Mechanical and metabolic determination of VO2 and fatigue during repetitive isometric contractions in situ

Repetitive isometric tetanic contractions (1/s) of the canine gastrocnemius-plantaris muscle were studied either at optimal length (Lo) or short length (Ls; approximately 0.9 . Lo), to determine the effects of initial length on mechanical and metabolic performance in situ. Respective averages of mechanical and metabolic variables were (Lo vs. Ls, all P < 0.05) passive tension (preload) = 55 vs. 6 g/g, maximal active tetanic tension (Po) = 544 vs. 174 (0.38 . Po) g/g, maximal blood flow (Q) = 2.0 vs. 1.4 ml . min-1 . g-1, and maximal oxygen uptake (VO2) = 12 vs. 9 micromol . min-1 . g-1. Tension at Lo decreased to 0.64 . Po over 20 min of repetitive contractions, demonstrating fatigue; there were no significant changes in tension at Ls. In separate muscles contracting at Lo, Q was set to that measured at Ls (1.1 ml . min-1 . g-1), resulting in decreased VO2 (7 micromol . min-1 . g-1), and rapid fatigue, to 0.44 . Po. These data demonstrate that 1) muscles at Lo have higher Q and VO2 values than those at Ls; 2) fatigue occurs at Lo with high VO2, adjusting metabolic demand (tension output) to match supply; and 3) the lack of fatigue at Ls with lower tension, Q, and VO2 suggests adequate matching of metabolic demand, set low by short muscle length, with supply optimized by low preload. These differences in tension and VO2 between Lo and Ls groups indicate that muscles contracting isometrically at initial lengths shorter than Lo are working under submaximal conditions.     

Partial cardiopulmonary bypass in rats for evaluating ischemia-reperfusion injury

The authors developed a miniaturized partial cardiopulmonary bypass model in rats by using membrane oxygenators. Sprague-Dawley rats underwent general anesthesia and tracheostomy for ventilation. Partial cardiopulmonary bypass was carried out through the jugular cannula (18 gauge) for venous blood drainage and through the femoral arterial cannula (24 gauge) at a flow of 50 ml/kg/min. Membrane oxygenators used in this study maintained arterial oxygen tensions (PaO2) at 300-500 mmHg and carbon dioxide tensions (PaCO2) at 25-35 mmHg, with a gas mixture of 95% O2 + 5% CO2 (n = 7) for at least 2 hr of bypass circulation. To test the feasibility of this system for investigation of ischemia-reperfusion injury, hypoxic challenges with gas mixtures of different oxygen concentrations were examined. After equilibration of the bypass circulation for 1 hr, the following gases were tested for 15 min: Group I, 95% air + 5% CO2 (FiO2 = 0.21, n = 5); Group II, 10% O2 + 5% CO2 + 85% N2 (FiO2 = 0.1, n = 5); and Group III, 95% N2 + 5% CO2 (FiO2 = 0, n = 5). Equilibrated PaO2 values after challenge with these gases for 15 min were as follows: Group I: 89.6 +/- 3.7, Group II: 53.8 +/- 1.4, Group III: 25.6 +/- 2.0 mmHg (p < 0.01 between Groups I and II, I and III, II and III; p < 0.01 vs. prehypoxic PaO2 values in all groups). PaO2 values returned to the previous level within 15 min after return to the standard gas mixture (95% O2 + 5% CO2) supply. This system provided stable cardiopulmonary bypass in rats for at least 2 hr and may be useful for investigation of ischemia-reperfusion injury.     

The effect of hemodilution with stroma-free hemoglobin and dextran on collateral perfusion of ischemic myocardium in the dog

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.     

Sonographic patterns by transcranial Doppler in acute cerebral infarction

Microcirculatory changes occur early in insulin-dependent diabetes mellitus (IDDM) and are believed to be an early feature of late diabetic complications, leading to reduced oxygen pressure and hypoxia in the skin and other tissues. Whether muscle oxygen supply is also altered is unknown. Therefore, the authors analyzed polarographic measurements of muscle oxygen tension in 44 healthy type I diabetic patients (mean age 28 years; mean diabetes duration 7 years) and in 57 healthy controls, matched for age, sex, and body mass index, and the corresponding influencing factors. Two measurements were taken at rest 60 minutes apart in the anterior tibial muscle. Muscle oxygen tensions did not differ between IDDM patients and controls (23.0 +/- 8.6 vs 25.3 +/- 9.0 mmHg) and were reproducible on repeated measurements (25.3 +/- 9.7 vs 25.5 +/- 7.4 mmHg). Coefficients of variation were 13.5 +/- 10.8% in IDDM patients and 13.1 +/- 9.3% in controls. Compared with controls, in IDDM patients hemoglobin A1c (HbA1c) and blood glucose concentrations were elevated, and arterial oxygen pressure was significantly lower. Muscle oxygen tensions were positively correlated with blood glucose concentrations in IDDM patients (Rho=0.48, P=0.002) but not with HbA1c or with insulin concentrations. The authors conclude that the polarographic measurement of muscle oxygen tension is a reliable method with good reproducibility. Hypoxia in the anterior tibial muscle of type I diabetic patients can be excluded. In IDDM patients the level of muscle oxygen tension is correlated with the level of blood glucose concentration.     

Partial transformation from fast to slow muscle fibers induced by deafferentation of capsaicin-sensitive muscle afferents

Mechanical and histochemical characteristics of the lateral gastrocnemius (LG) muscle of the rat were examined 21 days after capsaicin injection into the LG muscle. The capsaicin caused a decrease in generation rate of twitch and tetanic tension and an increase in fatigue resistance of LG muscle. The histochemical muscle fiber profile evaluated by myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide tetrazolium reductase methods showed an increase of type I and IIC fibers and a decrease of the type IIB in whole muscle, and a decrease of the IIA, IIX fibers in the red part accompanied by their increase in the white part. Therefore the capsaicin treatment, which selectively eliminated fibers belonging to the III and IV groups of muscle afferents, induced muscle fiber transformation from fast contracting fatiguing fibers to slowly contracting nonfatiguing ones.     

Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.     

High-risk mitral valve replacement in severe pulmonary hypertension--30 years experience

OBJECTIVE: In the past 30 years, 2316 patients underwent mitral valve replacement (MVR) at our institution; 382 of them had severe pulmonary hypertension (pulmonary artery pressure (PAP) > 50 mmHg; pulmonary vascular resistance (PVR), 690 +/- 46 dyn/s per m2). We reviewed our early and late results in this high-risk subgroup. METHODS: We used 336 mechanical and 46 biological devices for MVR. The follow-up was 95%, with an observation period of 3208 patient-years and a mean of 8.4 +/- 0.2 years per patient. The overall early mortality rate was 10.5% (n = 40) and stayed at about the same level over the years, although patients characteristics have changed to much older patients and more reoperations. To clarify this fact we divided our data in results according to the decades in which the operations were carried out. The clinical preoperative status and results were as follows (*P < 0.05; **P < 0.01 compared with previous decade). In the decades between 1963 and 1973 (I), 1974 and 1983 (11) and 1984 and 1993 (III) we operated on n = 95 (I), n = 185 (II), and n = 102 (III) patients with a mean age of 43 +/- 1 (I), 50 +/- 1** (II), and 58 +/- 1** (III) years. The incidence of reoperations among these patients was 3.2 (I), 4.9 (II), and 22.6%** (III). The early mortalities were 13.7 (I), 8.6* (II) and 10.8% (III); late mortalities lowered from 5.77 (I), over 4.95 (II), and up to 3.39%** (III) patients/year. The mean functional status according to New York Heart Association (NYHA) class improved from preoperatively 3.0 +/- 0.1 (I), 3.2 +/- 0.1 (II) and 3.3 +/- 0.1 (III) to 2.4 +/- 0.2 (I), 2.4 +/- 0.1 (II) and 2.3 +/- 0.1 (III) postoperatively. RESULTS: Compared with routine elective MVR with a mortality rate of 3.6% (P < 0.01), early mortality is high. But once the patient survives the perioperative course, late results show no difference compared with patients without pulmonary hypertension. The functional results as well are not significantly different. In spite of on average 15 years older multimorbid patients with therefore higher complication rates, early results improved slightly, which could be explained by better operative techniques, perioperative treatment and nursing (online monitoring with immediate therapeutic substitution). Surprisingly the increased number of reoperations had no negative impact on patients' outcomes. CONCLUSION: According to our results, we recommend MVR in severe pulmonary hypertension even in the elderly, with a high but acceptable risk and good long-term results.     

Fiber-type caffeine sensitivities in skinned muscle fibers from humans susceptible to malignant hyperthermia

BACKGROUND: The response to contracture tests may depend upon the relative proportion of muscle fiber types within the muscle specimen. To determine whether a difference in fiber-type caffeine sensitivities exists between malignant hyperthermia susceptible (MHS) and malignant hyperthermia-nonsusceptible (MHN) skeletal muscle, we compared the fiber-type caffeine sensitivities in chemically skinned muscle fibers dissected from vastus lateralis muscle from 15 MHS and 16 MHN patients. METHODS: Muscle fiber type was determined in each fiber by the difference in strontium-induced tension measurements and in 36 fibers, after contracture testing, by ATPase enzyme histochemistry. Caffeine sensitivity was defined as the threshold concentration inducing more than 10% of the maximal tension obtained with a calcium 1.6 x 10(-2) mM solution. RESULTS: Significant difference in the mean (+/- SD) caffeine sensitivity was found between type I MHS fibers (2.63 +/- 0.85 mM) versus type II MHS fibers (3.47 +/- 1.2 mM) and between type I MHN fibers (5.89 +/- 1.8 mM) versus type II MHN fibers (10.46 +/- 2.6 mM). The mean (+/- SD) caffeine sensitivities for a given muscle fiber type (I or II) were different between groups of MHS and MHN patients. Both type I and II MHS fibers had significantly lower caffeine sensitivities, and this increase in caffeine sensitivity was significantly smaller in type I than in type II fiber. CONCLUSIONS: The current study indicates that a truly MHS patient cannot have a false-negative result solely related to abnormal type II fibers contained in a given muscle strip. Although the occurrence of a very high proportion of type I fibers in MHN human muscle could result in a false-positive contracture outcome, such an occurrence is expected to be rare.     

Efficacy of combination chemotherapy with miconazole and G-CSF in deep mycosis accompanying hematological diseases

In order to examine the efficacy of the combination chemotherapy with miconazole and G-CSF, patients with deep mycosis and suspected deep mycosis were divided into 3 groups. Group I: miconazole and G-CSF were administered simultaneously. Group II: miconazole was administered later during G-CSF administration. Group III: only miconazole was administered. Of a total of 117 cases 105 cases were analyzed including group I 37 cases, group II 39 cases and group III 29 cases, excluding 12 dropout and inadequate cases. Of the 105 cases, deep mycosis were 31 and suspected deep mycosis were 74, and underlying diseases were hematological malignancies such as leukemias. Efficacy judged mainly by the change of fever was 62.2% (23/37) in group I, 43.6% (17/39) in group II, and 41.4% (12/29) in group III, respectively. Efficacy was better in the patients whose neutrophil counts increased from less than 500/microliters to more than 500/microliters (group I 75.0%, group II 72.7%) than in the patients whose neutrophil counts were less than 500/microliters throughout the time of miconazole administration (group I 33.3%, group II 33.3%). Adverse effects were minimal in 3 groups (group I 15.4%, group II 17.4%, group III 15.6%). It is concluded that the combination with miconazole and G-CSF is effective in the treatment of deep fungal infections.     

Cervical vascular injuries: a trauma center experience

BACKGROUND: We analyzed 76 patients with cervical vascular injuries from penetrating neck trauma (n = 528) between 1977 and 1990 at a level I trauma center to evaluate the role of angiography in diagnosis and management and to assess the course and outcome of these patients. METHODS: Patients who were hemodynamically unstable underwent immediate surgical exploration. Stable patients were subjected to diagnostic investigation. Angiography was routinely performed to diagnose vascular injury in zones I and III and zone II if the trajectory was in the vicinity of major vessels. Therapeutic embolization was performed when possible at angiography; all other vascular injuries were treated surgically. RESULTS: Thirteen patients (2.5%) died of penetrating neck trauma, in 12 of whom hemorrhage was the contributing factor (12/76; 15.8% of patients with vascular injury). In nine patients who were hemodynamically stable vascular injury was diagnosed by angiography: 5 (6.8%) of 73 in zone I and 3 (5.4%) of 56 in zone III, four of whom underwent therapeutic embolic occlusion of the injured vessel. Injuries to vertebral and subclavian arteries and subclavian and innominate veins were often multiple, causing exsanguination and death (6.8% in zone I). In three patients with no preoperative neurologic deficit, the internal carotid artery was ligated without complication; in all other patients injury to the common carotid or internal carotid artery was repaired, in six of them with polytetrafluoroethylene grafts. CONCLUSIONS: Selective management of penetrating neck trauma should include routine angiography in zones I and III. Injuries to the common and internal carotid arteries should be repaired. The internal carotid artery may be ligated in the absence of preoperative neurologic deficit. Arterial injuries in the neck can be repaired with polytetrafluoroethylene grafts.     

Effects of copper deficiency and copper loading on 67Cu in supernatants of rat organs

Eleven organs of the rat were studied 1 hr and 24 hr after the intravenous administration of 67CuCl2 and 67Cu-ceruloplasmin. The rats were normal, copper-deficient, or copper-laden. The amounts of stable copper and 67Cu in the whole organ and supernatant fractions, corrected for whole blood copper and 67Cu, were measured. The distribution of supernatant 67Cu was determined in three Sephadex G-100 chromatographic zones: Peak I (150,000 daltons), Peak II (31,000 daltons), and Peak III (11,000 daltons). All organs took up 67Cu from both sources, but there was a tendency for increased uptakes in copper-deficient rats and decreased uptake in copper-laden rats. Only lung, heart, and testis took up more 67Cu from 67Cu-ceruloplasmin than from 67CuCl2. Supernatant 67Cu tended to be in Peak I when the source was 67Cu-ceruloplasmin and in Peak II when the source was 67CuCl2. When 67Cu-ceroloplasmin was added to supernatant fractions in vitro, the 67Cu was in Peak I. However, when 67CuCl2 was added to supernatant fractions, Peak III predominated in kidney, brain, testis, and liver; Peak II predominated in none; and Peak I predominated in spleen, muscle, large and small bowel, stomach, lung, and heart. A high-molecular-weight copper-binding substance seems to be present in organ supernatant fractions.     

Targeted disruption of the TGA3 locus in Arabidopsis thaliana

BACKGROUND: Severe latissimus dorsi muscle damage may compromise cardiomyoplasty performance. We analyzed factors underlying the damage produced in 20 sheep latissimus dorsi muscles by isolating the influences of electrical stimulation, mobilization (with some loss of vascular supply), loss of normal resting tension, or a combination of these. METHODS: In group I (n = 3), the muscle was mobilized except for its neurovascular pedicle and reattached at normal resting length. In group II (n = 3), the muscle was mobilized and reattached at about 80% of resting length. Groups III (n = 6) and IV (n = 4) were as groups I and II except that continuous indirect stimulation at 2 Hz was added after 2 weeks. In group V (n = 4), the undisturbed muscle received stimulation alone. After 10 to 12 weeks, muscle samples were taken for morphometric analysis. RESULTS: Loss of resting muscle tension appeared to be the single most damaging intervention, though mobilization and stimulation had further deleterious effects. The worst damage was seen when all three factors were combined, when 60% of the muscle cross section was occupied by connective tissue and fat. The changes were significantly more severe in the distal than in the proximal part of the muscle, implicating ischemia as a contributory factor. CONCLUSIONS: Fiber damage reduces the effectiveness of muscle grafts used for cardiac assistance and merits further systematic investigation.     

Compartment pressure in nailed tibial fractures. A threshold of 30 mmHg for decompression gives 29% fasciotomies

During the past few years we have monitored tissue pressure in patients treated with intramedullary nailing of tibial shaft fractures. A value of 30 mmHg has been used as the threshold for fasciotomy. The purpose of this study was to evaluate this practice. Sixty-three patients were included in the series. Forty-three fractures were closed, 18 grade I (Gustilo) and two grade II. Tissue pressure measurements were performed in 43 patients. Eighteen legs were treated with decompressive fasciotomy, three on clinical findings alone, and 15 after measurement of a pressure higher than 30 mmHg. This gives a fasciotomy rate of 29%. At follow-up two patients were dead. All fractures were healed, and there were no major complications such as deep infection, extensive muscle necrosis, paresis or short-foot syndrome. Three fasciotomized patients had significantly reduced muscle strength compared with the contralateral leg.     

Study of the interface and its effect on mechanical properties of continuous graphite fiber-reinforced 201 aluminum

The formation of fiber-matrix interfacial reaction zone and its impact on mechanical properties of Gr/201 Al composite (41 vol pct fiber) was evaluated in the as-received condition and after heat treatment in vacuum at 450°C, 500°C, and 545°C temperatures for one day, and at 545°C for one week. After heat treatment the microstructures of matrix and interface were studied by transmission electron microscopy. This study revealed the presence of interfacial constituents Al₄C₃, Al₄O₄C, and TiB₂. The mean fiber-matrix reaction zone thickness showed an increase with increasing heat treatment temperature and time. The effects of heat treatment on interfacial shear strength, monotonic and cyclic tension/compression properties were evaluated. The results show that the interfacial shear strength not only depends on chemical reaction but also depends on the thickness of the reaction zone. An increase in reaction zone size reduces mechanical bonding considerably (thermal induced stresses). The growth of reaction zone was very detrimental to monotonic and cyclic tension/tension fatigue behavior. The mechanism of failure in tension/tension fatigue was the initiation of cracks at the interface and their subsequent propagation in the matrix. It was concluded that the reaction zone was the controlling factor in tension/tension fatigue. In contrast, the results showed that compressional fatigue was matrix dependent and was little sensitive to the size of the fiber/matrix interfacial reaction zone.     

Fatigue crack growth mechanisms at the microstructure scale in Al-Si-Mg cast alloys: Mechanisms in regions II and III

The fatigue crack growth behavior in Regions II and III of crack growth was investigated for hypoeutectic and eutectic Al-Si-Mg cast alloys. To isolate and establish the mechanistic contributions of characteristic microstructural features (dendritic α-Al matrix, eutectic phases, Mg-Si strengthening precipitates), alloys with various Si content/morphology, grain size level, and matrix strength were studied; the effect of secondary dendrite arm spacing (SDAS) was also assessed. In Regions II and III of crack growth, the observed changes in the fracture surface appearance were associated with changes in crack growth mechanisms at the microstructural scale (from a linear advance predominantly through primary α-Al to a tortuous advance exclusively through Al-Si eutectic Regions). The extent of the plastic zone ahead of the crack tip was successfully used to explain the changes in growth mechanisms. The fatigue crack growth tests were conducted on compact tension specimens under constant stress ratio,R=0.1, in ambient conditions.     

Mild hypothermia after cardiac arrest in dogs does not affect postarrest cerebral oxygen uptake/delivery mismatching

PURPOSE: To compare measurements of cerebral arteriovenous oxygen content differences (oxygen extraction ratios, oxygen utilization coefficients) in dogs after cardiac arrest, resuscitated under normothermia vs. mild hypothermia for 1-2 h or 12 h. METHODS: In 20 dogs, we used our model of ventricular fibrillation (no blood flow) of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled ventilation, normotension, normoxemia, and mild hypocapnia to 24 h. We compared a normothermic control Group I (37.5 degrees C) (n = 8); with brief mild hypothermia in Group II (core and tympanic membrane temperature about 34 degrees C during the first hour after arrest) (n = 6); and with prolonged mild hypothermia in Group III (34 degrees C during the first 12 h after arrest) (n = 6). RESULTS: In Group I, the cerebral arteriovenous O2 content difference was 5.6 +/- 1.6 ml/dl before arrest; was low during reperfusion (transient hyperemia) and increased (worsened) significantly to 8.8 +/- 2.8 ml/dl at 1 h, remained increased until 18 h, and returned to baseline levels at 24 h after reperfusion. These values were not significantly different in hypothermic Groups II and III. The cerebral venous (saggital sinus) PO2 (PssO2) was about 40 mmHg (range 29-53) in all three groups before arrest and decreased significantly below baseline values, between 1 h and 18 h after arrest; the lowest mean values were 19 +/- 19 mmHg in Group I, 15 +/- 8 in Group II (NS), and 21 +/- 3 in Group III (NS). Postarrest PssO2 values of < or = 20 mmHg were found in 6/8 dogs in Group I, 5/6 in Group II and 4/6 in Group III. Among the 120 values of PssO2 measured between 1 h and 18 h after arrest, 32 were below the critical value of 20 mmHg. CONCLUSIONS: After prolonged cardiac arrest, critically low cerebral venous O2 values suggest inadequate cerebral O2 delivery. Brief or prolonged mild hypothermia after arrest does not mitigate the postarrest cerebral O2 uptake/delivery mismatching.     

Alterations of lymphocyte subsets in patients with recurrent fetal wastage positive for antiphospholipid antibodies treated with Chinese herbal medicine

The delay technique is an established method of enhancing flap survival. This investigation attempts to determine which of two delay techniques results in the best delay effect by measuring their relative abilities to capture adjacent vascular territories in a rat model. A dorsal flap based on the iliac branch of the iliolumbar artery with a captured random zone corresponding to the axial territory of the lateral thoracic artery was used in the evaluation. Sprague-Dawley rats (350-400 g) were randomly assigned into three groups. Group I was the control group. In group II, the circumferential borders of the animal's dorsum were incised without undermining and the dominant pedicle of the lateral thoracic flap was divided. In group III, the medial and lateral borders of the flap were incised and undermined as a bipedicled flap, violating the musculocutaneous perforators. The dominant pedicle of the lateral thoracic artery was also divided. Group III had the greatest survival with only 9% of flap area necrosis compared to 28% and 21% for groups I and II, respectively. These differences were statistically significant. The results suggest that musculocutaneous perforators provide a substantial vascular source to the tissue at risk and should be considered in selecting a delay technique.     

Nitric oxide modulates basal and endothelin-induced coronary artery vascular smooth muscle cell proliferation and collagen levels

The mechanisms governing the pathological accumulation of collagen in the extracellular matrix following angioplasty are complex, but may involve interactions between endothelium-derived paracrine agents and vascular cellular components. We tested the hypothesis that nitric oxide (NO) directly decreases collagen levels and decreases endothelin (ET-1)-stimulated increases in levels of specific collagen subtypes in coronary vascular smooth muscle cells (VSMC). Cultured VSMC were incubated for 48 h with the NO donor CAS 754 (10(-4) M), ET-1 (10(-8) M), or ET-1 plus CAS 754. In some experiments, angiotensin II (Ang II; 10(-8) M) was utilized in place of ET-1. Soluble collagen types I and III were quantitated with an ELISA method, and cell counts were performed. CAS 754 significantly inhibited cell proliferation (-17+/-2% v control), basal total protein synthesis (-65+/-7% v control), and basal collagen type I levels (-39+/-6% v control), but not collagen type III levels. ET-1 and Ang II both significantly stimulated cell proliferation (26+/-5% v control), total protein synthesis (169+/-6% v control), and collagen type I levels (200+/-11% v control). Ang II, but not ET-1, significantly increased collagen type III levels. Co-incubations of ET-1 and CAS 754 resulted in a significant decrease in cell proliferation, protein synthesis, and collagen levels (-23+/-2% v control, 90+/-5% v control, and 63+/-3% v control, respectively) compared to ET-1 alone. In contrast, co-incubation of Ang II and CAS 754 had no significant effect on cell proliferation, protein synthesis, and collagen levels seen with Ang II alone. These results demonstrate that NO inhibits basal collagen levels and cell division. Additionally, NO alters ET-1 stimulation of VSMC proliferation, protein synthesis, and production of extracellular matrix components. Thus, an imbalance in key endothelium-derived compounds could significantly impact upon extracellular matrix deposition following mechanical revascularization.     

Value of dobutamine echocardiography in the detection of coronary disease in heart transplant patient. Groupe de Recherche VACOMED]

The value of Dobutamine stress echocardiography in the detection of coronary artery disease in heart transplant patients was studied in 64 patients at control coronary angiography 39 +/- 14 months after transplantation. Dobutamine was infused at progressively increasing doses (5 to 40 micrograms/kg/min) at 5 minute intervals, in order to reach 85% of the theoretical maximal heart rate or an ischaemic event. Echocardiography was analysed in the 4 standard views which were digitised allowing calculation of a regional wall motion score under basal conditions and at peak dosage in 16 left ventricular segments. Coronary angiography identified three groups: group I: 29 patients with normal coronary arteries; group II: 17 patients with non-significant coronary disease (diffuse or localised stenosis < 50%); group III: 9 patients with significant (> 50%) coronary disease. Dobutamine stress echocardiography showed regional wall motion abnormalities in 2/29 patients in group I, 13/17 patients in group II and all patients in group III (global sensitivity: 85%; specificity: 97%). The contractility score was significantly higher under basal conditions in group III (1.45 +/- 0.54) than in group I (1) and group II (1.17 +/- 0.23). At peak dose, the contractility score was unchanged in group I and increased significantly (p < 0.01) in the other two groups. The authors conclude that Dobutamine echocardiography is a reliable, non-invasive method of detecting coronary disease in cardiac transplant patients, and is particularly valuable for demonstrating myocardial ischaemia related to coronary lesions judged to be not significant at coronary angiography.     

A regional ultrastructural analysis of the cellular and synaptic architecture in the chinchilla cristae ampullares

The chinchilla crista ampullaris was studied in 10 samples, each containing 32 consecutive ultrathin sections of the entire neuroepithelium. Dissector methods were used to estimate the incidence of various synaptic features, and results were confirmed in completely reconstructed hair cells. There are large regional variations in cellular and synaptic architecture. Type I and type II hair cells are shorter, broader, and less densely packed in the central zone than in the intermediate and peripheral zones. Complex calyx endings are most common centrally. On average, there are 15-20 ribbon synapses and 25-30 calyceal invaginations in each type I hair cell. Synapses and invaginations are most numerous centrally. Central type II hair cells receive considerably fewer afferent boutons than do peripheral type II hair cells, but have similar numbers of ribbon synapses. The numbers are similar because central type II hair cells make more synapses with the outer faces of calyx endings and with individual afferent boutons. Most afferent boutons get one ribbon synapse. Boutons without ribbon synapses were only found peripherally, and boutons getting multiple synapses were most frequent centrally. Throughout the neuroepithelium, there is an average of three to four efferent boutons on each type II hair cell and calyx ending. Reciprocal synapses are rare. Most synaptic ribbons in type I hair cells are spherules; those in type II hair cells can be spherical or elongated and are particularly heterogeneous centrally. Consistent with the proposal that the crista is concentrically organized, the intermediate and peripheral zones are each similar in their cellular and synaptic architecture near the base and near the planum. An especially differentiated subzone may exist in the middle of the central zone.