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Biomedical subjects

L Wetstein

Publications and source records attributed to L Wetstein.

At least 37 records · Page 2Linked to original sources
PubMed1986

Effect of thromboxane synthetase inhibition on vulnerability to ventricular arrhythmia following coronary occlusion.

Release of thromboxane (TXA2) during acute myocardial infarction may be an important contributing factor in the genesis of ventricular fibrillation (VF). We assessed the effect of selective TXA2 inhibition on vulnerability to VF after total occlusion of the anterior descending coronary artery in chloralose-anesthetized cats. Animals were pretreated with vehicle or with CGS-13080, a TXA2 synthetase inhibitor, 3.0 or 9.0 mg/kg intravenously. There was an apparent dose-dependent protective effect following CGS-13080 administration, in which the decrease in VF threshold following coronary occlusion was attenuated. Also, the incidence of spontaneous ventricular arrhythmia in the first 30 minutes after occlusion was reduced by two thirds in the 9.0 mg/kg CGS-13080 group compared to the vehicle-treated animals. This protective effect does not appear to be due to a change in hemodynamics, effective refractory periods, or extent of ischemia. TXA2 released during coronary occlusion appears to be arrhythmogenic, and inhibiting its synthesis may be protective.

Animals↗
PubMed1986

Histopathologic correlates of inducible ventricular tachycardia in two experimental canine models of myocardial infarction.

Ventricular tachyarrhythmias are the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of ventricular tachyarrhythmias remains an important clinical goal. The purpose of this study was to correlate electrophysiologic and histopathologic parameters conducive to the initiation of sustained ventricular tachycardia using programmed electrical stimulation in two canine models of myocardial infarction. Histopathologic correlates included: infarct pattern (heterogeneous vs. homogeneous morphology), distribution (viable epicardial or endocardial rim), and size. Twenty-one adult dogs were randomly divided into two groups: (1) 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery (LAD); and (2) nine animals had permanent, complete occlusion of the LAD with latex embolization. Using programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted at both 1 and 2 weeks after infarction with the chest closed and opened each time. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001), the presence of a viable epicardial rim was an extremely important discriminating variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Non-uniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than homogeneous infarcts (p = 0.025). The presence of a large, non-uniform infarct was the best overall discrimination variable for inducibility (p = 0.0002). Thus, in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.

Animals↗
PubMed1986

Sensitivity and specificity of lingular segmental biopsies of the lung.

Open lung biopsy is frequently performed as an emergency procedure in patients with undiagnosed bilateral diffuse pulmonary disease. In many situations, this procedure is undertaken in hemodynamically compromised or septic patients. An expeditious and simple technique to make an accurate diagnosis would be extremely advantageous. Biopsy of the lingular segment addresses most of these issues. Lingular biopsies, however, have been thought to be unreliable. The purpose of the present study was to evaluate the accuracy of lingular open lung biopsies in patients with bilateral diffuse pulmonary disease. Twenty consecutive patients with bilateral diffuse pulmonary disease underwent exploratory left thoracotomy when all noninvasive measures failed to arrive at a definitive etiology. Patients ranged in age from 24 to 79 with a mean of 52.6 years. There were five women and 15 men. Biopsy of the lingula was taken, as well as another area of similar lung involvement. Histopathologic results of the lingular biopsies correlated 100 percent with those from the other segments of the lung. The entire procedure, including rigid bronchoscopic examination, was routinely performed in less than one hour. In conclusion, lingular biopsies, relatively minor surgical procedures, are extremely accurate (100 percent) in making definitive diagnoses.

Adult↗
PubMed1985

The effect of bretylium and clofilium on dispersion of refractoriness and vulnerability to ventricular fibrillation in the ischemic feline heart.

Bretylium has been shown to have a pronounced antifibrillatory effect. The purpose of this study was to examine the effects of bretylium on changes in vulnerability to ventricular fibrillation (VF) and refractoriness which occur during acute myocardial infarction. Right ventricular VF thresholds and effective refractory periods (ERP) at six left ventricular sites were measured before and serially after left anterior descending coronary occlusion in chloralose-anesthetized cats. In eight untreated animals, there was a decrease in VF thresholds of 73% (p less than 0.01) immediately after occlusion and dispersion of refractoriness (DR) (maximum difference in ERP between normal and ischemic left ventricular sites) increased from 18 +/- 4 to 50 +/- 6 msec (p less than 0.01). Five of eight animals manifested spontaneous VF within the first minutes of occlusion but none had nonsustained VF. Pretreatment with bretylium (10 to 20 mg/kg intravenously) increased resting ERP from 181 +/- 9 to 201 +/- 9 msec (p less than 0.05) and VF threshold from 32 +/- 5 to 85 +/- 7 mA (p less than 0.001). Bretylium also prevented spontaneous VF in all eight animals and abolished occlusion-related changes in VF and DR. Fourteen animals were similarly studied using clofilium, a bretylium congener which is devoid of sympatholytic effect (no effect on blood pressure response to bilateral carotid artery occlusion). Clofilium increased resting ERP and VF thresholds at both low (0.5 mg/kg intravenously) and high doses (5 mg/kg intravenously). High-but not low-dose clofilium blunted the fall in VF threshold after coronary occlusion. In addition, DR correlated with VF threshold changes at both doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Arrhythmia inducibility and ventricular vulnerability in a chronic feline infarction model.

Ventricular tachyarrhythmias are the cause of sudden cardiac death in ischemic heart disease. Reliable animal models are necessary to study techniques for identifying individuals at risk and to develop effective modes of therapy. The purpose of the present study was to evaluate the inducibility of ventricular tachyarrhythmias and vulnerability to ventricular fibrillation and to correlate these findings with changes in ventricular refractoriness in a chronic feline model. Twelve conditioned cats were randomly divided into two groups: group A, sham-operated controls (n = 5); or group B, permanent occlusion of the left anterior descending coronary artery (n = 7). Two weeks later, the following measurements were made: (1) assessment of refractory periods at several ventricular sites; (2) inducibility to ventricular tachyarrhythmias; and (3) determination of ventricular fibrillation threshold. After electrophysiologic testing, the animals were killed and the hearts were studied histologically. Ventricular fibrillation thresholds were significantly lower in group B compared with group A (13 +/- 3 vs 46 +/- 9 mA; p less than 0.01). One of the sham-operated controls had induction of nonsustained ventricular tachycardia, while six of the group B animals had reproducible, inducible ventricular tachyarrhythmias (p less than 0.01). There was a significant dispersion in effective refractory periods between normal and infarcted sites in group B (46 +/- 6 msec) not seen in group A (12 +/- 2 msec, p less than 0.01). The group A cats demonstrated minimal damage to the myocardium or cardiac architecture. Group B cats demonstrated extensive, transmural, homogeneous infarcts of approximately 30% of the anterior wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Nonarrhythmogenicity of therapeutic cryothermic lesions of the myocardium.

There is increasing interest in the application of surgical methods to the treatment of refractory ventricular tachyarrhythmias (VT). Cryothermic ablation is one of the more promising techniques. However, there is clinical concern that a cryothermic lesion may lead to later arrhythmias. Previous studies have shown that dogs with nonhomogeneous, transmural infarctions are susceptible to VT initiation using programmed electrical stimulation (PES). The purpose of this study was to compare the incidence of inducing VT in dogs with transepicardial cryothermic myocardial damage (Group A) versus dogs with nonhomogeneous transmural infarctions resulting from 2-hr occlusion of the left anterior descending coronary artery (LAD) and subsequent reperfusion (Group B). Twelve dogs in each group were studied 10-14 days later using PES with unipolar cathodal ventricular pacing and two ventricular extrastimuli. Initiation of VT was attempted from at least six normal intramyocardial sites in each dog along the distribution of the LAD and in close proximity (less than or equal to 1 cm) to areas of chronically cryoablated damaged tissue. All dogs survived the initial procedure. VT was not inducible in any dog in Group A. Histological as well as electrophysiological evaluation, including determination of regional excitability thresholds and refractory periods employing strength-interval curves, revealed that all of the Group A dogs had homogeneous transmural infarcts with variable subendocardial sparing. In conclusion (1) cryothermal injury produces homogeneous damage; and (2) the lesion produced is not arrhythmogenic at 7-14 days.

Animals↗
PubMed1985

Current status of coronary artery bypass grafting for coronary artery atherosclerosis.

Coronary artery bypass grafting has now undergone 18 years of proven benefit in the treatment of myocardial ischemic disease. The technique of CABG has been further extended to other situations in which myocardial blood supply is threatened, such as cardiac trauma, aneurysms of coronary arteries, and congenital lesions. The emphasis in choosing CABG over medical therapy in 1985 should be preservation of myocardium at jeopardy of infarction as well as relief of angina. Proximal stenoses in vessels subserving viable muscle that is ischemic at rest or with minimal exercise should be treated with reperfusion by angioplasty or CABG to prevent further injury. After infarction occurs and ventricular function is impaired, CABG is also necessary to preserve remaining myocardium at jeopardy. Such an aggressive approach seems warranted with today's excellent surgical results. Long-term results have also improved, as more attention has been paid to saphenous vein graft preparation, use of mammary artery grafts, complete revascularization, use of antiplatelet agents, control of spasm, and identification of hypercoagulable states that may require sodium warfarin (Coumadin). Angioplasty of vein grafts and distal anastomoses also appears promising to help extend the results of initial CABG. Figure 1 is our recommended approach for the treatment of coronary atherosclerosis.

Angina Pectoris↗
PubMed1985

Current status of surgery for ventricular tachyarrhythmias.

This article outlines the accepted histopathologic and electrophysiologic theories underlying the etiology of medically refractory ventricular tachyarrhythmias. It delineates the indications and techniques for the electrophysiologic study of the ventricle. Finally, the surgical procedures available as well as their indications and results are elucidated.

Animals↗
PubMed1985

Pacemaker therapy.

This article reviews the indications for pacemaker implantation and the techniques and devices currently in use. The management of patients who require permanent pacemakers and the potential complications involved are discussed. The article concludes with a brief synopsis of temporary pacing.

Arrhythmia, Sinus↗
PubMed1985

Cyclosporine in cardiac transplantation.

Cyclosporine is a new immunosuppressive drug that acts early in the exposure of a host to allogeneic stimulation. It is a peptide of fungal origin. It has selective action on T cells, leaving the other cells of the immune system intact. It acts by preventing the function of the early activation signals of T cells, such as the acquisition of receptors for Il 2 and Il 1. It is lipophilic, moderately well absorbed by the gut, and metabolized by the liver. Factors affecting absorption or hepatic metabolism alter the amount of cyclosporine available in the circulation. Circulating levels can be measured by radioimmunoassay or HPLC. Doses should be tailored to trough levels taken approximately 12 hours after an oral or intravenous dose or to individual pharmacokinetic curves. The drug is nephrotoxic, hepatotoxic, and neurotoxic. In addition, cyclosporine has been associated with hypertension, hemolytic-uremic syndrome, increased incidence of intravascular thrombotic events, hypertrichosis, gum hyperplasia, pericardial effusion, and lymphoproliferative disorders. Despite these complications, cyclosporine usage seems to have improved short-term cardiac allograft survival and to have reduced the complications associated with side effects of steroids. As a result, cyclosporine has spawned a resurgence of interest in cardiac transplantation, which will be of great benefit in prolonging the lives of patients with end-stage cardiac disease.

Animals↗
PubMed1985

Critical appraisal of programmed electrical stimulation for evaluating hearts prone to ventricular tachyarrhythmias.

Programmed electrical stimulation has provided a unique new opportunity to evaluate both mechanisms and treatment regimens aimed at preventing ventricular tachyarrhythmias. The variable results that have been reported from different laboratories, undoubtedly are due in part to the differences in programmed electrical stimulation protocols. Although it is unlikely that all laboratories will adapt the same programmed electrical stimulation protocol, it nevertheless is very important that the number of sites of stimulation, stimulus strength, stimulus duration, stimulus polarity, drive train length, and patient population all be listed in order for some comparison between laboratories to be made.

Animals↗
PubMed1985

Electrophysiologic studies of the ventricle.

Electrophysiologic assessment of ventricular tachyarrhythmias involves the application of paced ectopic beats at the discretion of the cardiologist and not by chance. Because this approach reproducibly induces the sort of symptomatic arrhythmias that are the major cause of death in our country, the procedure has attracted widespread interest. This methodology has accomplished two important alterations in the orientation of physicians to ventricular arrhythmias and sudden death. First, it has turned our focus away from innocent events such as ectopic beats and directed our attention to the architectural and electrophysiologic abnormalities that are the structural substrate for tachyarrhythmias. Second, it has taught us that malignant arrhythmias and sudden death can be treated empirically by repeatedly inducing VT under controlled conditions until a treatment is found. The physiologic and pharmacologic insight obtained with these early experiences will hopefully enable us to treat patients without the need for producing potentially lethal arrhythmias.

Anti-Arrhythmia Agents↗