Effects of hypothermia in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were hypoventilated to extrene hypercapnia (Paco₂?20 kPa) at Fio₂ 0.5, and allotted to a hypothermic group (31.5 ±0.l°C, n = 6) or a control group (39.6±0.2°C, n = 6). Compared with the controls, the hypothermic animals had higher Pao₂ (19.2 vs 15.6 kPa, P>0.05), Sao₂ (97.2 vs 89.3%), Sv?o₂ (78.7 vs 68.2%), end-tidal 0₂ (34.5 vs 24.8 kPa) and arterial pH (7.01 vs 6.91), (P>0.01), but lower Pv?o₂ (7.0 vs. 10.2 kPa) and Paco₂ (13.2 vs 23.5 kPa), (P>0.01). Hypothermia reduced O₂ delivery (Do₂), O₂ consumption (Vo₂) and CO₂ production by 40–45% (P> 0.05), but O₂ extraction ratio, i.e. VO₂, Do₂-¹. 100 (%), did not differ between groups. Hypothermic animals had lower heart rate (127 vs 223 beats.min-¹, P>0.05) and cardiac output (2.5 vs 3.9 l.min-¹, P>0.01). Subsequently, the inspired oxygen fraction (Fio₂) was decreased stepwise (0.3, 0.25, 0.21, 0.15, 0.10) at 30- min intervals. At Fio₂ 0.3, the hypothermic group had higher Pao₂ (10.0 vs 5.7 kPa), Sao₂ (91.3 vs 28.5%), Pv?o, (5.8 vs 3.4 kPa), Sv?o₂ (70.7 vs 10.3%), end-tidal O₂ (16.7 vs 8.5 kPa), O₂ delivery (344 vs 155 ml.min-¹), arterial pH (7.02 vs 6.94) and systemic vascular resistance (3850 vs 1652 dyn.s. cm-⁵(38500 vs 16520 μN. s. c m-⁵)) compared with the controls (P>0.01), while Paco₂ was lower (12.4 vs 22.7 kPa), as well as O₂ extraction ratio (23 vs 63%) and O₂ half saturation tension (4.3 vs 8.0 kPa) (P>0.01). Except for Pao₂, all differences between groups remained significant at Fio₂ 0.25. The control animals died during Fio₂ 0.25 and 0.21, while all hypothermic animals remained circulatorily stable. One hypothermic animal died after 12 min at Fio₂ 0.15 and the remainder after 6–39 min (mean 22 min) at Fio₂ 0.10. We conclude that hypothermia markedly improves whole-body oxygen balance, cardiovascular stability and survival in hypercapnic hypoxemia.     

Effects of hypothermia with and without buffering in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were hypoventilated to extreme hypercapnia (Paco₂=20 kPa) at Fio₂ 0.5, and allotted to receive hypothermia (=31.5˚C) and buffer infusion, (HB–group, n = 6) or to a hypothermic control group (H–group, n = 6). The HB–group had higher arterial pH (7.34 vs 7.09, P < 0.01) and plasma bicarbonate (58.8 vs 35.4 mmol–l^-1, P < 0.01) than the controls, but lower mean pulmonary arterial pressure (MPAP), (16 vs 23 mmHg (2.1 vs 3.1 kPa), P < 0.01) and pulmonary vascular resistance (PVR), (512 vs 699 dyn–s–cm^-5 (5120 vs 6990 μN–s–cm^-5), P < 0.05). Mixed venous Po₂ (Pvo₂) was lower in the HB–group (5.1 vs 6.8 kPa, P < 0.01), as well as serum potassium (2.8 vs 3.7 mmol l^-1, P <0.01) and ionized calcium (1.01 vs 1.29 mmol l^-1, P <0.01). Subsequently, the inspired oxygen fraction (Fio₂) was decreased stepwise (0.3, 0.25, 0.21, 0.15, 0.10) at 30 min intervals. At Fio₂ 0.3, the HB–group had lower Pvo₂ (6.6 vs 7.8 kPa, P <0.01), O₂ half saturation tension (3.6 vs 4.2 kPa, P <0.01), MPAP (17 vs 25 mmHg (2.3 vs 3.3 kPa, P <0.01) and PVR (598 vs 793 dyn–s–cm^-5 (5980 vs 7930 μN–S'cm^-5, P <0.05) compared with the controls, but higher arterial O₂ saturation (95.3 vs. 88.6%, P < 0.01) and O₂ content (17.7 vs 15.7 ml– 100 ml^-1, P <0.05). The groups did not differ in O₂ delivery, in spite of their difference in arterial O₂ content, because of a lower cardiac output in the HB–group (1.6 vs 2.2 l–min^-1, P <0.05). Mixed venous O₂ content, O₂ consumption and O₂ extraction did not differ between groups. Combined use of hypothermia and buffering did not improve survival in hypercapnic hypoxemia as compared to a hypothermic regimen without buffer.     

Effect of external high-frequency oscillation on severe cardiogenic pulmonary edema

Effective gas exchange can be maintained in animals without endotracheal intubation using external high-frequency oscillation (EHFO). The aim of this study was to evaluate the effect of EHFO in patients with respiratory failure due to severe cardiogenic pulmonary edema. Seven patients were ventilated with EHFO for 2h at 60 oscillations·min⁻¹, with a cuiras pressure of 36 cmH₂O (−26 to +10) and an inspiratory to expiratory ratio of 1:1, with EHFO. Blood gas values and hemodynamic parameters were measured. Significant increases were noted in cardiac index (2.3±0.5 to 2.5±0.5 l·m⁻²;P<0.05), stroke volume index (24±7 to 28±8 ml·m⁻²;P<0.05), and arterial O₂ pressure (Pao₂) (70±4 to 95±23 mmHg;P<0.01) without a change in pulmonary artery wedge pressure at 1 h after EHFO. The respiratory rate decreased from 28±3 to 22 ±3 breaths·min⁻¹ at 5 min after the termination of EHFO (P <0.01). Arterial CO₂ pressure (Paco₂) did not, however, decrease. Increased stroke volume without a change in pulmonary artery wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with EHFO. The use of EHFO may be effective not only for gas exchange but also for left ventricular function in patients with severe cardiogenic pulmonary edema.     

Increased lung clearance of isoflurane shortens emergence in obesity: a prospective randomized‐controlled trial

Background: There is a concern that obesity may play a role in prolonging emergence from fat‐soluble inhalational anaesthetics. We hypothesized that increased pulmonary clearance of isoflurane will shorten immediate recovery from anaesthesia and post‐anaesthesia care unit (PACU) stay in obese patients. Methods: After Ethics Review Board approval, 44 ASA I–III patients with BMI>30 kg/m² undergoing elective gynaecological or urological surgery were randomized after completion of surgery to either an isocapnic hyperpnoea (IH) or a conventional recovery (C) group. The anaesthesia protocol included propofol, fentanyl, morphine, rocuronium and isoflurane in air/O₂. Groups were compared using unpaired t‐test and ANOVA. Results: Minute ventilation in the IH group before extubation was 22.6±2.7 vs. 6.3±1.8 l/min in the C group. Compared with C, the IH group had a shorter time to extubation (5.4±2.7 vs. 15.8±2.7 min, P<0.01), initiation of spontaneous ventilation (2.7±2.3 vs. 6.5±4.5 min, P<0.01), BIS recovery >75 (3.2±2.3 vs. 8.9±5.8 min, P<0.01), eye opening (4.6±2.9 vs. 13.6±7.1 min, P<0.01) and eligibility for leaving the operating room (7.1±2.9 vs. 19.9±11.9 min, P<0.01). There was no difference in time for eligibility for PACU discharge. Conclusion: Increasing alveolar ventilation enhances anaesthetic elimination and accelerates short‐term recovery in obese patients.     

Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia

Purpose This study was performed in order to assess the effects of olprinone, a phosphodiesterase III inhibitor, on hepatic oxygen delivery (DO₂H), oxygen consumption (VO₂H), and mitochondrial oxidation in the liver of a porcine endotoxemia model. Methods Fourteen pigs received continuous infusion of endotoxin via the portal vein for 240 min. From t = 150 to t = 240 min, animals were randomly divided into two groups to receive saline (control [CONT]; n = 7), or olprinone (OLP; n = 7) via the central vein. Results In the OLP group, prior to olprinone treatment at 150 min, endotoxin induced significant decreases in the cardiac index (CI; from 120 ± 31 to 65 ± 13 ml·kg⁻¹·min⁻¹; P < 0.01) and DO₂H (from 3.58 ± 0.81 to 1.55 ± 0.49 ml·kg⁻¹·min⁻¹; P < 0.01), while VO₂H was maintained. After administration of olprinone (from t = 150 to t = 240 min), CI was unchanged, while DO₂H increased from 1.55 ± 0.49 to 1.93 ± 0.38 ml·kg⁻¹·min⁻¹ (P < 0.01) and VO₂H increased from 0.42 ± 0.28 to 0.69 ± 0.38 ml·kg⁻¹·min⁻¹ (P < 0.01). At t = 240 min, the oxidation level of cytochrome aa3 was significantly higher in the OLP group than in the CONT group (OLP, 66.2 ± 19.3% vs CONT, 26.4 ± 17.3%; P < 0.01). Conclusion Our data for this porcine endotoxemia model suggest that olprinone may have beneficial therapeutic effects in restoring not only systemic and hepatic circulation but also mitochondrial oxidation in the liver.     

Effects of neonatal estrogenization on rat bone development: A histomorphometric study

Summary The effects of a single dose of 500 μg of estradiol benzoate, administered on the first day of life, on rat bone development have been histomorphometrically studied at 15 days of age. Estrogenized animals presented decreased total tibial length (16.55±0.50 vs. 17.84±0.73 mm,P<0.05) and increased thickness of the cartilage growth plate (528.92±13.30 vs. 382.77±37.85 μm,P<0.01). This increase was mostly due to the presence of a wider (P<0.01) layer of hypertrophic cartilage in the estrogenized rats than in control ones. It might be related to the decreased number of chondroclasts (0.20±0.01 vs. 0.36±0.06 mm⁻¹,P<0.05) found in the resorption zone. Two metaphyseal zones have been considered. In the upper metaphyseal zone there was an increase in the surface density of the cartilaginous trabeculae (49.20±1.80 vs. 40.72±1.95 mm²/mm³,P<0.05), without changes in the volume density. It was related to the presence of thinner and more irregular trabeculae in the estrogenized animals. In the lower metaphyseal zone both the volume (0.19±0.01 vs. 0.14±0.01 mm³/mm³,P<0.01) and surface (34.83±3.01 vs. 26.52±2.46 mm²/mm³,P<0.05) densities of the osseous trabecular tissue were increased in estrogenized rats. No significant differences were found either in the number of osteocytes per area unit of osseous tissue or in the number of osteoclasts per unit length of trabecular osseous tissue.     

Abnormal cell calcium concentrations in cultured bone cells obtained from femurs of obese and noninsulin-dependent diabetic rats

Summary Cytoplasmic free calcium concentration [Ca²⁺]i was quantified in cultured bone cells with osteoblastic characteristics. The cells were obtained from femurs of obese (fa/fa) Wistar-Kyoto rats, from nonobese, noninsulin-dependent diabetic (NIDD) Sprague Dawley rats, and from their appropriate controls. [Ca²⁺]i was also determined in bone cells obtained fromin vivo insulin-treated NIDD rats. Obese (Wistar Kyoto) rats had increased body weight (313±13 vs. 249±4 g;P<0.01), decreased femur weights (0.68±0.05 vs. 0.89±0.05 g;P<0.05), similar glucose levels (148±5 vs. 139±3 mg/dl), and higher plasma insulin levels (6.0±0.5 vs. 0.7±0.1 ng/ml;P<0.01) when compared with their nonobese [(fa/+); (+/+)] littermates. Nonobese, NIDD rats, compared with their appropriate controls (nondiabetic Sprague Dawley rats) had higher plasma glucose levels (235±32 vs. 145±3 mg/dl;P<0.01) but their plasma insulins, body weights, and femur weights were similar to controls (0.7±0.1 vs 0.6±0.1 ng/ml; 302±4 vs. 318±14 g; 0.97±0.4 vs. 0.98±0.04 g, respectively). Long-term (4 weeks) daily insulin treatment (2 u/100 g) of the NIDD rats increased their plasma insulin (1.9 ng/ml;P<0.05) and body weight (369±13 g;P<0.05) but did not change their plasma glucose levels (225±5 mg/dl), or femur weights (0.98±0.4 g). [Ca²⁺]i in bone cells derived from the femurs of obese animals was higher than in cells derived from their nonobese littermates (156±22 vs. 71±13 nM;P<0.01). In bone cells from NIDD rats, [Ca²⁺]i was lower compared with controls (146±22 vs. 229±19 nM;P<0.001). Insulin treatment of the diabetic animals augmented the decrease in [Ca²⁺]i in their bone cells (68±11 nM;P<0.005 compared with nontreated rats). These data reveal that [Ca²⁺]i in cultured bone cells from obese nondiabetic and nonobese NIDD rats differs from that of their controls. Compared with their controls, the changes in [Ca²⁺]i in bone cells from the NIDD and obese animals were in opposite directions. Whether the underlying mechanisms for the changes in cell [Ca²⁺]i in nondiabetic obese and nonobese NIDD animals differ, and whether the changes in [Ca²⁺]i observed in the cultured cells reflect thein vivo condition in bone cells of these animals are questions that await further investigations.     

BILATERAL NEPHRECTOMY DELAYS GASTRIC EMPTYING OF A LIQUID MEAL IN AWAKE RATS

Aims: This study evaluates the effect of bilateral nephrectomy on the gastric emptying of a liquid meal. Methods: Male rats were submitted under anesthesia to cervical vessels cannulation and bilateral lumbar incision, followed or not by nephrectomy. Next day, they were gavage fed (1.5 mL) with phenol red (0.5 gmL^?1) in 5% glucose solution and sacrificed 0, 10, 20, 30 or 45 min later. A blood sample was obtained for biochemical analysis while gastric dye retention was determined by spectrophotometry. Data (mean ± SEM) were compared by ANOVA and Student–Newman–Keuls tests. Results: Gastric emptying values from nephrectomy group at 10, 20, 30 and 45 min were lower (P<0.05) than those of sham-operated animals (22.0 ± 4.0 vs. 38.9 ± 6.1%, 34.1 ± 1.4 vs. 66.9 ± 1.3%, 45.5 ± 6.1 vs. 64.9 ± 5.4% and 59.7 ± 2.4 vs. 81.5 ± 4.0%, respectively). Mean arterial pressure, blood volume, serum osmolarity, urea, creatinine and potassium values were higher (P < 0.05) in nephrectomy group than in sham-operated animals (143.3 ± 2.7 vs. 100.5 ± 4.1 mmHg, 15.7 ± 0.9 vs. 8.9 ± 1.1 mL 100 g^?1, 344.0 ± 10.8 vs. 299.4 ± 1.3 mOsm KgH₂O^?1, 344.0 ± 33.7 vs. 47.0 ± 2.8 mg dL^?1, 3.6 ± 0.3 vs. 1.1 ± 0.1 mg dL^?1, 6.4 ± 0.7 vs. 3.7 ± 0.2 mEq L^?1, respectively). The plasmatic Na⁺ values did not change (139.3 ± 2.0 in sham-operation vs. 123.0 ± 7.5 mEq L^?1 in nephrectomy). Conclusion: Acute loss of kidney function markedly delays the gastric emptying rates, which could be involved in gastrointestinal dysmotility complaints seen after renal failure.     

The effects of muscle-building exercise on bone mineral density of the radius,spine, and hip in young men

Summary We previously demonstrated that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)₂D, and urinary cyclic AMP. These studies were interpreted to mean that this form of exercise increases bone formation and modifies the vitamin D-endocrine system to provide more calcium for bone. The present investigation was carried out in normal young adult white men to determine the effects of exercise on bone mineral density at weight-bearing and nonweight-bearing sites. Twelve men who had regularly engaged in muscle-building exercises (use of weights, exercise machines, or both) for at least 1 year and 50 age-matched controls (aged 19–40 years) were studied. The body weights of the two groups were not different from each other (78±2 vs. 74±1 kg, NS). Bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry, and BMD of the midradius was measured by single-photon absorptiometry. It was found that muscle-building exercise was associated with increased BMD at the lumbar spine (1.35±0.03 vs. 1.22±0.02 g/cm²,P<0.01), trochanter (0.99±0.04 vs. 0.86±0.02 g/cm²,P<0.01), and femoral neck (1.18 ±0.03 vs. 1.02±0.02 g/cm²,P<0.001) but not at the midradius (0.77±0.02 vs. 0.77±0.01 g/cm², NS). These studies provide additional evidence that muscle-building exercise is associated with increases in BMD at weight-bearing sites but not at nonweight-bearing sites.     

Effects of propofol vs isoflurane on respiratory gas exchange during laparoscopic cholecystectomy

Background : Respiratory function and pulmonary gas exchange are affected in laparoscopic procedures where a pneumoperitoneum is introduced using CO₂. Previous studies have shown differing results concerning pulmonary gas exchange during laparoscopic procedures: Whereas in patients undergoing isoflurane anaesthesia decreases in PaO₂ are demonstrated, this factor remains unchanged in patients undergoing propofol anaesthesia. In the present study, the effects of propofol on pulmonary gas exchange were compared with those of isoflurane in patients undergoing elective laparoscopic cholecystectomy in a prospective randomised manner. Methods : Twenty ASA patients with physical status I and II were divided randomly between isoflurane (IG) and propofol groups (PG). After induction of anaesthesia patients were moderately hyperventilated. Respirator settings remained unchanged during pneumoperitoneum (PP) until 10 min after deflation of the peritoneal cavity. Blood gas analyses were performed at 5 time points: 15 min after induction of anaesthesia (giving pre-PP values), immediately before carbon dioxide insufflation (0 min PP), after both 30 and 60 min of PP and 10 min post PP. Inspiration plateau pressure (P_plat), compliance of the respiratory system, and both ins- and expiratory gas concentrations were continuously recorded by an Ultima V® monitor (Datex Corp., Helsinki, Finland). The difference between arterial and end-tidal CO₂ partial pressure (P(a-et)CO₂) was calculated so as to allow assessment of physiological dead space by the modified Bohr equation. Results : Pulmonary gas exchange differed significantly after 30 min of PP between the IG and the PG. At this time, PaO₂ was 19.5 ± 2.9 kPa (mean ± SD) in the IG and 23.1 ± 1.8 kPa in the PG (P<0.01), whereas PaCO₂ was 5.5 ± 0.37 kPa in the IG and 4.9 ± 0.27 kPa in the PG (P<0.01). These discrepancies remained until after carbon dioxide desufflation. At 10 min post PP, PaO₂ was 18.3 ± 2.6 kPa in the isoflurane group and 21.9 ± 2.2 kPa in the propofol group (P<0.01), whereas PaCO₂ was 5.4 ± 0.46 kPa in the IG and 4.8 ± 0.22 kPa in the PG (P<0.01). During carbon dioxide insufflation the P(a-et)CO₂ increased significantly in the IG from 0.47 ± 0.13 kPa to 0.76 ± 0.37 kPa (P<0.05), while the values in the PG remained constant. Conclusion : This study demonstrates that pulmonary gas exchange in patients with laparoscopic cholecystectomy is affected by the choice of anaesthetic procedure. During and after laparoscopic cholecystectomy using isoflurane as the anaesthetic, the PaCO₂ is significantly higher and the PaO₂ significantly lower than they are with propofol.     

Systemic capsaicin inhibits neuronal activation in the brainstem during postoperative ileus in the mouse

Introduction Neuronal inhibitory reflex mechanisms contribute to postoperative ileus after abdominal surgery. During this condition, sensory neurons in the brainstem are activated. We aimed to determine the contribution of capsaicin-sensitive afferents to central vagal sensitivity in mice during postoperative ileus. Materials and methods Under enflurane anesthesia, C57BL/6 mice were laparotomized and the small bowel was manipulated to induce ileus or was left untouched as a sham-treatment group. A subgroup of ileus animals was pre-treated with Capsaicin (1 μm/kg, i.p.) 48 h before small bowel manipulation. The animals were killed 24 h later and the brainstem was removed for Fos immunohistochemistry, which was quantified in the nucleus of the solitary tract (nTS). Spontaneous jejunal motility was recorded in vitro. Leukocyte infiltration in the intestinal muscularis was studied by myeloperoxidase staining as an index of postoperative inflammation. Results There were 30±9 Fos-positive neurons counted in the nTS after ileus and 6±2 in sham controls (Bregma −7.70 mm, P=0.01). A reduction to 8±3 was observed after Capsaicin pre-treatment in ileus animals (P<0.05). Peak amplitudes of spontaneous jejunal motility were 2±0.3 cmH₂O during postoperative ileus, 3±0.6 cmH₂O after ileus with capsaicin pre-treatment, and 10±2 cmH₂O in control animals (N=6, both P<0.05). The number of leukocytes infiltrating the muscularis was 39±9/mm² during ileus and 1.8±1/mm² in controls (mean±SEM, P<0.01, N=6). After capsaicin, this number increased to 72±28/mm² in ileus animals (P<0.05 vs control animals, N=7). Conclusion The inhibition of capsaicin-sensitive vagal afferent pathways appears to boost rather than to attenuate the inflammatory response during postoperative ileus, while intestinal motility remained unchanged. This suggests a protective role of the capsaicin-sensitive afferent innervation for the inflammatory phase of postoperative ileus. Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Effect of peak inspiratory flow on gas exchange, pulmonary mechanics, and lung histology in rabbits with injured lungs

Purpose The aim of this study was to evaluate, using a rabbit model, the little-known effect of different levels of peak inspiratory flow on acutely injured lungs. Methods Fourteen male rabbits (body weight, 2711 ± 146 g) were anesthetized and their lungs were injured by alveolar overstretch with mechanical ventilation until Pa_O2 was reduced below 300 mmHg. Injured animals were randomly assigned to: the P group—to receive pressure-regulated volume-control ventilation (PRVCV; n = 7); and the V group—to receive volume-control ventilation (VCV; n = 7). Other ventilator settings were: fraction of inspired oxygen (FI_O2), 1.0; tidal volume, 20 ml·kg⁻¹; positive end-expiratory pressure (PEEP) 5 cmH₂O; and respiratory rate, 20 min⁻¹. The animals were thus ventilated for 4 h. Throughout the protocol, ventilatory parameters and blood gas were measured every 30 min. After the protocol, the lung wet-to-dry ratio and histological lung injury score were evaluated in the excised lungs. Results Throughout the protocol, peak inspiratory flow and mean inspiratory flow values in the P group were significantly higher than those in the V group (26.7 ± 5.0 l·min⁻¹ vs 1.2 ± 0.2 l·min⁻¹, and 4.3 ± 0.3 l·min⁻¹ vs 1.1 ± 0.1 l·min⁻¹; P < 0.05). The wet-to-dry ratio in the P group was also significantly higher than that in the V group (7.7 ± 0.9 vs 6.3 ± 0.5; P < 0.05). More animals in the P group than in the V group had end-of-protocol Pa_O2/FI_O2 ratios below 200 mmHg (43% vs 0%; P = 0.06). Conclusion In rabbits with injured lungs, high peak inspiratory flow with high tidal volume (V_T) reduces the Pa_O2/FI_O2 ratio and increases the lung wet-to-dry ratio.     

Clearance of Drugs for Multiple Myeloma Therapy During In Vitro High‐Cutoff Hemodialysis

Current chemotherapy for multiple myeloma is based on bortezomib (BOR), dexamethasone (DEX), and thalidomide (THA). The purpose of the present study was to examine their clearance during high‐cutoff (HCO) hemodialysis and to accordingly apply the results to the dialytic removal of protein‐bound substances in general. During in vitro hemodialysis with human blood (blood, dialysate, and ultrafiltration flow rates 250, 500 and 5 mL/min, respectively) comparing a highly permeable HCO dialyzer (Theralite, 2.1 m²) to a high‐flux dialyzer (PFX; 2.1 m²), ultrafiltered volume was replaced by saline containing 30 g/L urea. After recirculation for equilibration, BOR was injected, and arterial and venous samples were drawn after 10, 11, and 12 min to measure the plasma clearance (K) of both urea and BOR. The same procedure was performed with THA and DEX. By mathematical simulation, the influence of varying plasma albumin concentrations (C_HSA) on the protein‐bound drug fraction (PBF) and K was assessed. Plasma K values of HCO and PFX for THA, BOR, and DEX were about 40% (80 ± 7 vs. 65 ± 6 mL/min; P < 0.05), 70% (40 ± 8 vs. 33 ± 4 mL/min; P < 0.05), and 65% (47 ± 11 vs. 38 ± 7 mL/min; P < 0.05), respectively—lower (P < 0.0001) compared with urea (125 ± 7 vs. 122 ± 5 mL/min). K was highest (P < 0.0001) for THA. K was negatively correlated with C_HSA (THA, r² = 0.58, P < 0.001; BOR, r² = 0.24, P < 0.05; DEX, r² = 0.22, P < 0.05). C_HSA continually decreased (P < 0.05) over time only with HCO, resulting in lower calculated PBF. Compared with BOR and DEX (minimum 72 and 56%, respectively), the PBF of THA (37%) was significantly lower (P < 0.001). A mathematical simulation based on the K values of urea and the drugs reliably estimated PBF (r² = 0.886, P < 0.001). Drugs for multiple myeloma therapy are significantly removed with both HCO and PFX, with important implications for the dosing and timing of administration, particularly in patients with cast nephropathy receiving extended dialysis. If the K_urea of a dialyzer and the PBF of any given drug are known, K_drug can be reliably estimated by mathematical simulation.     

Haemodynamic changes in human kidney allografts following administration of nifedipine: assessment with doppler spectrum analysis

Cyclosporin (CyA) has been demonstrated to increase the vascular resistance of renal allografts (RVR), whereas calcium channel blocking agents like nifedipine may counteract this effect. In this study RVR was calculated from renal blood flow (RBF), measured by the clearance of para-aminohippurate (PAH), and mean arterial pressure (MAP). Analysis of Doppler spectra obtained under ultrasonographic guidance was used as a non-invasive method of assessing renal haemodynamics. A comparison was made between these two methods to detect changes in renal haemodynamics which were caused by the administration of 10 mg nifedipine orally to 11 renal transplant recipients treated with CyA. RBF increased significantly (444 ± 176 vs 559 ± 192 ml/min per 1.73 m²; P < 0.05) despite a decrease in MAP (116 ± 10 vs 101 ± 11 mm Hg; P < 0.05) after administration of nifedipine. Calculated RVR decreased from 0.31 ± 0.17 to 0.20 ± 0.07 mmHg × min/ml (P < 0.05). Results of Doppler spectrum analysis were in concordance with these observations. Resistance index (RI) in interlobar arteries decreased from 0.60 ± 0.04 to 0.56 ± 0.06 (P < 0.05) and acceleration time (T_max) of the Doppler spectrum decreased from 133 ± 32 to 98 ± 32 ms (P < 0.05). Theoretically, a lower RI and decreased T_max indicate a reduced vascular resistance and changes in vascular wall compliance, respectively. Analysis of Doppler spectra may thus become a useful device for non-invasive assessment of acute changes in RVR.     

Heart Rate Variability,Left Ventricular Functions,and Cardiac Autonomic Neuropathy in Patients Undergoing Chronic Hemodialysis

Objective.?Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). Methods.?Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P₁ and P₂) and the central frequencies (F₁ and F₂) of low and of high frequency spectral bands were recorded. Results.?End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 ± 21.1 mL vs. 34.0 ± 14.3 mL and 131.5 ± 37.3 mL vs. 96.9 ± 18.9 mL, p<0.01, p<0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 ± 2.4% vs. 63.7 ± 10.1% and 0.29 ± 0.01 vs. 0.34 ± 0.07, p<0.001, p<0.05, respectively). P1 and P2 were decreased in Group II than in Group I (136.2 ± 173.9 m s² vs. 911.0 ± 685.5 and 96.5 ± 149.6 vs. 499.7 ± 679.5, p<0.001, p<0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p<0.01, r = 0.68 p<0.001, r = 0.65 p<0.002, r = 0.66 p<0.02, and r = 0.69 p<0.01). Conclusion.?As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.     

Effect of a Miniaturized Cardiopulmonary Bypass System on the Inflammatory Response and Cardiac Function in Neonatal Piglets

The cognitive impairment and hemodynamic instability after neonatal cardiac surgery with cardiopulmonary bypass (CPB) might be exacerbated by hemodilution. Therefore, this study investigated the impact of different bloodless prime volumes on the hemodynamics and the inflammatory response by a miniaturized CPB system in neonatal piglets. The bypass circuit consisted of a Capiox RX05 (Capiox Baby RX, Terumo Corp., Tokyo, Japan) oxygenator and 3/16 internal diameter arterial and venous polyvinyl chloride tubing lines, with a minimum 75 mL prime volume. Twelve 1‐week‐old piglets were placed on a mild hypothermic CPB (32°C) at 120 mL/kg/min for 2 h. The animals were divided into two groups, based on the volume of the prime solution. The priming volume was 75 mL in Group I and 175 mL in Group II. No blood transfusions were performed, and no inotropic or vasoactive drugs were used. The interleukin‐6 (IL‐6) and thrombin‐antithrombin (TAT) complex levels, as well as right ventricular and pulmonary functions, were measured before and after CPB. Group I had low levels of IL‐6 and TAT immediately after CPB (4370 ± 2346 vs. 9058 ± 2307 pg/mL, P < 0.01 and 9.9 ± 7.7 vs. 25.1 ± 8.8 ng/mL, P < 0.01, respectively). Group I had significantly improved cardiopulmonary function, cardiac index (0.22 ± 0.03 vs. 0.11 ± 0.05 L/kg/min, P < 0.001), and pulmonary vascular resistance index (7366 ± 2860 vs. 28 620 ± 15 552 dynes/cm⁵/kg, P < 0.01) compared with Group II. The miniaturized bloodless prime circuit for neonatal CPB demonstrated that the influence of hemodilution can reduce the subsequent inflammatory response. In addition, a low prime volume could therefore be particularly effective for attenuating pulmonary vascular resistance and right ventricular dysfunction in neonates.     

Quantification of Operational Learning in Minimal Invasive Extracorporeal Circulation

Minimal invasive extracorporeal circulation (MiECC) has initiated important new efforts within science and technology towards a more physiologic perfusion. In this study, we aim to investigate the learning curve of our center regarding MiECC. We studied a series of 150 consecutive patients who underwent elective coronary artery bypass grafting by the same surgical team during the initial phase of MiECC application. Patients were randomly assigned into two groups. Group A (n = 75) included patients operated on MiECC, while group B (n = 75) included patients operated with conventional cardiopulmonary bypass (cCPB). The primary end‐point of the study was to identify whether there is a learning curve when operating on MiECC. The following parameters were unrelated with increasing experience, even though the results favored MiECC use: reduced CPB duration (102.9 ± 25 vs. 122.2 ± 33 min, P <0.001), peak troponin release (0.07 ± 0.02 vs. 0.1 ± 0.04 ng/mL, P < 0.01), peak creatinine levels (0.97 ± 0.24 vs. 1.2 ± 0.3 mg/dL, P < 0.001), duration of mechanical ventilation (14.1 ± 7.2 vs. 36.9 ± 59.8 h, P < 0.01) and ICU stay (2.1 ± 0.7 vs. 4.4 ± 6.4 days, P < 0.01). However, need for intraoperative blood transfusion showed a trend towards a gradual decrease as experience with MiECC system was accumulating (R² = 0.094, P = 0.007). Subsequently, operational learning applied to postoperative hematocrit and hemoglobin levels (R² = 0.098, P = 0.006). We identified that advantages of MiECC technology in terms of reduced hemodilution and improved end‐organ protection and clinical outcome are evident from the first patient. Optimal results are obtained with 50 cases; this refers mainly to significant reduction in the need for intraoperative blood transfusion. Teamwork from surgeons, anesthesiologists, and perfusionists is of paramount importance in order to maximize the clinical benefits from this technology.     

Chronology of renal scarring in males with Alport syndrome

We investigated the onset of renal scarring in 62 males (aged 4 – 26 years) with Alport syndrome by measuring cortical interstitial volume fraction [Vv (interstitium/cortex)] and percentage global glomerular sclerosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as controls. Creatinine clearance at the time of biopsy was available for 43 Alport patients. A statistically insignificant correlation between age and Vv (interstitium/cortex) was observed in normal subjects (r = +0.47, slope = 0.0009, P = 0.07). In the Alport patients, age was significantly correlated with Vv (interstitium/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine clearance (r = –0.33, P = 0.04). Creatinine clearance was inversely correlated with Vv (interstitium/cortex) (r = –0.78, P = 0.001) and global glomerular sclerosis (r = –0.74, P = 0.001). The correlation with creatinine clearance was especially strong for Vv (interstitium/cortex) values above the normal range, i. e., >0.2 (r = –0.82, P = 0.001), and was absent for Vv (interstitium/cortex) <0.2 (r = –0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per 1.73 m² occurred more frequently in patients with Vv (interstitium/cortex) values >0.2 (P <0.0001) and in patients with >10% globally sclerosed glomeruli (P <0.001). Patients ≤ or >10 years of age differed in Vv (interstitium/cortex) [0.13±0.09 (mean ±SD) vs. 0.24±0.026, P <0.001], the frequency of Vv (interstitium/cortex) >0.2 (3/32 vs. 15/31, P <0.0001), the frequency of >10% globally sclerosed glomeruli (3/33 vs. 11/30, P <0.05), mean creatinine clearance (113±7 vs. 84±10 ml/min per 1.73 m², P = 0.057), and the frequency of creatinine clearance <80 ml/min per 1.73 m² (1/20 vs. 11/23, P <0.01). Thus, reduced creatinine clearance in males with Alport syndrome is associated with Vv (interstitium/cortex) >0.2 and >10% globally sclerosed glomeruli. These are frequently detectable in the 2nd decade. We hypothesize that most Alport males will require intervention during the 1st decade for optimal preservation of kidney function. Received July 7, 1997; received in revised form October 23, 1997; accepted October 26, 1997     

Sodium nitroprusside after cardiac surgery: systemic and splanchnic blood flow and oxygen transport

Background: Vasoactive drugs may interfere with splanchnic blood flow and tissue oxygenation. Sodium nitroprusside (SNP) is widely used in the treatment of postoperative hypertension after cardiac surgery, but the effects of SNP and other vasodilators on splanchnic blood flow have not been well documented. Methods: The effects of SNP on systemic blood flow, oxygen transport and gastric intramucosal pH (pH_i) were studied in 12 patients with arterial hypertension after coronary artery bypass grafting. In 9 of these patients, the effect on regional (splanchnic and leg) blood flow and oxygen transport was also measured. Hemodynamic and regional blood flow responses were measured before and during SNP infusion (mean 2.8±1.7 μg/kg/min, range 0.6-6.3 μg/kg/min), when the goal of the vasodilator treatment, mean arterial pressure 70–80 mmHg, had been reached. Results: SNP increased splanchnic (0.65±0.22 vs. 0.87±0.37 L·min^-1·m^-2, P<0.01) and femoral blood flow (0.15±0.04 vs. 0.21±0.06 L·min^-1·m^-2, P<0.05) in parallel with cardiac index (2.6±0.6 vs. 3.3±0.7 L·min^-1·m^-2, P<0.01). Fractional regional blood flows did not change. Mean gastric intramucosal pH decreased slightly (7.40±0.07 vs. 7.37±0.06, P<0.05). Both systemic (420±85 vs. 495±90 mL·min^-1·m^-2, P<0.05) and femoral oxygen delivery (25±5 vs. 32±10 mL·min^-1·m^-2, P<0.05) increased, but neither systemic nor regional oxygen consumption changed. Conclusions: These results suggest that vasoregulation is well preserved during treatment of early postoperative hypertension with SNP, and that SNP has no adverse effects on splanchnic tissue oxygenation.     

Metabolic effects of erythropoietin in patients on peritoneal dialysis

Insulin and lipid metabolism were studied in seven patients (19±1 years) with end-stage renal disease on continuous cycling peritoneal dialsysis (CCPD) before and after 6 months of therapy with human recombinant erythropoietin (EPO) to correct anemia. Hematocrit increased from 22.2±1.8% to 34.8±1.8% (P<0.001) following EPO treatment. Serum ferritin (P<0.05) and serum iron (P<0.01) decreased significantly after anemia correction. There were no significant differences in the height, weight, anthropometric measures, or intakes of protein and total calories in the patients before and after the 6 months of EPO therapy. There were no differences in serum biochemical parameters, including 1,25-dihydroxyvitamin D₃ and parathyroid hormone in these patients before and after 6 months of EPO therapy. Residual renal function and Kt/V_urea were also not different before and after 6 months of EPO therapy. The hyperinsulinemic euglycemic clamp technique was used to measure insulin sensitivity. Before EPO, insulin sensitivity was low in patients on CCPD (238±19 mg/m² per min) compared with controls (320±30; P<0.01). After 6 months of EPO therapy, insulin sensitivity increased by 28% (305±26, P<0.01 vs. pre-EPO values), so that these values were no longer different from control values. The hyperglycemic clamp technique was used to measure insulin secretion. Before EPO, both early- and late-phase insulin secretion were elevated in patients on CCPD compared with controls (P<0.01 in both cases). These indices of insulin secretion decreased significantly (P<0.01) following 6 months of EPO. Before EPO, plasma triglycerides, total cholesterol, low-density lipoprotein, cholesterol, and apolipoprotein B were elevated in patients compared with controls. These lipid concentrations decreased significantly following 6 months of EPO. Thus, treatment of anemia by EPO is associated with improvements in insulin and lipid abnormalities in uremic patients on CCPD. Received September 23, 1997; received in revised form January 20, 1998; accepted January 22, 1998