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Biomedical subjects

M J Shea

Publications and source records attributed to M J Shea.

At least 55 records · Page 3Linked to original sources
PubMed1985

Antiarrhythmic and electrophysiologic actions of clofilium in experimental canine models.

Clofilium was studied in three experimental models. In non-ischemic and chronically infarcted canine hearts, clofilium (0.5-2 mg/kg) produced a dose-dependent increase in electrical ventricular fibrillation threshold (VFT), but prolonged the effective refractory period (ERP) of normal myocardium in only the non-ischemic heart. When chronically infarcted hearts were subjected to programmed electrical stimulation, 1 mg/kg of clofilium inhibited the re-induction of either ventricular tachycardia or ventricular fibrillation in 5 of 6 animals and slowed the rate of the induced tachycardia in the sixth. Clofilium, however, failed to alter ventricular refractory periods of normal myocardium at either twice diastolic threshold current (176 +/- 5 ms control vs. 187 +/- 9 ms post-clofilium, P greater than 0.05) or at 10 mA (134 +/- 6 ms control vs. 137 +/- 13 ms post-clofilium, P greater than 0.05). In addition, chronic administration of clofilium (2 mg/kg, i.v., followed by 1 mg/kg every 12 h) was ineffective in decreasing mortality in a canine model of sudden coronary death. Of 10 saline-treated conscious animals subjected to an electrically-induced intimal lesion of the left circumflex coronary artery in the presence of a previous ischemic insult, all 10 died suddenly of ventricular fibrillation within 173 +/- 45 min after current application. Under similar conditions, 7 clofilium-treated animals died suddenly within 249 +/- 88 min (P greater than 0.05) after current application while 3 animals survived (P greater than 0.10). Clofilium did, however, elevate the effective refractory period in these animals (150 +/- 3 ms saline-treated vs. 195 +/- 7 ms clofilium-treated). It is concluded from our data that there is little relationship between clofilium's electrophysiologic actions in normal myocardium and antiarrhythmic effects. Furthermore, simple prolongation of refractoriness in normal non-ischemic myocardium may be insufficient for the prevention of ventricular fibrillation which develops in response to a transient ischemic event superimposed on a chronically injured myocardium.

Animals↗
PubMed1985

Transient ischemia in angina pectoris: frequent silent events with everyday activities.

To help characterize episodes of transient myocardial ischemia, 80 patients with chronic stable angina and evidence of obstructive coronary disease were studied by ambulatory electrocardiographic (ECG) monitoring outside the hospital to detect both symptomatic and asymptomatic episodes of ST-segment depression. In addition, patients were tested on an outpatient basis by means of positron emission tomography to assess regional coronary blood flow under different conditions. All patients showed ECG evidence of transient ischemia, with or without symptoms, while active outside the hospital. In-hospital testing showed that symptomatic and asymptomatic disturbances in regional coronary blood flow occurred with normal everyday activities and were not caused by physical exertion involving marked increases in heart rate and blood pressure. Most of these provocations were followed by a decrease in coronary blood flow in a poststenotic segment of myocardium and, like the ischemic events monitored out of hospital, the majority were silent. Many of these features characterizing the activity of ischemic heart disease may not be apparent from a patient's anginal history or results of hospital diagnostic testing.

Activities of Daily Living↗
PubMed1985

Clinical problems in coronary disease are caused by wide variety of ischemic episodes that affect patients out of hospital.

Transient ischemia arising from proximal events in epicardial coronary arteries causes important symptoms, such as angina pectoris, and is usually studied in the hospital with provocative tests. However, Holter monitoring of ST-segment disturbances in patients out of the hospital has shown frequent asymptomatic evidence of ischemia that is surprisingly prolonged and that is not associated with the obvious tachycardia of exercise or stress. Positron emission tomography has been developed to measure the regional myocardial uptake of a cation (rubidium-82) in order to assess repeatedly the directional changes in regional coronary blood flow during these events. This method has been used to show that both symptomatic and asymptomatic episodes of ST depression are reliably associated with disturbances in regional myocardial perfusion. The daily activities of patients have been analyzed and reproduced in the hospital to assess the effects of cold stimulation, mental arithmetic, cigarette smoking, and exercise. Physical exercise was associated with angina, ST-segment change, and regional abnormalities of myocardial perfusion, including decreased perfusion in poststenotic segments. The other tests caused the same disturbances in myocardial perfusion; these perfusion disturbances were mostly asymptomatic and surprisingly prolonged, with periods of recovery that were two to five times longer than the ST-segment disturbance and the pain. Current studies using a structured diary indicate that the episodes of transient ischemia occurring out of the hospital are more frequently associated with different levels of mental arousal than with any other activity. Physical exercise is a relatively infrequent cause of transient ischemia. The examination of coronary blood flow using provocative tests derived from the patients' own activities out of the hospital have confirmed that, irrespective of the pattern of angina, patients have frequent episodes of asymptomatic transient ischemia that are surprisingly prolonged and that these episodes occur in response to previously unsuspected ordinary daily activities. The disturbances in coronary blood flow usually include a regional decrease in myocardial perfusion that can only be explained by pathophysiologic events in the proximal epicardial coronary arteries.

Activities of Daily Living↗
PubMed1985

Clinical evaluation of transient myocardial ischemia during daily life.

Ambulatory ST-segment monitoring has been introduced in an attempt to obtain an objective measure of transient myocardial ischemia during daily life. Serial observations conducted out of the hospital have produced a picture of the nature and activity of ischemic heart disease that differs markedly from that obtained by conventional assessment. Episodes of transient ischemia appear to be more frequent and prolonged than is suggested by the occurrence of chest pain. Furthermore, only a minority of episodes are associated with tachycardia, and most occur at heart rates well below those achieved during exercise testing. This suggests that mechanisms other than an excessive increase in myocardial oxygen demand may be responsible for the many episodes occurring outside the hospital. Accurate interpretation of this new information depends on the reliability of transient ST-segment depression as a marker of ischemia. In 100 normal volunteers, episodes of significant ST-segment depression similar to that observed in patients with angina were rare (2 percent). Positron emission tomography with rubidium-82 was used to study regional myocardial perfusion during transient ST-segment depression with and without pain in patients with angina and coronary disease. All episodes of painless ST-segment depression and 97 percent of episodes with angina were accompanied by tomographic evidence of ischemia. This much broader view of ischemic heart disease, revealed by studies performed out of the hospital during patients' ordinary daily activities, has important implications for the objective assessment of symptoms, the relief of ischemia, and the prevention of myocardial damage.

Activities of Daily Living↗
PubMed1985

Free radicals in ischemic myocardial injury.

Myocardial ischemia causes release of chemotactic factors, migration of neutrophils, peroxidation of lipids, and depletion of free radical scavengers. The invading neutrophils may injure the myocardial vasculature and sarcolemma by generating oxygen free radicals. Several agents that affect neutrophils or oxygen radicals were evaluated in a canine model of regional myocardial ischemia and reperfusion. Anesthetized dogs underwent occlusion and reperfusion of the left circumflex coronary artery. Infarct zone, area at risk of infarction, and total left ventricle were quantified by gravimetric and planimetric analysis. Limitation of infarct size by ibuprofen was associated with marked suppression of leukocyte accumulation within the ischemic myocardium. Neutrophil depletion by antiserum resulted in similar reductions of infarct size and was accompanied by a reduction in leukocyte infiltration. A combination of oxygen radical scavengers, superoxide dismutase plus catalase, decreased myocardial injury whether infusion began before occlusion or 75 min after occlusion. None of the treatments significantly altered hemodynamic indices of myocardial oxygen demand. Reduction of infarct size by ibuprofen, neutrophil antiserum, and free radical scavengers indicates that neutrophils and oxygen radicals participate in producing the irreversible damage to the myocardium during ischemia and reperfusion.

Animals↗
PubMed1985

The independent effects of oxygen radical scavengers on canine infarct size. Reduction by superoxide dismutase but not catalase.

Previous studies demonstrated a significant reduction of ultimate infarct size in the canine heart by the combined administration of superoxide dismutase plus catalase. This study was performed to assess the independent effects of each enzyme on ultimate infarct size due to ischemia/reperfusion. Dogs received 2-hour infusions of superoxide dismutase, catalase, or albumin (controls) via the left atrium beginning 15 minutes before and ending 15 minutes after a 90-minute occlusion of the left circumflex coronary artery. The dogs were killed 6 hours after reperfusion. After histochemical staining, infarct and risk area masses were calculated by gravimetric and planimetric analysis. Infarct size expressed as a percentage of the area at risk was: superoxide dismutase, 19 +/- 5; catalase, 30 +/- 5; and controls, 40 +/- 3. Infarct size in the superoxide dismutase group, but not the catalase group, was significantly less than in controls (P less than 0.05). No significant differences in hemodynamics or area at risk were observed that could explain the differences in infarct size. The results indicate that superoxide dismutase alone protects reperfused ischemic myocardium as well as does the combination of superoxide dismutase and catalase. The beneficial effect of superoxide dismutase and insignificant effect of catalase suggest that tissue damage during ischemia and reperfusion may be mediated largely by superoxide anion but not by hydrogen peroxide.

Animals↗
PubMed1984

Effect of OKY-1581, a thromboxane synthetase inhibitor, on coronary thrombosis in the conscious dog.

OKY-1581, a new thromboxane synthetase inhibitor, was studied in a conscious canine model of coronary thrombosis. After thoracotomy with placement of a left circumflex coronary artery flow probe and implantation of an electrode into the circumflex artery, animals were assigned randomly to the following groups: 0.9% NaCl vehicle control or OKY-1581 1 mg/kg every 4 intravenously for 24 h. During the drug treatment period, a 50 microA anodal current was passed through the circumflex electrode, and venous blood was obtained for platelet aggregation studies. As compared to control animals, the OKY-1581 treated animals developed a greater mean coronary flow at the end of the treatment period, smaller thrombi by wet weight, smaller infarcts, and fewer ventricular arrhythmias. Ex vivo platelet aggregation studies revealed significant inhibition of aggregation to standard aggregating agents for the drug treated group only. OKY-1581 is an effective antithrombotic agent which maintains coronary flow after a thrombogenic stimulus, presumably via blockade of the synthesis of thromboxane by blood platelets.

Acrylates↗
PubMed1984

Beneficial effects of nafazatrom on ischemic reperfused myocardium.

The effect of nafazatrom, a new antithrombotic agent, was studied in a canine model of regional myocardial ischemia. Nafazatrom was administered 1 mg/kg intravenously every 6 h for 48 h. After 24 h of drug or placebo administration, animals underwent 90 min of occlusion of the proximal left circumflex coronary artery followed by gradual reperfusion over a period of 30 min. Twenty-four hours later, the animals were sacrificed and infarct size was determined by histochemical staining with triphenyltetrazolium chloride. Nafazatrom-treated animals had a significant reduction in infarct size expressed as a percent of the anatomical area at risk for infarction: 21 +/- 5% in the treated group vs. 41 +/- 5% in the control group (X +/- S.E.M., P less than 0.05). Histological examination confirmed the gross results of postmortem histochemical staining. Salvage of ischemically jeopardized tissue appeared to be unrelated to myocardial oxygen demand as there were no hemodynamic differences between groups. The beneficial effects of nafazatrom are presumably related to a limitation of autolytic processes on the heart during and after ischemia as a result of the drug's ability to inhibit lipoxygenase and to prevent the enzymatic degradation of prostacyclin.

Animals↗
PubMed1984

The beneficial effects of nafazatrom (BAYg6575) on experimental coronary thrombosis.

An in vivo model of coronary artery thrombosis in the conscious dog was used to evaluate the potential antithrombotic effect of nafazatrom (BAYg6575). A silver wire electrode was implanted in the left circumflex coronary artery (LCX) and was used at a later time to deliver a 50 uA anodal current for 24 hours to the intimal surface of the vessel. The resulting injury to the endothelium was accompanied by the adhesion, aggregation, and subsequent formation of an occlusive thrombus in the LCX of vehicle-treated dogs. Nafazatrom was given as an intravenous dose of 1 mg/kg for 48 hours, before anodal stimulation of the coronary artery was initiated, and was repeated every 6 hours during anodal stimulation for a total treatment period of 72 hours. As compared to vehicle-treated control dogs, the dogs treated with nafazatrom had smaller thrombi, preservation of coronary blood flow, a lesser degree of ischemic injury in the myocardial region subserved by the LCX, and less frequent premature ventricular complexes during the final 12 hours of the study period. Concomitant ex vivo platelet aggregation studies revealed significant inhibition of platelet aggregation in response to collagen and adenosine diphosphate in drug-treated dogs. The results of these investigations provide evidence that nafazatrom prevents in vivo development of occlusive coronary artery thrombi in response to disruption of the endothelial surface of the vessel.

Adenosine Diphosphate↗
PubMed1984

Preparation of human serum [methyl-11C]methylalbumin microspheres and human serum [methyl-11C]methylalbumin for clinical use.

Safely-injectable suspensions of human serum [methyl-11 C] methylalbumin microspheres have been prepared via the reaction of human serum albumin microspheres with [11C]methyl iodide, itself prepared in a novel one-pot synthesis from cyclotron-produced [11C]carbon dioxide. The preparation takes only 30 min from the end of radionuclide production and proceeds in 22% radiochemical yield based on the activity of [11C]carbon dioxide used and decay-corrected. It has been shown that such microspheres are highly stable in vivo and may be used as reference blood flow markers in positron emission tomography (PET). Similarly, safely-injectable and radiochemically pure solutions of human serum [methyl-11C] methylalbumin have been prepared in 31% radiochemical yield and in 40 min from the end of [11C]carbon dioxide production via the reaction of [11C]methyl iodide with human serum albumin. This radiopharmaceutical is intended for studies of lung permeability and blood-brain barrier permeability by PET.

Animals↗
PubMed1984

Validation of quantitation of regional myocardial blood flow in vivo with 11C-labeled human albumin microspheres and positron emission tomography.

Use of radiolabeled microspheres is a standard method to measure regional myocardial perfusion in animals. Human albumin microspheres have been given safely to patients, but positron-emitting 68Ga-labeled human albumin microspheres are characterized by an unstable radiolabel. A new labeling procedure that covalently binds 11C (t1/2 = 20.3 min) to human albumin microspheres via 11CH3I was developed. Seven open-chest and two closed-chest dogs were studied. Reference and 11C-labeled human albumin microspheres (2 to 25 mCi) were both injected into the left atrium. Positron tomographic images were obtained of the myocardial distribution of the 11C-labeled microspheres. Timed arterial withdrawal was used for both reference gamma-labeled microspheres and 11C-labeled human albumin microspheres. Myocardial tissue samples matched to tomographic slices were well-counted for calculation of reference values of regional myocardial perfusion. Serial venous blood samples for residual 11C activity of 30 and 60 min after injection were less than 1% of the myocardial 11C concentration demonstrating a stable 11C bond to the human albumin microspheres. Regional myocardial perfusion calculated by this technique correlated well with values obtained with reference microspheres (r = .97) over a range of 0.2 to 3.5 ml/min/g. Correction for wall thickness improved the slope of the regression equation from y = 0.71 x -0.03 to y = 0.88 X -0.05. Thus, 11C human albumin microspheres are stable radiochemically and can be used as a quantitative measure of regional myocardial perfusion.

Animals↗
PubMed1983

Prostaglandins and prostaglandin inhibitors in ischemic heart disease.

The evidence for a role of the prostaglandin system in myocardial ischemia and its consequences is still fragmentary. We review the factors that alter the relation between thromboxane A2 and prostacyclin production such that vasoconstriction, platelet aggregation, and the tendency toward thrombus formation are increased. Strategies to prevent platelet aggregation by interfering with the production of thromboxane A2 or by stimulation or administration of prostacyclin are currently under investigation in a number of centers. The ubiquity of the prostaglandin system and our incomplete understanding make careful long-term clinical trials and observations essential if we are to be sure that the net effect of these attempts is beneficial.

Animals↗
PubMed1982

The effect of diltiazem on coronary thrombosis in the conscious canine.

The effect of diltiazem vs. saline was studied in a conscious canine model of coronary thrombosis. Diltiazem given as a 0.75 mg/kg loading dose intravenously followed by 0.4 mg/kg intravenously every 4 h for 24 h had no significant effect on thrombus wet weight, left ventricular infarct size, frequency of ventricular arrhythmias or ex vivo platelet aggregation. The search for antithrombotic agents using in vitro or ex vivo platelet aggregation studies should include concomitant in vivo thrombosis studies using therapeutic dosages of the drug in question.

Animals↗
PubMed1981

Invasive fungal infections in patients with chronic mucocutaneous candidiasis.

Patients with chronic mucocutaneous candidiasis have persistent Candida infection of nails, skin, and mucous membranes, but rarely, if ever, does an invasive fungal infection develop. We describe two patients with chronic mucocutaneous candidiasis who died of fungal infection; one had C albicans meningitis and the second had Cryptococcus neoformans meningitis. The cases of four other patients with chronic mucocutaneous candidiasis and invasive fungal infection, three with crytococcosis and one with histoplasmosis, have been reported previously. Immunological profiles on these six patients revealed no differences from those of other patients with chronic mucocutaneous candidiasis without invasive fungal infection. Three of the four patients who received amphotericin B were cured of their infection; three patients died, including one patient with overwhelming cryptococcosis who had received intensive antifungal therapy and transfer factor.

Adolescent↗
PubMedDate not supplied

Aortic dissection presenting as spinal cord ischemia with a false-negative aortogram.

This article presents a case of type III aortic dissection presenting as a spinal cord syndrome with a prospectively negative initial aortogram. The patient serendipitously illustrates a multimodality approach to aortic dissection imaging. The advantages and disadvantages of conventional radiography, aortography, computed tomography, echocardiography, and magnetic resonance imaging are discussed.

Aortic Dissection↗
PubMedDate not supplied

Clinical experience with the Nimbus pump.

The Nimbus pump is an indwelling, electromagnetic powered left ventricular (LV) assist device inserted transfemorally. The inflow cannula (7 mm) is positioned across the aortic valve and the pump in the descending aorta. Indications for insertion include cardiogenic shock despite maximal medical support and PCWP greater than 18 mmHg, MAP less than 90 mmHg, and Cl less than 2 L/min/m2. Twelve patients underwent the attempt at surgical insertion of the Nimbus pump. Diagnoses included eight acute myocardial infarctions (AMI), two ischemic cardiomyopathy, one postpartum cardiomyopathy, and one transplanted heart rejection. Eight (67%) of twelve patients had successful insertion. One patient had peripheral vascular disease preventing passage, and three had femoral vessels too small for insertion (less than 7.5 Hagar dilator). Five patients with the diagnosis of AMI had successful insertion and three (60%) underwent sufficient LV recovery for removal of the device; the other two patients died of stroke and ventricular arrhythmias, respectively. Three patients with the diagnosis of cardiomyopathy had progression of the disease process, and their needs exceeded the capabilities of the pump and they died of multiorgan failure. The Nimbus pump is an attractive LV assist device because of its pumping capacity (3.5 L/min) and minor surgical procedure for insertion. However, its application is limited because of access route and size. The device appears to work well for patients in cardiogenic shock after AMI (60% recovery) but does not appear indicated for patients with cadiomyopathy.

Adult↗