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Biomedical subjects

M Y Flugelman

Publications and source records attributed to M Y Flugelman.

At least 19 recordsLinked to original sources
PubMed1992

Atrial natriuretic peptide in severe heart failure: response to controlled changes in atrial pressures during intravenous nitroglycerin therapy.

Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe congestive heart failure (New York Heart Association functional class IV), and the response of the peptide was studied during changes in cardiac filling pressures induced by a 24-hour infusion of nitroglycerin. In the control state plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the administration of nitroglycerin, natriuretic peptide levels decreased (p less than 0.005) with changes matching very closely the decreases in pulmonary arterial wedge and right atrial pressures, a 1% mean decrease in the peptide level for every 1.5 to 2% mean change in atrial filling pressures. In patients with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting increase in atrial pressures was accompanied by an appropriate secondary increase in the plasma ANP level. During the 24-hour study period there was a direct linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure). The findings were no different in a subgroup of five patients receiving simultaneous treatment with captopril, except that plasma renin activity was higher and the aldosterone level lower than in the control group by a factor of approximately 2.5. The close relationship and tracking of atrial pressure and natriuretic peptide curves suggested that the sensitivity of the atrial stretch response to changes in atrial filling pressures was maintained in severe congestive heart failure.

Aged↗
PubMed1992

Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter.

BACKGROUND: Gene transfer into the arterial wall may provide a novel therapeutic strategy for the treatment of coronary artery restenosis. Previously described methods for gene transfer into the arterial wall require total vessel occlusion for 30 minutes. We sought to develop a protocol for gene transfer within a more clinically relevant time frame. METHODS AND RESULTS: We used a perforated balloon (Wolinsky) catheter to inject retroviral vector-containing virions into rabbit aortas in vivo. The virions were injected within 1 minute. Aortas were removed 5-14 days after injection and analyzed for evidence of gene transfer. In initial studies, nine rabbits were injected with a vector expressing the beta-galactosidase gene, and nine rabbits were injected with either non-beta-galactosidase-containing vectors or with a vehicle control. Histochemical staining of aortic tissues revealed blue (positive) cells in eight of nine experimental rabbits and six of nine controls. Because of the lack of specificity of the beta-galactosidase detection system, we adopted a polymerase chain reaction-based protocol in which oligonucleotide primers were used to amplify specific vector-related sequences from aortic tissue extracts. The polymerase chain reaction protocol, calibrated with standards containing known numbers of transduced cells, revealed low amounts of vector-related sequences in six of 12 vector-injected rabbits and in one of 13 controls (p less than 0.03). Comparison with standards indicated that fewer than 100 transduced cells were present in a 2-cm length of the injected aortic tissue. CONCLUSIONS: Although in vivo gene transfer through an infusion balloon catheter can be accomplished within 1 minute, the therapeutic use of this protocol is limited by the small number of cells that are transduced.

Animals↗
PubMed1992

Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro.

Intravascular stents, currently in experimental human use for recurrent arterial stenosis, are plagued by subacute thrombosis. As a therapeutic approach to stent-related thrombosis, we and others have suggested coating stents with endothelial cells before implantation. In a previous study we demonstrated the feasibility of coating stents with endothelial cells that were genetically modified to secrete large amounts of human tissue plasminogen activator. In the present study we attempted both to develop a clinically applicable protocol for stent seeding and to test whether seeded cells would remain adherent to stents after exposure to pulsatile flow. Endothelial cells were harvested from the saphenous veins of sheep with survival of the donor animals. Harvested cells were transduced with a retroviral vector containing a marker gene and seeded onto catheter-mounted stents under sterile conditions. Scanning electron microscopy revealed complete coverage of the stent surfaces by seeded cells. Stents were expanded and exposed to pulsatile flow in vitro. Substantial cell retention was observed on the lateral stent surfaces by light microscopy and scanning electron microscopy; fewer cells were seen on the luminal and abluminal surfaces. Removal of seeded cells from flow-exposed stents by trypsin digestion resulted in the recovery of approximately 70% of the seeded cells. These cells were viable and healthy as judged by their ability to proliferate to confluence with the same kinetics as control (non-flow-exposed) cells. Autologous genetically modified endothelial cells can be seeded onto catheter-mounted stents in a sterile manner, and stent deployment under flow conditions results in substantial retention of viable cells.

Animals↗
PubMed1991

Clinical, psychological and thallium stress studies in patients with chest pain and normal coronary arteries.

The clinical and psychological profiles of 36 consecutive patients with chest pain and normal coronary arteries (study group) were compared to those of 34 patients with chest pain and significant coronary arterial disease (control group). All 70 patients were hospitalized for chest pain at least once prior to coronary angiography. The features of a typical episode of chest pain were similar in the normal coronary arteries and coronary arterial disease groups, but the female patients with normal coronary arteries had a shorter duration of a typical episode of chest pain, and the male patients with normal coronary arteries had a lower frequency of positive effort tests. Psychological testing showed the women with normal coronary arteries to have a tendency to increased somatization, anxiety, and a lower ability to identify origin of difficulties. The patients in the normal coronary and coronary arterial disease groups had psychological profiles typical of patients with chronic somatic disease. A psychiatric interview demonstrated an increased frequency of depressive trait (score 0-2) in the normal women (0.6 +/- 0.8 vs 0, P less than 0.05), and a tendency to increased somatization, anxiety, and sleeping disorders. Increased somatization was found in the normal coronary men (1.1 +/- 0.7 vs 0.5 +/- 0.7, P less than 0.05). Twenty-five patients of the normal coronary group underwent quantitative thallium stress studies, and 13 patients (52%) had evidence of stress-induced myocardial perfusion defect. There were no differences in the clinical and psychological profiles of the patients with normal and those with pathological thallium stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Chest Pain↗
PubMed1991

Effect of nisoldipine on exercise performance in heart failure following myocardial infarction.

The effects of the second generation calcium channel blocking drug nisoldipine on subjective and objective measurements of exercise performance were studied in 19 patients with moderate to severe heart failure (9 New York Heart Association functional class 2, 9 class 3 and 1 class 4) due to fixed ventricular dysfunction following myocardial infarction. Nisoldipine (10 mg 3 times daily) or placebo were administered for 8 weeks in a double-blind parallel study, assessing exercise performance by symptom-limited treadmill exercise testing using a modified Naughton protocol. Nisoldipine was well-tolerated and produced a small increase in peak estimated workload performed (6.2 +/- 2.9 to 8.2 +/- 3.0 METs, p = 0.06). The rate of perceived exertion (Borg scale) increased from 17.5 +/- 2.2 to 18.8 +/- 1.2 (p less than 0.02). The higher workload was performed at a lower peak systolic blood pressure (p = 0.03), higher peak heart rate (p = 0.06) and identical double product (NS). There was no change in resting and peak heart rate and blood pressure or in exercise performance in patients receiving placebo. Resting left ventricular ejection fraction, measured by radionuclide ventriculography, was unchanged after 8 weeks both in the placebo (21 +/- 9 to 20 +/- 9%) and nisoldipine (34 +/- 17 to 36 +/- 19%) groups.

Aged↗
PubMed1991

Failure of long-term digitalization to prevent rapid ventricular response in patients with paroxysmal atrial fibrillation.

Digitalis is frequently prescribed to patients with paroxysmal atrial fibrillation to reduce the ventricular rate during subsequent paroxysms. To verify the validity of this assumption, we determined the ventricular rate during paroxysmal atrial fibrillation in 13 patients receiving long-term digoxin therapy (mean plasma digoxin level + 1.28 +/- 0.4 ng/ml) and compared it with that of a group of 14 patients who had not taken digoxin or beta-adrenergic and calcium-blocking agents before the attack. The treated and the untreated groups were similar statistically. The mean ventricular rate of the digitalized patients was 121 +/- 15 beats per minute, while that of the patients in the control group was 118 +/- 16 beats per minute. It is concluded that long-term digoxin therapy is not effective in reducing the ventricular response in patients with paroxysmal atrial fibrillation despite adequate therapeutic levels.

Aged↗
PubMed1990

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease.

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

Adult↗
PubMed1990

Nitrate tolerance in heart failure: differential venous, pulmonary and systemic arterial effects.

The hemodynamic profile of tolerance to intravenous nitroglycerin was studied in 9 patients with New York Heart Association Class III to IV congestive heart failure. After rapid dosage build-up to the maximal tolerated dose (decrease in pulmonary wedge pressure to 10 mm Hg or systolic blood pressure to 90 mm Hg), nitroglycerin (525 +/- 548 micrograms/min) was administered at a constant continuous intravenous infusion for a total of 24 hours. The extent of nitrate tolerance at 24 hours was calculated as the percentage loss of the benefit achieved at time of peak effect of nitroglycerin. Tolerance had a different time course and magnitude in the venous, arterial and pulmonary circulations. At 24 hours, right atrial pressure and pulmonary vascular resistance returned to control values in most patients, while 40 to 50% of the effect on systemic vascular resistance, cardiac index and pulmonary wedge pressure was maintained. These findings emphasize the importance of precise definitions in studies relating to nitrate tolerance.

Adult↗
PubMed1990

Predicting late restenosis after coronary angioplasty by very early (12 to 24 h) thallium-201 scintigraphy: implications with regard to mechanisms of late coronary restenosis.

To examine whether late coronary restenosis may be predicted by abnormalities of myocardial perfusion in the early hours after successful percutaneous transluminal coronary angioplasty and to study in greater detail the mechanisms involved in the development of late coronary restenosis after angioplasty, a prospective study was undertaken in 90 consecutive patients. Thallium-201 scintigrams were recorded at rest and during the stress of atrial pacing, 12 to 24 h after angioplasty, and the results were related to the findings at angiography in 70 patients undergoing late cardiac catheterization. A reversible thallium-201 perfusion defect was found in 39 (38%) of 104 myocardial regions supplied by the dilated coronary vessel and identified a subset of patients at high risk of late (6 to 12 months) angiographic restenosis (sensitivity 77%, specificity 67%). In contrast, late coronary restenosis developed in only 7 (11%) of 65 vessels and in 5 (14%) of 37 patients with a nonischemic thallium-201 scintigram on day 1 (p less than 0.005). Multivariate logistic regression analysis of 14 possible preangioplasty and periangioplasty clinical and angiographic variables selected reversible perfusion defect on the thallium-201 scintigram on day 1 (p = 0.016) and immediate postangioplasty residual coronary narrowing (p = 0.004) as significant independent predictors of late restenosis, with younger patient age as an additional less powerful predictor (p less than 0.05). The findings have important implications regarding the pathogenesis of late coronary restenosis in patients undergoing successful angioplasty and they imply that in the majority of these patients pathophysiologic events in the early minutes and hours after angioplasty may determine the development of late restenosis.

Adult↗
PubMed1990

Brucellosis in patients with heart disease: when should endocarditis be diagnosed?

Three patients, 2 with congenital valvular heart disease and 1 with a prosthetic aortic valve developed brucellosis. Brucella melitensis was isolated from blood of all 3 patients. The clinical and microbiological features suggested Brucella endocarditis and following successful antibiotic therapy, no surgery was required. The salient diagnostic features are discussed with emphasis on the management and prognosis of patients with Brucella endocarditis.

Adolescent↗
PubMed1989

Identifying patients at high risk for restenosis after percutaneous transluminal coronary angioplasty for unstable angina pectoris.

To study the determinants of late restenosis after percutaneous transluminal coronary angioplasty (PTCA) performed in patients with unstable angina pectoris, a prospective study was undertaken in 90 patients. Primary PTCA success was achieved in 84 (93%) patients, dilating 116 of 118 coronary narrowings (1.4/patient), while major complications during PTCA occurred in only 1 patient (1 death). Eighty-two patients (114 dilated arteries) were followed for 25 +/- 11 months: 68 (83%) were in New York Heart Association functional class I or II, 11 (13%) in class III, and there were 3 deaths. Late restenosis was found in 16 (25%) of 65 lesions (29% of 49 patients) studied by angiography 9 +/- 7 months after PTCA. Restenosis was more frequent in left anterior descending coronary artery lesions (p = 0.07) and in those which at the time of PTCA had multiple irregularities (67 vs 14%, odds ratio 12.5, p = 0.002), decreased coronary perfusion (Thrombolysis in Myocardial Infarction grade less than 3) (50 vs 15%, odds ratio 5.7, p = 0.02) or intraluminal thrombus (67 vs 19%, odds ratio 8.7, difference not significant). Multiple irregularities (p = 0.003) and decreased flow (p = 0.02) remained independent predictors of restenosis (goodness of fit 0.88) after adjustment for 12 pre- and peri-PTCA clinical and angiographic variables by logistic regression analysis. These data underline the feasibility of early revascularization by PTCA in patients with unstable angina pectoris. Careful follow-up should be instituted in patients with multiple irregular lesions, decreased coronary perfusion or intraluminal thrombus at the time of PTCA. In such patients, late restenosis may be the rule rather than the exception.

Adult↗
PubMed1989

[Percutaneous transluminal coronary angioplasty after coronary artery bypass].

Anginal syndrome may recur early of several years after coronary artery bypass surgery (CABS), and may be due to narrowing of a bypass graft, progression of pre-existing coronary artery lesions, or the appearance of new lesions. Repeat CABS is associated with considerable morbidity and mortality. We therefore performed percutaneous transluminal angioplasty (PTCA) in saphenous or internal mammary bypass grafts or native coronary arteries in 23 patients after CABS. We successfully dilated 35 of 37 lesions (95%) present in 33 of 35 vessels (94%) of 21 of 23 patients (91%). The mean vessel narrowing decreased from 86 +/- 22% to 13 +/- 19% (p less than 0.001) and in all 21 patients with angiographic evidence of success functional capacity improved. Single vein grafts were successfully dilated in 9 patients. None developed acute myocardial infarction or needed emergency surgery, but 1 had a cerebral embolism. PTCA is effective therapy for recurrent angina after CABS, and in many patients is preferable to another operation.

Angina Pectoris↗
PubMed1989

[Annulo-aortic ectasia].

Aortic regurgitation due to annular aortic ectasia was diagnosed in a 29-year-old woman with heart failure. The primary pathology of this disease is cystic medial necrosis of the ascending aorta with aneurysm formation and dilation of the aortic valve annulus. In successful surgical correction, the ascending aorta was replaced by a dacron prosthesis, the aortic valve by a prosthetic disc valve and the coronary arteries were reimplanted into the aortic graft.

Adult↗
PubMed1989

Hepatitis during measles in young adults: possible role of antipyretic drugs.

Fifty-six per cent of 118 young adults observed during a recent measles epidemic had some disturbance on liver function tests. Five per cent developed overt jaundice. Patients treated for fever with paracetamol were found to have significantly higher rates of transaminase impairment compared to those treated with dipyrone. Sixty-five and 58% of patients given paracetamol had elevated ALT and AST levels, respectively. Only 15% of patients given dipyrone had elevated levels of these two enzymes (p less than 0.01 for ALT and p less than 0.02 for AST). The mean levels of transaminases and bilirubin in the paracetamol-treated patients were significantly higher than those found in the dipyrone-treated patients [92 +/- 86 vs. 42 +/- 49 IU (p less than 0.02) for AST and 12 +/- 6.0 vs. 7.0 +/- 2.0 mumoles per liter (p less than 0.01) for bilirubin]. The cumulative dose of paracetamol in those who had impaired liver function was higher than that ingested by patients who did not develop liver damage, although still within the usual therapeutic range [11.6 +/- 5.8 vs. 7.6 +/- 4.2 gm (p = 0.02)]. The possible ways in which measles infection and paracetamol in combination can lead to hepatic damage are discussed.

Acetaminophen↗
PubMed1989

Effect of the second-generation calcium channel blocking drug nisoldipine on diastolic left ventricular dysfunction in heart failure.

The effect of intravenous nisoldipine (0.12 microgram/kg/min) on diastolic left ventricular (LV) dysfunction was studied from simultaneous hemodynamic and radionuclide measurements in 12 patients with New York Heart Association class II to IV cardiac failure. The initial LV filling fraction was low, the peak LV filling rate normalized for end-diastolic volume was decreased, and the pulmonary capillary wedge pressure (PCWP) was high and associated with clinical shortness of breath. Nisoldipine produced an increase in LV filling fraction from 36 +/- 17% to 43 +/- 20% (p = 0.003). The increase in filling took place in both early and late diastole: peak early filling rate (PFR) increased in 11 of the 12 patients (p = 0.02) and late diastolic filling rate (atrial [A] wave in eight of them (NS). When the determinants of these changes, were examined further, it was found that in the control state PFR was inversely related to LV end-systolic volume (r = 0.77), whereas the A wave was related in exponential fashion to PCWP (preload) (r = 0.79). Nisoldipine did not change the slope of these relationships, and it did not alter the end-diastolic pressure-volume relationship, implying that inherent myocardial relaxation and distensibility were unaltered by the drug. In summary, nisoldipine improved measurements of diastolic LV dysfunction in patients with cardiac failure. This study illustrates the importance of considering ventricular loading conditions when analyzing and interpreting measurements of diastolic ventricular dysfunction. The measured changes in diastolic LV function during infusion of nisoldipine appear to be due to alterations in ventricular loading conditions rather than to a direct myocardial effect of the drug.

Aged↗
PubMed1988

Persistent painless ST-segment depression after exercise testing and the effect of age.

The relation between the duration of ischemic ST-segment depression (1 mm or more 60 ms after the J point) and the clinical awareness of chest pain was studied in 31 patients (aged 39-73 years) undergoing symptom-limited, graded treadmill exercise testing. The response of these patients to nitrate therapy (spray or sublingual tablet) given immediately on cessation of exercise was also studied. During exercise, angina pectoris appeared at an estimated workload of 4.6 +/- 2.2 metabolic equivalents (METS) (mean +/- SD), and pathological ST-segment depression at 4.9 +/- 1.9 METS (p = NS.) On cessation of exercise, angina disappeared after 3.0 +/- 1.9 min, but ST-segment depression persisted for more than twice as long (6.6 +/- 4.1 min) (p less than 0.0001). The ratio of time to ST-segment recovery/time to relief of pain (a quantitative measure of silent ischemia during recovery) increased with age (r = 0.49, p = 0.002), and in 16 patients over 60 years of age was higher than in 15 younger patients (3.6 +/- 2.5 vs. 2.1 +/- 1.4) (p less than 0.04). The silent ischemia ratio after exercise tended to decrease, although not significantly so (p = 0.2), in patients who received oral nitrates; there was no difference in the response to spray or tablet in this regard. We conclude that ST-segment depression frequently persists after relief of exercise-induced angina pectoris and more so in elderly patients.

Administration, Sublingual↗