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Biomedical subjects

Stuart D Rosen

Publications and source records attributed to Stuart D Rosen.

9 recordsLinked to original sources
PubMed2006

Effects of long-term oral dipyridamole treatment on coronary microcirculatory function in patients with chronic stable angina: A substudy of the persantine in stable angina (PISA) study.

AIMS: A meta-analysis of 13 randomized placebo-controlled trials demonstrated a benefit for dipyridamole therapy, particularly with longer duration of treatment. Although the mechanism of this effect is not well understood, dipyridamole increases endogenous tissue adenosine, which may have a beneficial effect on myocardial perfusion. Therefore, we measured the effects of dipyridamole on myocardial blood flow (MBF) and coronary flow reserve (CFR) by using positron emission tomography and H2O in patients with coronary artery disease. METHODS: Forty-four patients with angiographically documented coronary artery disease were double-blind randomized to either oral dipyridamole [200 milligrams (mg) twice daily (bd)] or placebo as add-on to conventional antianginal treatment for 24 weeks. MBF was measured at rest and during dobutamine stress at baseline and study completion for the region subtended by the most severe coronary artery stenosis (Isc) and remote myocardium subtended by arteries with minimal or no disease (Rem). CFR was calculated as MBF-peak/MBF-rest. RESULTS: Thirty-five patients completed the study. Isc MBF-rest decreased in patients receiving dipyridamole (0.10 mL/minute/g; P = 0.03) and increased in the placebo group (0.16 mL/minute/g; P = 0.01) during the 24-week study. No significant change in MBF-peak was demonstrated in either group. Consequently, Isc-CFR increased significantly in patients receiving dipyridamole (1.65 +/- 0.47 vs 1.83 +/- 0.67; P < 0.05). By contrast, Isc-CFR decreased significantly in those receiving placebo (1.74 +/- 0.44 versus 1.38 +/- 0.46; P < 0.03). No change was seen in Rem-CFR territories. CONCLUSIONS: At the end of treatment, a reduction in baseline MBF but no significant changes in hyperemic MBF were observed in ischemic myocardial territories, and therefore the significance of the observed improvement in CFR remains unclear.

Administration, Oral↗
PubMed2005

Abnormal regional left ventricular mechanics in treated hypertensive patients with 'normal left ventricular function'.

Global systolic and diastolic LV function assessed by conventional echocardiographic indices is often normal in patients with controlled hypertension, with or without left ventricular hypertrophy. However, it is not certain whether regional myocardial function in these patients remains normal. We investigated 26 patients and 10 age matched normal controls, by means of long axis M-mode echocardiography. There was no significant difference in age, sex distribution, heart rate, blood pressure and routine ECG measurements between the two groups. Although there was significant LVH in patients compared to normal controls, LV cavity size and global systolic function, assessed by shortening fraction, ejection fraction and mean velocity of circumferential fibre shortening did not differ between the two groups, nor did LV diastolic function, assessed by the mitral flow pattern. However, LV regional mechanics, as assessed by multiple long axis M-mode echocardiograms differed significantly, in both systole and diastole, between the two groups. Compared to controls, the total longitudinal systolic excursion in both LV free wall and ventricular septum were significantly reduced in patients, and so was maximum early relaxation and atrial contraction in the LV free wall. The mean rate of systolic excursion in all 3 sites did not differ between the two groups, but the mean rate of early relaxation in both LV free wall and ventricular septum was significantly decreased in patients compared to normal controls. In conclusion, the evaluation of LV dysfunction in patients who have achieved good blood pressure control requires more than a conventional echocardiographic assessment. The assessment of regional mechanics described in the present paper offers an easy and sensitive method for the detection of subtle signs of LV mechanical inefficiency associated with LVH.

Adult↗
PubMed2005

Assessment of the long-term reproducibility of baseline and dobutamine-induced myocardial blood flow in patients with stable coronary artery disease.

UNLABELLED: Although physical exercise is the preferred stimulus for cardiac stress testing, pharmacologic agents are useful in patients who are unable to exercise. Previous studies have demonstrated short-term repeatability of exercise and adenosine stress, but little data exist regarding dobutamine (Dob) stress or the long-term reproducibility of pharmacologic stressors in coronary artery disease (CAD) patients. PET allows accurate, noninvasive quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The aim of the study was to investigate the long-term reproducibility of Dob stress on MBF and CFR in CAD patients using PET. METHODS: Fifteen patients with chronic stable angina and angiographically proven CAD (>70% stenosis in at least 1 major coronary artery) underwent PET with (15)O-labeled water and Dob stress at baseline (time [t] = 0) and after 24 wk (t = 24). MBF at rest and MBF during Dob stress were calculated for the whole left ventricle, the region subtended by the most severe coronary artery stenosis (Isc), and remote myocardium subtended by arteries with minimal or no disease (Rem). Reproducibility was assessed using the Bland-Altman (BA) repeatability coefficient and was also expressed as a percentage of the mean value of the 2 measurements (%BA). RESULTS: Dob dose (30 +/- 11 vs. 031 +/- 11 microg/kg/min; P = not significant [ns]) and peak Dob rate.pressure product (20,738 +/- 3,947 vs. 20,047 +/- 3,455 mm Hg x beats/min; P = ns) were comparable at t = 0 and t = 24. There was no significant difference in resting or Dob MBF (mL/min/g) between t = 0 and t = 24 for the whole left ventricle (1.03 +/- 0.19 vs. 1.10 +/- 0.20 and 2.02 +/- 0.44 vs. 2.09 +/- 0.57; P = ns for both), Isc (1.05 +/- 0.24 vs. 1.10 +/- 0.26 and 1.79 +/- 0.53 vs. 1.84 +/- 0.62; P = ns for both), or Rem (1.03 +/- 0.23 vs. 1.10 +/- 0.26 and 2.27 +/- 0.63 vs. 2.26 +/- 0.63; P = ns for both) territories. Global (1.98 +/- 0.40 vs. 1.90 +/- 0.46; P = ns) and regional CFR (Isc: 1.65 +/- 0.40 vs. 1.67 +/- 0.47, and Rem: 2.25 +/- 0.57 vs. 2.06 +/- 0.51; P = ns) were reproducible. The BA repeatability coefficients (and %BA) for MBF in ischemic and remote territories were 0.3 (28%) and 0.26 (24%) at rest and 0.49 (27%) and 0.58 (26%) during Dob stress. CONCLUSION: In patients with clinically stable CAD, Dob induces reproducible changes in both global and regional MBF and CFR over a time interval of 24 wk. The reproducibility of MBF and CFR with Dob was comparable with the short-term repeatability reported for adenosine and physical exercise in healthy subjects.

Angina, Unstable↗
PubMed2004

Is central nervous system processing altered in patients with heart failure?

AIMS: Breathlessness is a cardinal symptom of heart failure and the altered regulation of breathing is common. The contribution of abnormal central nervous system activity has not previously been investigated directly, although abnormal autonomic responses have been described. Our aim was to assess whether heart failure patients exhibit different patterns of regional brain activation after exercise stress. METHODS: We used positron emission tomography with H2(15)O, to measure changes in regional cerebral blood flow (rCBF) and absolute global cerebral blood flow (gCBF) in 6 male class II/III heart failure patients and 6 normal controls. Breathlessness (0-5 visual analogue scale) and respiratory parameters were measured at rest, after horizontal bicycle exercise and during isocapnic hyperventilation. CBF was measured in each condition in all subjects. RESULTS: Both groups were similarly breathless after exercise and the respiratory parameters were comparable. rCBF differences for the main comparison (exercise vs hyperventilation) were: activation of the right frontal medial gyrus (P < 0.001, Z = 4.90) and left precentral gyrus (P < 0.03, Z = 4.66) in controls but not in patients. Both groups had rCBF increases in the left anterior cingulate (P < 0.05, Z = 4.67) and right dorsal cingulate cortex (P < 0.05, Z = 4.66). The gCBF did not differ between exercise, isocapnic hyperventilation and rest in patients but, in controls, gCBF was greater after exercise compared to either isocapnic hyperventilation or rest. CONCLUSION: Heart failure patients had a distinct pattern of regional cortical activity with exercise-induced breathlessness but unvarying CBF values between conditions. These central neural differences in activity may contribute to some features of heart failure, such as variability in symptoms and autonomic dysregulation.

Aged↗
PubMed2002

Myocardial beta-adrenoceptor density one month after acute myocardial infarction predicts left ventricular volumes at six months.

OBJECTIVE: To investigate whether myocardial beta-adrenoceptor (beta-AR) downregulation precedes and predicts left ventricular (LV) dilation after acute myocardial infarction (AMI), we measured beta-AR density within four weeks of AMI and correlated it with serial measurements of LV volumes. BACKGROUND: Patients who develop heart failure following AMI have an increased sympathetic drive to the heart within the first four weeks after infarction. METHODS: We prospectively studied 61 patients in whom AMI was the first presentation of coronary artery disease (CAD) and with no signs of heart failure. The LV volumes were measured one, three, and six months after AMI by echocardiography. Beta-AR density was measured using positron emission tomography with S-[(11)C]CGP 12177. Seventeen matched healthy volunteers served as controls. RESULTS: Whole heart beta-AR density was lower in patients than in controls (6.25 +/- 0.98 pmol/g vs. 8.32 +/- 2.14 pmol/g, p < 0.0001). In patients, beta-AR density was inversely correlated with end-systolic and end-diastolic volumes six months after AMI. Patients whose LV was dilated at six months had a lower beta-AR density in noninfarcted myocardium than patients without dilation (6.15 pmol/g vs. 6.98 pmol/g, p = 0.008). In addition, beta-AR density in noninfarcted myocardium was higher when the infarct-related artery was patent (6.87 +/- 1.14 pmol/g vs. 5.76 +/- 0.86 pmol/g occluded, p < 0.01). CONCLUSIONS: Myocardial beta-AR density is reduced after AMI in the absence of heart failure, and the reduction predicts later LV dilation. These data are suggestive of an enhanced sympathetic drive to the heart, having an important etiologic role in LV remodeling after AMI.

Aged↗
PubMed2002

Low frequency spectral component of heart rate variability and myocardial beta-adrenoceptor density after acute myocardial infarction.

OBJECTIVE: The low frequency spectral component (LF; 0.04-0.15 Hz) of heart rate variability (HRV) is considered to be an index of sympathetic modulation of sinus node activity under physiological conditions, although the relationship is less clearly defined in non-physiological conditions. Several cardiovascular diseases are characterized by an absent or blunted 24-h pattern of the LF spectral component. The aim of the present study was to investigate the relationship between chronically increased neural sympathetic efferent drive to the heart, quantified in terms of downregulation of myocardial beta-receptors, and the 24-h power of the LF spectral component in patients after acute myocardial infarction. METHODS: In 24 patients, HRV was analyzed for a 24-h period, one month after an uncomplicated Q wave myocardial infarction. The following time domain measures and spectral components were calculated: mean RR, SDNN, SDANN, RMSSD, SDNN index, pNN50, and very low frequency (VLF), low frequency (LF) and high frequency (HF) spectral components. The density of beta-adrenoceptors was measured in vivo by positron emission tomography (PET) with 11-CGP-12177. RESULTS: Post-AMI patients had normal plasma levels of adrenaline and noradrenaline (respectively 1.48 +/- 0.18 and 0.28 +/- 0.03 IU/L) but reduced myocardial beta-adrenoceptor density (6.86 +/- 0.24 pmol/g). Patients had similar heart rates but lower values of SDNN and SDANN compared with control subjects. The absolute and normalized power of the spectral components were similar in the two groups, but the usual day-night oscillation was blunted in patients. Moreover, the day-night change in the power of the LF spectral component was positively related (r = 0.51; p < 0.001) to the myocardial beta-adrenoceptor density. CONCLUSIONS: The loss of the day-night oscillation of the LF spectral component appears to be a significant marker of sustained sympathetic over-activity in post-AMI patients.

Acute Disease↗
PubMedDate not supplied

Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: Implications for pharmacologic stress testing in coronary artery disease.

BACKGROUND: Mechanistic differences between pharmacologic stressors may offer different clinical benefits. Therefore the effects of dobutamine and adenosine on absolute myocardial blood flow (MBF) and coronary flow reserve (CFR) were compared. METHODS AND RESULTS: We divided 36 patients (mean age, 61 +/- 8 years) with coronary artery disease into 2 groups based on stenosis severity as follows: greater than 50% but less than 75% (n = 16) and greater than 75% (n = 20). In addition, 18 normal volunteers (mean age, 46 +/- 7 years) served as control subjects. Groups of equal sizes received either dobutamine or adenosine. MBF at rest and peak MBF were measured by use of positron emission tomography in territories subtended by the stenosis (ischemic) and remote myocardium (remote), whereas left ventricular MBF was used in control subjects. CFR was calculated as peak MBF divided by MBF at rest. CFR was significantly greater with adenosine than with dobutamine stress in control subjects and remote CFR. Ischemic CFR was blunted to a similar degree with each stressor. Therefore adenosine achieved flow heterogeneity across all coronary stenosis severities greater than 50%. However, dobutamine achieved flow heterogeneity only in the presence of a severe coronary stenosis greater than 75% despite provoking a greater ischemic stimulus. CONCLUSION: Adenosine stress demonstrated a higher sensitivity and dobutamine demonstrated a higher specificity with quantitative perfusion imaging. Therefore adenosine is superior for diagnostic perfusion imaging, whereas dobutamine is better suited in combination with visual imaging and in the functional assessment of a known coronary stenosis.

Adenosine↗