Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium.

Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%). These data demonstrate enhanced and sustained activity of the nonoxidative glycolytic pathway after a prolonged occlusion with reperfusion in canine myocardium. Because glycogen stores remain depleted, exogenous glucose becomes an important myocardial substrate under these pathologic conditions.

The pharmacological properties of the peptide, endothelin.

1. The effect of endothelin (ET-1) has been studied on isolated vascular and non-vascular preparations, using both functional and competition radioligand binding techniques. The effects of endothelin on blood pressure were studied in both anaesthetised, chemically denervated normotensive and spontaneously hypertensive rats (SHR). 2. Endothelin elicited contractile responses in the rat thoracic aorta, perfused mesenteric bed, rabbit mesenteric artery and portal vein. The maximal responses in the rat aorta were enhanced by removal of the endothelium, and were reduced in the presence of either a cyclo-oxygenase inhibitor (indomethacin) or a thromboxane receptor antagonist (SQ 29,548). In terms of potency, the most sensitive preparation was the rat endothelium-denuded aorta and rat perfused mesenteric bed (-log EC50 values = 8.2 +/- 0.07 and 8.2 +/- 0.12, mean +/- s.e.mean, n = 4, respectively). In the perfused mesenteric bed of the rat the maximum response to endothelin (219 +/- 12 mmHg, n = 4) was greater than that to either phenylephrine (maximal response = 67 +/- 9 mmHg; n = 4) or KCl (maximal response = 110 +/- 6 mmHg, n = 4). 3. Endothelin elicited contractile responses of the guinea-pig isolated ileum, oesophageal muscularis mucosae and uterus. Responses were also observed in the rat fundic strip and paced left atria. The guinea-pig urinary bladder, trachea, rat vas deferens and anococcygeus exhibited little or no response to endothelin at the concentrations studied (1 x 10(-12)-3.2 x 10(-8) M). Of the above preparations, the ileum and oesophageal muscularis mucosae were the most sensitive to endothelin (-log EC50 = 8.5 +/- 0.11 and 8.4 +/- 0.06, n = 6, respectively), exhibiting potencies similar to those observed in the endothelium-denuded aorta of the rat. 4. In competition-radioligand binding studies, endothelin did not displace either [3H]-PN 210-100 or [125I]-(-)-omega-conotoxin GVIA from binding sites in membranes from rat cerebral cortex and, skeletal muscle or from guinea-pig cerebral cortex and hippocampus, respectively. This indicates a lack of direct interaction of endothelin at the dihydropyridine binding site and the N-type calcium channel, respectively. However, in functional studies, contractile responses to endothelin (1 x 10(-8) M) in the endothelium-denuded aorta of the rat were potently reversed by nifedipine, verapamil, and prenylamine (-log IC50 values = 8.0 +/- 0.13, 7.2 +/- 0.09 and 6.6 +/- 0.08, n = 4-8, respectively). In addition, the responses to endothelin were virtually abolished in the presence of Krebs physiological salt solution containing no calcium but with 1 x 10-M EDTA added. Preequilibration with either (-)-w-conotoxin (1 x 10-6M) or tetrodotoxin (1 x 10-6M) did not affect responses to endothelin. 5. In chemically denervated rats, endothelin (1pmolkg-'-10nmolkg- , i.v.) exhibited pressor responses, which were unaffected by a 3 h pretreatment with indomethacin. In the SHR, the effects on blood pressure were not significantly different from those observed in normotensive animals at any of the doses studied. A transient (duration < 30 s) depressor response was also observed in all groups studied at a dose of 0.1-1 nmol kg-1 i.v. 6. In conclusion, endothelin is a potent contractile agonist in both vascular and non-vascular muscle. It appears to elicit responses partly via the entry of extracellular calcium (by a mechanism distinct from that of other calcium facilitators) and partly by release of endoperoxides.

Characterization of 5-HT3 and 'atypical' 5-HT receptors mediating guinea-pig ileal contractions in vitro.

1. Neuronal 5-hydroxytryptamine (5-HT) receptors mediating contraction of guinea-pig ileal segments have been characterized in vitro by the use of methysergide to block 5-HT1-like and 5-HT2 receptors. Concentration-response curves to 5-HT were biphasic (first phase, defined as those responses occurring between 1 nM and 0.32 microM 5-HT, -log EC50 = 7.15 +/- 0.08; second phase, defined as these responses occurring between 0.32 microM and 32 microM 5-HT, -log EC50 = 5.32 +/- 0.03) but monophasic to 5-methoxytryptamine (-log EC50 = 7.0 +/- 0.08) and 2 methyl 5-HT (-log EC50 = 5.2 +/- 0.13). The maximal response of the first phase to 5-HT and the maximal response to 5-methoxytryptamine were 30 +/- 4% and 35 +/- 5% respectively of the maximum response to the second phase of the 5-HT concentration-effect curve (set at 100%). In contrast, the maximal response to 2-methyl-5-HT equalled that obtained with 5-HT (second phase). 2. The responses comprising the second phase of the concentration-effect curve to 5-HT were antagonized by 1 microM ICS 205-930, ondansetron, granisetron, quipazine, N-methyl-quipazine and (R,S)-zacopride and the following pKB values, with 5-HT as the agonist, were obtained at the 5-HT3 receptor: ICS 205-930 7.61 +/- 0.05, ondansetron 6.90 +/- 0.04, granisetron 7.90 +/- 0.04, (S)-zacopride 8.11 +/- 0.06, (R,S)-zacopride 7.64 +/- 0.11, and (R)-zacopride 7.27 +/- 0.06. 3. Under conditions of 5-HT1-like, 5-HT2 and 5-HT3 receptor blockade, the following rank order of agonism was observed: 5-HT > 5-methoxytryptamine = renzapride > (S)-zacopride > (R,S-zacopride > 5-carboxamidotryptamine > BRL 24682 > (R-zacopride > metoclopramide > 2-methyl-5-HT > sulpiride. 8-Dihydroxydiphenylaminotetralin (8-OHDPAT), GR 43175, N,N-dipropyl-5-carboxamidotryptamine, ondansetron, ICS 205-930, granisetron, quipazine and N-methyl-quipazine were inactive as agonists and antagonists. Relative to 5-HT, (R,S)-zacopride acted as a partial agonist (intrinsic activity, alpha = 0.80; -log EC50 = 6.3 + 0.12; -log KA = 6.1 + 0.03) as did (R)-zacopride (alpha = 0.4, -log EC,0 5.7 + 0.08, -log KA = 5.5 + 0.11). (S)-zacopride acted as a full agonist (-log EC,0 = 6.9 + 0.03). ICS 205-930 (3 microM) antagonized competitively responses to 5-HT, 5 methoxytryptamine, (RS)- and (S)- zacopride and 5-carboxamidotryptamine yielding -log KB estimates ranging from 6.1-6.5. 4. It is concluded that two different 5-HT receptors mediate excitatory neuronal responses in the guineapig ileum. 5-HT3 receptors mediate the second phase of the biphasic concentration-response curve, whereas a receptor with properties distinct from the 5-HT1-like, 5-HT2 and 5-HT3 subtypes mediates the initial phase of the concentration-response curve. This receptor, which exhibits a close similarity to the 5-HT4 subtype is: (1) stimulated by 5-methoxytryptamine but not 2-methyl-5-HT; (2) stimulated selectively by certain substituted benzamides; (3) recognizes the optical isomers of zacopride and (4) is blocked by relatively high concentrations ICS 205-930 (pKB = 6.0-6.5) but not ondansetron, granisetron, quipazine or N-methyl-quipazine.

Respiratory mechanics in anesthetized young patients with kyphoscoliosis. Immediate and delayed effects of corrective spinal surgery.

To our knowledge, the effects of corrective spinal surgery on total respiratory mechanics and its components in anesthetized patients with kyphoscoliosis have not been previously reported in detail. We studied 13 patients with kyposcoliosis; their mean (+/- SD) age was 24.7 +/- 2.1 years; eight underwent anterior and posterior spinal fusions (AF and PF, respectively) two weeks apart (group A), four underwent PF alone (group B), and one had a three-stage procedure. Mean total respiratory elastance (Ers), static and dynamic lung elastance (Est,L and Edyn,L, respectively), chest wall elastance (Ew), and lung resistance (RL) were derived according to previously described methodology. In group A, Ers and Ew increased by 39 percent and 58 percent, respectively, following AF and by 20 percent and 129 percent following PF, while Est,L and Edyn,L did not change or declined following PF. Lung resistance increased 19 percent and 41 percent by the end of AF and PF, respectively, in group A. In group B, Ew more than doubled, resulting in a 39 percent increase in Ers. Increases in Ers, Ew, and respiratory flow resistance observed at the time of spinal corrective surgery for kyphoscoliosis may result from rib cage trauma and changes in airway caliber related to microatelectasis and uneven distribution of mechanical properties within the lungs. Spinal correction results in immediate and short-term deterioration of respiratory mechanics measured under anesthesia.

Respiratory elastic load compensation in anesthetized patients with kyphoscoliosis.

To evaluate the effects of abnormal respiratory mechanics and neuromuscular drive on the various components of elastic load compensation, we studied 16 anesthetized patients with kyphoscoliosis whose mean passive and active respiratory elastance (Ers and E'rs, respectively), active respiratory resistance, and peak inspiratory occlusion pressure were, respectively, 89, 84, 100, and 37% greater and inspiratory duration (TI) 13% less than corresponding values in 13 anesthetized controls. Ers comprised approximately 66% of effective elastance (E*rs) in both groups. E'rs, reflecting the role of the force-length properties of the active inspiratory muscles in increasing the internal impedance, comprised 83.8 and 86.1% of E*rs in the kyphoscoliosis patients and controls, respectively (P less than 0.001). This demonstrates the influence of increased intrinsic elastance and resistance and decreased TI on tidal volume defense in kyphoscoliosis patients in the absence of vagal modulation. In some patients the difference between Ers and E*rs was substantial, despite an unchanged or even shortened TI, suggesting that the Hering-Breuer reflex may affect stability through ways other than altering TI (e.g., via graded volume-dependent "terminal inhibition"). Characteristics of elastic load compensation in anesthetized kyphoscoliosis patients are similar to those of anesthetized normal subjects.

Surgical treatment of adult scoliosis. A review of two hundred and twenty-two cases.

We evaluated the cases of 222 patients older than twenty years in whom scoliosis was the primary diagnosis. No patient had had prior surgical treatment. The diagnoses were idiopathic scoliosis in 160 patients, paralytic scoliosis in forty-four, and congenital scoliosis in eleven, and there were miscellaneous diagnoses in seven patients. The average age of the patients when first seen was 30.7 years. The indications for operation were pain, progression of the curve, magnitude of the curve, and cardiopulmonary symptoms. Preoperative traction, including halo-femoral traction, did not result in increased correction when compared with the initial supine side-bending roentgenogram. A one-stage fusion was performed in 174 patients and multiple-stage procedures, in forty-eight patients. At an average follow-up of 3.6 years the average loss of correction was 6.2 degrees, 68 per cent of the patients were free of pain, and a solid fusion had been obtained in all but six patients. Complications developed in 53 per cent of the patients, the most common problems being pseudarthrosis, urinary tract infection, wound infection, instrumentation problems, a pulmonary disorder, and loss of lumbar lordosis. Paraplegia occurred in one patient. The over-all mortality rate was 1.4 per cent. Complications increased with age, and the highest mortality rate was in patients with congenital scoliosis who had cor pulmonale.

Combined anterior and posterior spine fusion in cerebral palsy.

Two-staged anterior and posterior spine fusion with instrumentation was evaluated in 17 cerebral palsy patients, ages 11 to 30 years. Functional benefits included improved sitting balance and, in ambulators, no loss of independence. Curve correction averaged 60%. The pseudarthrosis rate of 18% was lower than previously reported for patients with anterior or posterior fusions alone. Instrumentation complications occurred in 50% of patients with athetosis. The combined anterior and posterior fusion for thoracolumbar and lumbar curves appeared to give the best correction, highest rate of fusion, and fewest complications in this complex patient group.

Spinal fusion in Duchenne's muscular dystrophy.

Thirteen patients with Duchenne's muscular dystrophy underwent spinal fusion and Harrington instrumentation between 1967 and 1979. Curve progression was the most common indication for surgery. Cardiorespiratory evaluation was most important in the timing of surgery. After 12 months of immobilization, all spines fused. Major and minor complications occurred in eight of 13 patients. The major benefit of surgery was improved or maintained sitting balance. Surgery is not recommended for patients with symptomatic cardiomyopathy, vital capacity less than 40%, a nonfunctional cough, or rapidly progressive deterioration in muscle strength with a projected life span of less than two years.

Scoliosis and cor pulmonale.

Twenty patients with cor pulmonale due to scoliosis and associated spine deformities seen at the Twin Cities Scoliosis Center in the past 20 years have been reviewed. The average age was 37 years. The average scoliosis was 135 degrees and ranged from 90 degrees to 200 degrees. Fifteen patients were placed in halo traction, nine of whom went on to surgical stabilization. Of the nine patients having surgical treatment, five had postpoliomyelitis curves, two had congenital, one had infantile idiopathic, and one had frontometaphyseal dysplasia. The best results were in the postpoliomyelitis group, with an average pretreatment vital capacity of 595 cc and posttreatment vital capacity of 1071 cc; the average PaO2 increased from 55 to 64 mm Hg, and the average PaCO2 decreased from 52 to 43 mm Hg. The only death in the postpoliomyelitis group occurred six years postoperatively. Of the four nonpoliomyelitis patients having surgery, only one survived, the patient with frontometaphyseal dysplasia. The difference between the poliomyelitis and nonpoliomyelitis groups was striking. Patients with cor pulmonale due to spine deformity should have careful evaluation and a trial of halo traction. If the vital capacity improves, the PaO2 increases, and the PaCO2 decreases, then surgical stabilization can often be successfully accomplished. If these parameters do not improve in traction, then surgical treatment can be abandoned.

Lateral electrical surface stimulation in idiopathic scoliosis. Experience in two private practices.

One hundred twenty-six patients with idiopathic scoliosis were treated by lateral electrical surface stimulation. Of these, 39 patients satisfied a strict set of protocols and were evaluated as a group. In this subgroup, curves averaged 28 degrees (range, 20-38 degrees). Thirty-eight percent exhibited initial curves greater than 30 degrees. Thirty percent of patients had a Risser sign of 0. Follow-up was from 6 months to 6 years. Progression was greater than 5 degrees in 48% and greater than 10 degrees in 35%. The final curve was greater than 40 degrees in 30%. Twenty-eight required fusion. Compared with natural history studies, these results are acceptable, and the authors continue to offer lateral electrical surface stimulation as a method of nonoperative care for progressive idiopathic scoliosis.

The lumbar lordosis below Harrington instrumentation for scoliosis.

This retrospective study evaluates lumbar lordosis in 43 patients before and after Harrington instrumentation into the lumbar spine. The authors measured overall lumbar lordosis, lordosis of unfused lumbar levels, and sagittal vertical axis. Lordosis decreased progressively in lower levels of fusion. The increase in lordosis below the fusion did not compensate for the overall loss of lordosis. The sagittal vertical axis moved forward, producing a subtle, asymptomatic form of flat back syndrome.

Spine fusion in cerebral palsy with L-rod segmental spinal instrumentation. A comparison of single and two-stage combined approach with Zielke instrumentation.

The benefits of achieving rigid internal fixation and eliminating the need for postoperative external orthotic support with L-rod spinal instrumentation made it desirable for use in the surgical treatment of neuromuscular scoliosis. From May 1981 to May 1985, 31 severely involved cerebral palsy patients with progressive spinal deformity underwent posterior fusion and L-rod instrumentation. All patients except one were nonambulatory. Surgical indications included prevention of curve progression, correction of pelvic obliquity, and achievement of balanced spinal alignment in order to improve sitting balance and tolerance without external spinal orthotic support. Ten patients (Group I), with an average age of 15.2 years, with double major or flexible paralytic C-curves or scoliosis measuring less than 70 degrees, underwent posterior fusion and L-rod instrumentation only. Twenty-one patients (Group II), with an average age of 22.1 years, with thoracolumbar, lumbar, or rigid paralytic C-curves or scoliosis measuring greater than 70 degrees, underwent initial anterior release, bone grafting, and Zielke instrumentation followed by second-stage L-rod instrumentation. In Group I, scoliosis averaged 57 degrees and postoperatively 27 degrees (53% correction). In Group II, scoliosis averaged 88 degrees and postoperatively 36 degrees (63% correction). Fifteen Group II patients had posterior fusion extend into the sacrum using the Galveston technique. Six Group II patients were not fused into the sacrum. Scoliosis and pelvic obliquity were corrected in both groups. Torso decompensation improved to 2.7 cm in the Galveston group, but increased to 5.6 cm at follow-up in the patients not fused into the sacrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical and functional results of spine fusion in spinal muscular atrophy.

From 1965 to 1987, 84 spinal muscular atrophy patients were followed at Rancho Los Amigos Medical Center (RLAMC). Twenty-seven patients were excluded from this study due to insufficient medical documentation (16), lack of follow-up (5), and death (6); leaving 57 patients in the general study group. Group I (34 patients) had posterior spinal fusion (PSF) with Harrington rod instrumentation (HRI); mean age at surgery was 12 years, average preoperative curve was 57 degrees, average postoperative correction was 42%, with a loss of correction of 9 degrees. The complication rate in this group was 35%. The average follow-up interval was 9 years (range, 4-19 years). Group II (six patients) underwent PSF with Luque segmental spinal instrumentation (SSI); mean age at surgery was 11 years, preoperative curves averaged 37 degrees, average postoperative correction was 42% with a loss of correction of 3 degrees. The complication rate in this group was 16%. Follow-up was 3.5 years. Physical therapy and occupational therapy evaluations were done preoperatively and postoperatively at 2- and 5-year intervals. Information was gathered in three categories: 1) ambulation, 2) equipment use, and 3) functional activities. After fusion, sitting tolerance was maintained but additional use of mobile arm supports, lapboards, and reaching aides was necessary for all patients. The ability to perform activities such as drinking, self-feeding, and self-hygiene declined during the 2 years immediately following surgery but improved by 5 years. Surgical patients never approached their preoperative skill levels. Therapy evaluations further demonstrated that there were no difference in function between either operative group.

Functional activities in spinal muscular atrophy patients after spinal fusion.

Spinal muscular atrophy patients present with weakness, greater in the proximal muscles, leading to scoliosis and limited upper extremity function. The purpose of this study is to identify unique aspects of these patients and to understand how spinal fusion affects their function. Forty patients underwent Harrington or Luque rod instrumentation with functional evaluations preoperatively and 2 and 5 years postoperatively. Biomechanical assessment of function is important. Flexibility of the spine is functionally advantageous because distal strength is used to align weaker proximal segments. Postoperatively, lack of spinal flexibility resulted in a decline in gross motor function and increased use of UE aids due to a change in the trunk position in the weaker patients. The stronger patients' activities were maintained. Earlier mobilization in patients with Luque procedures did not improve postoperative function.

Spinal fusion using zielke instrumentation: a preliminary report.

Nineteen patients underwent anterior spinal fusion with Zielke instrumentation, followed by a posterior spinal fusion with Harrington instrumentation, for severe thoracolumbar and lumbar scoliosis. The transthoracic-retroperitoneal approach and Zielke technique used by the authors are presented, in addition to surgical results and complications. The Zielke method of anterior spinal instrumentation provided improved correction of scoliosis, derotation, and rigid stabilization.

Pathology and morphometry of the paraspinous muscles in nonidiopathic scoliosis.

The muscle fibers in 19 patients with nonidiopathic scoliosis were generally small, especially on the concave side of the curve. Type 1 fibers were more frequently atrophic than type 2 fibers, but the former usually remained larger than the latter. Type 1 preponderance was greater on the convex side of the curve; type 2A preponderance occurred bilaterally. These changes are similar to those of idiopathic scoliosis. They resemble those of endurance training or stretch and are interpreted as secondary to the curve.

Wound infections following spinal fusion with posterior segmental spinal instrumentation.

Twenty-three of 238 patients (9.7%) developed wound infections following segmental spinal instrumentation. When the infected group and a matched control group were compared, the infected group had a significantly higher number of patients with cerebral palsy and myelodysplasia (nonambulatory), patients with wound hematomas, patients with fusions that extended into the sacral region, and patients who were incontinent of urine. A high incidence of infections with gram-negative aerobic bacilli correlated with the extension of the surgery into the sacral region and bowel and/or bladder incontinence. Prophylactic antibiotics with broader coverage for gram-negative bacilli may be warranted for these procedures. Postoperative wound infections were managed by surgical drainage and debridement as well as antibiotics. Removal of the hardware was not necessary to control the infection in these patients who underwent segmental spinal instrumentation.