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Biomedical subjects

H F Mizgala

Publications and source records attributed to H F Mizgala.

At least 19 recordsLinked to original sources

Arterial expression of the plasminogen activator system early after cardiac transplantation.

OBJECTIVES: Recent studies suggest that alterations in tissue thrombolysis as well as the inward migration of cells may be specific events that contribute to coronary artery narrowing after cardiac transplantation. Plasminogen activators and inhibitors play a central role in governing not only tissue thrombolysis, but also vascular cell migration. The purpose of this study was to examine arterial wall expression of the plasminogen activation system in coronary arteries during graft vascular disease initiation and progression. METHODS: Using in situ hybridization and immunocytochemistry, the expression patterns of uPA and PAI-1 in coronary arteries from cardiac allografts were compared to those of young individuals without disease. RESULTS: Both PAI-1 and uPA were over-expressed early after transplantation and as late as 27 months post grafting. Over-expression of these molecules preceded morphological evidence of graft vascular disease. Of special note was the adventitial expression of uPA and PAI-1 in microvessels and myofibroblasts. In contrast, the expression of uPA and PAI-1 in normal coronary arteries was confined to endothelial cells of the central lumen, as well as low levels of expression in intimal and medial smooth muscle cells. CONCLUSIONS: Despite morphologic similarities between normal and transplant coronary arteries, differences were noted in the vascular expression pattern of uPA and PAI-1. The exact role of these molecules in graft vascular disease requires further study; however, it is intriguing to consider that a local imbalance in the plasminogen system may contribute to arterial wall thrombosis and/or excessive cell migration and the genesis of complex vascular lesions.

Adolescent

A computerized system for morphometric analysis of digitized images of histologically prepared arterial cross sections.

A method is described for computerized, operator-assisted, morphometric measurement of histologically prepared arterial cross sections. The system is composed of an image cytometer equipped with a one power lens and a digitizing camera interfaced with an imaging board residing in a PC computer. Algorithms were developed for automated segmentation of the areas of interest. The method is rapid, objective, accurate and requires minimum operator intervention. It gives reliable and reproducible results in the measurement of all elements of the cross section including circumference, area of the media, circumference of the internal elastic lamina, area of the lumen and percent occlusion of the lumen by the intimal thickening. While manual measurements using computerized planimetric methods give similar results, this method is an order of magnitude faster (1-2 min vs. 10-20 min per cross section) thus facilitating the study of large numbers of specimens. A blinded re-measurement of 284 sections of artery for reproducibility yielded r values of 0.86-0.97.

Adult

Successful treatment of deglutition syncope with oral beta-adrenergic blockade.

A case of deglutition syncope of 20 years' duration in a patient without cardiac or esophageal disease is presented. The therapeutic efficacy of beta-blockade is documented by symptomatic improvement, repeat esophageal balloon inflation and tilt-table testing. This suggests the Bezold-Jarisch reflex or sympathetic nervous system may be involved in the pathogenesis of deglutition syncope.

Administration, Oral

British Columbia sends patients to Seattle for coronary artery surgery. Bypassing the queue in Canada.

Concern about waiting lists for elective procedures has become a highly visible challenge to the universal health insurance program in Canada. In response to lengthening queues for patients waiting for cardiac surgery, British Columbia made contracts with four Seattle hospitals to send a total of 200 patients for coronary artery bypass surgery. This article examines the cause of the queue for cardiac surgery in British Columbia and the events that led to outside contracting. Global hospital budgets and restrictions on capital expansion have limited hospital capacity for cardiac surgery. This constrained supply, combined with periodic shortages in critical care nurses and cardiac perfusion technologists, has resulted in a rapid increase in the waiting list. Reducing wide variations in the lengths of queues for individual surgeons may afford an opportunity to reduce long waits. While the patient queue for cardiac surgery has sparked a public debate about budget limits and health care needs, its clinical impact remains uncertain.

British Columbia

Failure to pace following high dose antiarrhythmic therapy--reversal with isoproterenol.

A patient with resistant ventricular tachycardia treated with a combination of antiarrhythmic agents is described. Sudden onset of a wide complex ventricular rhythm with periods of asystole and failure to achieve transvenous pacing were observed, presumably due to antiarrhythmic drug toxicity. Inability to pace was reversed by the infusion of isoproterenol.

Amiodarone

The calcium channel blockers: pharmacology and clinical applications.

The calcium channel blockers provide an exciting and effective new therapeutic tool in the management of ischaemic cardiac syndromes and may prove popular and effective in the treatment of a variety of other disorders. They have provided a new approach to treatment and have added new insights into the pathogenesis of ischaemic cardiac syndromes. Their introduction into clinical practice has been swift and many of our concepts regarding their pharmacologic activities in man remain based on theoretic considerations. Their expanding clinical use and further comparative studies will undoubtedly provide further information in regard to indications, adverse effects, drug interaction and long-term safety. Particular caution is advised when they are combined with certain antiarrhythmic agents, digitalis and particularly beta adrenergic blocking agents. Little is known about their interaction with various general anaesthetic agents and for this reason particular vigilance is required as more patients receiving these agents are admitted for surgical procedures.

Calcium Channel Blockers

Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs.

A subgroup of 22 patients with variant angina who had responded well to calcium antagonist drugs were studied to determine if ergonovine testing could help assess the need for continued therapy. Before treatment all 22 patients exhibited angina with S-T elevation during ergonovine testing done in the coronary care unit according to a previously described protocol with sequential ergonovine doses of 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4 mg administered at 5 minute intervals. After 9.4 +/- 4.7 (range 1 to 24) months of treatment (nifedipine 7 patients, diltiazem 3, verapamil 8, perhexiline 3, nifedipine and diltiazem 1), all patients were free from anginal attacks. Medication was discontinued and ergonovine testing repeated 24 to 48 hours later (3 weeks for perhexiline). In 12 of the 22 patients, angina or S-T segment shifts did not occur during the second ergonovine test to a maximal dose of 0.4 mg. Treatment was not restarted in these patients and all 12 remain free of variant anginal attacks 4.2 +/- 2.9 (range 1 to 13) months later. In seven patients angina and S-T elevation occurred during the second ergonovine test, in the same electrocardiographic leads as during the test before treatment. In three patients the ergonovine test induced angina with S-T depression in the leads where S-T elevation had occurred during the previous test. Treatment was reinstituted in these 10 patients with a positive test. No complications resulted from ergonovine testing in any patient. We conclude that in many patients with variant angina, symptoms will disappear spontaneously and the ergonovine test will revert to negative. Treatment with calcium antagonist drugs can probably be safely discontinued in some patients with variant angina; ergonovine testing appears to be helpful in identifying such patients. Longer periods of follow-up are required to confirm that symptoms do not recur.

Adult

Ergonovine testing in a coronary care unit.

This study describes the results of ergonovine testing in 100 consecutive patients who underwent this procedure in a coronary care unit. All patients had recently undergone coronary arteriography. A bolus injection of ergonovine was administered at 5 minute intervals in the following doses (mg): 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4. The criterion for a positive test was the appearance of S-T elevation greater than 1 mm. The test was positive in all 17 patients known to have variant angina and in 18 (40 percent) of 45 patients who had a history of chest pain judged strongly suggestive of variant angina but who had no electrocardiogram recorded during pain. Of 38 patients with a history of chest pain classified as not entirely typical of variant angina, only 1 (2.6 percent) had a positive test. Of the 64 patients with a negative ergonovine test, 47 had chest pain and 25 had nausea but none had more serious complications. Ventricular arrhythmia accompanied S-T elevation in 18 of the 36 patients with a positive test but occurred in only 4 of the 64 with a negative test (p < 0.0005). No patient needed treatment with antiarrhythmic drugs. Four of the 36 patients with a positive test had serious complications: severe transient hypotension (2 patients), recurrent episodes of angina with S-T elevation (1 patient) and a subendocardial infarction (1 patient). Thus, ergonovine testing is useful in patients with a typical clinical history of variant angina but without an electrocardiogram recorded during pain. In this study, a small but definite incidence of serious complications occurred during a positive test.

Adult

Refractory variant angina controlled with combined drug therapy in a patient with a single coronary artery.

A young man with a single left coronary artery and refractory variant angina is described. Spontaneous coronary artery spasm developed during coronary arteriography at the site of a 50% fixed left anterior descending coronary artery stenosis. Frequent episodes of rest angina with transient ST segment elevation persisted in hospital in spite of treatment with three different calcium antagonist drugs. Symptoms disappeared only when the combination of nifedipine, diltiazem, isosorbide dinitrate, and nitroglycerin ointment were given. Ergonovine testing was used to objectively assess the response to treatment.

Adult

Previously undiagnosed variant angina as a cause of chest pain after coronary artery bypass surgery.

Variant angina was diagnosed after coronary artery bypass surgery in six patients over a 22-month period. Although all six patients had at least occasional angina at rest preoperatively, all but one had predominantly exertional angina. After surgery, rest angina with transient ST-segment elevation appeared in all six after an asymptomatic interval of 1 week to 4 years. In two patients the involved artery had not been bypassed, in two patients it was perfused by a patent graft and in two patients the graft to the involved vessel was occluded. Treatment with calcium antagonist drugs (four cases) or isosorbide dinitrate (one case) eliminated symptoms; one patient spontaneously became asymptomatic. The diagnosis of variant angina should be considered when rest angina occurs after bypass surgery, particularly if exertional angina is absent and grafts are patent.

Adult

Hemodynamic effects of a single oral dose of nifedipine following acute myocardial infarction.

The hemodynamic effects of a single oral dose of 20 mg of nifedipine were studied in 21 stable patients after an acute myocardial infarction before withdrawal of Swan-Ganz and intra-arterial catheters. The drug appears safe, and no significant untoward effects were noted. Significant hemodynamic changes were present between 15 and 120 minutes after ingestion with a peak at 60 minutes. Mean arterial pressure decreased from 81+/-2.7 (SEM) to 71+/-2.3 mm Hg (P<0.001), and systemic vascular resistances decreased from 1438+/-88 to 1144+/-63 dynes/sec/cm5 (P<0.001). Cardiac index increased from 2.7+/-0.1 to 3.1+/-0.1 L/min/sq m (P<0.01) and heart rate from 79 +/- 3 to 82 +/- 4 (P<0.01). The pressure-rate product decreased from 10.3 X 10(3) to 9.5 X 10(3) (P<0.05), and pulmonary wedge pressure was unchanged from 12 mm Hg. The hemodynamic changes were similar whether patients were receiving propranolol or not. The afterload reducing effect was potentially most beneficial in the subgroup of patients with depressed left ventricular function where cardiac index increased by 20 percent.

Administration, Oral