Combined Infusion Research Articles

A combination light-pipe, soft-tipped suction, and infusion cannula instrument for macular translocation

PURPOSE: To describe a combination light-pipe, soft-tipped suction needle, and infusion cannula instrument for use in macular translocation surgery. METHODS: Macular translocation surgery was performed in human cadaver and live rabbit eyes with a combination light-pipe, soft-tipped suction needle, and infusion cannula instrument. RESULTS: A combination light-pipe, soft-tipped suction needle, and infusion cannula can be used for macular translocation. This instrument is useful for relocating the retina after a 360 peripheral retinotomy is created. It can also be used for macular translocation with the scleral imbrication technique when superior movement of the fovea is required. When used in combination with another soft-tipped suction needle instrument, this surgical instrument allows precise bimanual placement of the retina with simultaneous infusion of liquid perfluorocarbon for fixating the macula to its new location. CONCLUSION: A combination light-pipe, soft-tipped suction needle, and infusion cannula instrument may be a useful tool for macular translocation surgery.

Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake

Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (-120 to -20 min), a control (-20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 microg. kg(-1). min(-1)) was infused along with intraportal insulin (1.2 mU. kg(-1). min(-1)) and glucagon (0.5 ng. kg(-1). min(-1)). Hepatic sinusoidal insulin was four times basal (73 +/- 7 microU/ml) and glucagon was basal (55 +/- 7 pg/ml). Glucose was infused peripherally (0-300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 microg and 0.1 microg. kg(-1). min(-1) from 120 min on. ACh was infused intraportally at 3 microg. kg(-1). min(-1) from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg. kg(-1). min(-1)) from output (2.1 +/- 0.3 and 1.1 +/- 0.2) to uptake (2.8 +/- 0.9 and 2.6 +/- 0.6) and lactate balance (micromol. kg(-1). min(-1)) from uptake (7.5 +/- 2.2 and 6.7 +/- 1.6) to output (3.7 +/- 2.6 and 3.9 +/- 1.6) by 120 min in the control and test protocols, respectively. Thereafter, in the control protocol, NHGU tended to increase slightly (3.0 +/- 0.6 mg. kg(-1). min(-1) by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 +/- 0.6 and 4.6 +/- 0.6 mg. kg(-1). min(-1) by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery.

Regulation of serotonin release by GABA and excitatory amino acids.

Regulation of serotonin release by gamma-aminobutyric acid (GABA) and glutamate was examined by microdialysis in unanaesthetized rats. The GABA(A) receptor agonist muscimol, or the glutamate receptor agonists kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolaproprionate or N-methyl-D-aspartate were infused into the dorsal raphe nucleus (DRN) while extracellular serotonin was measured in the DRN and nucleus accumbens. Muscimol produced decreases, and the glutamate receptor agonists produced increases in serotonin. To determine if these receptors have a tonic influence on serotonergic neurons, glutamate or GABA(A) receptor antagonists were infused into the DRN. Kynurenate, a nonselective glutamate receptor blocker, produced a small, 30% decrease in serotonin. A similar decrease was obtained with combined infusion of AP-5 and DNQX into the DRN. The GABAA receptor blocker bicuculline produced an approximately three-fold increase in DRN serotonin. In conclusion, glutamate neurotransmitters have a weak tonic excitatory influence on serotonergic neurons in the rat DRN. However, the predominate influence is mediated by GABA(A) receptors.

Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity.

Insulin-induced stimulation of muscle glucose uptake (MGU) is impaired in people with type 2 diabetes. To determine whether insulin-induced stimulation of splanchnic glucose uptake (SGU) is also impaired, we simultaneously measured leg glucose uptake (LGU) and SGU in 14 nondiabetic subjects and 16 subjects with type 2 diabetes using a combined organ catheterization-tracer infusion technique. Glucose was clamped at approximately 9.3 mmol/l, while insulin concentrations were maintained at approximately 72 pmol/l (low) and approximately 150 pmol/l (high) for 3 h each. Endogenous hormone secretion was inhibited with somatostatin. Total body glucose disappearance was lower (P < 0.01) and glucose production higher (P < 0.01) during both insulin infusions in the diabetic compared with the nondiabetic subjects, indicating insulin resistance. Splanchnic glucose production was higher (P < 0.05) in the diabetic subjects during the low but not the high insulin infusion. SGU was slightly lower in the diabetic than in the nondiabetic subjects during the low insulin infusion and 50-60% lower (P < 0.05) during the high insulin infusion. LGU (P < 0.001), but not SGU, was inversely correlated with the degree of visceral adiposity. The contribution of the indirect pathway to hepatic glycogen synthesis did not differ in the diabetic and nondiabetic subjects. In contrast, both flux through the UDP-glucose pool (P < 0.05) and the contribution of the direct pathway to glycogen synthesis (P < 0.01) were lower in the diabetic than in the nondiabetic subjects, indicating decreased uptake and/or phosphorylation of extracellular glucose. On the other hand, glycogenolysis was equally suppressed in both groups. In summary, type 2 diabetes impairs the ability of insulin to stimulate both MGU and SGU. The defect appears to reside at a proximal (e.g., glucokinase) metabolic step and is not related to the degree of visceral adiposity. These data suggest that impaired hepatic glucose uptake as well as MGU contribute to hyperglycemia in people with type 2 diabetes.

Paclitaxel by 1-h infusion in combination with carboplatin in advanced non-small cell lung carcinoma (NSCLC)

In our previous study, FCCC 93-024, paclitaxel by 24-h infusion combined with carboplatin yielded a response rate of 62% and median survival of 54 weeks in advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose-limiting, requiring the routine use of granulocyte-colony stimulating factor (G-CSF). Based on the reported activity of 1-h paclitaxel infusion in NSCLC and minimal myelosuppression at doses of 135 and 200 mg/m2 every 3 weeks and the suggestion of a dose–response relationship, we launched an intrapatient dose escalation trial of combination carboplatin and 1-h paclitaxel. Chemotherapy-naı̈ve patients with advanced NSCLC received paclitaxel 175 mg/m2 1-h and carboplatin dosed to a fixed targeted area under the concentration–time curve (AUC) of 7.5 at three weekly intervals for six cycles. In the absence of grade 4 myelosuppression, paclitaxel was escalated by 35 mg/m2/cycle on an intrapatient basis to a maximum dose of 280 mg/m2 by cycle 4. G-CSF was not routinely used. 57 patients (pts) were accrued from November 1994 through to April 1996. 44 pts (77%) had Eastern Cooperative Oncology Group (ECOG) performance status 1. Median age was 64 (range: 34–80) years. Cumulative peripheral sensory neuropathy proved dose-limiting and prohibitive in the first 20 evaluable patients (cohort A): grade ⩾1 in 15 patients (75%), grade 3 in 6 (30%), generally occurring at paclitaxel doses ⩾215 mg/m2 and obligating 3 patients to have treatment halted in the absence of disease progression. The protocol, therefore, was revised and the initial paclitaxel dose reduced to 135 mg/m2 with intrapatient dose escalation of 40 mg/m2/cycle to a maximum dose of 215 mg/m2, recapitulating the original dosing schema used in FCCC 93-024. 35 patients were enrolled in this second cohort (B); 33 proved evaluable. Whilst 17 (52%) experienced peripheral sensory neuropathy, grade 3 neurotoxicity developed in only 3 (9%). Myelosuppression also was less pronounced, with 42% exhibiting grade 4 granulocytopenia and 30% grade ⩾3 thrombocytopenia in cohort B compared with 70% and 50%, respectively in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median survival was 48.5 weeks, 1-year survival rate 45% and 2-year survival rate 18%. Of 33 evaluable patients in cohort B, 9 (27%) had major objective responses. Median survival was 46 weeks, 1-year survival rate 47% and 2-year survival rate 12%. Combination paclitaxel by 1-h infusion and carboplatin at a fixed targeted AUC of 7.5 is active in advanced NSCLC. Neurotoxicity, not myelosuppression, proved dose-limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses may be associated with lower response rates, but do not appear to compromise survival.

Is Skeletal Muscle Luxury Perfusion the Main Hemodynamic Effect of High-Dose Insulin in Cardiac Surgery?

Insulin, in combination with glucose and potassium (GIK), can be used in heart surgery to improve hemodynamic performance. This study evaluates the role of skeletal muscle vasodilation in hemodynamic effects of high-dose GIK therapy early after coronary surgery. Thirty-three male patients undergoing coronary artery bypass grafting were included in a prospective, randomized and controlled study. Eleven patients received infusions of mixed amino acids (11.4 g) and insulin solution (225 IU insulin, glucose with the glucose clamp technique, and potassium), 11 patients received infusions of mixed amino acids (11.4 g) and 11 patients served as control subjects. During combined insulin and amino acid infusion, cardiac output increased by 13+/-3% (+0.6+/-0.2 L x min(-1)) and systemic vascular resistance decreased by 24+/-3% (-320+/-46 dyn x s x cm(-5)). The changes differed from those in the control group (CO: -0.2+/-0.1 L x min(-1), p < 0.05; SVR: +136+/-42 dyn x s x cm(-5), p < 0.05). Changes in skeletal muscle perfusion and leg vascular resistance did not differ significantly among the groups. At most, changes in leg blood flow could explain 40% of the changes in cardiac output. Skeletal muscle luxury perfusion is not the main hemodynamic effect of high-dose insulin in the early postoperative period after coronary surgery.

Vascular ATP-dependent potassium channels, nitric oxide, and human forearm reactive hyperemia.

Vascular ATP-dependent potassium (K+ATP) channels open and contribute to reactive hyperemia (RH) in animals. The contribution of K+ATP channels to ischemic vasolidation during RH and interactions with endothelium-derived nitric oxide have not been well characterized in human subjects. RH blood flow responses (mL/dL) following 5 minutes of cuff occlusion were measured using strain-gauge plethysmography in 22 normal human subjects age 42 +/- 2 years. Measurements were obtained at baseline and following intra-arterial administration of the K+ATP channel closer glibenclamide, the nitric oxide synthase inhibitor L-N-monomethyl arginine (L-NMMA), or both drugs simultaneously. Glibenclamide (100 micrograms/min) did not change basal flow (2.7 +/- 0.3 to 2.7 +/- 0.3 mL/min/dL), but L-NMMA (8 mumol/min) and combined glibenclamide and L-NMMA significantly (p < 0.05) decreased basal flow (3.0 +/- 0.5 to 2.0 +/- 0.2 and 3.3 +/- 0.5 to 2.5 +/- 0.3, respectively). Glibenclamide significantly (p < 0.01) decreased RH flow (18.2 +/- 1.3 to 14.8 +/- 1.3) and excess flow (5.3 +/- 1.2 to 1.3 +/- 1.3). L-NMMA significantly (p < 0.05) decreased RH flow (21.2 +/- 1.8 to 18.9 +/- 1.9) and tended to decrease excess flow (6.1 +/- 2.2 to 3.9 +/- 2.5). Combined drug infusion significantly (p < 0.1) decreased RH flow (21.6 +/- 2.2 to 18.0 +/- 2.4) and excess flow (6.3 +/- 1.6 to 1.6 +/- 1.6), with reductions in RH and excess flow similar to those following glibenclamide infusion alone. We conclude that forearm vascular K+ATP channels are closed at baseline. They open and contribute to RH vasodilation. The addition of nitric oxide inhibition to K+ATP channel blockade does not result in additive or synergistic inhibition of RH.

Duration and distribution of experimental muscle hyperalgesia in humans following combined infusions of serotonin and bradykinin

The present study examined distribution and duration of muscle hyperalgesia to pressure stimuli after intramuscular bolus-infusions of serotonin (5-HT, 20 nmol) and bradykinin (BKN, 10 nmol) in 10 volunteers. Infusions were given into the tibialis anterior (TA) muscle over 20 s with an inter-infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer at the injection site (10 cm below the patella), 2, 5, and 10 cm distal from the injection site, and at the ankle. Control assessments of PPTs were done at the contralateral TA and ankle. Skin sensibility was assessed with a Von Frey hair at the same sites. All measurements were done before and 5, 20, 40, and 60 min after infusions. The VAS-peak after BKN was significantly higher ( P<0.05) compared with 5-HT and the second infusion of NaCl. The duration of the increase in VAS after 5-HT+BKN was significantly longer ( P<0.05) compared with the infusions of NaCl. The local pain area after infusion of BKN was significantly larger ( P<0.05) compared with 5-HT and control infusions. Cutaneous sensibility to tactile stimuli was not affected by any of the combinations. PPTs at the injection site and 2 cm (5, 20, and 40 min) were significantly decreased ( P<0.05) after 5-HT+BKN compared with baseline and isotonic saline. In addition, PPTs were significantly decreased ( P<0.05) after 5-HT+BKN at 5 cm (5 and 20 min) and 10 cm (5 min). Serotonin may enhance the effect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle hyperalgesia, lasted for up to 40 min and located within the muscle. No widespread hyperalgesia to the ankle and other leg (tested at 10 cm below the patella and ankle) was observed suggesting a predominant peripheral origin of the experimentally induced hyperalgesic stage.

Adaptation of solid phase extraction to an automated column switching method for online sample cleanup as the basis of a facile and sensitive high-performance liquid chromatographic assay for paclitaxel in human plasma

An improved method for assaying paclitaxel in human plasma by high-performance liquid chromatography (HPLC) with UV detection at 227 nm has been developed by adapting previously reported sample preparation methods and chromatographic conditions to facilitate semi-automated sample cleanup using a column switching technique. Manual sample manipulations were limited to isolating the drug and internal standard from plasma (1.0 ml) by liquid–liquid extraction using tert-butyl methyl ether. The sample extract was initially loaded onto a short cartridge column containing a cyanopropyl stationary phase. During the predetermined time interval that the drug and internal standard eluted from the cartridge, 1.50–2.20 min, a fully automated 6-position switching valve was used to direct the effluent onto an octylsilica analytical column. The same mobile phase, composed of acetonitrile–methanol–ammonium acetate buffer (pH 5.0; 20 mM) (76:19:105, v/v/v) and delivered at flow rate of 1.0 ml/min, was used for both separations. The overall retention times of paclitaxel and the internal standard were 10.9 and 18.1 min, respectively. The analytical method was thoroughly validated for quantitating paclitaxel in plasma at concentrations ranging from 6 to 586 nM (5–500 ng/ml). The lowest concentration of paclitaxel measured with acceptable day-to-day accuracy (100.2%) and precision (RSD 11.7%, n=21, 5 months) was 6 nM (5 ng/ml). The sensitivity and selectivity of the assay proved to be more than adequate for monitoring steady-state plasma concentrations of the drug when administered to cancer patients as a 96 h continuous intravenous infusion in combination with other anticancer agents, such as doxorubicin and topotecan. Moreover, the heart-cutting procedure prevented the problematic introduction of interfering nonpolar plasma components onto the analytical column, thereby enhancing sample throughput while decreasing the technical demands of the assay. The method was found to be extremely reproducible and robust during extended use for the routine analysis of plasma specimens acquired from several clinical trials.

Differences in estimates of forearm protein synthesis between leucine and phenylalanine tracers following unbalanced amino acid infusion.

We compared the leucine (Leu) and phenylalanine (Phe) tracer-determined response of forearm protein synthesis (PS) before and after stimulation of protein anabolism by intravenous infusion of Leu-enriched, Phe-deficient amino acids and insulin (increased to approximately 100 microU/mL) with the euglycemic clamp. Six healthy subjects received primed-constant infusions of L-[ring-2H5]-Phe and L-[1-(14)C]-Leu, and steady-state forearm Phe and Leu kinetics were determined. Following the combined infusion, the arterial Leu concentration increased approximately 70% (P < .001), whereas Phe decreased about 15% (P < .01). Forearm PS and net balance (NB) increased (P < .05 or less v basal) using both amino acid tracers. However, the relative increments observed with the Leu tracer were more than 75% larger (P < .05 or less) than those observed with the Phe tracer, even when the data were corrected for the standard relative abundance of these two amino acids in forearm protein(s). Thus, the calculated changes of forearm PS and NB in response to an unbalanced amino acid infusion with hyperinsulinemia were affected by the plasma level of leucine and phenylalanine, whose tracers were used to estimate forearm protein turnover. Since these two essential amino acids share the same transport system, a competition at this level cannot be excluded.

Postoperative pain relief in the morbidly obese patient: Feasibility study of a combined dipyrone/tramadol infusion

The aim of the prospective clinical study was to test the feasibility of a dipyrone/tramadol combination for pain therapy after laparoscopic and open obesity surgery. The study group was made up of 29 surgical patients; 14 following a median laparotomy and 15 following a laparoscopic approach. All received a continuous intravenous infusion of dipyrone (metamizol) and tramadol for pain relief. The surgical procedure (laparotomy or laparoscopy), body mass index, postoperative analgesic requirement and pain intensity (visual analogue scale (VAS 1–10)) were documented. Following laparotomy, the combination infusion provided effective analgesia. On the first and fourth postoperative days, the pain scores at rest were 1.5 and 2.3 respectively. The pain scores did not increase significantly with movement (2.7 and 2.2 respectively). Following laparoscopic gastric banding the pain scores were less than 2.0 at rest and with movement on the first postoperative day. On the fourth postoperative day the pain scores at rest and with movement were 0.2. This feasibility study suggests that a combination of the strong non-opioid dipyrone and the atypical opioid tramadol provides good analgesia following laparotomy and laparoscopic surgery for morbid obesity.

Inpatient experience with remifentanil.

Inpatient experience with remifentanil.

Hemodynamic and metabolic alterations associated with intravenous infusion of a combination of adenosine triphosphate and magnesium chloride in conscious horses

Abstract Objective To determine hemodynamic and metabolic effects of IV infusion of ATP-MgCl2 combination and maximal safe IV infusion rate in conscious horses. Animals 6 adult female horses. Procedure All horses received an IV infusion of ATP-MgCl2 combination, beginning at a rate of 0.05 mg of ATP/kg of body weight/min, which was increased by 0.05 mg/kg/min increments at 10-minute intervals until a rate of 1.0 mg/kg/min was achieved. Data were collected prior to the start of the infusion, at the end of each infusion rate, and at 15-minute intervals for the next hour after discontinuation of the infusion. Measured or calculated hemodynamic variables included cardiac output, cardiac index, heart rate, stroke volume, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistances. Arterial blood gas tensions, CBC, plasma biochemical profiles, urine volume and specific gravity, and selected clinical signs of disease also were evaluated. Results Intravenous infusion of ATP-MgCl2 significantly increased cardiac output, decreased systemic vascular resistance, and caused mild pulmonary hypertension. Magnitude of the hemodynamic alterations was dependent on rate of infusion. Maximal safe infusion rate for these horses was 0.3 mg/kg/min. All horses became lethargic, and their appetites diminished during the infusion; 5 horses had mild signs of abdominal discomfort. Flank sweating was observed in all horses as infusion rate increased. Urine volume and specific gravity and hematologic, biochemical, and arterial blood gas alterations were detected during and after infusion. Conclusions and Clinical Relevance Intravenous administration of ATP-MgCl2 in healthy, conscious, adult horses caused various metabolic and hemodynamic alterations that were without appreciable detrimental effects. (Am J Vet Res 1999;60:1140–1147)

Salvage chemotherapy with high-dose leucovorin (lv) and 5-fluorouracil (5-fu) 48-hour continuous infusion (ci) in combination with conventional doses of cyclophosphamide (c) in anthracycline/taxane refractory metastatic breast cancer (mbc) patients. A phase II study

Salvage chemotherapy with high-dose leucovorin (lv) and 5-fluorouracil (5-fu) 48-hour continuous infusion (ci) in combination with conventional doses of cyclophosphamide (c) in anthracycline/taxane refractory metastatic breast cancer (mbc) patients. A phase II study

Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) concentrations have been found to be decreased in diabetic humans and rats. To investigate further the regulation of plasma Ca in diabetes, first we measured Ca(2+), P, Mg, parathyroid hormone(1-34) (PTH), and total and free 1,25(OH)(2)D(3) in male spontaneously diabetic rats 7 and 28 days after the onset of glycosuria. Secondly, we studied changes in the levels of PTH and 1,25(OH)(2)D(3) in response to hypocalcaemia induced by an i.v. infusion of EGTA (2.5%, wt/vol.) for 24 h, and changes in the levels of 1,25(OH)(2)D(3) in response to an i.v. infusion of rat PTH (10 microgram over 24 h) without or with concomitant EGTA infusion (producing hypercalcaemia or normo/hypocalcaemia respectively), in diabetic and control rats. Ca(2+), P, Mg and PTH concentrations remained within the control ranges after 7 and 28 days of glycosuria; 1,25(OH)(2)D(3) concentrations were decreased after 7, but not after 28, days of glycosuria. PTH concentrations showed a similar rise during EGTA-induced hypocalcaemia in control and diabetic rats compared with saline-infused rats, whereas 1,25(OH)(2)D(3) concentrations were unchanged in both groups. Total and free 1,25(OH)(2)D(3) levels were comparably (about 3-fold) increased during PTH, but not during combined PTH and EGTA infusion in control and diabetic rats. Total 1, 25(OH)(2)D(3) concentrations were lower in the diabetic groups infused with saline or PTH than in their respective controls, and there was a similar trend in the PTH+EGTA-infused group; free 1, 25(OH)(2)D(3) levels, however, were normal or increased in the diabetic groups, confirming our previous data. The novel finding of this study is that, despite severe insulin deficiency and altered 1, 25(OH)(2)D(3) levels, the in vivo response of PTH levels to hypocalcaemia and the in vivo response of 1,25(OH)(2)D(3) levels to PTH in diabetic rats are comparable with those found in nondiabetic rats.

Treatment of Autonomic Hyperreflexia in a Quadriplegic Patient by Epidural Anesthesia in the Postoperative Period

Treatment of Autonomic Hyperreflexia in a Quadriplegic Patient by Epidural Anesthesia in the Postoperative Period

Oxygen delivery does not limit cardiac performance during high work states.

This study tested the hypothesis that the loss of myocardial high-energy phosphates (HEP), which occurs during high cardiac work states [J. Zhang, D. J. Duncker, Y. Xu, Y. Zhang, G. Path, H. Merkle, K. Hendrich, A. H. L. From, R. Bache, and K. Uğurbil. Am. J. Physiol. 268: (Heart Circ. Physiol. 37): H1891-H1905, 1995], is not the result of insufficient intracellular O(2) availability. To evaluate the state of myocardial oxygenation, the proximal histidine signal of deoxymyoglobin (Mb-delta) was determined with (1)H nuclear magnetic resonance spectroscopy (MRS), whereas HEP were examined with (31)P MRS. Normal dogs (n = 11) were studied under basal conditions and during combined infusion of dobutamine and dopamine (20 micrograms . kg(-1). min(-1) iv each), which increased rate-pressure products to >50,000 mmHg. beats. min(-1). Creatine phosphate (CP) was expressed as CP/ATP, and myocardial myoglobin desaturation was normalized to the Mb-delta resonance present during total coronary artery occlusion. This Mb-delta resonance appeared at 71 parts per million downfield from the water resonance. CP/ATP decreased from 2. 22 +/- 0.12 during the basal state to 1.83 +/- 0.09 during the high work state (P < 0.01), whereas DeltaP(i)/CP increased from 0 to 0.21 +/- 0.04 (P < 0.01). Despite these HEP changes, Mb-delta remained undetectable. In contrast, when a coronary stenosis was applied to produce a similar decrease in CP/ATP, Mb-delta reached 0.38 +/- 0.10 of the value present during total coronary occlusion. These data demonstrate that Mb-delta is readily detected in vivo during limitation of coronary blood flow sufficient to cause a decrease of myocardial CP/ATP. However, similar HEP changes that occur at high work states in the absence of coronary occlusion are not associated with a detectable Mb-delta resonance. The findings support the hypothesis that the myocardial HEP changes observed at high work states are not due to inadequate O(2) availability to the mitochondria and emphasize the limitations of interpreting HEP alterations in the absence of knowing the level of myocyte oxygenation.

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.

It is unknown whether and to what extent changes in various endothelial functions and adrenergic responsiveness are related to the development of microvascular complications in type 1 diabetes. Therefore, endothelium-dependent and endothelium-independent vasodilatation, endothelium-dependent hemostatic factors, and one and two adrenergic vasoconstrictor responses were determined in type 1 patients with and without microvascular complications. A total of 34 patients with type 1 diabetes were studied under euglycemic conditions on two occasions (11 without microangiopathy, 10 with proliferative and preproliferative retinopathy previously treated by laser coagulation, 13 with microalbuminuria, and 12 healthy volunteers also were studied). Forearm vascular responses to brachial artery infusions of N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, acetylcholine (ACh), clonidine, and phenylephrine were determined. The ACh infusions were repeated during coinfusion of L-arginine. Furthermore, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator antigen levels, von Willebrand factor antigen levels, tissue factor pathway inhibitor (TFPI) activity, and endothelin-1 levels were measured. No differences in endothelium-dependent or endothelium-independent vasodilatation or adrenergic constriction were observed between the diabetic patients and the healthy volunteers. In comparison to the first ACh infusion, the maximal response to repeated ACh during L-arginine administration was reduced in the diabetic patients, except in the patients with proliferative and preproliferative retinopathy previously treated by laser coagulation. In these patients, the combined infusion of L-arginine and ACh resulted in an enhanced response. TFPI activity was elevated, and PAI-1 activity was reduced in the type 1 diabetic patients. Furthermore, PAI-1 activity was positively correlated with urinary albumin excretion (r = 0.48, P < 0.01) and inversely correlated with the vasodilatory response to the highest ACh dose (r = -0.37, P < 0.05). The response to the highest ACh and L-NMMA dose were positively correlated with mean arterial blood pressure (r = 0.32, P < 0.01; r = 0.41, P < 0.01, respectively). Forearm endothelium-dependent and endothelium-independent vasodilatation and adrenergic responsiveness were unaltered in type 1 diabetic patients with and without microvascular complications. Relative to healthy control subjects, endothelium-dependent vasodilatation was depressed during a repeated ACh challenge (with L-arginine coinfusion) in the diabetic patients without complications or with microalbuminuria. In contrast, this vasodilatation was enhanced in the patients with retinopathy. Elevation of TFPI was the most consistent marker of endothelial damage of all the endothelial markers measured.

Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep.

Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate in many species, but the mechanisms involved are unclear. We investigated whether cortisol-induced renal vasodilatation in conscious sheep depends on interactions with prostaglandins or angiotensin II. Intravenous infusion of cortisol (5 mg/h) for 5 h increased renal conductance (RC) by 1.06 +/- 0.24 ml. min-1. mmHg-1 more than vehicle. During intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1), the cortisol-induced increase in RC (0.28 +/- 0.21 ml. min-1. mmHg-1) was significantly reduced. The cortisol-induced rise in RBF (103 +/- 17 ml/min) was not significantly reduced by indomethacin treatment (76 +/- 9 ml/min). Combined intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1) with Nomega-nitro-L-arginine (2.0 mg. kg-1. h-1), a nitric oxide synthase inhibitor, abolished the cortisol-induced increases in both RC and RBF. Inhibition of angiotensin II synthesis with intravenous captopril (40 mg/h) blocked the renal vasoconstrictor action of angiotensin I but did not inhibit the cortisol-induced increases in RBF and RC. This study provides evidence that nitric oxide and prostaglandins play a role in cortisol-induced renal vasodilatation but indicates that this response is independent of an interaction with angiotensin.

Multicultural Content in Social Work Graduate Programs

ABSTRACT This paper reports the results of a national survey of Deans and Directors of graduate social work programs and of social work faculty responsible for teaching graduate-level multicultural courses. The findings indicate the use of a combined infusion and designated course model is the most prominent in addressing the CSWE diversity curriculum content requirement. Although there is substantive content on traditionally oppressed minority populations, there is an increasing number of groups and topics under the banner of diversity. There is heavy reliance on traditional teaching methods and little consistency in the educational resources used to teach the courses. The demographic composition and perceptions of social work faculty who teach multicultural courses are reported. The implications of the findings are discussed.