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Arrhythmogenic right ventricular dysplasia.

A 23-year-old man presented with recurrent exercise-induced ventricular tachycardia (VT), complicated by systemic embolisation. Catecholamine--sensitive VT was reproduced on exercise testing and programmed electrical stimulation, displaying features suggestive of enhanced automaticity as well as re-entry. Both 2D-echocardiography and gated heart pool scan showed localised dyskinetic bulging in the right ventricle. A diagnosis of arrhythmogenic right ventricular dysplasia was made. This condition should be excluded in all young patients with otherwise unexplained ventricular arrhythmias.

Adult↗

Mutants of adenovirus type 12 after adaptation to growth in tumor cell lines. II. Reproducible acquisition of additional sequences after adaptation to a human cervical cancer line.

Adaptation of adenovirus type 12 to growth in a human cervical cancer line (C4/1) results in the reproducible selection of viral mutants carrying additional DNA sequences at the right-hand end of the genome which range in size from 190 to 400 base pairs. The viral mutants have selective growth advantage in comparison to the non-affected wild type, even after subsequent passages in human KB cells, commonly used for adenovirus propagation. Detailed restriction endonuclease analysis of one of the mutant DNAs shows that the additional sequences are located within the terminal 195 base pairs of the right end of the genome.

Adenoviruses, Human↗

An apparatus to measure flexor tendon excursion and angular motion of the distal interphalangeal joint in a rabbit model.

Investigators evaluating flexor tendon adhesions have utilized visual, histological, and gross mechanical methods in reporting their results. We have developed a device to measure tendon excursion and distal interphalangeal joint motion for a small animal model. The device was tested for accuracy and reproducibility using the rabbit hindfoot. There was no statistical difference between the right and the left in 30 pairs of feet. This device provides an accurate method to quantify tendon excursion and relative adhesion formation in a rabbit model without destroying the specimen.

Animals↗

Determination of right ventricular ejection fraction by thermodilution technique--a comparison to biplane cineventriculography.

Determination of right ventricular ejection fraction (RVEF) provides information about global right ventricular function, which may be important for the management of patients with various heart diseases. Right ventricular ejection fraction can be determined by new thermodilution techniques using fast-response thermistors. To evaluate the validity of these methods, thermodilution measurements were compared with biplane cineventriculography in 22 patients undergoing cardiac catheterization. In all patients standard deviation of RVEF was below 5%. Mean RVEF, determined by thermodilution, was 52% +/- 9%, ranging from 32% to 71% and correlated significantly with the results of angiography (RVEF: 52% +/- 9%) (r = 0.80, SEE +/- 5%, n = 22, p less than 0.001). Correlation was good especially in patients with small right ventricles (less than 160 ml) (r = 0.91, SEE +/- 5%, n = 13, p less than 0.001), lower heart rates (less than 65/min) (r = 0.84, SEE = +/- 6%, n = 12, p less than 0.001) and cardiac output below 5.51/min (r = 0.88, SEE +/- 6%, n = 11, p less than 0.001). Thus, if valid catheter placement is possible, right ventricular ejection fraction can be determined by thermodilution technique with good reproducibility and sufficient accuracy compared to biplane angio. Validation of this method in larger patient populations with various heart diseases is necessary.

Aged↗

Characterization of a mouse model of chronic uremia.

A mouse model of renal failure, which is induced by the sequential electrocoagulation of the right renal cortex and left nephrectomy, was examined for the capacity to reproduce the characteristics of chronic uremia. Assessment was conducted six weeks after the second surgical procedure in 13 week old female C57BL/6 inbred mice with renal failure and in normal and sham-operated controls. The surgery, which was well tolerated, was free of local and systemic signs of inflammation or infection. Growth was significantly delayed in all animals post surgery however renal failure mice presented the most severe growth retardation. Biochemical analysis of plasma revealed multiple abnormalities with commensurate elevations of urea and creatinine. In addition to the expected hyperphosphatemia, hyperkalemia and acidosis, a significant increase in cholesterol was present. Furthermore, in contrast to controls, renal failure mice produced large volumes of urine which contained significant levels of protein. Renal failure mice presented profound hematological changes in the red cell series in which anemia was evident. Changes in plasma biochemistry and in bone histology revealed the presence of severe secondary hyperparathyroidism. It was therefore concluded that the described mouse model of chronic renal failure presented characteristics consistent with those observed clinically in end-stage renal disease.

Animals↗

Effect of E-4031, a new class III antiarrhythmic drug, on reentrant ventricular arrhythmias: comparison with conventional class I drugs.

We evaluated the antiarrhythmic efficacy of E-4031, a new class III drug, and compared it with that of conventional class I and II antiarrhythmic agents in terms of electrophysiological actions on refractoriness and conduction in a 7-day-old canine model of myocardial infarction. Sustained monomorphic VT was reproducibly induced in 26 dogs by a premature stimulation method from the right ventricle. Class I drugs (disopyramide, aprindine, flecainide) prevented VT induction in 5 of 13 dogs, and propranolol and E-4031 prevented it in 6 of 6 and 6 of 7 dogs, respectively. The effective refractory period (ERP) was determined at 47 epicardial sites overlying the infarct in each experiment by a S1S2 method. The standard deviation (SD) of the mean ERP of these sites was used as an index of ERP dispersion. The extent of ERP prolongation produced by class I drugs and E-4031 was significantly more marked than that produced by propranolol. However, the SD was increased by class I drugs and E-4031, but not by propranolol. Class I drugs increased the ERP dispersion mainly by an effect on the transmural infarct zone in which the control ERP was more prolonged than in the normal zone. E-4031 tended to prolong the ERP in both the normal and infarct zones, and had a minimal tendency to increase ERP dispersion. In contrast, propranolol decreased the ERP dispersion between zones. Conduction velocity calculated by epicardial mapping was significantly decreased by flecainide, but not by E-4031. We conclude that the antiarrhythmic effect of E-4031 depends largely on its ability to prolong refractoriness without suppressing conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transtracheal electrical stimulation of the spinal cord for intraoperative monitoring of the motor pathway.

Because of the suppressant effects of anesthetic drugs and muscle relaxants on motor responses elicited by either magnetic or electrical transcranial stimulation, intraoperative monitoring of the motor system, and especially monitoring of lower limb function, presents many difficulties. The upper part of the spinal cord was stimulated in 14 anesthetized and relaxed dogs with a cathode attached to the intratracheal tube and an anode fixed above the upper cervical spinous processes. Action potentials evoked by single and serial stimuli were recorded from the exposed right femoral nerve and quadriceps muscle Averaging was necessary for serial stimulations. Reproducible early and late responses to both single and serial stimulations were recorded during regular anesthesia. The origin of the different responses is discussed. Transtracheal stimulation of the spinal cord is easy to perform and the responses recorded from the peripheral nerve or limb muscle are well reproducible in regular anesthesia. The method seems to be appropriate for intraoperative monitoring of the thoracolumbar spine.

Action Potentials↗

The influence of age on weight-bearing joint reposition sense of the knee.

Knee joint-position sensitivity has been shown to decline with increasing age, with much of the research reported in the literature investigating this age effect in non-weight-bearing (NWB) conditions. However, little data is available in the more functional position of weight-bearing conditions. The objective of this study was to identify the influence of age on the accuracy and nature of knee joint-position sense (JPS) in both full weight-bearing (FWB) and partial weight-bearing (PWB) conditions and to determine the effect of lower-extremity dominance on knee JPS. Sixty healthy subjects from three age groups (young: 20-35 years old, middle-aged: 40-55 years, and older: 60-75 years) were assessed. Tests were conducted on both the right and left legs to examine the ability of subjects to correctly reproduce knee angles in an active criterion-active repositioning paradigm. Knee angles were measured in degrees using an electromagnetic tracking device, Polhemus 3Space Fastrak, that detected positions of sensors placed on the test limb. Errors in FWB knee joint repositioning did not increase with age, but significant age-related increases in knee joint-repositioning error were found in PWB. It was found that elderly subjects tended to overshoot the criterion angle more often than subjects from the young and middle-aged groups. Subjects in all three age groups performed better in FWB than in PWB. Differences between the stance-dominant (STD) and skill-dominant (SKD) legs did not reach significance. Results demonstrated that for, normal pain-free individuals, there is no age-related decline in knee JPS in FWB, although an age effect does exist in PWB. This outcome challenges the current view that a generalised decline in knee joint proprioception occurs with age. In addition, lower-limb dominance is not a factor in acuity of knee JPS.

Adult↗

Dopamine microinjected into the nucleus ambiguus elicits vagal bradycardia in spinal rats.

To investigate the effects of dopamine (DA) on vagal efferent activity, DA was microinjected into the right nucleus ambiguus (NA) in rats. Experiments were done in 19 urethane anaesthetized, artificially ventilated spinal (C1) rats. Sites in the right NA containing cardioinhibitory neurons were identified by observing a marked and reproducible decrease in heart rate (HR; 64.9 + 2.8 bpm; n = 36) elicited by microinjecting L-glutamate (GLU; 1.5. nmol in 10 nl). No decreases in arterial pressure (AP) were obtained at these sites. Microinjection of DA (1-15 nmol in 10 nl) into 24 of these 36 sites caused a dose-dependent decrease in HR. The responses to 1 nmol and 3 nmol DA were blocked by (+/-)-sulpiride, a specific D2 receptor antagonist (0.1 nmol in 10 nl). A higher dose of (+/-)-sulpiride (1 nmol in 10 nl) was required to block the responses to 15 nmol of DA. Bradycardia elicited by even the lowest amount of DA (1 nmol) was not blocked by SCH-23390, a specific D1 receptor antagonist. These experiments demonstrate that the bradycardia caused by microinjection of DA into the NA is due to the excitation of dopamine D2 receptors present on vagal preganglionic cardioinhibitory neurons controlling HR.

Animals↗

Dedifferentiation of atrial myocytes during atrial fibrillation: role of fibroblast proliferation in vitro.

OBJECTIVES: Severe myocyte alterations, characterized by enlarged myocytes and myolysis, is observed in fibrillating and dilated atria and contributes to atrial fibrillation. The aim of this study was to determine the nature of this cellular remodeling process and factors involved in its regulation. METHODS: In vivo, contractile proteins were studied in 24 human right atrial specimens by means of immunohistochemical techniques. In an attempt to reproduce in vitro the myocyte remodeling and to study its regulation, human atrial myocytes were cultured (n=27) and analyzed immunocytochemically; intracellular Ca(2+) transients (Ca(i)-tr) in response to electrical stimulation were monitored using Fura-2/AM. RESULTS: In diseased specimens, sarcomeres, seen at the periphery of myolytic myocytes, stained positively with antibodies against sarcomeric proteins of the Z-band (alpha-actinin and titin epitope T12) but not with antibodies against titin epitope T11 (I-band) or desmin (intermediate filament). beta-myosin heavy chain (MHC) and smooth muscle alpha-actin, two proteins of the fetal program, were re-expressed. In culture, diseased myocytes also showed myolysis and glycogen accumulation; their sarcomeres stained positively with anti-alpha-actinin, anti-T12, anti-beta-MHC and anti-smooth muscle alpha-actin but not with anti-titin T11 or anti-desmin antibodies. At confluence, myocytes regained a normal sarcomeric apparatus and were excitable, as shown by electrical Ca(i)-tr triggering. This redifferentiation process was inhibited by fibroblast proliferation. CONCLUSION: In diseased atria, myolytic myocytes are in a dedifferentiated state resembling that of immature muscle cells. In vitro, fibroblast proliferation prevents the reversibility of this cellular alteration.

Actinin↗

Effects of pulmonary afterload on the hemodynamics after the hemi-Fontan procedure.

A computational fluid dynamics study based on the application of the finite volume method has been performed to investigate the effects of the pulmonary afterload on the hemodynamics after the hemi-Fontan procedure. This operation is generally used as part of a series of staged procedures to treat complex congenital malformations of the heart. It consists of re-directing the superior vena caval flow from the right atrium into the pulmonary arteries, by-passing the right ventricle while excluding the inferior caval flow from the lungs. To reproduce correctly the pulmonary afterload conditions, a simplified lumped-parameter mechanical model of the pulmonary circulation has been developed and linked to the finite volume solver. In addition, the effect of a stenosis in the left pulmonary artery was also examined. In this paper the adopted methodology is presented, together with some of the preliminary results. The model has been used to simulate the local fluid dynamics for different values of the pulmonary arteriolar resistance and lung resistances, allowing a quantitative evaluation of the dissipated energy and the flow distribution into the lungs. The results show that both flow distribution into the lungs and energy dissipation after the hemi-Fontan procedure are only minimally affected by the pulmonary arteriolar resistance.

Biomedical Engineering↗

[Recurrent paroxysmal neck swellings as the primary manifestation of a pheochromocytoma].

A 45-year-old female had been suffering for about 6 months almost daily from paroxysmal neck swellings with occasional difficulties in swallowing and from non-specific abdominal complaints. Hormone analyses, performed because of the marked blood pressure increase up to 210/120 mm Hg during such an attack, revealed an increase in vanillyl mandelic acid and epinephrine concentrations in the 24-hour urine. CT demonstrated a tumour of 4 x 5 x 5 cm size in the region of the right adrenal. The paroxysmal neck swellings and blood pressure increase could be reproduced by means of pressure applied over the tumour range with the ultrasound transducer. The tumour was extirpated and histology revealed a phaeochromocytoma. For more than one year now the patient has been free from complaints. To date, recurrent neck swellings have not been reported in association with a phaeochromocytoma. Possible causes may be an enhanced congestion of the deep neck vessels during paroxysmal blood pressure increase or an enhanced response by the adrenoreceptors of these vessels to the released catecholamines.

Adrenal Gland Neoplasms↗

The effects of large doses of methylprednisolone on neurologic recovery and survival in the Mongolian gerbil following three hours of unilateral carotid occlusion.

Using a scoring system designed to assess the severity of neurologic deficit in gerbils during and after temporary unilateral carotid occlusion, the effects of large doses of methylprednisolone sodium succinate (MPSS: Solu-Medrol sterile powder) on experimental stroke have been examined. By scoring gerbils hourly for torso curvature, circling, inability to walk, ptosis, barrel rolling, opisthotonus, generalized seizures, and loss of righting reflex, their level of neurologic deficit can be easily, quantitatively, and reproducibly evaluated. Approximately 37% of gerbils subjects to a 3-hour unilateral carotid occlusion attained average scores of 4.0-4.5 during the first hour. There was a slight, though not significant, worsening (increase) of scores over the 3-hour occlusion period that was not altered by pretreatment of gerbils with 60 mg/kg of MPSS 10 minutes before occlusion. Following removal of occlusion at 3 hours, gerbils recovered only minimally during the ensuing 4-hour period, with deficit scores remaining around 3.2 +/- 0.3. Pretreatment of gerbils with 60 mg/kg of MPSS, however, resulted in a striking improvement in their deficit scores to 1.6 +/- 0.2 (p less than 0.05) by 2 hours after occlusion removal. Treatment of gerbils with lower (30 mg/kg) or higher (100 mg/kg) doses of MPSS was not as effective in promoting improvement. The survival of 3-hour occluded gerbils was significantly enhanced by pretreatment with 60 mg/kg of MPSS. Vehicle-treated gerbils had survival rates of 41.7%, 16.7%, and 16.7% at 24 hours, 48 hours, and 7 days, respectively, compared with 90.9%, 72.7%, and 45.4%, respectively, for MPSS-treated gerbils.

Animals↗

The use of resonant frequency measurements for the noninvasive assessment of mechanical stiffness of the healing tibia.

A study was performed to assess the usefulness of measuring the resonant frequency of vibration of the tibia as a determinant of its flexural rigidity in fracture healing. The measurement system consisted of an electronic tapper that struck the anteromedial distal surface of the tibia and an accelerometer, held against the proximal surface, that received the response. Custom software displayed the frequency spectrum from which the first mode bending frequency of the tibia could be pinpointed. We have found that resonant frequency was highly correlated to the log of tibial flexural rigidity, with an exponent of 0.582 (r2 = 0.815). In human volunteers, a series of four tests at monthly intervals showed a reproducibility of approximately 3% (95% confidence interval) with no significant variability between right and left legs. In 14 patients with healing tibial fractures, resonant frequency ratio (healing/injured leg) was correlated to time ratio (time of test/time healed) by a second-order polynomial fit (r2 = 0.58).

Adolescent↗

Intrathoracic far-field electrocardiogram allows continuous monitoring of ischemia after total coronary occlusion.

INTRODUCTION: Recording of intrathoracic far-field electrocardiograms (FF-ECG) via can and electrodes of implantable cardioverter-defibrillators (ICD) is a promising method for continuous monitoring of myocardial ischemia. We assessed the hypothesis that experimentally induced ischemia provokes segment changes in the FF-ECG that can be detected by the ICD. METHODS AND RESULTS: In seven pigs with an ICD implanted in the left pectoral region and electrodes placed in the right ventricle and the superior vena cava, we occluded all major coronary arteries in proximal and distal locations for 180 s each. Surface and FF-ECGs were compared for presence and time course of ischemic ST segment changes. Reliable detection of ischemia by ST segment analysis was possible in all (38/38) experiments. Maximum deviation from baseline was larger in FF-ECG (1.21 mV) than surface ECG leads (0.23 mV, P < 0.01) for all occlusion sites. Ischemia could be detected earlier (P < 0.05) in the FF-ECG, with a sensitivity of 100%, 93%, and 100% after occlusions in the left anterior descending, left circumflex, and right coronary arteries, respectively. CONCLUSION: Intrathoracic FF-ECG allows reliable and reproducible detection of experimentally induced ischemia originating from all major coronary arteries and therefore could be an interesting tool for clinicians in monitoring high risk patients.

Animals↗

Serial noninvasive assessment of progressive pulmonary hypertension in a rat model.

Current methods used to investigate pulmonary hypertension in rat models of the disease allow for only one to two measurements of pulmonary artery (PA) pressure in the life of a rat. We investigated whether transthoracic echocardiography can be used to assess the progression of pulmonary hypertension in rats at multiple time points. Serial echocardiographic measurements were performed over a 6-wk period on rats injected with monocrotaline (MCT) or placebo. Development of a midsystolic notch in the PA waveform, a decrease in the PA flow acceleration time (PAAT), an increase in right ventricular (RV) free-wall thickness, and the development of tricuspid regurgitation (TR) were observed as pulmonary hypertension developed. Changes in the PA waveform and PAAT began in week 3 of disease development as the PA systolic pressure (PASP) reached 25-30 mmHg according to right heart catheterization. The RV free-wall thickness increased significantly by week 5 (PASPs 40-50 mmHg). Development of quantifiable TR occurred in week 6 or at PASPs > 65 mmHg. A linear correlation was found between the PAAT and PASP in the range of 30-65 mmHg and between the RV-right atrial pressure gradient (derived from TR velocity) and PASP at pressures >65 mmHg, which enabled a noninvasive estimate of the PASP over a wide range of pressures based on these parameters. These data indicate that transthoracic echocardiography can be used for monitoring the progress of pulmonary hypertension in a rat model.

Animals↗