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Biomedical subjects

P J Scanlon

Publications and source records attributed to P J Scanlon.

At least 91 records · Page 5Linked to original sources

Mechanism of the effect of bretylium on the ventricular fibrillation threshold in dogs.

Experiments were performed to determine the importance of sympathetic blockade vs a direct myocardial effect as a mechanism for the antifibrillatory action of bretylium. The ventricular fibrillation (VF) threshold was determined in open-chest, anesthetized dogs by scanning the vulnerable period with either a single electrical stimulus (10 ms) or a train of electrical stimuli (14 pulses, 4 ms, 100 Hz). Using the train-of-pulses technique, the VF threshold increased from 6.8 +/- 0.6 mA to 29.7 +/- 6.4 mA 15 minutes after a 10-mg/kg intravenous bolus of bretylium (p less than 0.001, n = 8). There was no further significant change in the train-of-pulses VF threshold at 2 or 4 hours. Beta-adrenergic blockade with timolol (0.2 mg/kg) increased the train-of-pulses VF threshold from 6.7 +/- 1.6 mA to 24.5 +/- 5.2 mA (p less than 0.01 n = 8) and prevented any further significant change in response to bretylium. When single electrical pulses were used to scan the vulnerable period, bretylium at doses of 10 mg/kg (n = 8) and 100 mg/kg (n = 6) did not alter the VF threshold over a 4-hour observation period. The administration of timolol, alone or in combination with bretylium, did not significantly alter the single-pulse VF threshold. The failure of bretylium to alter the single-pulse VF threshold was not dependent on the site of stimulation. Stimulation of the right sympathetic cardiac nerves showed that 15 minutes of bretylium treatment was sufficient to completely inhibit adrenergic neuronal transmission to the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Digoxin and the susceptibility of the canine heart to countershock-induced arrhythmia.

This study investigated the effects of therapeutic and subtoxic doses of digoxin on the risk of ventricular tachycardia (VT) after graded, transthoracic shocks in anesthetized dogs. A series of direct current shocks (5, 10, 25, 50, 75, 100, 150 and 200 J) was delivered to 33 normal dogs and 6 dogs with a healed (32 +/- 7 days) myocardial infarct (MI). In 10 untreated dogs, the duration of post-shock VT was highly reproducible when 3 separate series of shocks were delivered at 2-hour intervals. In 6 normal dogs treated with oral digoxin (0.5 mg/day for 5 to 7 days), a series of shocks delivered before and during treatment (serum levels 1.5 +/- 0.5 ng/ml) resulted in the same duration of post-shock VT. In 18 normal and 6 dogs with MI, a series of shocks was given before and 90 minutes after a therapeutic dose of digoxin (0.05 mg/kg intravenously). At this dose of digitalis (serum level 2.5 +/- 1.0 ng/ml), there was no difference in the duration of post-shock VT in either normal dogs or dogs with MI. A third series of shocks was given after achieving subtoxic digitalization with additional intravenous digoxin (0.01 mg/kg) every 30 minutes until a premature ventricular stimulus evoked a repetitive ventricular response. The subtoxic doses of digitalis (serum levels 13.9 +/- 4.7 ng/ml) increased the duration of post-shock VT in both normal dogs (100%) and dogs with MI (700%) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ventricular fibrillation during coronary angiography: reduced incidence in man with contrast media lacking calcium binding additives.

The intracoronary injection of contrast media during coronary angiography occasionally results in ventricular fibrillation. Experimental studies have implicated the calcium sequestering agents, sodium citrate and EDTA in Renografin 76 (RG76), as contributing to this complication. Angiovist 370 (AV370) is a contrast medium similar to RG76 except that it contains disodium calcium EDTA instead of EDTA and sodium citrate. To determine if contrast media lacking sodium citrate and EDTA will result in a lower incidence of ventricular fibrillation in man, this investigation compared the incidence of contrast media-induced ventricular fibrillation in patients undergoing coronary angiography with RG76 to that with AV370. Group A consisted of 2,500 consecutive patients undergoing coronary angiography with RG76 and group B consisted of 2,000 subsequent consecutive patients in whom AV370 was employed as the contrast medium. There was no significant difference between groups A and B with respect to the volume of contrast media used per patient (153 +/- 49 ml vs 154 +/- 45ml), age (58.4 +/- 10 vs 58.6 +/- 10 years), sex (70% male vs 70% male), ejection fraction (59 +/- 17 vs 60 +/- 20), history of mitral valve disease (5.8% vs 7.1%), history of aortic valve disease (6.7% vs 6.5%), prior coronary artery bypass graft surgery (6.6% vs 7.3%), or extent of coronary artery disease. Fifteen episodes of contrast media-induced ventricular fibrillation occurred in group A (incidence 0.6%) whereas two episodes occurred in group B (incidence 0.1%) (p less than 0.02). Each patient was successfully defibrillated and no adverse sequelae resulted. Thus the present investigation suggests that the incidence of ventricular fibrillation during coronary angiography can be significantly decreased by using contrast media lacking sodium citrate and EDTA.

Aged↗

Dilated cardiomyopathy: functional status, hemodynamics, arrhythmias, and prognosis.

The natural history of dilated cardiomyopathy is variable, and the prognosis difficult to predict. Several clinical and hemodynamic parameters have been proposed as prognostic indicators. Reports on the relationship between ventricular arrhythmias, degree of hemodynamic impairment, and sudden death are controversial. To define accurately the prognosis in dilated cardiomyopathy, 55 patients with this clinical syndrome underwent clinical evaluation, radionuclide ventriculography, echocardiography, 12-lead electrocardiography, and 24 hr ambulatory monitoring, and the data thus obtained were evaluated based on predictive value. Over a follow-up period of 14.1 +/- 7.9 months, 11 patients (20%) died, all suddenly. Univariate analysis revealed that patients with more severe functional impairment (P = 0.0449), lower cardiac index (P = 0.0226), lower ejection fraction (P = 0.0426), and higher pulmonary artery wedge pressure (P = 0.0314) had greater mortality risk. Age, duration of symptoms, 12-lead electrocardiographic abnormalities, and atrial arrhythmias were not predictive of higher mortality. The number of PVCs per hr, the occurrence of couplets, the degree of PVCs prematurity, and the presence, frequency, rate, and duration of ventricular tachycardia did not have prognostic significance. A stepwise discriminant analysis identified functional class, cardiac index, and presence or absence of multiform PVCs as the group of variables that together could more accurately predict outcome in our dilated cardiomyopathy patients. Using a formula derived from the results of this analysis, the outcomes of 36 of 49 patients (74%) was correctly predicted, with a specificity of 100% and a sensitivity of 70%.

Adult↗

The training for and practice of percutaneous transluminal coronary angioplasty: results of two surveys.

In order to gain understanding of how percutaneous transluminal coronary angioplasty (PTCA) is taught and practiced in the United States, two questionnaires were devised to survey all adult cardiology training programs and all adult cardiac catheterization laboratories in this country. Of the 184 programs that responded to the training questionnaire, 102 (55%) teach PTCA, usually in the form of fellowship training and especially as a specialized year, and less commonly in the form of a preceptorship. Though many programs expose trainees to an adequate number of cases as defined by the program directors, at least 37% do not. Of 388 laboratories responding to the practice questionnaire, 74% perform PTCA. The total number of PTCA's in this country seems to be doubling yearly, but many laboratories do relatively few cases per year, and 79% of physicians doing PTCA do fewer than one case per week. Average laboratory success rate for PTCA is in the range of 80-85%. Though there is now a proliferation of PTCA training programs, 93% of those practicing angioplasty are self- or preceptor-trained, and have not learned the procedure as part of a fellowship.

Angioplasty, Balloon↗

Clinical aspects of virus/immune myocarditis.

Although a cause-and-effect relationship between viral infection and myocarditis remains inferential, two distinct clinical syndromes can be identified. During the early viral phase, the cardiac manifestations emerge while the symptoms of active viral infection are also present. During the chronic phase, symptoms of the viral infection may be remote or nonexistent, and identification of active myocarditis is contingent upon an aggressive diagnostic approach with endomyocardial biopsy and gallium 67 imaging. The exact incidence of myocarditis in patients with heart failure of unknown cause is unclear due to lack of standardization of histologic parameters. There are no other clinical clues to the presence of myocarditis in those patients presenting with cardiomyopathy or ventricular arrhythmia. For further clarification of the incidence and various presentations of myocarditis a large multi-center trial is necessary.

Acute Disease↗

Prognosis and treatment of cardiomyopathy and myocarditis.

Dilated cardiomyopathy is a heterogeneous group of disorders with a prognosis that is dependent upon the severity of presenting clinical and hemodynamic abnormalities. Although this condition is characterized by a high mortality, spontaneous improvement is noted in 25% of cases. Standard therapeutic modalities are nonspecific and consist of the therapy of congestive heart failure and ventricular arrhythmia. Recent studies suggest that beta blockade and cardiac transplantation may soon become accepted modalities in this condition. Acute viral myocarditis is a common disease that has a good prognosis, however occasionally progression to chronic myocardial disease has been identified. The therapy of acute viral myocarditis should be limited to symptomatic treatment, anti-coagulation, and bed rest. When chronic myocarditis is identified on endomyocardial biopsy in patients with heart failure of unknown cause, the treatment differs little from that of dilated cardiomyopathy with the exception that recognizing that efficacy has not been proven; immunosuppressive therapy may be added in life-threatening situations. Future studies will be directed at further clarification of the prognosis of each of these conditions with intensive evaluation of the role of beta blockade and immunosuppression.

Acute Disease↗

Ventricular fibrillation during coronary angiography: an analysis of mechanisms.

To investigate the mechanisms of ventricular fibrillation (VF) during coronary angiography, we assessed ventricular automaticity, local QT intervals, local conduction characteristics, and the ability to induce arrhythmias with premature ventricular stimulation in 30 dogs after intracoronary injections of 4 to 6 cc of Renografin 76 (RG 76). Ventricular automaticity was measured in six dogs as the idioventricular escape rate following intense vagal stimulation and was unchanged (51 +/- 6 vs 52 +/- 6 bpm, p greater than 0.05) with 6 cc of RG 76. In addition, 8 of 10 injections of 6 cc of RG 76 produced VF at a heart rate of 200 bpm compared to only 2 of 10 injections at a heart rate of 80 bpm (p less than 0.05). Composite and bipolar plunge electrodes were placed in the region perfused by the left anterior descending coronary artery (LAD) and circumflex coronary artery to assess QT intervals and conduction characteristics. RG 76, 4cc, produced a 116 +/- 18 msec increase in the QT intervals recorded from the region perfused by the LAD, resulting in a marked dispersion in repolarization. Both local bipolar and composite electrograms showed minimal conduction delay, which rarely extended beyond the QRS of a lead II ECG during atrial paced rhythm. As premature beats (spontaneous or induced) conducted through the region of QT prolongation, marked conduction delay was recorded from bipolar electrograms, while composite electrograms recorded continuous fractionated electrical activity spanning the diastolic interval at the onset of VF.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

In vivo effects of acute changes in osmolality and sodium concentration on myocardial contractility.

Effects of acute changes in osmolality and sodium concentration (Na) on myocardial contractility (MC) were examined in anesthetized dogs. Using a carotid to left anterior descending bypass, 4 cc of NaCl and/or dextrose of varying osmolality as injected and the percentage of change in MC measured. At Na = O mEq/L, a positive inotropic response occurred, which varied inversely as osmolality increased from 300 (MC = 100 +/- 23%) to 700 mOsm/L (MC = 39 +/- 10%, p less than 0.01). Similar ranges of positive responses of lesser magnitude were noted at Na = 75 mEq/L. At Na = 150, 190, or 350 mEq/L, similar increments in osmolality caused an increasingly negative inotropic response. An inverse relationship between Na and MC was noted with osmolality held constant. Injections of the nonionic contrast agent, P297, in 5% dextrose or 0.9% NaCl, resulted in 28 +/- 3% or -17 +/- 4% (p less than 0.01) change in MC, respectively. Sodium concentration and osmolality have independent effects on MC. Hyperosmolality/hypernatremia causes a negative inotropic response while hyponatremia causes a positive one.

Animals↗

A database management system for cardiovascular disease.

The Loyola Open-Heart Registry is a fully operational database that has hundreds of programs designed to input, modify, verify, maintain, update and analyze its raw data. It contains retrospectively collected data on approximately 4000 patients who underwent coronary bypass (CABG) or cardiac valve replacement (CVR) from January 1970 to May 1981. Since 1981 we have collected detailed information on approximately 1300 patients per year. The system is described in clinical and technical terms. The means of data acquisition and input are described and a flow chart for the collection of data is provided. The system's hardware is described briefly, and the nature and limitations of the software are discussed. Specific datasheets are described, and examples of output retrievals are provided. A few comments are made regarding the administrative aspects of database management. The entire paper is summarized, and our future plans and areas of development are described.

Cardiovascular Diseases↗

A nonsteroid anti-inflammatory drug exacerbates Coxsackie B3 murine myocarditis.

Nonsteroid anti-inflammatory drugs are often used to treat myalgias and arthralgias in enteroviral infections, but their effects on acute viral myocarditis are unknown. The effect of the nonsteroidal anti-inflammatory drug, ibuprofen, on acute viral myocarditis was studied in 75 four week old male BALB/c mice infected with 1.75 X 10(7) plaque-forming units of Coxsackie virus B3 on day 0. Ibuprofen was given intraperitoneally at a dose of 15 mg/kg body weight daily. The mice were assigned to four groups--Group I, 18 uninfected mice given ibuprofen on days 1 to 14; Group II, 18 infected, untreated mice; Group III, 20 infected mice given ibuprofen on days 1 to 14; and Group IV, 17 infected mice given ibuprofen on days 7 to 14. Nine animals in Group I, eight in Group II and seven in Group III were killed on day 7; the remaining mice were killed on day 14. Heart viral cultures and histologic analysis were done. Cultures at days 7 and 14 were all negative. Inflammation and necrosis analyzed in each animal were graded 0 to 4, with grade 4 representing widespread inflammation and necrosis. The heart was histologically normal in all 18 uninfected mice (Group I) given ibuprofen only. Inflammation and necrosis were not significantly different in Group II (infected, untreated) and Group III (infected, treated beginning day 1) mice killed at day 7. Inflammation scores of mice killed on day 14 were 2.1 +/- 0.6 (Group II), 3.1 +/- 0.7 (Group III) and 2.9 +/- 1.0 (Group IV infected, treated days 7 to 14).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The use of programmed electrical stimulation to assess the fibrillatory propensity of ionic and nonionic contrast media.

Coronary angiography occasionally results in ventricular fibrillation. To compare the fibrillatory propensity of conventional ionic and nonionic contrast media, we measured QT intervals and performed programmed electrical stimulation during intracoronary injection of Renografin 76 (R76), Hypaque 76 (H76), and iopamidol (IOP) in 16 open chest dogs. In ten dogs the incidence of ventricular fibrillation following induction of a single premature ventricular beat after every fourth atrial paced beat was 19/20 with R76, 8/20 with H76, and 0/20 with IOP (P less than .001). When two premature beats were induced, the incidence of ventricular fibrillation was 20/20 with R76, 19/20 with H76, and 1/20 with IOP (P less than .001). In six additional dogs, the mean prolongation of the QT interval was 170 +/- 20 msec with R76, 105 +/- 14 msec with H76, and 63 +/- 9 msec with IOP (P less than .001). Thus, programmed electrical stimulation readily induces ventricular fibrillation during intracoronary injection of conventional ionic contrast media. The incidence of ventricular fibrillation parallels the amount of QT interval prolongation produced. H76, which lacks EDTA and sodium citrate, is less fibrillatory than R76. However, the nonionic medium IOP appears far less fibrillatory than either R76 or H76.

Angiography↗

Pacemaker malfunction simulated by amplifier saturation.

In this case report, pacemaker malfunction is simulated by prolonged pauses after each pacemaker discharge. The pauses were due to saturation of the input of the telemetry monitor amplifier by the discharge voltage of the pacemaker. It is important to recognize amplifier saturation as a form of artifact that can mimic pacemaker malfunction.

Aged↗

Myocarditis confirmed by biopsy presenting as acute myocardial infarction.

Two cases of acute myocardial infarction occurred in association with myocarditis, which was confirmed by biopsy. The first patient suffered an anteroseptal and the second patient an inferior wall myocardial infarction shortly after an acute viral illness. In both patients, coronary angiography showed normal coronary arteries, and right ventricular endomyocardial biopsy confirmed myocarditis. Histological abnormalities attributable to ischaemic heart disease were absent. The first patient's condition became stable after immunosuppressive treatment. Myocarditis resolved spontaneously within three months in the second patient. Coronary artery spasm and myocardial involvement with a systemic disease were unlikely. Endomyocardial biopsy in patients with acute myocardial infarction and normal coronary arteries may be useful in identifying myocarditis associated with myocardial necrosis. Myocarditis in acute myocardial infarction in the absence of coronary artery obstruction has not previously been documented during life.

Adolescent↗

Effect of sympathetic tone on ventricular arrhythmias during circumflex coronary occlusion.

To determine if the sympathetic nervous system exerts an arrhythmogenic effect on the ischemic myocardium independent of heart rate, the proximal circumflex coronary artery was occluded for 1 h in 62 open-chest, anesthetized dogs. The atrial rate was maintained at 200/min, and the vagosympathetic trunks were transected in all dogs. The total incidence of ventricular fibrillation was 35% in 20 dogs with intact stellates and not significantly different from the incidence of ventricular fibrillation (15%) in another 20 dogs in which both stellate ganglia had been decentralized. Electrical stimulation of the left ansae subclavia (3 Hz, 2 ms, 6-8 V) in the remaining 22 dogs significantly increased the incidence of ventricular fibrillation to 73% (P less than 0.05). The magnitude of S-T segment elevation in the lead II electrocardiogram 90 s after occlusion was 0.69 +/- 0.08 mV in the group with left ansae stimulation and significantly elevated (P less than 0.01) compared with dogs with intact stellates (0.35 +/- 0.06 mV) and with the denervated dogs (0.19 +/- 0.05 mV). The data indicate that the sympathetic nervous system is capable of a direct arrhythmogenic influence on the ischemic myocardium independent of heart rate. The rate-independent arrhythmogenic effects of the sympathetic nervous system may be mediated by an increase in severity of the ischemic insult.

Animals↗

Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial.

It has been suspected that the increased sympathetic activity seen in patients with chronic congestive heart failure from dilated cardiomyopathy may be harmful. We therefore tested the long-term effect of metoprolol on eight patients in a double-blind, randomized protocol and 12 patients in an unblinded, crossover protocol who were treated for 12 months (range 10 to 24), and compared them with 16 similar subjects who were treated with placebo for 10 months (range 6 to 12) in a double-blind, randomized protocol. Patients were followed by serial clinical assessment, treadmill testing, radionuclide ventriculography, and echocardiography. Metoprolol-treated patients had an improvement in mean exercise capacity by 3 mets (p less than .0001) while experiencing a significant improvement in functional classification (p less than .001) during both the double-blind and open-label crossover studies and had an improved ejection fraction during the double-blind study (p less than .02). These improvements were not seen in matched control subjects receiving placebo. Seven of 20 patients receiving long-term metoprolol therapy had resolution of nearly all symptoms of heart failure, doubled their exercise capacity, and had progressive improvement in resting radionuclide left ventricular ejection fraction (12.6 +/- 3% to 26.9 +/- 6%) and echocardiographic left ventricular end-diastolic dimension (7.7 +/- 0.5 to 6.5 +/- 0.5 cm). Only one of 21 patients treated was intolerant of metoprolol. We conclude that metoprolol can be given safely to a select group of patients with dilated cardiomyopathy in doses that substantially reduce both resting and exercise heart rates. Long-term beta-blockade improved functional class and exercise capacity in 14 of 20 patients while producing an exceptional clinical response in seven that was accompanied by improved resting parameters of left ventricular function.

Adult↗