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R Soufer

Publications and source records attributed to R Soufer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Autoregulation of myocardial glycogen concentration during intermittent hypoxia.

During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined hypoxic stimulus on the rat heart while varying its workload. In intact rats, hypoxia reduced myocardial glycogen approximately 30% and increased both the fraction of glycogen synthase in its physiologically active (GS I) form (from 0.24 +/- 0.06 to 0.82 +/- 0.07; P < 0.005) and glycogen synthesis (from 0.087 +/- 0.011 to 0.375 +/- 0.046 mumol.g-1.min-1; P < 0.005). Reducing cardiac work (with propranolol or heterotopic transplantation) reduced glycogen breakdown, glycogen synthase activation, and glycogen synthesis in parallel, stepwise fashion in intact rats. Correspondingly, hypoxia increased GS I activity in the perfused heart in vitro, but only under conditions where glycogen was consumed. This suggests myocardial glycogen synthase is activated by systemic hypoxia and catalyzes rapid posthypoxic glycogen synthesis. Hypoxic glycogen synthase activation appears to be a proportionate, wholly intrinsic response to local glycogenolysis, operating to preserve myocardial glycogen stores independent of any extracardiac mediator of carbohydrate metabolism.

Animals↗
PubMed1995

Kinetic analysis of technetium-99m-labeled nitroimidazole (BMS-181321) as a tracer of myocardial hypoxia.

BACKGROUND: Experimental data have indicated that [99mTc]-nitroimidazole (BMS-181321) is preferentially taken up in hypoxic tissue; its kinetics, however, has not been fully investigated. The purpose of this study was to address the relation between perfusate oxygen level and myocardial retention of [99mTc]nitroimidazole. METHODS AND RESULTS: Bolus injection and constant infusion experiments were performed in Langendorff buffer-perfused rat hearts in normoxic and hypoxic conditions. Data were acquired with a pair of NaI detectors. The initial clearance rate of [99mTc]nitroimidazole was approximately 20 seconds and independent of perfusate oxygen level. The slow clearance rate was greater than 3 hours in all perfusion conditions. The tissue retention of [99mTc]nitroimidazole varied from 0.61 +/- 0.14% in normoxic conditions to 5.94 +/- 1.16% in the most severe hypoxic conditions. In addition, tissue retention was inversely proportional to perfusate oxygen level in a sigmoidal manner. The constant infusion experiments established that the binding rate at 25% oxygen level (1.94 +/- 0.38 mL of perfusate/min-g dry wt) was twofold of that at 40% and sevenfold at 100%. The binding rate of [99mTc]nitroimidazole was independent of the perfusion sequence, suggesting irreversible binding. CONCLUSIONS: These data indicate that [99mTc]nitroimidazole may be a useful tracer for the identification of myocardial hypoxia. A sigmoidal relation was demonstrated for the uptake of the tracer, which suggests that a threshold level of hypoxia is necessary for the uptake of the tracer.

Animals↗
PubMed1995

Prognostic implications of mental stress-induced silent left ventricular dysfunction in patients with stable angina pectoris.

Thirty patients with stable angina pectoris and ischemia on stress perfusion imaging underwent continuous ambulatory left ventricular (LV) function monitoring. Mental stress was induced by mental arithmetic. Fifteen patients developed transient LV dysfunction during mental arithmetic. Patients were followed for 2 years for adverse cardiac events. Twelve patients had cardiac events over 1 year (myocardial infarction in 4, and unstable angina in 8). Nine of 15 patients (60%) with and only 3 of 15 (20%) without mental stress-induced LV dysfunction developed cardiac events (p = 0.025). A higher proportion of patients with cardiac events were taking beta blockers (p = 0.01) and had lower resting heart rates (p = 0.002) than those without cardiac events. There was no difference in the baseline characteristics between the groups of patients with and without cardiac events. At 2-year follow-up, 10 of 15 patients (67%) with mental stress-induced LV dysfunction had adverse events compared with only 4 of 15 (27%) with no mental stress-induced LV dysfunction (p = 0.025). Thus, in this cohort of patients with stable angina pectoris, mental stress-induced LV dysfunction was associated with higher cardiac events on follow-up. The exact mechanism of this association is not clear. Mental stress may be a trigger for adverse cardiac events in these patients. Transient LV dysfunction in response to mental stress may be a marker of abnormal cardiovascular reactivity to emotional and psychological stimuli in patients with coronary artery disease and may be useful for risk stratification.

Adrenergic beta-Antagonists↗
PubMed1995

Comparison of sestamibi single-photon emission computed tomography with positron emission tomography for estimating left ventricular myocardial viability.

Technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi [MIBI]) is distributed in the myocardium according to blood flow. Reports comparing stress rest sestamibi protocols with reinjection thallium or resting fluorodeoxyglucose (FDG), or both, in patients with coronary artery disease have shown appreciable discordance regarding myocardial viability in these settings. We performed this analysis with regard to regional comparisons within discordant segments and made comparisons in a subset of patients who underwent revascularization. Thirty-seven patients with coronary artery disease had single-photon emission computed tomography MIBI, N-13 ammonia/18FDG positron emission tomography (PET), and radionuclide ventriculography performed at rest. One hundred two segments were viable and 29 were nonviable by both MIBI and FDG. The concordance was 71%. In MIBI nonviable/FDG viable segments, most of the discordance was in the inferior wall. In MIBI nonviable discordant segments, FDG accurately predicted an increase in percent regional ejection fraction (preoperative 36% [+/- 5 SE] to postoperative 48% [+/- 5.5 SE][p < 0.0006]). MIBI underestimates myocardial viability as assessed by PET. Seventy-one percent of myocardial segments were concordant by both quantitative sestamibi single-photon emission computed tomography and FDG PET. Discordance in MIBI nonviable segments was predominantly in the inferior wall. PET can be helpful in detecting myocardial viability in patients suspected of having had MIBI nonviability in the inferior wall.

Adult↗
PubMed1995

Reverse redistribution on planar thallium scintigraphy: relationship to resting thallium uptake and long-term outcome.

Reverse redistribution (RR) of thallium-201 has been associated with both acute and healed myocardial infarction, and with recent thrombolysis. The physiologic basis for RR in coronary artery disease (CAD) is unclear but may be related to an admixture of viable and scarred myocardium within the RR segment. We performed thallium reinjection imaging at rest to better characterize RR defects in patients with chronic CAD. We found enhanced uptake of 201Tl in 52% of RR segments after reinjection, consistent with significant regional viability that was not evident on redistribution images. We then used a logistic multiple regression analysis to determine whether RR alone or in combination with other scintigraphic findings could predict patient outcome. The results showed that severe RR was an independent predictor of patient outcome. We conclude that RR may have prognostic significance in chronic CAD.

Aged↗
PubMed1995

Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl-11C]iomazenil.

The central benzodiazepine receptor tracer [N-methyl-11C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with [11C]methyl iodide. The [11C]CH3I (prepared by reduction of [11C]CO2 with LiA1H4 followed by reaction with HI) was reacted with noriomazenil in N,N-dimethylformamide and Bu4N+OH- for 1 min at 80 degrees C and purified by HPLC (C18, 34% CH3CN/H2O 7 mL/min). The product was obtained with synthesis time 35 +/- 5 min (mean +/- SD, n = 7), radiochemical yield (EOB) 36 +/- 16%, radiochemical purity 99 +/- 1%, and specific activity 5100 +/- 2800 mCi/mumol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of [11C]iomazenil in an adult baboon or healthy human volunteer, radioactivity accumulated in the cortex with time-activity curves in agreement with results obtained with [11C]flumazenil PET and [123I]iomazenil SPECT studies. The count rate was sufficient to obtain quantitative images up to 2 h post-injection with a 14 mCi injection. These results suggest that [11C]iomazenil will be a useful agent for measuring benzodiazepine receptors in vivo by positron emission tomography.

Adult↗
PubMed1995

Relationship between reverse redistribution on planar thallium scintigraphy and regional myocardial viability: a correlative PET study.

UNLABELLED: The purpose of this study was to assess myocardial metabolic activity in the area of reverse redistribution and determine the prognostic value of reverse redistribution and PET imaging. Reverse redistribution is thought to be a manifestation of reperfusion therapy and associated with a favorable clinical outcome. Preliminary observations from the Thrombolysis and Myocardial Infarction (TIMI) trial suggest that reverse redistribution is associated with higher incidence of future cardiac events. METHODS: Thirty-two patients with chronic coronary artery disease and reverse redistribution on planar thallium scintigraphy had PET 13NH3/18FDG imaging. Radionuclide angiocardiography was performed in 23 patients. RESULTS: Fifty segments showed reverse redistribution on planar thallium images; 19 segments had normal 13NH3 and 18FDG uptake and 17 were ischemic by PET criteria. Thus, a total of 72% (36 of 50) of reverse redistribution segments were PET viable. Sixty-one percent of segments with abnormal regional wall motion and reverse redistribution were PET scar. On follow-up, 31% (10/32) had a cardiac event (nine unstable angina and one myocardial infarction). Fifty percent of patients (5/10) with cardiac events had severe reverse redistribution and PET viability versus 9% (2/22) without cardiac events (p = 0.01). CONCLUSIONS: The majority of thallium reverse redistribution segments was PET viable as judged by 18FDG uptake. Viability in areas of reverse redistribution is not inferred by regional wall motion analysis. Regional PET viability identifies patients with reverse redistribution with a higher likelihood of future cardiovascular events. PET viability assessment may be helpful with the impact of reverse redistribution on planar thallium scintigraphy.

Aged↗
PubMed1993

Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease.

OBJECTIVES: We examined the relationship of the psychological profile to left ventricular dysfunction induced during mental stress. BACKGROUND: The contribution of psychological factors to mental stress-provoked silent myocardial ischemia has not been explored. METHODS: Thirty patients with chronic stable coronary artery disease and a reversible defect on stress thallium-201 imaging completed a psychological assessment by questionnaire and Structured Interview, serially administered mental stress and brief walking exercise. Blood pressure, electrocardiogram (ECG) and left ventricular indexes were obtained by ambulatory serial radionuclide ventriculography. Silent ventricular dysfunction was defined by a decrease > or = 0.05 in ejection fraction or > or = 1 mm in ST segment on the ECG in the absence of symptoms. RESULTS: Of the 30 patients, 15 (Group I) had evidence of silent left ventricular dysfunction during mental arithmetic. The other 15 (Group II) showed no change. In addition, 18 of 30 patients had this dysfunction during the Structured Interview. Both ischemic and nonischemic groups developed comparable and significant increases in heart rate and blood pressure. Group I patients were distinguished by higher scores on measures of aggressive responding (p < 0.001), trait anger (p < 0.0001), hostile affect (p < 0.003) and an index of behavioral reactivity (p < 0.003) and a lower score on anger control (p < 0.001). No other variables, including historical and clinical indexes, discriminated between the two groups. CONCLUSIONS: Patients with coronary artery disease and mental stress-provoked silent ventricular dysfunction were distinguished by a psychological profile consistent with emotional reactivity to social interaction and mental provocation, with anger as the predominant affective state. Patients with such a profile may be at risk of frequent silent left ventricular dysfunction.

Adult↗
PubMed1992

Long-term outcome in patients with congestive heart failure and intact systolic left ventricular performance.

Congestive heart failure (CHF) is typically associated with impaired left ventricular (LV) systolic performance. Few reports exist describing the long-term outcome in patients with CHF and normal LV systolic function. Fifty-two patients initially hospitalized with CHF and intact LV function (ejection fraction greater than or equal to 45%) were followed for 7 years. Mean age when initially identified was 71 +/- 11 years (range 36 to 96), and average LV ejection fraction was 61 +/- 11%. CHF was graded by a clinicoradiographic index, with a mean of 7.0 +/- 2.3 (range 3 to 12, 13 indicates worst CHF). A third heart sound was present in 19 patients (37%), and 17 (33%) had presented with acute pulmonary edema. Principal cardiovascular diagnoses were coronary artery disease in 27 (52%), hypertensive heart disease in 16 (31%) and restrictive cardiomyopathy in 7 (13%). At 7 years, cardiovascular mortality was 46% (24 of 52), and noncardiovascular mortality was 10% (5 of 52). Survival was not correlated with age, principal diagnosis, third heart sound, pulmonary edema at presentation, LV ejection fraction, or presence or degree of LV diastolic dysfunction. Cardiovascular morbidity, consisting of nonfatal recurrent CHF, myocardial infarction, unstable angina or other cardiovascular events occurred in 29% (15 of 52). Combined cardiovascular mortality and morbidity was 75% (39 of 52). In patients with CHF, intact LV systolic function does not confer the same favorable prognosis it defines in other clinical situations. For such patients, the risk of future cardiovascular events is high, a finding that should be considered when designing therapeutic strategies in this group.

Adult↗
PubMed1992

The radionuclide assessment of left ventricular diastolic filling: methodology and clinical significance.

The radionuclide measurement of diastolic performance may provide a rapid noninvasive index available in the clinical setting. These measurements may be used to detect coronary artery disease, manifestations of hypertensive heart disease, isolated diastolic heart failure, and hypertrophic cardiomyopathy. The various radionuclide methods to measure diastolic filling are influenced by technological considerations, as well as applying the results in the appropriate clinical context. The importance of these derived measurements and how they correspond to various pathophysiological presentations will be discussed.

Diastole↗
PubMed1992

Left ventricular diastolic function during positive end-expiratory pressure. Impact of right ventricular ischemia and ventricular interaction.

The individual and additive effects of positive end-expiratory pressure (PEEP) and right coronary artery (RCA) occlusion on left ventricular end-diastolic pressure-volume relations (LVEDPVR) were examined in six anesthetized dogs. Right ventricular (RV) and left ventricular (LV) ejection fractions (EF), end-diastolic volume (EDV) and end-systolic volumes (ESV) were measured by thermodilution as PEEP was added before and after RCA occlusion. PEEP alone caused a decline in cardiac output, transmural left atrial pressure (LAP) (6.0 +/- 0.6 to 3.2 +/- 1.4 mm Hg, p less than 0.05), and LVEDV (49 +/- 3 to 36 +/- 4 ml, p less than 0.05). RVEDV, the mean slope (+/- SD) of the LVEDPVR (0.37 +/- 0.16 to 0.30 +/- 0.19) and LAP at a common LV volume (35 ml, V35) did not change with PEEP. RCA occlusion caused cardiac output and RVEF (38 +/- 5 to 27 +/- 5%, p less than 0.05) to decline and RVESV (25 +/- 4 to 33 +/- 6 ml, p less than 0.05) to increase. RVEDV, the slope of the LVEDPVR, and LAP at V35 were unchanged from baseline. The addition of PEEP after RCA occlusion caused cardiac output to decline further. However, unlike before occlusion, there was no change in LAP (6.5 +/- 1.3 to 5.0 +/- 1.4 mm Hg) despite a decline in LVEDV (47 +/- 3 to 29 +/- 6 ml, p less than 0.05). RVESV and RVEDV increased with PEEP after RCA occlusion as did LAP at V35. The slope of the mean LVEDPVR tended to increase (0.98 +/- 1.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Thallium-201 for assessment of myocardial viability: quantitative comparison of 24-hour redistribution imaging with imaging after reinjection at rest.

Redistribution thallium-201 imaging 2 to 4 h after exercise may be incomplete and therefore may be inadequate to fully assess myocardial variability. Late redistribution imaging 24 h after exercise has been proposed to overcome this limitation of thallium stress imaging. However, because of poor count density the image quality on these studies is often suboptimal. In the present study the diagnostic information on 24-h planar thallium redistribution images was compared with that on images obtained after a reinjection of thallium at rest. Eighty-four patients with a stress thallium-201 defect had delayed redistribution imaging after 2 to 4 h and 24 h later, and again after an injection of thallium at rest. Defect reversibility on 24-h redistribution images was compared quantitatively with that on images after injection of thallium at rest. The quality of thallium images at rest was consistently better than that of 24-h redistribution images. Poor quality studies occurred in 13% of 24-h redistribution images compared with 0.4% of the studies at rest. Significantly more defect reversibility was detected on images after the reinjection at rest. Of 41 patients who appeared to have a fixed defect at 2- to 4-h redistribution imaging, 11 (27%) had a reversible defect by 24-h redistribution imaging compared with 29 (71%) after thallium-201 reinjection. No clinical variables at the time of stress testing were predictive of late defect reversibility. It is concluded that in patients with fixed a thallium defect at 2 to 4 h after exercise, reimaging after a reinjection at rest provides better diagnostic information than does 24-h late redistribution imaging.

Adult↗
PubMed1991

Reproducibility of quantitative planar thallium-201 scintigraphy: quantitative criteria for reversibility of myocardial perfusion defects.

Fifty-two paired stress/delayed planar 201TI studies (27 exercise studies, 25 dipyridamole studies) were processed twice by seven technologists to assess inter- and intraobserver variability. The reproducibility was inversely related to the size of 201TI perfusion abnormalities. Intraobserver variability was not different between exercise and dipyridamole studies for lesions of similar size. Based upon intraobserver variability, objective quantitative criteria for reversibility of perfusion abnormalities were defined. These objective criteria were tested prospectively in a separate group of 35 201TI studies and compared with the subjective interpretation of quantitative circumferential profiles. Overall, exact agreement existed in 78% of images (kappa statistic k = 0.66). We conclude that quantification of planar 201TI scans is highly reproducible, with acceptable inter- and intraobserver variability. Objective criteria for lesion reversibility correlated well with analysis by experienced observers.

Coronary Disease↗
PubMed1990

Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance.

Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second [edv/s]) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling.

Aged↗
PubMed1990

Coronary flow limits right ventricular performance during positive end-expiratory pressure.

The effect of positive end-expiratory pressure (PEEP) on right ventricular performance and myocardial blood flow was determined in 16 dogs before and after right coronary artery (RCA) occlusion. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV) and end-ejection volume were measured by thermodilution. Right ventricular end-ejection pressure-volume relations (RVEEPVR) were determined at baseline and at 20 cm H2O PEEP, both before and after RCA occlusion. In four of the dogs, RVEEPVR were also determined at 10 cm H2O PEEP after RCA occlusion. With intact RCA flow, RVEF declined with PEEP (37 +/- 5 to 19 +/- 6%) with no significant change in EDV (50 +/- 11 to 42 +/- 11 ml) or end-ejection volume (31 +/- 7 to 36 +/- 9 ml). RVEEPVR and right ventricular myocardial blood flow were also unchanged with PEEP. After RCA occlusion, RVEF declined with PEEP (27 +/- 4 to 15 +/- 5%) in association with a significant increase in end-ejection volume (39 +/- 8 to 49 +/- 10 ml), but no change in EDV (53 to 55 ml). In addition, RVEEPVR and myocardial blood flow declined with RCA occlusion, and declined further with 20 cm H2O, but not with 10 cm H2O PEEP, after RCA occlusion. Therefore, in this experimental model, right ventricular performance was adversely affected during PEEP when right coronary blood flow was limited.

Animals↗