigen, recognized by the murine monoclonal antibody psi 3, was present in all but the basal layer of involved psoriatic skin but was absent from uninvolved and normal skin; (3) fibronectin, which normally localizes in the dermis and the epidermal-dermal junction, was also detected intra- and extracellularly in the psoriatic epidermis. These results indicate that the alterations in keratinocyte maturation found in psoriasis do not arise from a truncation of the normal maturation pathway but rather reflect the onset of an abnormal pathway of differentiation characterized by the expression of psi 3 antigen and fibronectin and the premature appearance of involucrin.     

Plasma renin substrate sensitivity to oestrogens and oestrogen metabolism in cirrhosis

Abstract. Oestrogen stimulation of plasma renin substrate (PRS) was studied in men with alcoholic cirrhosis. PRS values, before and I,2,4 and 6 days after a single oral administration of 100 pg of an oestrogen derivative, 11 β -methoxy-17–ethynyl-1,3,5(10)-estratriene-3,17 β -diol (Moxestrol), were measured by radioimmunoassay of generated angiotensin I in five men with normal liver function and five men with alcoholic cirrhosis. Basal PRS was 0.93 ± 0.22 nmol/ml (mean ± 1 SD) in the normal men and significantly lower (P<0.01) in the men with cirrhosis (0.33±0.14 nmol/ml). Two days after administration of Moxestrol, PRS rose significantly but transiently (P<0.05) to 1.41 ±0.42 nmol/ml in the normal men and to 0.47 ± 0.15 in the cirrhotic men, the relative increase (˜50%) being similar in both groups. A study of the plasma kinetics and urinary excretion of Moxestrol was also performed to evaluate its metabolic clearance rate and absorption. Since the intestinal absorption of [¹⁴C] Moxestrol was not depressed in cirrhotic men, the low PRS values recorded are probably the consequence of hepatocyte dysfunction.     

Relevance of Antibody Valency in EGF Receptor Modulation

Binding characteristics of a monovalenl bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition.     

POSTOPERATIVE ANALGESIA WITH EXTRADURAL CLONIDINE

The analgesic effect of extradural clonidine was evaluated ina double-blind study. In the recovery room, following orthopaedicor perineal surgery 20 ASA I and II patients were allocatedrandomly to two groups. The extradural clonidine (EC) groupreceived clonidine 2 µg kg^–1 in isotonic salinesolution 15 µg ml^–1. The extradural saline (ES)group received the equivalent volume of plain isotonic salinesolution. Pain was evaluated by a visual analogue scale (VAS)at 15-min intervals for the first 2 h and subsequently at 30-minintervals for the following 4 h. Morphine 5 mg was given s.c.when patients complained of pain after extradural saline orclonidine. In the EC group, the mean (SD) maximum pain reliefwas 68.2 (24.1)% of the initial VAS score, but it was only 14.7(25.2)% in the ES group. The mean duration of analgesia, beforeinjection of morphine, was significantly longer in the EC group(210 (87) min) compared with the ES group (45 (27) min) (P <0.001). Drowsiness and moderate hypotension were observed inthe EC group.     

Renin uptake by the right kidney in the rat following partial clamping of the left renal artery

Abstract. Renin secretion from both kidneys was studied in eleven Wistar rats for 40 min after partial clamping of the left renal artery. ¹⁴C Inulin and ³H para aminohippuric acid clearance and the arterial and venous plasma renin concentrations were measured in each kidney during control and experimental procedures.
After clamping, the arterial plasma renin concentration increased and correlated positively with the plasma renin concentration in both renal veins. However, the plasma renin concentration of the right renal vein was lower than the arterial concentration (P<0–01). The slope correlating the two variables is significantly lower than unity ( P < 0–05, n - 19). As the left kidney secreted a large amount of renin, calculation of secretion by the right kidney decreased to negative values, implying renin uptake by this kidney.
These data suggest the existence of a balance between the two kidneys. Renin secretion appears to maintain an equilibrium between release by the juxtaglomerular apparatus and removal from the blood into interstitial space. Release seems to predominate in the hypo perfused kidney, and removal in the contralateral kidney. This may result from the increase of the circulating angiotensin II, since we observed a direct correlation between renin uptake and the arterial plasma renin concentration.     

A comparison of the STORZ video laryngoscope and standard direct laryngoscopy for intubation in the Pediatric airway – a randomized clinical trial

Introduction:  Direct laryngoscopy can be challenging in infants and neonates. Even with an optimal line of sight to the glottic opening, the viewing angle has been measured at 15°. The STORZ DCI video laryngoscope (Karl Storz, Tuttlingen, Germany) incorporates a fiberoptic camera in the light source of a standard laryngoscope of variable sizes. The image is displayed on a screen with a viewing angle of 80°. We studied the effectiveness of the STORZ DCI as an airway tool compared to standard direct laryngoscopy in children with normal airway.
Methods:  In this prospective, randomized study, 56 children (ages 4 years or younger) undergoing elective surgery with the need for endotracheal intubation were divided into two groups: children who underwent standard direct laryngoscopy using a Miller 1 or Macintosh 2 blade (DL) and children who underwent video laryngoscopy using the STORZ DCI video laryngoscope with a Miller 1 blade (VL). Time to best view (TTBV), time to intubate (TTI), Cormack–Lehane (CL), and percentage of glottis opening seen (POGO) score were recorded.
Results:  TTBV in DL was 5.5 (4–8) s and 7 (4.2–9) s in VL. TTI in DL was 21 (17–29) s and in VL 27 (22–37) s ( P  = 0.006). The view as assessed by POGO score was 97.5% (60–100%) in DL and 100% (100–100%) in the VL ( P  = 0.003). Data are presented as median and interquartile range and analyzed using t -test.
Discussion:  This study demonstrates that the STORZ DCI video laryngoscope provides an improved view to the glottis in children with normal airway anatomy, but requires a longer time for intubation.     

Echocardiographic Assessment of the Interventricular Delay of Activation and Correlation to the QRS Width in Dilated Cardiomyopathy

The aim of the study was to define criteria for left ventricular pacing in dilated cardiomyopathy (DCM) using an echocardiographic evaluation of interventricular electromechanical delay (IMD) and a correlation of IMD to QRS duration. Standard 12-lead ECG and echocardiography with pulsed Doppler tissue imaging (DTI) were recorded in 35 DCM patients (mean age 58 +/- 11 years) with QRS duration from narrow (80 ms) to broad (222 ms) patterns. The timefor left ventricular activation was evaluated from the onset of QRS to the onset of aortic flow (Q-Ao) by standard pulsed Doppler (SP) or to the onset of mitral annulus systolic wave (Q-Mit) (DTI). The time for right ventricular activation was determinedfrom the onset of QRS to the onset of pulmonary flow (Q-Pulm) (SP) or to the onset of tricuspid annulus systolic wave (Q-Tri) (DTI). (Q-Ao)-(Q-Pulm) and (Q-Mit)-(Q-Tri) determined IMD for each method, respectively. QRS width and IMD showed correlation coefficients of r = 0.86 ([Q-Ao]-[Q-Pulm]) and r = 0.82 ([Q-Mit]-[Q-Tri]) (P < or = 0.001 ). Mean IMD of 77 +/- 15 ms (SP) and 88 +/- 26 ms (DTI) were noted for QRS width above 150 ms. Left ventricle delayed activation was positively correlated to QRS widening with both methods, (r = 0.90, [Q-Ao]), (r = 0.83, [Q-Mit]) (P < or = 0.001). In conclusion, QRS duration is a good marker of an interventricular mechanical asynchrony. According to IMD correction, left ventricular pacing may be mainly proposed to symptomatic DCM patients with QRS duration > 150 ms.