Neutrophil and platelet dynamics at organ level after cardiopulmonary bypass: an in vivo study in neonatal pigs.

The aim was to investigate if organ dysfunction is a consequence of cell accumulation in the tissue and whether this accumulation is caused by the cardiopulmonary bypass (CPB) procedure. Twenty-six piglets were used in the sham group (sternotomy, n=12) or in the CPB group (sternotomy, CPB, n=14). Isotope-labeled autologous (99m)Tc-neutrophils (PMNs) and (111)In-platelets were infused and dynamically followed at organ level with a gamma camera before, during, and 4 h after termination of CPB. The CPB group showed a 49% increase in (99m) Tc-PMNs in the kidneys in the postoperative period compared to a decrease of 2% in the sham group. A less marked decrease was observed in the lungs and peripheral blood between the two groups. The increased radioactivity at organ level post-CPB could be due to changes in flow, extraction in the organ or accumulation of cells, especially in the kidneys and lungs, and might contribute to temporary organ dysfunction postoperatively.

99mTc-Sestamibi SPECT is a useful technique for viability detection: results of a comparison with NH3/FDG PET.

OBJECTIVE: Assessment of myocardial viability by 99mTc-Sestamibi Single Photon Emission Computerized Tomography (SPECT) has been suggested as a more readily available and cheaper alternative to Positron Emission Tomography (PET) with 13N-ammonia (NH3) and 18F-fluoro-deoxy-glucose (FDG). We hypothesized that a semi-quantitative evaluation by SPECT could delineate myocardial viability with an acceptable concordance to PET. DESIGN: Fifty patients (age 57+/-7 years; ejection fraction 28 +/- 8%), with ischemic cardiomyopathy, underwent SPECT and PET imaging in random order. Viability by SPECT was defined as a defect size <50% of the segment area, or a defect representing > or =50% of the segment but with a mean activity > or =50% of peak activity. PET viability was defined as a perfusion score >2 and FDG score < or =2 (five-point scale, 0 = normal, 4 = absent activity). RESULTS: By segmental comparison to PET. SPECT yielded a sensitivity and specificity of 87% and 82% for detection of viable myocardium. The positive and negative predictive values were 96% and 58%, respectively. CONCLUSION: In patients with severe ischemic cardiomyopathy 99mTc-Sestamibi SPECT can delineate viable myocardium with an acceptable segmental concordance to NH3/FDG PET.

Functional significance of recruitable collaterals during temporary coronary occlusion evaluated by 99mTc-sestamibi single-photon emission computerized tomography.

OBJECTIVES: The present study evaluated the impact of recruitable collaterals on regional myocardial perfusion measured by 99mtechnetium (Tc)-sestamibi single-photon emission computerized tomography (SPECT) during temporary coronary occlusion and related these estimates to the coronary wedge pressure and electrocardiographic (ECG) ST-segment changes. BACKGROUND: Clinical variables (angina and ECG changes) and intracoronary flow and pressure recordings have indicated a protective role of recruitable collaterals on myocardial perfusion during percutaneous transluminal coronary angioplasty (PTCA). METHODS: Thirty patients (mean age 55 years, SD 9; 20 men) with stable angina pectoris and proximal nonocluding single-vessel left anterior descending coronary artery (LAD)-stenosis scheduled for PTCA were included. Visualization of recruitable collaterals by ipsilateral and contralateral contrast injection, registration of coronary wedge pressure and injection of 99mTc-sestamibi during 90-s LAD occlusions were undertaken. A rest perfusion study was performed within four days before PTCA. As an estimate of the severity of regional hypoperfusion during occlusion, an occlusion/rest count ratio was calculated (mean defect pixel count during occlusion divided by mean pixel count in identical regions at rest). RESULTS: The scintigraphic occlusion/rest count ratio was higher in patients with recruitable collaterals (n = 16), 67 +/- 11%, compared to patients without collaterals (n = 14), 60 +/- 6% (p < 0.05). The occlusion/rest count ratio correlated with the coronary wedge pressure (R2 = 0.34; p < 0.001). The occlusion/rest count ratio was lower, 61 +/- 6%, in patients with ST-segment elevation (n = 23) versus 74 +/- 9% in patients without ST-segment elevation (n = 7) (p < 0.0001). CONCLUSIONS: Using 99mTc-sestamibi SPECT imaging during brief episodes of coronary occlusion, the severity of regional myocardial hypoperfusion was reduced by the presence of recruitable collaterals in a selected patient population with proximal LAD stenoses. Our results demonstrate a protective effect of recruitable collaterals on myocardial perfusion during temporary coronary occlusion.

Vertebral blood flow and bone mineral density during long-term corticosteroid treatment: An experimental study in immature pigs.

STUDY DESIGN: Bone mineral density and regional blood flow were measured in pigs during long-term methylprednisolone treatment. OBJECTIVES: To investigate possible changes in bone mineral density and vertebral blood flow during long-term glucocorticoid treatment. SUMMARY OF BACKGROUND DATA: Steroid-induced vertebral osteonecrosis preferentially involves endplates and adjacent cancellous bone. The precise etiology of vertebral osteonecrosis during long-term glucocorticoid treatment is unknown. METHODS: Twenty-four 10-week-old female Danish landrace sister pigs from 12 litters were treated in two groups. Twelve animals received oral methylprednisolone for 3 months at a daily dose of 100 mg. The 12 sister pigs received no steroid treatment and served as controls. Regional blood blow was measured by means of microspheres in predefined regions of the C6, T11, and L6 vertebrae. In vitro DEXA scanning of the L2-L4 vertebra was performed to assess bone mineral density. RESULTS: Vertebral cancellous bone and endplate regional blood flow were decreased in the C6 and L6 vertebrae among corticosteroid-treated pigs compared with that of controls.- Width-adjusted lumbar vertebral bone mineral density (g/cm3) was unchanged, whereas projectional lumbar vertebral bone mineral density (g/cm2) was decreased in corticosteroid-treated pigs. CONCLUSIONS: Long-term methylprednisolone treatment decreases vertebral bone blood flow mainly in cancellous bone and endplates. This may be an important factor in the pathogenesis of osteonecrosis secondary to glucocorticoid treatment. Lumbar vertebral bone mineral density was unchanged in growing pigs on long-term glucocorticoid treatment when expressed as volumetric bone density. The effect of glucocorticoid treatment on vertebral bone mineral density appears to depend on whether it is expressed as projectional (g/cm2) or volumetric bone mineral density (g/cm3). Vertebral and longbone growth was reduced during methylprednisolone treatment.

Clinical assessment of indication for ACE-inhibitor treatment early after acute myocardial infarction.

An investigation was conducted to assess whether an algorithm based on simple clinical information would suffice to classify patients with acute myocardial infarction, with respect to indication for angiotensin-converting-enzyme inhibitor treatment. One hundred consecutive patients with myocardial infarction were prospectively studied. Based on clinical, radiological, electrocardiographic and biochemical information, the patients were classified as having (a) significantly depressed left ventricular function (ejection fraction < or = 40%) justifying treatment with angiotensin-converting-enzyme inhibitors (ACEI), (b) preserved ventricular function (ejection fraction > 40%) making ACEI unnecessary, or (c) indeterminate ventricular function, requiring further examination. Using a blinded design, ejection fraction was determined by echocardiography and radionuclide ventriculography. A clinical assumption of reduced left ventricular function had a predictive value of an echocardiographically determined ejection fraction < or = 40% of 83% (n = 23). Clinical criteria of good ventricular function had a predictive value of ejection fraction > 40% of 96% (n = 24). In these two groups clinical misclassification occurred in five patients with ejection fraction within the range of 39-45%. Left ventricular function was found to be clinically indeterminate in 53 of the 100 patients. Ejection fraction values assessed by radionuclide ventriculography (n = 44) were on average 9.3%-points lower than echocardiographic values. The indication for ACEI can apparently be determined on the basis of readily available clinical information in approximately 50% of patients with acute myocardial infarction.

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis.

BACKGROUND: Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium. METHODS AND RESULTS: Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement. Echocardiography and radionuclide ventriculography were performed prior to, and 18 months (n = 41) after, the operation. Postoperative follow-up to a maximum of 7.7 years was 100% complete. Pre-operatively, all patients had an increase in both the left ventricular mass index (202 +/- 67 g.m-2) and the muscle cell diameter (41 +/- 8 microns); other morphological data included a muscle cell nucleus volume of 752 +/- 192 microns3, a muscle cell mass index of 163 +/- 54.m-2, and a fibrous tissue mass index of 39 +/- 16 g.m-2. Patients with a pre-operative episode of clinical left ventricular failure (n = 19) had significantly greater morphological variables than those without. Pre-operative ejection fraction and other measures of systolic function correlated inversely with the morphological data, except for the fibrous tissue mass index; diastolic function indices correlated inversely with all the morphological variables. At the 18-month re-study, the same general picture was noted, but with an underlying strengthening, especially of the muscle cell mass index. Overall, the mass index dropped to 152 +/- 51 g.m-2 (P < 0.0001), but in 17% of the patients it became normal; the mass index at 18 months was directly correlated to morphological variables. A high muscle cell nucleus volume was identified as an independent predictor of early and late mortality. CONCLUSIONS: Abnormalities of the hypertrophied left ventricular muscle cell and the degree of muscle hypertrophy are, to some degree, underlying determinants of pre-operative symptomatology, pre- and postoperative ventricular function, and early and late mortality after valve replacement for aortic stenosis. Incomplete hypertrophy impaired results, was related to pre-operative myocardial structural abnormalities.

[Mortality and worsening of prognosis for patients with aortic stenosis while on the waiting list]. / Mortalitet og prognoseforringelse for patienter med aortastenose på kirurgisk venteliste.

In a prospective study, 99 consecutive patients with an operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients were divided into three groups: group 1 (N = 81) with an uneventful stay on the waiting list; group 2 (N = 11) with significant worsening of a prognostic index; and group 3 (N = 7) with patients who died during the waiting time. The waiting list death rate was 13.5%/patient-year compared with a post-AVR death rate of 4.9% patient-year (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According to a prognostic index (Cox regression model) at inclusion, group 2 patients had a predicted 7-year post-AVR survival probability of 72%, but only of 61% according to their prognostic index immediately preoperatively; their observed 7-year post-AVR survival was 60%. Logistic regression analysis identified high age, short duration of symptoms, signs of severe hypertrophy and strain in the ECG, female gender, and deranged left ventricular diastolic function (related to severely increased left ventricular muscle mass) as independent predictors of prognostic worsening and death while on the waiting list. The predictive models did not allow sufficiently accurate identification of the patients at risk during the waiting period. The consequences of a surgical waiting period averaging 6 months are serious for AS patients. The death rate is high and a subgroup worsens its prognostic profile with a significantly reduced post-AVR long-term survival as the result.

Impact of size mismatch and left ventricular function on performance of the St. Jude disc valve after aortic valve replacement.

BACKGROUND: The hemodynamic function of the St. Jude valve may change relative to changes in left ventricular function after aortic valve replacement for aortic stenosis. From theoretical reasons one may hypothesize that prosthetic valve hemodynamic function is related to left ventricular failure and mismatch between valve size and patient/ventricular chamber size. METHODS: Forty patients aged 24 to 82 years who survived aortic valve replacement for aortic stenosis with a standard St. Jude disc valve (mean size, 23.5 mm; range, 19 to 29 mm) were followed up prospectively with Doppler echocardiography and radionuclide left ventriculography preoperatively and 9 days, 3 months, and 18 months after the operation with assessment of intravascular hemolysis at 18 months. Follow-up to a maximum of 7.4 years (mean, 6.3 years) was 100% complete. RESULTS: Left ventricular muscle mass index decreased from 198 +/- 62 g.m-2 preoperatively to 153 +/- 53 g.m-2 at 18 months (p < 0.001), paralleled by a significant increase in left ventricular ejection fraction, peak ejection rate, and peak filling rate; only 18% of the patients had normal left ventricular muscle mass index and only 32% normal ventricular function (normal left ventricular ejection fraction, peak ejection rate, peak filling rate, early filling fraction, and late filling fraction during atrial contraction) at 18 months. Prosthetic valve peak Doppler gradient dropped from 20 +/- 6 mm Hg at 9 days to 17 +/- 5 mm Hg at 18 months (p < 0.05). Reduction of left ventricular muscle mass index was unrelated to peak gradient and size of the valve. Peak gradient at 18 months rose with valve orifice diameter of 17 mm or less (by 6 mm Hg), orifice diameter/body surface area of 9 mm.m-2 or less (by 5 mm Hg), left ventricular enddiastolic dimension (by 23 mm Hg per 10 mm increase), and impaired ventricular function (by 3 mm Hg). All but 2 patients (5%) had intravascular hemolysis; none had anemia. Two patients with moderate paravalvular leak had the highest serum lactic dehydrogenase levels; 4 patients with trivial leak had higher serum lactic dehydrogenase levels than those without leak. Serum lactic dehydrogenase levels rose with moderate paravalvular leak, impaired ventricular function, and valve orifice diameter. Six patients with trivial or moderate paravalvular leak had a cumulative 7-year freedom from bleeding and thromboembolism of 44% +/- 22% compared with 87% +/- 5% for those without leak (p < 0.05). CONCLUSIONS: The peak gradient of the St. Jude aortic valve dropped marginally over the first 18 postoperative months in association with incomplete left ventricular hypertrophy regression and marginal improvement of ventricular function. Mismatch between valve size and ventricular cavity size or patient size and impaired function of a dilated ventricle significantly compromised the performance of the St. Jude valve. Probably explained by platelet destruction or activation, paravalvular leak was related to bleeding and thromboembolic complications.

Left ventricular systolic and diastolic function in aortic stenosis. Prognostic value after valve replacement and underlying mechanisms.

AIMS: The aims of the study were to examine the prognostic value of pre-operative left ventricular systolic and diastolic function on early, and late mortality after valve replacement for aortic stenosis, and to identify possible underlying mechanisms. METHODS AND RESULTS: Ninety-one prospectively recruited consecutive patients with a mean age of 61 years underwent valve replacement for aortic stenosis with concomitant coronary artery bypass grafting in 32 and a minimum postoperative observation period of 5.4 years. There were six early (< or = 30 days postoperatively) and 19 late deaths, and 18 deaths from specific causes (cardiac and prosthetic valve related). Early mortality occurred exclusively among patients with a combined subnormal left ventricular systolic function (subnormal ejection fraction or peak ejection rate, or supranormal time-to-peak ejection--duration of systole ratio) and a subnormal fast filling fraction. In Cox regression models on crude mortality and specific deaths, a subnormal ejection fraction and a fast filling fraction of < or = 45% were the only independent risk factors. Patients with none of these risk factors had normal sex- and age-specific survival, those with any one factor had an early, and those with both factors a massive early and a late excess mortality, with 5-year crude survival of 92%, 77%, and 50%, respectively (P < 0.0001). Systolic wall stress was without prognostic value. Further analyses indicated that impairment of left ventricular function occurred with increasing muscle mass over two phases: (1) diastolic dysfunction characterized by a pattern of severe relative concentric hypertrophy; (2) the addition of systolic dysfunction characterized by a more dilated, less concentric chamber geometry. Coronary artery disease seemed to provoke the latter development sooner. CONCLUSIONS: Impaired systolic and diastolic left ventricular function, irrespective of afterload, were decisive independent pre-operative risk factors for early as well as late mortality after aortic valve replacement for aortic stenosis. The adverse influence of concentric hypertrophy was the main underlying mechanism. Operative intervention, before impairment of diastolic and systolic function, should be advocated.

Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis.

In a prospective study 99 consecutive patients with operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting-time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients were divided into three groups: group I (n = 81) with an uneventful stay on the waiting list (including one patient who declined the AVR offer); group II (n = 11) with significant worsening of a prognostic index; and group III (n = 7) with patients who died during the waiting-time. The waiting-list death rate was 13.5 +/- 5.0% patient-year-1 compared with a post-AVR death rate of 4.9 +/- 0.9%. patient-year-1 (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According to their prognostic index at inclusion, group II patients had a predicted (by a Cox model) 7-year post-AVR survival probability of 72%, but only of 61% according to their prognostic index immediately preoperatively; their observed 7-year post-AVR survival was 60%. Logistic regression analysis identified high age, short duration of symptoms, severe hypertrophy and strain in the ECG, female sex, and deranged left-ventricular diastolic function (related to severely increased left-ventricular muscle mass) as independent predictors of death on the waiting-list and prognosis worsening. From a clinical viewpoint, the predictive models did not allow sufficiently accurate identification of the patients at risk during the waiting-time. The consequences of a surgical waiting-time averaging 6 months are serious for AS patients. The death rate is high and a subgroup worsen their prognostic profile, with significantly reduced post-AVR long-term survival as the result.

Pharmacokinetics and dosimetry of [111In] F(ab')2 fragments against prostatic acid phosphatase after intraprostatic injection for immunoscintigraphy in prostate cancer.

The purpose of this study was to investigate the pharmacokinetics and dosimetry of using [111In]-labelled F(ab')2 fragments against prostate acid phosphatase (FC-3001, Orion Corporation Farmos, Finland) for the detection of metastatic prostate cancer. Five patients in all were subjected to intraprostatic injection of 1 mg FC-3001 labelled with 85-100 MBq [111In]. In four of the patients the biodistribution was studied by sequential whole-body counting, gamma-camera scintigraphy of the abdomen in antero-posterior and postero-anterior projections. Blood and urine samples were collected sequentially up to 72 h after injection. Initially, significant amounts of antibody fragments were released from the site of injection. After the first 4 h, 22.0% of injected antibody (2.2-41.3% ID) remained in the prostate and was slowly released with a final half-life of 80.4 h (49.9-141.8 h). Labelled antibody appeared in the blood shortly after injection and was cleared from the blood with a final half-life of 27.7-300.9 h. The liver, the bone marrow and, in two patients, the kidneys accumulated antibody fragments in significant amounts during the period of investigation. An apparent relationship between the initial whole-body clearance and renal uptake is described. The effective dose averaged 0.37 mSv/MBq (range 0.24-0.52 mSv/MBq). The highest equivalent doses were received by the kidneys (0.46-2.81 mGy/MBq) the liver (0.44-1.59 mGy/MBq) and the bone marrow (0.37-0.57 mGy/MBq). Only in two of the patients with known metastases were pathological foci seen. The disappointing imaging results were probably caused by the biphasic release of antibody from the prostate, and indicates that intraprostatic injection of this antibody has no advantage for imaging, as well as being unpleasant for the patient. The biodistribution of the antibody following release from the prostate is similar to but more variable than the biodistribution seen in patients after intravenous injection of labelled antibodies.

HIDA-cholescintigraphy in normals. Value of interrupting the migrating motor-complex (MMC).

The value of interrupting the migrating motor-complex (MMC) and computer-assisted technique in HIDA cholescintigraphy was studied in 10 healthy subjects. Sequential scintigrams were sufficient for evaluating biliary-bowel transit time, visualization of the gall bladder and liver wash-out. However, the point of dynamic equilibrium between net uptake and emptying of the tracer of the gall bladder and hepatic areas, required computer assisted technique. Finally, interruption of the MMC resulted in biliary-bowel transit within one hour in all, but only gall bladder visualization in 8, whereas in the fasting state the gall bladder was visualized in all, but with prolonged biliary-bowel transit in one subject.

Reproducibility of iodine-123-hippuran renoscintigraphy in the normal pig at various flow rates.

Twenty-two pigs with normal kidney function and upper urinary tracts were examined with renoscintigraphies once a week for 4 weeks. In order to study the influence of urine flow on the reproducibility, renoscintigraphies were undertaken during various urinary flow rates. Renal split function was reproducible at any level of and independent of the urinary flow rates. For parenchymal and pelvic mean transit times a normogram was constructed for selected urinary flow intervals. An inverse relationship to urine production was seen. Parenchymal and pelvic transit times were fully reproducible when data were compared in two or three consecutive examinations of the same kidney at the same urinary flow rate. Both parenchymal and pelvic mean transit times were however significantly different (p less than 0.001) in kidneys studied from one urinary flow rate to another. Single kidney hippuran clearance was fully reproducible when compared in the same urinary flow interval. However a significant difference was found (p less than 0.05) when single kidney hippuran clearance was compared in renographies undertaken at different urinary flow intervals. Furthermore the study suggests that the size of hippuran clearance is dependent on the urine production, since an increase in hippuran clearance was seen in relation to increase in urinary flow. In conclusion this pig study showed, that monitoring of the urinary flow rate is extremely important in this very commonly used clinical investigation, and that the investigation should be performed in the same state of hydration at any renography to obtain reproducible results.