Comparison of 99mTc-sestamibi-18F-fluorodeoxyglucose dual isotope simultaneous acquisition and rest-stress 99mTc-sestamibi single photon emission computed tomography for the assessment of myocardial viability.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

Measurement of myocardial beta-adrenoceptor density in clinical studies: a role for positron emission tomography?

The beta-adrenoceptor (beta-AR) plays an important role in the regulation of heart function and has been extensively studied in recent decades. In vitro studies have shown down-regulation of beta-AR density in heart failure and cardiac conditions that may lead to heart failure. As in vitro measurements on cardiac tissue samples do not allow longitudinal and regional assessment of myocardial beta-ARs in humans, new methods are being developed to measure beta-ARs in vivo using positron emission tomography (PET). Studies using PET and the radioligand [(11)C]CGP 12177 have shown promising results that are in agreement with those of in vitro studies. However, the radiochemical synthesis of [(11)C]CGP 12177 is very demanding, preventing its widespread use. Hence, new radioligands are being developed using simpler methods of radiochemical synthesis. ( S)-[(11)C]CGP 12388 has been presented as a promising new radioligand. So far, in vivo measurements of beta-AR density using PET have mainly been performed to confirm in vitro studies. Using the full potential of PET, performance of regional measurements and longitudinal studies might add further knowledge on the pathophysiological role of the beta-AR in cardiac disease and the effect of interventions. Furthermore, PET might gain a role in the clinical management of patients with abnormalities of cardiac contractile function.

Positron emission tomography using(18)F-fluoro-deoxyglucose and euglycaemic hyperinsulinaemic glucose clamp: optimal criteria for the prediction of recovery of post-ischaemic left ventricular dysfunction. Results from the European Community Concerted Action Multicenter study on use of(18)F-fluoro-deoxyglucose Positron Emission Tomography for the Detection of Myocardial Viability.

AIMS: To assess the accuracy of positron emission tomography to predict recovery of global cardiac function after revascularization in patients with coronary artery disease. METHODS AND RESULTS: One hundred and seventy-eight patients (157 male, 58+/-10 years) with coronary artery disease and left ventricular dysfunction (mean ejection fraction 39+/-14%) were enrolled in six European centres. They underwent a common protocol for the assessment of viability using(18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography during a standardized euglycaemic hyperinsulinaemic glucose clamp before revascularization by either surgery (n=140) or angioplasty (n=38). Seven patients were excluded because of incomplete revascularization of a dysfunctional region. Based on the recovery of global ejection fraction 2-6 months after revascularization, patients were classified into two groups: 82 patients who had a >5% improvement in ejection fraction postoperatively, and 89 patients without postoperative ejection fraction improvement. Optimal cut-off points for postoperative improvement of global cardiac function were computed, using receiver operating curve analysis. The highest sensitivity (79%) and specificity (55%) for predicting postoperative ejection fraction improvement by positron emission tomography was found when three or more dysfunctional segments had a relative FDG uptake >45% of normal remote myocardium (overall accuracy 67%). CONCLUSIONS: In a large cohort of coronary patients with impaired ejection fraction, FDG positron emission tomography demonstrated high sensitivity and moderate specificity to predict improvement of cardiac function after coronary revascularization.

No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium.

OBJECTIVES: We sought to prospectively compare nitrogen-13 (13N)-ammonia/18fluorodeoxyglucose (18FDG) positron emission tomography (PET)-guided management with stress/rest technetium-99m (99mTc)-sestamibi single-photon emission computed tomography (SPECT)-guided management. BACKGROUND: Patients with evidence of jeopardized (i.e., ischemic or viable) myocardium may benefit from revascularization, whereas patients without it should be treated with drugs. Both PET and SPECT imaging have been proven to delineate jeopardized myocardium. When patient management is based on identification of jeopardized myocardium, it is unknown which technique is most accurate for long-term prognosis. METHODS: In a clinical setting, 103 patients considered for revascularization with left ventricular wall motion abnormalities and suspicion of jeopardized myocardium underwent both PET and SPECT imaging. The imaging results were used in a randomized fashion to determine management (percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass graft surgery [CABG] or drug treatment). Follow-up for cardiac events (cardiac death, myocardial infarction and revascularization) was recorded for 28 +/- 1 months. The study was designed to have a power of 80% to detect a 20% difference in the event rate between PET- and SPECT-based management. RESULTS: Management decisions in 49 patients randomized to PET (12 who had PTCA, 14 CABG and 23 drug therapy) were comparable with 54 patients randomized to SPECT (15 who had PTCA, 13 CABG and 26 drug therapy). In terms of cardiac event-free survival, no differences between PET and SPECT were observed (11 vs. 13 cardiac events for PET and SPECT, respectively; p = NS by the Kaplan-Meier statistic). CONCLUSIONS: No difference in patient management or cardiac event-free survival was demonstrated between management based on 13N-ammonia/18FDG PET and that based on stress/rest 99mTc-sestamibi SPECT imaging. Both techniques may be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Impairment of myocardial blood flow reserve in patients with asymptomatic left ventricular dysfunction: effects of ACE-inhibition with perindopril.

Myocardial blood flow (MBF) reserve is impaired in patients with symptomatic chronic heart failure. Whether this is already present in asymptomatic left ventricular (LV) dysfunction, and whether it is affected by angiotensin converting enzyme (ACE) inhibition, is unknown. We examined MBF in 20 patients with asymptomatic LV dysfunction and compared them to healthy volunteers. MBF (reserve) was assessed with positron emission tomography (PET) and N-13 ammonia at rest, during dipyridamole stress test (DST) and during cold pressor test (CPT). Further, in the LV-dysfunction group, we studied the effects of 3 months treatment with ACE inhibition with a second PET study. Patients were randomized double-blind to perindopril 4 mg daily or placebo. MBF at rest was similar in controls and patients. DST-induced MBF reserve, however, was decreased in patients vs. controls (1.71+/-0.2 vs. 2.62+/-0.5, respectively p < 0.05). Also CPT-induced MBF was lower in patients (1.14+/-0.06 vs. 1.23+/-0.03, p < 0.05). After 3 months double-blind treatment, CPT-induced MBF decreased in the placebo group (from 1.12+/-0.02 to 0.93+/-0.06), but was preserved in the perindopril group (from 1.16+/-0.08 to 1.14+/-0.08 shifts from baseline: -0.19+/-0.05 vs. -0.02+/-0.07 respectively p = 0.07). This was compatible with a trend to a smaller increase in coronary vascular resistance during CPT (1.23+/-0.08 vs. 1.03+/-0.06, placebo vs. perindopril, p = 0.06). In patients with asymptomatic LV dysfunction, MBF, both after vasodilation and after CPT, is already impaired. ACE inhibition with perindopril during this short-term treatment had no significant effects.

Imaging of beta-adrenoceptors in the human thorax using (S)-[(11)C]CGP12388 and positron emission tomography.

We report positron emission tomography studies of beta-adrenoceptors in the human thorax with (S)-[(11)C]CGP12388 (4-(3-(2'-[(11)C]-isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one). Beta-adrenoceptors have previously been quantified using (S)-[(11)C]CGP12177 (4-(3-tert-butylamino-2-hydroxypropoxy)-2H-benzimidazol-2[(11)C]-one), but (S)-[(11)C]CGP12388 is more easily prepared and therefore more suitable in a clinical setting. (S)-[(11)C]CGP12388 was administered to five healthy volunteers on two separate days (control and pindolol block study). Arterial plasma samples were used to determine clearance, metabolites, and protein binding of the radioligand. Heart, lung and spleen showed high uptake of radioactivity, which was strongly suppressed (68-77%) by pindolol. Plasma clearance of (S)-[(11)C]CGP12388 was rapid, binding to plasma proteins was low (53+/-4%), and the radioligand was slowly metabolized. (S)-[(11)C]CGP12388 produces high-quality images of the human thorax. Uptake of (S)-[(11)C]CGP12388 in heart, lung and spleen represents binding to beta-adrenoceptors. (S)-[(11)C]-CGP12388 seems useful for imaging of beta-adrenoceptors in a clinical setting.

Numerical simulation of the influence of a left ventricular assist device on the cardiovascular system.

The PUCA (pulsatile catheter) pump is a left ventricular assist device (LVAD) capable of unloading the left ventricle (LV) and improving coronary flow by providing a counterpulsation effect. It consists of an extracorporeal located membrane pump, coupled to a transarterial catheter that enters the body via a superficial artery and ends in the LV. Blood is aspirated from the LV and pumped in the ascending aorta through the same catheter guided by a valve system. Timing and frequency of the PUCA pump influence its efficacy. To study the influence of several pump parameters a numerical model of the device and the circulatory system has been developed. Results of animal experiments were used to validate the model. Optimization studies resulted in a pump configuration with a stroke volume of 50 cc and pump:heart frequency mode of 1:2 that starts ejection at the beginning of diastole.

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND: Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur. METHODS: We studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (k(mono)) were assessed at rest and during submaximal dobutamine infusion (20 microg/kg body weight per min). RESULTS: Global MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 +/- 0.21 vs. 2.7 +/- 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = -0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 +/- 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 +/- 0.13 vs. 1.90 +/- 0.18, p < 0.05). During dobutamine infusion k(mono) was higher in the mismatch regions than in the normal regions (0.104 +/- 0.017 vs. 0.087 +/- 0.016 min(-1), p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest k(mono) (r = -0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism. CONCLUSIONS: Patients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC.

Automated ejection fraction determination from gated myocardial FDG-PET data.

BACKGROUND: The aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography (PET) scans. METHODS: We retrospectively analyzed the data of 20 patients who underwent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA). Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard. RESULTS: Both QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y = 0.90 x x-5.9, r = 0.86, P < .0001; y = 0.80 x x+3.3, r = 0.84, P < .0001, respectively). The correlation between FPM and QGS left ventricular ejection fraction results was even higher (y = 0.89 x x+8.6, r = 0.97, P < .0001). Bland-Altman plots showed systematic differences in the left ventricular ejection fraction of -9.6% +/- 7.5% (QGS vs ERNA), -3.8% +/- 7.8% (FPM vs ERNA), and -5.8% +/- 3.5% (QGS vs FPM). Further comparison of the left ventricular volumes revealed systematic difference between QGS and FPM. Our results indicate that the correlation between the different left ventricular ejection fractions shows little sensitivity to errors in the left ventricular volumes; however, the exact relationship is influenced by these errors. CONCLUSION: It is concluded that the automated determination of the left ventricular ejection fraction from gated PET data has significant potential; its results are highly and significantly correlated with ERNA. However, the methods presented here require additional calibration before final accuracy and clinical applicability can be determined.

Left ventricular beat to beat performance in atrial fibrillation: dependence on contractility, preload, and afterload.

OBJECTIVE: To assess independent determinants of beat to beat variation in left ventricular performance during atrial fibrillation. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Seven patients with chronic non-valvar atrial fibrillation. INTERVENTIONS: Invasive and non-invasive haemodynamic variables were assessed using a non-imaging computerised nuclear probe, a balloon tipped flow directed catheter, and a non-invasive fingertip blood pressure measurement system linked to a personal computer. MAIN OUTCOME MEASURES: Left ventricular ejection fraction, left ventricular volume, ventricular cycle length, pulmonary capillary wedge pressure, and measures of left ventricular afterload (end systolic pressure/stroke volume) and contractility (end systolic pressure/end systolic volume) were calculated on a beat to beat basis during 500 consecutive RR intervals. A statistical model of the beat to beat variation of the ejection fraction containing these variables was constructed by multiple regression analysis. RESULTS: Positive independent relations with ejection fraction were found for preceding RR interval, contractility, and end diastolic volume, while inverse relations were found for afterload, preceding end systolic volume, and preceding contractility (all variables, p < 0. 0001). A relatively strong interaction was found between end diastolic volume and afterload, indicating that ejection fraction was relatively more enhanced by preload in the presence of low afterload. CONCLUSIONS: The varying left ventricular systolic performance during atrial fibrillation is independently influenced by beat to beat variation in cycle length, preload, afterload, and contractility. Beat to beat variation in preload shows its effect on ventricular performance mainly in the presence of a low afterload.

Parametric polar maps of regional myocardial beta-adrenoceptor density.

UNLABELLED: Quantification of myocardial beta-adrenoceptor density (Bmax) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of Bmax. METHODS: Dynamic PET with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[11C]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimaz ole-2)-on hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean Bmax of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate Bmax(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in Bmax(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of Bmax obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating Bmax. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (Bmax(PMF1/2/3)) were compared with Bmax(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated Bmax outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. RESULTS: The differences between the two methods of calculating Bmax were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. CONCLUSION: When using PET for the quantification of beta-adrenoceptor density, the regional variation in Bmax can be reliably assessed using the parametric polar map approach.

Evaluation of the optimal driving mode during left ventricular assist with pulsatile catheter pump in calves.

The pulsatile catheter (PUCA) pump, a left ventricular assist device, was tested during acute experiments in calves using asynchronous and ECG-synchronous assist modes. The aim of the study is to compare ECG-synchronous and asynchronous assist and to find the optimal driving mode for the PUCA pump with respect to left ventricular myocardial oxygen consumption (LV MVO2), pump flow, and coronary flow. LV MVO2 decreased significantly during the asynchronous (from 7.77 to 6.46 ml/min/100 g) as well as during the ECG-synchronous mode (from 8.88 to 7.84 ml/min/100 g). The pump flow was highest during the ECG-synchronous assist (2.94 L/min), followed by the asynchronous assist (2.79 L/min). The peak coronary flow depended strongly on pump ejection timing and showed the best flow patterns during the ECG-synchronous assist. We concluded that for PUCA pump support both asynchronous and ECG-synchronous assists significantly reduce LV MVO2 and that the pump flow generated is enough to maintain the systemic circulation. However, we find the ECG-synchronous mode preferable because this mode optimizes coronary flow patterns at the same time.

Ischemia and left ventricular dysfunction: a reciprocal relation?

There is convincing evidence that (prolonged) episodes of myocardial ischemia lead to impairment of left ventricular (LV) function and ultimately to chronic congestive heart failure (CHF), but whether the opposite is also true has not been well established. We studied this issue in two groups of CHF patients with positron emission tomography (PET) by using [13N]ammonia (13NH3) as a tracer. In the first protocol we compared 12 patients with idiopathic dilated cardiomyopathy (who have normal coronary arteries) with 12 healthy controls. In the second protocol we studied a group of 24 patients with documented coronary artery disease (CAD). In this protocol, we compared patients with normal LV function to those with LV dysfunction and CHF. In patients with cardiomyopathy, myocardial blood flow at rest was normal but flow reserve (after dipyridamole infusion) was significantly impaired (1.7 +/- 0.08) compared with normal subjects (2.7 +/- 0.04; p <0.05). Furthermore, by examining [18F]fluorodeoxyglucose (18FDG) uptake, a perfusion-metabolism mismatch was observed in 24 +/- 6% of the myocardium in patients with cardiomyopathy as opposed to 0% of normals (p <0.05). In patients with CAD, myocardial blood flow reserve (measured in non-stenotic arteries to non-infarcted area) was impaired in CHF patients (1.7 +/- 0.06) compared to those with normal LV function (2.3 +/- 0.05; p <0.05). In both groups of CHF patients, the impairment of blood flow reserve showed a significant correlation with the severity of CHF. In conclusion, myocardial blood flow reserve is impaired in patients with CHF in proportion to the degree of CHF. Metabolic studies with 18FDG further show that, in patients with idiopathic dilated cardiomyopathy and CHF, flow-metabolism mismatch is present in a substantial part of the myocardium, suggesting a pathogenetic role for ischemia.

A mathematical model for the heterogeneity of myocardial perfusion using nitrogen-13-ammonia.

UNLABELLED: Heterogeneity of left ventricular myocardial perfusion is an important clinical characteristic. Different aspects of this heterogeneity were analyzed. METHODS: The coefficient of variation (v), characterizing heterogeneity, was modeled as a function of the number of segments (n), characterizing spatial resolution of the measurement, using two independent pairs of mutually dependent parameters: the first pair describes v as a power function of n, and the second pair adds a correction for n small. n was varied by joining equal numbers of neighboring segments. Local similarity of the perfusion was characterized by the correlation between the perfusions of neighboring segments. Genesis of the perfusion distribution was modeled by repeated asymmetric subdivision of the perfusion into a volume among two equal subvolumes. These analyses were applied to study the differences between 16 syndrome X patients and 16 age- and sex-matched healthy volunteers using 13N-ammonia parametric PET perfusion data with a spatial resolution of 480 segments. RESULTS: The heterogeneity of patients is higher for the whole range of spatial resolutions considered (2 < or = n < or = 480; for n = 480, v = 0.22 +/- 0.03 and 0.18 +/- 0.02; p < 0.005). This is because the first pair of parameters differs between patients and volunteers (p < 0.005), whereas the second pair does not (p > 0.1). For both groups of subjects there is a significant positive local correlation for distances up to 30 segments. This correlation is a formal description of the patchy nature of the perfusion distribution. CONCLUSION: When comparing values of v, these should be based on the same value of n. The model makes it possible to calculate v for all values of n < or = 480. Mean perfusion together with the two pairs of parameters are necessary and sufficient to describe all aspects of the perfusion distribution. For n small, heterogeneity estimation is less reliable. Patients have a higher heterogeneity because their perfusion distribution is more asymmetrical from the third to the seventh generation of subdivision (8 < or = n < or = 128). Therefore, a spatial resolution of n > or = 128 is recommended for parametric imaging of perfusion with PET. Patients have only a very slightly more patchy distribution than volunteers. The differences in perfusion between areas with low perfusion and areas with high perfusion is larger in patients.

Relative changes in regional cerebral blood flow during spinal cord stimulation in patients with refractory angina pectoris.

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H(2)(15)O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at T1 modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.

Development of a new introduction technique for the pulsatile catheter pump.

The pulsatile catheter (PUCA) pump is an intraventricular blood pump that can be introduced into the left ventricular cavity through a superficial artery (transarterially) or directly through the thoracic aorta during open chest conditions. When positioned, the pump aspirates blood from the left ventricle and transports it into the ascending aorta. A pneumatic driving system allows the blood to be ejected in early diastole of every second or third heart beat. The main goal of this study was to develop an easy, fast, safe surgical introduction technique. Four different means of catheter introduction were tested in 20 acute open chest experiments with calves: introduction without any guidance at all, introduction by x-ray guidance only, introduction using a guide wire plus x-ray guidance, and introduction using a guiding pressure catheter. Introducing the PUCA pump catheter into the left ventricular cavity using a pigtail guiding pressure catheter proved to be easy. The large bore pump catheter followed the guiding catheter and passed the aortic valve well. The position of the PUCA pump could be monitored from the pressure patterns derived from the guiding catheter.

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging.

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127+/-31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21 ml.min-1.100 g-1 (groups A and B vs normals, P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2. 91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1+/-4.5 vs 17.0+/-3.0, P<0.05). In group B (coefficient of variation 19.4+/-3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Normal values and reproducibility of left ventricular filling parameters by radionuclide angiography.

BACKGROUND: In physiologic situations age, heart rate (HR) and left ventricular ejection fraction (EF) may influence left ventricular filling rate. In this study, we determined normal values for radionuclide angiography (RNA) derived diastolic filling parameters, the correlations with age, HR and EF and their reproducibility. METHODS: The study was performed in 20 patients, 40-76 years old (mean 57), with normal findings at coronary angiography and left ventriculography. The first RNA was performed at rest (RNA1). Then, five minutes bicycle ergometry was performed and the patients were allowed five minutes rest before RNA was repeated (RNA2). From the left ventricular time activity curve we determined peak filling rate (PFR), time to peak filling rate (TPFR) and atrial contribution (AC) to ventricular filling. RESULTS: Values for PFR1 were 2.2 +/- 0.6 EDV/sec (PFR2 2.4 +/- 0.7 EDV/sec, r = 0.82), for TPFR1 198 +/- 22 msec (TPFR2 203 +/- 24 msec, r = 0.45) and for AC1 31 +/- 11% (AC2 31 +/- 10%, r = 0.72). The correlations of PFR and TPFR with age were statistically significant (respectively r = -0.68 and r = 0.48, P < 0.05). PFR was also influenced by HR and EF (resp. r = 0.51 and r = 0.50, P < 0.05). TPFR however was not influenced by HR and EF, whereas AC was positively correlated with HR (r = 0.79, P < 0.01). CONCLUSIONS: Radionuclide angiography is a reliable and reproducible method to assess parameters of diastolic left ventricular filling in individual patients. It may therefore be used to serially follow diastolic function. When used for interindividual comparison the dependency of RNA derived left ventricular filling parameters on age, HR and EF should however be considered.