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Biomedical subjects

M Papouchado

Publications and source records attributed to M Papouchado.

At least 19 recordsLinked to original sources

Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep.

We have recently reported that in pigs with chronic myocardial ischemia heart transfection with a plasmid encoding the 165 isoform of human vascular endothelial growth factor (pVEGF165) induces an increase in the mitotic index of adult cardiomyocytes and cardiomyocyte hyperplasia. On these bases we hypothesized that VEGF gene transfer could also modify the evolution of experimental myocardial infarct. In adult sheep pVEGF165 (3.8 mg, n=7) or empty plasmid (n=7) was injected intramyocardially 1 h after coronary artery ligation. After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF group and 18.2+/-2.1% in the empty plasmid group (P<0.02). The mechanisms involved in infarct size reduction (assessed in additional sheep at 7 and 10 days after infarction) included an increase in early angiogenesis and arteriogenesis, a decrease in peri-infarct fibrosis, a decrease in myofibroblast proliferation, enhanced cardiomyoblast proliferation and mitosis of adult cardiomyocytes with occasional cytokinesis. Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in VEGF-treated group than in empty plasmid group 15 days after myocardial infarction. We conclude that plasmid-mediated VEGF gene transfer reduces myocardial infarct size by a combination of effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration.

Animals↗

Reversible acute myocardial injury following air bag deployment.

This case report is about a 62 year old woman who was involved in an accident while driving her car, during which the driver side air bag deployed. She experienced intense anterior chest pain that radiated to her left arm after the accident, but was otherwise well; there was no significant medical history. An electrocardiogram done one and half hours after admission revealed 1 mm ST segment elevation in leads V2 and V3 and troponin 1 level was raised. She underwent cardiac catheterisation but three months after the accident both ECG and echocardiographic studies were normal. It is suggested that she underwent cardiac contusion rather than a myocardial infarction.

Accidents, Traffic↗

Cardiac pacing systems and implantable cardiac defibrillators (ICDs): a radiological perspective of equipment, anatomy and complications.

Cardiac pacing is a proven and effective treatment in the management of many cardiac arrhythmias. Implantable cardiac defibrillators (ICDs) are beneficial for certain patient groups with a history of serious, recurrent ventricular dysrhythmias, with a high risk of sudden cardiac death. Pacemaker devices take many forms and are highly visible on the chest radiograph. The radiographic appearances of ICDs and pacemakers can be similar and are subject to similar complications. The anatomical approach to the implantation, the type of device used and anatomical variations will all affect the appearance of these devices on the chest film. Pacemaker complications identified radiographically include pneumothorax, lead malpositioning, lead displacement or fracture, fracture of outer conductor coil, loose connection between the lead and pacemaker connector block, lack of redundant loops in paediatric patients and excessive manipulation of the device by the patient (Twiddler's syndrome). This pictorial review highlights the role of chest radiography in the diagnosis of post-cardiac pacing and ICD insertion complications, as well as demonstrating the normal appearances of the most frequently implanted devices.

Arrhythmias, Cardiac↗

Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer.

Replacement of the cell loss occurring after acute myocardial infarction has been proposed as a potential treatment to prevent heart remodeling and failure. On account that cardiomyocytes express VEGF receptors and that VEGF triggers mitogen-activated protein kinases, we investigated if VEGF gene transfer may induce cardiomyocyte replication. In a pig model of chronic myocardial ischemia achieved by Ameroid occlusion of the left circumflex coronary artery, we observed that direct intramyocardial injection of a plasmid encoding human VEGF(165) induced a several-fold increase in cardiomyocyte mitotic index and in the number of cardiomyocyte nuclei per unit volume as compared with pigs receiving plasmid devoid of gene. Despite images of conventional cytokinesis were not observed, the fact that caryokinesis is an obligatory step for cell division suggests that our finding may contribute to the issue of heart regeneration and may potentially widen the therapeutic spectrum of VEGF gene transfer.

Animals↗

Early experience with transmission of data from moving ambulances to improve the care of patients with myocardial infarction.

We conducted a feasibility study of a mobile unit capable of recording a 12-lead electrocardiogram (ECG) and transmitting it to a receiving hospital workstation. Two ambulances were equipped with the mobile unit and the ECGs recorded were compared with standard ECGs recorded on the hospital ward after admission. In six months, 62 patients participated in the study. The ambulance crew transmitted messages to the coronary care unit for 56 patients. Thirty-five patients were directed to the coronary care unit, four were directed to the emergency department as no beds were available and then transferred to the coronary care unit later, and the remaining 23 were directed to the emergency department. Comparative hospital and mobile ECGs were available for 31 patients. Although the mobile unit recorded smaller R- and S-wave deflections than on the standard hospital ECGs, the medical and nursing staff were able to differentiate between normal and abnormal tracings. The mobile unit may be useful to triage patients with chest pain before they reach hospital.

Ambulances↗

Long-term survival of VDD pacing.

UNLABELLED: All patients with VDD systems implanted at a tertiary pacing center were identified from a computer database and data collected on pacing indications, follow-up duration, rate response, reasons for programming changes, and implant P wave amplitudes. RESULTS: 366 implants were identified for which complete data were available for 335 leads implanted in 316 patients. The mean follow-up period was 24.1 months, and age at implant was 73.5 +/- 11.8 years. During follow-up, 19 patients died (6%) and 62 (19.6%) were followed elsewhere. Indications for pacing were complete heart block, 56.6%; intermittent AV block, 21.8%; postablation complete heart block, 5.4%; 2:1 AV block, 13%; and others, 3.2%. Two groups: no mode change (NMC, n = 280) and mode change (MC, n = 36) were identified. Reasons for reprogramming in the MC group were as follows: atrial sensing, 11; AF/atrial flutter, 18; chronotropic incompetence, 3; and others 4. Significantly more MC patients had rate response programmed ON (44.4% vs 22.1%, P < 0.05). No significant differences between the two groups were found in other variables, including male gender (55.5% vs 54.6%), length of follow-up (27.1 +/- 17.8 vs 23.8 +/- 20.6 months), age at last follow-up (72 +/- 12.3 vs 75.9 +/- 11.9 years), and P wave amplitude (1.7 +/- 0.9 vs 1.8 +/- 0.9 mV). CONCLUSION: Reprogramming of VDD systems is infrequent. When necessary, it is usually prompted by atrial arrhythmias or failure of atrial sensing. When adequate atrial chronotropy has been verified, VDD is an acceptable alternative to DDD pacing and survives well over the long term.

Aged↗

Evolution of atrial signals from a single lead VDD pacemaker. AddVent European Multicentre Study Group.

The atrial sensing capabilities of a new single pass lead VDD pacing system (Pacesetter AddVent) were assessed in a prospective multicenter study of 101 implants during the period July 1994 through March 1996. The pacing lead (Pacesetter AV Plus) has a unique quadripolar 4-in-line connector and uses a pair of ring electrodes with an interelectrode spacing of 12 mm for atrial sensing. The mean age of the patients (51 men) was 73 years (range 19-91). Seventy-five patients had complete heart block; the others had 2:1 AV block. Wide variations were found in signal amplitude: mean P wave amplitude, measured over four cycles in the supine position, was 2.4 +/- 1.9 mV at implant, dropping to 1.9 +/- 1.7 mV predischarge, and remaining constant at follow-up but with a narrower range. Holter monitoring was undertaken in 24 patients, with a total of 550 monitored hours. Mean AV synchrony was 98.2% +/- 4.6% (excluding premature ventricular contractions), with 20 patients (83%) showing > 99% AV synchrony, with atrial sensing at 0.1 mV where needed. No oversensing was observed in any patient. There was a low incidence of atrial fibrillation (2%) and sinus bradycardia (0%). The findings show that the range of atrial signals, although wide initially, converges over the first year and remains adequate for reliable AV synchronous pacing.

Adult↗

Atrial natriuretic factor modifies noradrenaline release in a sodium-free medium.

1. The effects of atrial natriuretic factor (ANF) on 3H-noradrenaline (3H-NA) release evoked by a sodium-free medium (SFM) were studied. The experiments were carried out in rat hypothalamic slices incubated in vitro. 2. ANF (1, 10 and 100 nM) decreased NA release evoked by the omission of sodium in a concentration-dependent way. When calcium was omitted from a SFM, NA output was partially diminished. However, if ANF was added to the SFM/calcium free medium NA secretion showed no modifications. 3. Present results suggest that, in rat hypothalamus, NA release evoked by Na+ omission is divided into two fractions: one independent of and the other dependent on extracellular calcium. In addition, ANF modifies NA release evoked by SFM dependent on extracellular calcium.

Animals↗

Limitations of chest radiography in discriminating between aortic dissection and myocardial infarction: implications for thrombolysis.

It has been stated that chest radiographic features of aortic dissection are a contraindication to intravenous thrombolysis in patients with suspected acute myocardial infarction. Excluding aortic dissection could significantly delay such treatment in patients who would benefit from thrombolysis. Initial chest radiographs of 18 patients with acute aortic dissection and 25 patients with acute myocardial infarction were evaluated. The radiographs were studied by two experienced radiologists for signs of aortic dissection. No radiographic signs or combinations of signs accurately distinguished aortic dissection from myocardial infarction. Patients with chest radiographic signs suggesting aortic dissection but with clinical features suggesting myocardial infarction should not be denied the benefits of immediate intravenous thrombolysis.

Aortic Dissection↗

Attenuation of nitrate effect during an intermittent treatment regimen and the time course of nitrate tolerance.

The long-term efficacy of transdermal nitrate therapy, in particular the ability of a single patch to provide 24 h prophylaxis against angina, has been questioned. Two mechanisms have been suggested for this loss of effect: the development of pharmacological tolerance, and premature patch exhaustion. This study was designed to investigate this problem, and in particular to investigate the time course of treatment failure. It comprised a randomized, double-blind, cross-over comparison of transdermal glyceryl trinitrate and matching placebo transdermal patches. Significant treatment effects were demonstrated by several criteria for 8 h of continuous therapy, with some limited effect persisting for 15 h. Loss of effect began to develop very soon after treatment was initiated and progressed in a steady, linear fashion so that there was virtually no treatment effect after 24 h. In contrast, during intermittent therapy, treatment effects were maintained on the second day following a nitrate-free interval. Significant benefit was demonstrated for up to 32 h (i.e. 8 h of treatment on day 2). Both nitrate-free intervals (12 and 16 h) seemed to be equally effective in maintaining efficacy after 3 h of treatment on the second day, although this was still somewhat attenuated compared with day 1. These results confirm that loss of therapeutic efficacy of transdermal nitrate is due to the development of tolerance and not premature patch exhaustion. In contrast to previous studies, however, they suggest that tolerance can only partly be reversed by intermittent therapy and also that the onset of tolerance is so rapid that it is well established in less than a day's treatment.

Administration, Cutaneous↗

The effect of oral dosing of xamoterol on systolic time intervals in man and xamoterol plasma concentrations in heart failure patients.

1. Six healthy male human volunteers of mean age 30.8 years (range 23-37) were given single oral doses of xamoterol (20, 50, 100 or 250 mg) and placebo with a 1 week interval between each dose. Xamoterol produced a significant decrease in systolic time intervals (QS2I, LVETI and PEPI) and a significant increase in systolic blood pressure indicating a positive inotropic effect on the heart at rest. The changes in QS2I were dose-related. Maximum decreases in QS2I were noted 1 to 2 h after dosing and were achieved with a dose of 100 mg. 2. In a second study, oral administration of xamoterol at 3 doses (100, 200 or 300 mg) and placebo were studied in 12 patients of mean age 60.4 years (range 52-73) with mild to moderate heart failure. Each dose was given twice daily for 7 days in a random order. Each dose of xamoterol produced a significant decrease in systolic time intervals indicating a positive inotropic effect on the heart at rest in patients with heart failure. It was not possible to distinguish between the effects of the three doses of xamoterol. 3. In heart failure patients, peak plasma concentrations of xamoterol occurred 1 to 2 h after dosing at all dosage levels and there was a linear relationship between dose and plasma concentration. 4. In both studies xamoterol was well tolerated and only minor adverse experiences were reported. 5. We conclude that, at rest, xamoterol has a positive inotropic effect on the heart when given orally to healthy volunteers or patients with mild to moderate heart failure.

Adult↗

Single-breath breath-holding estimate of pulmonary blood flow in man: comparison with direct Fick cardiac output.

1. Resting pulmonary blood flow (Q), using the uptake of the soluble inert gas Freon-22 and an indirect estimate of lung tissue volume, has been estimated during breath-holding (Qc) and compared with direct Fick cardiac output (Qf) in 16 patients with various cardiac disorders. 2. The effect of breath-hold time was investigated by comparing Qc estimated using 6 and 10 s of breath-holding in 17 patients. Repeatability was assessed by duplicate measurements of Qc in the patients and in six normal subjects. 3. Qc tended to overestimate Qf, the bias and error being 0.09 l/min and 0.59, respectively. The coefficient of repeatability for Qc in the patients was 0.75 l/min and in the normal subjects was 0.66 l/min. For Qf it was 0.72 l/min. There was no significant difference in Qc measured at the two breath-hold times. 4. The technique is simple to perform, and provides a rapid estimate of Q, monitoring acute and chronic changes in cardiac output in normal subjects and patients with cardiac disease.

Adult↗

The relationship of symptoms to performance in paced patients with breathlessness.

Eighteen adult patients presenting with breathlessness associated with bradycardia, and whose breathlessness was diminished or abolished by permanent pacing, were studied at least one month after this procedure in order to examine the relationship between symptoms and exercise performance. All were pacing-dependent at rest and were studied over successive two-weekly periods at set rates of 50, 70 and 90 beats min-1 in a double-blind, balanced and randomized trial. The degree of breathlessness was closely related to exercise capacity judged by 6-min walk testing, effort scores and weekly pedometer distance. Overall results were worse at 50 beats min-1 than the two faster rates. For a given individual, changing of ventricular rate caused parallel alterations in symptoms and performance. The 6-min walking test was a useful guide to disability in these patients, tightly linked to the symptoms of effort and breathlessness, and may be of clinical value in assessing mild heart failure. The pedometer readings were influenced more by the patients' walking habits than by fitness.

Adult↗

Improved control of atrial fibrillation with combined pindolol and digoxin therapy.

This study has compared the effect on heart rate control of the addition of pindolol 15 mg bd or verapamil 40 mg tds to maintenance digoxin therapy in 12 patients with chronic atrial fibrillation. The study was performed in a randomized cross-over fashion. Treatment effects were assessed by 24-h ambulatory electrocardiography and symptomatic improvement by symptom scores. The results show that the combination of pindolol and digoxin provides better control of atrial fibrillation. With an attenuation of daytime tachycardia, prevention of nocturnal bradycardia and reduction in the length of nocturnal pauses in rhythm. Overall heart rate variability was significantly less with digoxin and pindolol (523 beats min-1 h-1) than with digoxin and verapamil (745 beats min-1 h-1). We conclude that, in the dosages employed, combined digoxin and pindolol therapy is superior to either digoxin and verapamil in combination or digoxin alone for the treatment of atrial fibrillation.

Adult↗

Anomalous origin of the anterior descending coronary artery from a non-dominant right coronary artery.

We present a patient with rheumatic mitral valve disease with anomalous origin of the anterior descending coronary artery. The coronary anatomy was unusual for two reasons; firstly, the anterior descending coronary artery was a branch of a non-dominant right coronary artery, and secondly it passed to the left in the interventricular septum beneath the right ventricular infundibulum. As far as we are aware, this anatomical variation has not been described before and it appears to be of no haemodynamic significance.

Angina Pectoris↗