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Biomedical subjects

T J Ryan

Publications and source records attributed to T J Ryan.

At least 19 recordsLinked to original sources

Fibrinogen degradation product fragment D induces endothelial cell detachment by activation of cell-mediated fibrinolysis.

We studied the effects of fibrinogen degradation product (FDP) fragment D on endothelial monolayer integrity and the mechanisms of fragment D-induced endothelial cell detachment from the substratum. Incubation of bovine pulmonary artery endothelial cells (BPAEC) with fragment D caused concentration- and time-dependent cell detachment from the substratum. The optimal response occurred at fragment D concentrations of 2 microM and required an incubation time of 24 h. BPAEC challenged with fragment D increased the concentration and activity of urokinase-type plasminogen activator (uPA) in the conditioned medium within 2 to 4 h of incubation. Fragment D also induced the release of tissue-type plasminogen activator, but to a lesser extent than uPA. Fragment D concurrently increased plasminogen activator (PA) activity in a concentration-dependent manner. Increased PA activity was followed by augmentation of cell-associated plasmin activity and subsequent increase in the degradation of 125I-fibrinogen and 125I-vitronectin precoated in the subendothelial matrix. Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment. We conclude that FDP fragment D increases secretion of endothelial PAs and enhances the generation of plasmin, thereby contributing to proteolysis of extracellular matrix and endothelial cell detachment. Fragment D may be a critical mediator linking activation of fibrinolysis to vascular endothelial injury in inflammatory disorders.

Amino Acid Sequence

Exercise stress testing. Correlations among history of angina, ST-segment response and prevalence of coronary-artery disease in the Coronary Artery Surgery Study (CASS).

To determine to what extent the diagnostic accuracy of stress testing is influenced by the prevalence of coronary-artery disease, we correlated the description of chest pain, the result of stress testing and the results of coronary arteriography in 1465 men and 580 women from a multicentered clinical trial. The pre-test risk (prevalence of coronary-artery disease) varied from 7 to 87 per cent, depending on sex and classification of chest pain. A positive stress test increased the pre-test risk by only 6 to 20 per cent, whereas a negative test decreased the risk by only 2 to 28 per cent. Aothough the percentage of false-positive results differed between men and women (12 +/- 1 per cent versus 53 +/- 3 per cent P less than 0.001), this difference was not seen in a subgroup matched for prevalence of coronary-artery disease. We conclude that the ability of stress testing to predict coronary-artery disease is limited in a heterogeneous population in which the prevalence of disease can be estimated through classification of chest pain and the sex of the patient.

Angina Pectoris

Predictive value of electrocardiographic patterns in localizing left ventricular asynergy in coronary artery disease.

Transmural myocardial infarction by ECG (ECG-MI) was correlated with left ventricular asynergy by biplane left cineventriculography in 200 patients with coronary artery disease. The ability of individual ECG-MI patterns to predict and correctly localize asynergy was: anterior--98 per cent (43 of 44), inferior--82 per cent (36 of 44), true posterior--73 per cent (11 of 15). Of various combinations of criteria for true posterior ECG-MI, the pattern of an R wave and upright T wave in Lead V1 was most predictive of posterior asynergy--80 per cent (8 of 10). The LAO projection demonstrated a wall motion abnormality not appreciated in the RAO in 8 per cent (10 of 122) of cases of inferoposterior asynergy and enhanced assessment of asynergy in 30 per cent (36 of 122) of cases. It is concluded that: (1) ECG-MI has a high predictive accuracy for left ventricular asynergy, (2) an R-wave and upright T wave in Lead V1 is the best ECG predictor of posterior asynergy, and (3) the LAO projection makes an important contribution to the assessment of regional asynergy in coronary artery dieseas.

Electrocardiography

Left ventricular false aneurysm after coronary bypass surgery: radionuclide diagnosis and surgical resection.

A patient with left ventricular pseudoaneurysm formation resulting from myocardial infarction 4 years after coronary bypass surgery is described. The pseudoaneurysm was diagnosed with gated cardiac blood pool imaging and was subsequently successfully surgically repaired. Postoperative pericardial abnormalities predisposing to the possible development of a false aneurysm are discussed. Also, clinical situations in which pseudoaneurysm should be suspected are described, and appropriate diagnostic approaches are outlined.

Coronary Artery Bypass

The effects of gravity on delayed and transplanted delayed tubed flaps.

Altering the position (elevated or dependent) had no immediate effect on the blood supply of delayed or transplanted delayed tubed flaps. However, after 72 hours the mean survival length in the dependent tubes was less than that in the elevated tubes. (This difference was only significant in the delayed untransplanted flaps, and not so in the delayed transplanted flaps). All of the dependent tubes had a significant increase in water content (compared to the elevated tubes). This increase was greater in the transplanted delayed tubed flaps. The tissue pCO2 levels were significantly increased after 24 hours in the dependent transplanted tubes, reflecting poor circulation and ischemia in them. The rate of clearance of subcutaneously injected technetium-99m was significantly increased in the dependent transplanted tubes after 72 hours, while in the elevated tubes the clearance rate was similar to that in normal skin. The morphological appearance of the vessels in these flaps complemented the results of the functional study.

Animals

The blood vessels of psoriasis.

The true microcirculation is the flow of fluid and its contents through the tissues. This is controlled by blood vessels and lymphatics. Both are abnormal in psoriasis and may significantly contribute to its pathogenesis. The type of vasculature characteristic of psoriasis is common to many pathological states and probably influences the metabolism of the tissues in such a way as to maintain the pathology in status quo. It imparts to the tissue a special vulnerability but also encourages repair.

Humans

The predictive value of anginal chest pain as an indicator of coronary disease during exercise testing.

To determine the significance of anginal chest pain during exercise testing, a series of 302 patients undergoing coronary arteriography with exercise testing was reviewed. Of the 302 patients, 85 had ischemic ECG changes and chest pain (Group I); 87 patients had ischemic ECG changes but no chest pain (Group II); 25 patients had chest pain but no ischemic ECG changes (Group III); 105 patients had neither chest pain nor ischemic ECG changes (Group IV). Coronary artery disease was present in 95% of Group I, 75% of Group II, 72% of Group III, and 28% of Group IV. Of those patients with coronary disease, multiple vessels were involved in 94% of Group I, 51% of Group II, 67% of Group III, and 21% of Group IV. The predictive value for presence and extent of coronary disease showed Group I greater than Groups II and III greater than Group IV (p less than 0.025). We conclude that (1) anginal chest pain during exercise testing predicts the presence and extent of coronary disease more accurately than its absence; (2) the presence of chest pain even without an ischemic ECG response during exercise testing appears to be as predictive of coronary disease as an ischemic ECG response alone; and (3) the combination of anginal chest pain during exercise testing and an ischemic ECG response is highly predictive of multivessel coronary artery disease.

Angina Pectoris

Angiotensin converting enzyme inhibition in patients with congestive heart failure.

The etiology of afterload elevation in congestive cardiac failure is unclear, but experimental evidence suggests a role for the renin-angiotensin system in maintaining elevated peripheral vascular resistance. The angiotensin converting enzyme inhibitor SQ20,881 was administered to eight patients with congestive cardiac failure (four hypertensives, four normotensives) during or one day after diagnostic cardiac catheterization. Various hemodynamic measurements performed before and during blockade indicate that this agent caused improvement in cardiac function in all patients by decreasing afterload. This improvement correlated with the decrease in total vascular resistance but was independent of the baseline blood pressure and plasma renin activity. These results suggest that inhibition of angiotensin converting enzyme is a worthwhile approach to the treatment of congestive heart failure, although its exact mechanism of action remains unclear.

Aged

ST segment changes post-infarction: predictive value for multivessel coronary disease and left ventricular aneurysm.

To ascertain whether exercise testing might predict multivessel coronary disease and left ventricular aneurysm after a myocardial infarction, 154 patients with a single documented myocardial infarction who had both exercise testing and coronary angiography were grouped according to whether they had greater than or equal to 1 mm ST depression, greater than or equal to 1 mm ST elevation, or neither during exercise testing: 83 patients developed ST depression alone (group 1); 22 patients had ST elevation with concomitant ST depression in other leads (group 2); 19 patients had ST elevation alone (group 3); and 30 patients had no ST changes (group 4). Multivessel disease, defined as greater than or equal to 70% luminal narrowing in two or more coronary vessels, was present in 76% (63 of 83) of group 1, 91% (20 of 22) of group 2, 21% (four of 19) of group 3, and 13% (four of 30) of group 4. A left ventricular aneurysm was present in 31% (26 of 83) of group 1, 68% (15 of 22) of group 2, 79% (15 of 19) of group 3, and 40% (12 to 30) of group 1. We conclude that ST changes during exercise testing in patients after a myocardial infarction can reliably predict the extent of coronary disease and the presence of a left ventricular aneurysm; ST depression with or without ST elevation predicts multivessel disease; ST elevation alone or a negative exercise test suggests single vessel involvement; and ST elevation with or without ST depression predicts left ventricular aneurysm.

Adult

ST-segment elevation during recovery from exercise. A new manifestation of Prinzmetal's variant angina.

Four patients underwent exercise testing because of a history of pain in the chest; all four developed marked elevation of the S-T segment only during recovery after exercise. Three of the four patients showed ST-segment depression during exercise, but ST-segment elevation was absent until two or more minutes after cessation of exercise. ST-segment elevation after exercise was accompanied by hypotension in three patients and by ventricular arrhythmias in one. Subsequent coronary angiographic studies revealed normal or minimally diseased coronary arteries in two patients and significant coronary lesions in the other two. Review of the literature shows that contrary to the prevailing belief, over half of the patients with Prinzmetal's variant angina have electrocardiographic changes diagnostic of ischemia during exercise testing. Over half of the patients with abnormal findings on tests during exercise display ST-segment elevation as a manifestation of ischemia; however, delayed ST-segment elevation of the type seen in these four patients is distinctly uncommon, having previously been described in only three individual case reports. The pathophysiology of this response is uncertain but may relate to rapid alterations in the autonomic balance during recovery after exercise.

Adult

Trifascicular and complete heart block with anterior myocardial infarction. Electrocardiographic patterns and long-term medical management.

A 45-year-old man exhibited various patterns of delay in trifascicular conduction, culminating in complete heart block during acute myocardial infarction. A temporary pacemaker was utilized for the short period of heart block. Delay in ventricular conduction subsided, and the patient refused implantation of a permanent pacemaker. Ventricular irritability, which was detected eight months later, was suppressed with administration of digitalis, guided by testing with acetylstrophanthidin. Neither heart block nor delay in ventricular conduction recurred during 43 months after the infarction. In certain patients with heart block complicating anterior myocardial infarction, long-term prognosis may be dictated by coronary and myocardial residual function, rather than by the hazard of recurrent heart block.

Bundle-Branch Block

Angiotensin II inhibition. Treatment of congestive cardiac failure in a high-renin hypertension.

A patient with intractable congestive cardiac failure secondary to renovascular hypertension and severe coronary artery disease was infused with the competitive antagonist of angiotensin II, saralasin acetate. The infusion produced an impressive increase in cardiac output and left ventricular stroke work index in parallel with a striking decrease in the systemic and pulmonary vascular resistance, the coronary resistance, and the myocardial oxygen consumption. It is suggested that angiotensin inhibition may present advantages over other forms of treatment of congestive cardiac failure in selected cases.

Angiotensin II