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Serial determination of tumor necrosis factor-alpha content in rat sciatic nerve after chronic constriction injury.

Wallerian degeneration, induced after injury to a peripheral nerve, is associated with upregulation of proinflammatory cytokines, which are suggested to contribute to the development of lesion-induced neuropathic pain. In chronic constrictive injury (CCI), an animal model of injury-induced painful mononeuropathy, inhibition of synthesis, release, or function of the cytokine tumor necrosis factor-alpha (TNF) results in reduced pain-associated behavior. Here, changes of TNF content in rat sciatic nerves after CCI (days 0, 0.5, 1, 3, 7 and 14) were investigated by enzyme-linked-immunoassay. Low levels of TNF were already detectable in control nerves. Concentrations increased rapidly after CCI, with a maximum (2.7-fold) at 12 h, and remained elevated on a lower level until day 3. Baseline levels were reached again at day 14. These results indicate that TNF is produced at an early time point in the cascade of events resulting in Wallerian degeneration and hyperalgesia following peripheral nerve injury. Given that only prophylactic treatment with TNF inhibitors efficiently reduces hyperalgesia in CCI, TNF seems to contribute to the initiation of neuropathic pain in this model.

Animals↗

Calcium channels and cation transport ATPases in cardiac hypertrophy induced by aortic constriction in newborn rats.

Cardiac enlargement due to gradual pressure overload was induced by abdominal aortic constriction in 2-day-old rats. On day 90, the functional performance of the left ventricle was assessed by acute load test (ligation of ascending aorta) in open-chest anaesthetized animals. Two subgroups, designated compensated and decompensated hypertrophy (CH and DH), were distinguished on the basis of the functional reserve of left ventricle, which was significantly impaired in DH but not in CH, and of right ventricle weight, which was markedly increased in DH but not significantly modified in CH. In total particulate fractions prepared from hypertrophied left ventricles, the levels (per g tissue) of sarcoplasmic reticulum Ca(2+)-transport systems were decreased, either slightly (by 13-16%: [3H]ryanodine binding) or moderately (by 28%: thapsigargin-sensitive Ca(2+)-ATPase activity). The number of sarcolemmal L-type Ca2+ channels ([3H]PN200-110 binding) was not modified significantly, while that of beta 1-adrenoceptors ([3H]CGP-12177 binding) was reduced, especially in the DH group (by 39%). Na+,K(+)-ATPase activity was reduced by 28% in CH and 41% in DH. [3H]Ouabain binding experiments (saturation and dissociation) indicated the existence of two high-affinity binding sites, attributable to the Na+, K(+)-ATPase alpha 3 and alpha 2 subunit isoforms; while the relatively minor alpha 3 component did not change significantly in hypertrophied ventricles, the alpha 2 component was markedly down-regulated, decreasing by 57% in CH and 82% in DH.

Animals↗

Congenital constriction of the foramen of Monro.

We report two cases of hydrocephalus in adults. The radiological investigations and direct inspection during surgery in one of the cases indicate that the hydrocephalus is caused in both cases by a benign stricture in the region of the foramen of Monro and that this constriction is congenital. This origin of hydrocephalus has not been reported previously in adults.

Adult↗

Early hypercyanotic spells unrelated to ductal constriction in tricuspid atresia with infundibular stenosis.

Clinical, echocardiographic, hemodynamic, and angiographic findings were reviewed in 16 consecutive patients with tricuspid atresia (TA) and normally related great arteries, seen at the University of Florida between 1984 and 1990, to determine when and in which hypercyanotic spells (HS), unrelated to ductal constriction, occurred. Such spells developed in six patients (38%) and were life-threatening and refractory to medical management in three patients. Most HS (five of six) occurred in the first 2 months of life. Angiography done at the time of diagnosis revealed similar morphological features in all patients subsequently experiencing HS; infundibular stenosis due to anterior malalignment in the conal septum. These findings suggest a predisposition for development of early HS in TA patients with apparent infundibular stenosis due to anterior malalignment of the conal septum. Further study and a heightened clinical awareness are needed in such patients.

Angiography↗

Development and reversal of pressure-induced cardiac hypertrophy. Light and electron microscopic study in the rat under temporary aortic constriction.

Light and electron microscopy, combined with morphometry, were utilized to study myocardial cell modifications induced by a temporary abdominal aortic constriction in the rat. During the early stage of active hypertrophy, cell enlargement in the subendocardial layers of the left ventricle was predominant. This enlargement may be partly due to intracellular edema, characteristic of cell damage. Degenerative foci leading to fibrous scars were found primarily in the subendocardium and midwall layers. The times taken by the different cell structures to adapt to modifications of the load were rather different; some adapted very rapidly (nucleoli, intercalated discs), while others were much slower (cell diameter, mitochondria).

Animals↗

Hemorrhoids. Measuring the constrictive force of rubber bands.

In ligating hemorrhoids with rubber bands, weaker constrictive force lessens liability to subsequent bleeding but increases that for venous block without complete arterial block. A method applicable in the office is described to assess this force. Thirteen samples of rubber bands tested exhibited very wide differences of this force and also of hysteresis. Some attributes of the desirable rubber band are submitted.

Constriction↗

Noninvasive vacuum constriction device in the management of erectile dysfunction.

The effectiveness of a device designed to overcome erectile impotence was assessed in 21 patients: 5 patients with vasculogenic impotence due to venous leakage, 6 with diabetes mellitus with or without atherosclerotic cardiovascular disease, 2 paraplegic patients after spinal cord injury, 3 severely obese patients and 5 patients with psychogenic impotence. They were instructed how to use the device, which uses suction to induce penile engorgement and maintains erection with a constriction band. A total of 17 patients (81%) achieved an erection or an erection-like state that was satisfactory for intercourse. No serious ill effect from the use of the device has been reported. In selected patients the device is an alternative to either surgical placement of penile prosthesis, intracavernous injection of vasoactive drugs or sexual abstinence.

Adult↗

Cardiac hypertrophy in rats after supravalvular aortic constriction. II. Inhibition of cellular autophagy in hypertrophying cardiomyocytes.

Adult male Sprague-Dawley rats were killed by retrograde perfusion fixation 3, 7, 14, 21 and 35 days after supravalvular aortic constriction (n = 33) or sham-operation (n = 25). Subepicardial specimens of the left ventricular myocardium were evaluated by conventional electron microscopic morphometry, and in addition were examined for the occurrence of autophagic vacuoles (AVs) using large test areas (3.9 X 10(4) micron 2 per animal). The quotient of mitochondrial to myofibrillar volume fraction was largely unchanged during hypertrophy but was reduced by 25% compared with controls after termination of growth at 35 days. During the process of hypertrophy which eventually led to an increase in average single cell volume of the cardiomyocytes by 78%, the volume fraction and the numerical density of AVs was significantly lower than in sham-operated rats. The most striking difference was observed 7 days after the operations, the stage at which the growth rate of the cardiomyocytes relative to controls was at its maximum of 4.5% per day. At this point the volume fraction as well as the numerical density of AVs were reduced by about 50% compared with controls. At 14 and 21 days after operation, when the relative growth rate of the hypertrophying cardiomyocytes was still 2% and 1% per day, the AV volume fraction was reduced to a lesser extent (by 47% and 28%, respectively). After termination of adaptive growth at 35 days significant differences in fractional volume and numerical density of AVs were no longer detectable. These results suggest that degradation of cytoplasmic components is inhibited in cardiomyocytes undergoing hypertrophy. Such an anticatabolic reaction seems to play an important role in establishing the positive balance of cellular metabolism generally required for growth processes.

Animals↗

Mitral regurgitation after pericardiectomy for constrictive pericarditis.

We report a case of constrictive pericarditis in which trace mitral valve regurgitation was detected preoperatively and temporarily worsened after a pericardiectomy was performed. The early postoperative data suggested that the increased mobility of the lateral wall, in conjunction with an increase in the left ventricular volume, might be one of the causes of the perioperative mitral valve dysfunction. The mitral valve function returned to the preoperative baseline thirteen months after the pericardiectomy.

Adult↗

Indications, results, and pitfalls in the surgery of constrictive pericarditis.

Constrictive pericarditis is a rare disease with an often unclear etiology. There may be a long delay between the onset of the underlying disease and the onset of clinical symptoms, which are fatigue, abdominal swelling, peripheral edema and breathlessness. However, if clinically apparent, these symptoms may progress rapidly and severely disable the affected patient. Diagnosis is achieved by the clinical presentation, echocardiography and/or MRI and right heart catheterization. The standard therapy is an extended pericardiectomy to restore an unlimited inflow and outflow as well as an unrestricted diastolic function of both ventricles. The risks of this procedure are related to dense adhesions between the 2 pericardial layers and severe calcifications especially of the epicardium. Incomplete removal results in persistent diastolic restriction while lacerations of the underlying myocardium may lead to diffuse and extensive bleeding and finally to myocardial dysfunction. Also, the postoperative course may be complicated by persistent low output syndrome or acute ventricular dilatation. However, early surgical intervention in the hands of experienced surgeons offers the best prognosis.

Diagnostic Imaging↗

Amelioration of hyperalgesia by kinin receptor antagonists or kininogen deficiency in chronic constriction nerve injury in rats.

OBJECTIVE: The present study was designed to examine the involvement of bradykinin in thermal and mechanical hyperalgesia induced by chronic constriction nerve injury (CCI) using B1 and B2 receptor antagonists and mutant kininogen-deficient rats. METHODS: Sprague-Dawley (SD) rats and Brown Norway (B/N-) rats given CCI treatment on day 0, were used as a model of neuropathic pain. Either a kinin B1 antagonist des-Arg9-[Leu8]-bradykinin or the receptor B2 antagonist HOE-140 was constantly infused into the left jugular vein of SD rats on days 15 to 22 after CCI. Vehicle-treated rats and sham-operated rats without nerve injury were also prepared as controls. In all rats, we observed pain behavior, and measured the latency period of paw withdrawal from the thermal stimuli and, with von Frey filaments, the mechanical pain threshold, before surgery and on days 14 and 22 after CCI. B/N-Katholiek rats, which congenitally lack plasma kininogen and release no kinin, were also tested for hyperalgesic parameters. Expression of kinin receptor mRNA in the dorsal root ganglia was detected by RT-PCR. RESULTS: Most of the rats (88%) showed some pain behavior, which was reduced to 67% by a B1 antagonist and to 57% by a B2 antagonist infused between days 15 to 22. Thermal hyperalgesia was significantly reduced from 7.25 +/- 0.41 sec (mean +/- SEM) to 8.36 +/- 0.41 sec in paw withdrawal latency on day 22 by a B1 antagonist and from 7.24 +/- 0.19 sec to 8.23 +/- 0.21 sec by a B2 antagonist (P < 0.05). Mechanical hyperalgesia was also ameliorated from 0.02 +/- 0.007 g force to 0.16 +/- 0.08 g force in pain threshold by a B1 antagonist and from 0.03 +/- 0.007 g force to 0.10 +/- 0.003 g force on day 22 by a B2 antagonist. Moreover, deficient B/N-Katholiek rats showed a low incidence of thermal and mechanical hyperalgesia on day 14. Expression of both B1 and B2 receptor mRNAs was detected in the lumbar dorsal ganglia ipsilateral to the site of the nerve injury. CONCLUSION: These data suggests that kinin were at least partly involved in yielding nociceptor hypersensitivity up to day 14 after CCI. Bradykinin and its B1 and B2 receptors were involved in the maintenance of hyperalgesia.

Animals↗

[Acute and chronic-constrictive pericarditis].

Acute pericarditis is an inflammatory disease of the pericardium of variable etiology. A viral infection may sometimes precede symptoms but frequently the etiology re-mains unknown (idiopathic pericarditis). The disease is typically associated with left-sided chest pain and ECG abnormalities mimicking acute myocardial infarction. At physical examination the characteristic finding is a pericardial friction rub. A pericardial effusion of varying extent may be present or develop in the course of the disease. Pericardial tamponade, which may develop insidiously, represents a life-threatening complication. Pathophysiologically, filling of the cardiac chambers is impeded resulting in orthopnea, tachycardia, and eventually shock. Emergency pericardiocentesis is the treatment of choice. Constrictive pericarditis is the result of a chronic inflammation of the pericardium. Clinically it is characterized by dyspnea during exercise, symptoms of right heart failure and typical hemodynamic findings. Treatment primarily includes surgical removal of the thickened pericardium.

Acute Disease↗

Pharmacological characterisation of place escape/avoidance behaviour in the rat chronic constriction injury model of neuropathic pain.

RATIONALE: Classical pain tests performed in animals routinely measure evoked nociceptive behaviours. These almost exclusively reflect sensory processing of nociceptive transmission, although a recently described place escape/avoidance paradigm may be used to selectively assess affective pain processing. OBJECTIVE: To establish if drugs with proven analgesic efficacy selectively attenuate sensory-discriminative or affective-motivational aspects of nociceptive processing. METHODS: The mu-opioid receptor agonist morphine, the anti-epileptic gabapentin, the anti-depressant duloxetine, the 5HT1A receptor agonist 8-OH-DPAT, the GABA(A) receptor agonist gaboxadol and the mixed cannabinoid receptor agonist WIN55,212-2 were tested after systemic administration in the chronic constriction injury (CCI) model of neuropathic pain. For the place escape/avoidance paradigm, CCI rats had free access between the 'non-aversive' dark and 'aversive' light side of an enclosed chamber. Either the injured or non-injured hindpaw was routinely stimulated if the rat was in the dark or light area, respectively. Escape/avoidance behaviour was defined as a shift from the dark to the light area. Mechanical allodynia and hyperalgesia were determined prior to and following escape/avoidance testing. RESULTS: Morphine (3 and 6 mg/kg), gabapentin (50 and 100 mg/kg), duloxetine (10 and 30 mg/kg) and 8-OH-DPAT (0.1 and 0.5 mg/kg) attenuated the time spent by CCI rats in the light area; gaboxadol (1 and 3 mg/kg) and WIN55,212-2 (0.3 and 1 mg/kg) were ineffective. Only gabapentin and 8-OH-DPAT attenuated mechanical nociceptive behaviours at non-sedative doses. CONCLUSIONS: The place escape/avoidance paradigm may enable discrimination between selected drug classes on distinct components of sensory and affective pain processing in rats with neuropathic pain.

Analgesics↗

The role of ductal constriction in transient stenosis of the left pulmonary artery.

To confirm the hypothesis that narrowing of the left pulmonary artery is produced by ductal closure, Doppler velocities in the pulmonary arteries from 20 premature infants with a patent duct were compared to velocities from 20 with a closed duct. In infants with a patent duct, the mean Doppler velocity in the main, right, and left pulmonary arteries were, respectively, 86 cm/sec +/- 5 standard error (SE), 120 +/- 7, and 125 +/- 8. With closed duct, the comparable velocities were 102 cm/sec +/- 7, 129 +/- 8, and 190 +/- 11. The only significant difference was the higher velocity in the left pulmonary artery associated with a closed duct (p = 0.00003). This physiologic origin of left-branch stenosis associated with ductal constriction should be considered when a murmur is detected after administration of indomethacin (in addition to possible persistent ductal flow), and as an explanation for some murmurs in the normal newborn. No anatomic or physiologic support was found for the theories that murmurs in the neonate were due to ductal flow, or to acute angulation of the branch pulmonary arteries.

Blood Flow Velocity↗

CT and MRI findings in a child with constrictive pericarditis.

Constrictive pericarditis is rare in children. We report computed tomography (CT) and magnetic resonance imaging (MRI) findings in a 3-year-old girl. She had a swollen abdomen that increased in two months. CT and MRI showed a thickened pericardium (5.2 mm) without calcification. Both atria were enlarged and ventricles were relatively small. The engorged inferior vena cava had 2.8x the diameter of the descending aorta at the same level. Symptoms were dramatically improved after pericardiectomy. The histopathological features confirmed chronic pericarditis.

Child, Preschool↗

Fatal outcome of constrictive pericarditis in rheumatoid arthritis.

This is a report of a 39-year-old patient diagnosed with seropositive rheumatoid arthritis at the age of 17. The patient died 2 years after the onset of extra-articular cardiac symptoms. This case demonstrates the devastating course of progressive constrictive pericarditis under sole medical therapy and emphasizes the importance of early radical pericardectomy to avoid progression of disease and secondary complications with fatal outcome. Further, we discuss risk factors, diagnostic caveats, diagnostic tests and therapy of hemodynamically relevant contrictive pericarditis.

Adult↗

Assessment of ventricular coupling with real-time cine MRI and its value to differentiate constrictive pericarditis from restrictive cardiomyopathy.

The purpose of this study was to evaluate the use of respiratory-related ventricular coupling to differentiate patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). In 18 histologically proven cases of CP, 6 patients with inflammatory pericarditis (IP), 15 RCM patients and 17 normal subjects, real-time cine MRI was performed in the cardiac short-axis (basal half of the ventricles) during operator-guided deep respiration. The images were analyzed for ventricular septal position and shape during early ventricular filling. Early diastolic septal inversion (I) or flattening (F) was found in all CP (I:15,F:3), and in all IP (I:2,F:4), but seldom in normals (F:1) and not in RCM. The septal abnormalities occurred at the onset of inspiration and rapidly disappeared with the next heartbeats. The amount of ventricular coupling was evaluated by quantifying the difference in the maximal septal excursion between inspiration and expiration. This parameter, normalized to the biventricular diameter, was significantly larger in CP (20.0+/-4.5%, P<0.0001) and IP (14.8+/-3.2%, P<0.0001) patients than in normals (7.0+/-2.4%), whereas RCM patients had a trend toward decreased excursion (4.2+/-1.7%, P=0.11). A cut-off value of 11.8% (mean normals +2 SD) enabled to differentiate CP patients from normals and RCM patients completely. Real-time cine MRI can easily depict increased ventricular coupling, which may be helpful to better differentiate between CP and RCM patients, especially in patients with normal or minimally thickened pericardium. The increase in coupling in IP patients is likely caused by decreased compliance of the inflamed pericardial layers.

Aged↗