Myocardial fatty acid metabolism during acute cardiac allograft rejection.

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-123 jodo-heptadecanoic acid (123J-HDA) with a specific activity of > 2 x 10(17) Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10-56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up.

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.

Whole-body scintigraphy with 99Tcm-MIBI, 18F-FDG and 131I in patients with metastatic thyroid carcinoma.

We assessed the relative usefulness of whole-body planar scintigraphy with 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI), 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG-RS) rectilinear scanning and with diagnostic and therapeutic doses of 131I, for the detection of local recurrences and metastatic lesions in 12 patients with thyroid carcinoma and elevated thyroglobulin serum levels. All images were evaluated independently by three experienced observers to define the number and location of metastatic lesions. 18F-FDG-RS and 99Tcm-MIBI scintigraphy provided similar results, but the tracer that allowed the detection of the highest number of metastases was 99Tcm-MIBI. Both 99Tcm-MIBI scintigraphy and 18F-FDG-RS appear to be more sensitive than 131I scintigraphy for the detection of metastases of thyroid carcinoma. Tomographic acquisitions were also performed on a limited field of view in each subject and, as expected, 18F-FDG-PET was more sensitive than 18F-FDG-RS. 99Tcm-MIBI scintigraphy, a widely available and relatively non-expensive technique, therefore sems suitable for the assessment and follow-up of patients with metastatic thyroid carcinoma and does not require the withdrawal of hormone therapy for lesion imaging.

Cardiac troponin I release correlates with myocardial infarction size.

Cardiac troponin I, creatine kinase, and creatine kinase MB activity were tested in serial blood samples from 15 patients with first-time Q wave acute myocardial infarction (2 anterior and 13 inferior wall infarctions). All patients received intravenous thrombolytic therapy. Cardiac troponin I and creatine kinase MB activity were compared with scintigraphic estimates of myocardial scar (single photon emission computed tomography [SPECT] with 99mTechnetium-isonitrile [Tc-sestamibi]) on late images at rest about 5 weeks after myocardial infarction. Scintigraphic defect sizes ranged from 3.2 to 41.2% (median: 27.3%) of left ventricle. Cardiac troponin I increased and peaked in parallel with creatine kinase MB activity, and the peak values correlated with each other (r = 0.76, p = 0.002). Troponin I stayed increased for several days longer than creatine kinase and creatine kinase MB activity. It could be detected at least until the 4th day after admission. Significant correlation coefficients were found between 99mTc-isonitrile defect sizes and areas under cardiac troponin I curves (r = 0.53, p = 0.042) and between 99mTc-isonitrile defect sizes and cumulative creatine kinase MB activity release (r = 0.64, p = 0.01). Animal studies have already shown a very close correlation between histologic infarct size and SPECT 99mTc-isonitrile defect size. Therefore, our results indicate that cardiac troponin I release in patients with acute myocardial infarction is also correlated with infarct size.

[Thallium scintigraphy of the myocardium. Uniform research protocols of the Austrian Society for Nuclear Medicine]. / Die Thalliumszintigraphie des Myokards. Einheitliches Untersuchungsprotokoll der Osterreichischen Gesellschaft für Nuklearmedizin.

A uniform protocol for thallium scintigraphy of the myocardium has been issued in Austria to avoid difficulties in interpreting results and to avoid repeated examinations to save expenses and radiation burden. From the beginning of 1995 this protocol will be used in the Austrian departments of Nuclear Medicine, differences from this protocol have to be mentioned separately. In this protocol the procedure of examination, bicycle and pharmacological stress testing and vasodilatation, acquisition techniques for planar and SPECT imaging, data processing and quality control of devices are defined.

Bone mineral densitometry in dialyzed patients: quantitative computed tomography versus dual photon absorptiometry.

Reduced bone mineral density (BMD) increases risk of fractures, thus making it necessary to monitor patients suffering from chronic renal failure and consecutive disturbance of bone metabolism. In order to evaluate the reliability of available methods, bone mineral density of the lumbar spine assessed with single energy computed tomography (QCT) was compared with bone mineral density of the lumbar spine, femoral neck, Ward's triangle and trochanteric region measured by dual energy photon absorptiometry (DPA) in 45 hemodialyzed patients with a mean hemodialysis duration of 35 +/- 26 months (SD). Depending on the measurement site and method 4-34% of dialyzed patients suffered from reduced BMD (z-score < -2). The highest correlation (r = 0.61, p < 0.01) was found between QCT of the spine, trabecular bone, and DPA of Ward's triangle. One year after baseline measurement bone mineral density was reassessed after randomization to either QCT or DPA in 14 and 18 patients, respectively. Whereas lumbar spine and femoral neck did not change, mean BMD showed a decrease at the measurement sites of Ward's triangle (DPA), trochanteric region (DPA) and trabecular bone of the spine (QCT), which, however, was statistically not significant. Cortical BMD of the spine assessed with QCT showed an increase. Although there is some reduction in bone density at most sites in hemodialyzed patients, no significant bone loss could be demonstrated over the course of 1 year.

Technetium-99m human immunoglobulin scintigraphy in psoriatic arthropathy: first results.

Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that 99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. 99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, 99mTc-MDP and 99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus 99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions.

Cardiac troponin T release in acute myocardial infarction is associated with scintigraphic estimates of myocardial scar.

BACKGROUND: This study compared clinical-chemical estimates of infarct size with scintigraphic estimates of myocardial scar in patients with first-time acute myocardial infarction (AMI). METHODS: Levels of the cardiac isoform of the contractile protein troponin T (TnT), of creatine kinase (CK), and of the isoenzyme MB of CK (CK MB) were tested in serially drawn blood samples from 21 patients (two females and 19 males; median age, 55 years). Of these 21 patients, five had anterior- and 16 had inferior-wall AMI; all patients received intravenous thrombolytic therapy. Single-photon emission computed tomography (SPECT) with technetium-99m-isonitrile (Tc-sestamibi) was performed at rest after the onset of AMI (median time, 5 weeks). Scintigraphic defects were calculated using "bull's-eye" polar coordinate maps. All patients had an uncomplicated course between discharge and myocardial scintigraphy. RESULTS: Scintigraphic defect sizes ranged from 3.2% to 47.8% of the left ventricle (median, 27.3%). Cardiac TnT and CK MB release correlated closely with each other and with scintigraphic estimates of myocardial scar. Significant correlates were found between cardiac TnT and CK MB peak values (r = 0.87, P = 0.0001), CK MB peaks and Tc-sestamibi defect sizes (r = 0.73, P = 0.0014), and TnT peaks and scintigraphic defect sizes (r = 0.73, P = 0.0011). CONCLUSIONS: Because animal studies have already shown a very close correlation between histologic infarct size and SPECT Tc-sestamibi defect size, our results indicate that cardiac TnT is a useful marker to assess infarct size noninvasively in man.

Correlation of atrial natriuretic peptide and cyclic guanosine monophosphate plasma concentrations in patients with heart disorders during rest and exercise.

The concentration of atrial natriuretic peptide was measured in order to evaluate its importance in patients suffering from a variety of cardiac diseases. There was a correlation between plasma concentrations of atrial natriuretic peptide and its "second messenger" cyclic guanosine monophosphate (cGMP) in all of the cases examined. We investigated the relationship between atrial natriuretic peptide and cGMP plasma concentrations during rest and exercise in comparison with the scintigraphically assessed left- and right-ventricular ejection fraction in patients with chronic heart disease (n = 20), and after orthotopic heart transplantation (n = 16); plasma concentrations were also measured in healthy controls (n = 14). Atrial natriuretic peptide and cGMP concentrations showed a similar correlation during rest and exercise with r = 0.74 and r = 0.81, respectively. With the exception of patients after heart transplantation, a significant negative correlation was seen between the left ventricular ejection fraction and atrial natriuretic peptide or cGMP plasma concentrations during rest conditions (r = 0.76 or 0.58, respectively). No correlation was apparent between plasma concentrations of atrial natriuretic peptide or cGMP and the left- or right ventricular ejection fraction during exercise. The concentrations of atrial natriuretic peptide and cGMP in plasma differed significantly between healthy controls and patients during rest and exercise. It is noteworthy that atrial natriuretic peptide and cGMP concentrations were markedly higher in patients after heart transplantation than in patients suffering from chronic heart disease. Our results indicate that plasma atrial natriuretic peptide and cGMP concentrations are sensitive markers of cardiac impairment.

Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy.

The long-term efficacy of physiologic dual-chamber (DDD) pacing in the treatment of end-stage idiopathic dilated cardiomyopathy was evaluated in a longitudinal study of up to 5 years in 17 patients. The considerable clinical improvement achieved after implantation of a pacemaker programmed for DDD pacing at an atrioventricular delay of 100 ms was maintained throughout the follow-up period or until death and was associated with a consistent decrease in New York Heart Association class and an increase in left ventricular ejection fraction. Cardiothoracic ratio, heart rate and echocardiographic dimensions progressively decreased, and systolic and diastolic blood pressures increased. Median survival time was 22 months. During follow-up, 4 patients received donor hearts, 9 had a sudden death at home without defined cause or after a thromboembolic event, and 1 died from adenocarcinoma. Three patients survived the follow-up. No patient needed rehospitalization owing to a worsening of heart failure after pacemaker implantation. An interruption of pacing in DDD mode for 2 to 4 hours was followed within the first months by a marked decrease in left ventricular ejection fraction and an increase in cardiothoracic ratio and echocardiographic dimensions, but this response consistently decreased during follow-up. The data indicate that DDD pacing can be recommended as a useful tool in the long-term treatment of end-stage idiopathic dilated cardiomyopathy, with progressive improvement in cardiac function and a reduction of the dilatation of the left ventricle.

Atrial natriuretic peptide (ANP), aldosterone, angiotensin II and renin in the 'low T3 syndrome' in organ donors.

The present prospective study was conducted in order to investigate the effect of an acute decrease in serum T3 levels on ANP, aldosterone, angiotensin II, renin and ADH. All patients showed a pathologic TRH stimulation test prior to organ harvesting. Our patients developed secondary T3 hypothyroidism of different severity dependent on intensive care unit (ICU) stay. T3 values in group 1 (ICU stay > or = 77 h) were smaller than 70 ng/dl, those of group 2 (ICU stay < or = 53 h) were greater than 70 ng/dl. In both groups a severe elevation of plasma renin activity was measured, with almost high-normal values for ANP in group 1 and slightly elevated values in group 2 [not significant (n.s.)]. Results demonstrate that, contrary to patients who are not critically ill, brain-dead patients develop a dissociation of the renin-angiotensin-aldosterone mechanism. No statistical significant difference was found between the groups in serum levels of ADH and aldosterone. This endocrine dissociation, however, seems to have no clinical significance with regard to organ function after transplantation in kidney recipients.

Hepatocellular transplantation into the lung for temporary support of acute liver failure in the rat.

Because hepatocyte transplantation into the spleen or the peritoneal cavity, although successful in rats, is more difficult and less successful in larger animals, the lung was chosen for its accessibility and its high oxygen content as a new site for hepatocyte implantation for treatment of acute hepatic failure. Acute hepatic failure was induced by a combination by a portocaval side-to-side shunt and an 80% liver resection, which was associated with a greater than 90% mortality. Hepatocyte transplantation was performed either by injection of 1 x 10(7) cells via the jugular vein (100% mortality) or 5-7 x 10(7) cells transcutaneously into the right lung (92% survival). After injection of the cell-free supernatant into the lung, 53.3% of the animals survived. If more than 90% of the liver was resected, none of the animals survived despite hepatocyte or supernatant injection. From these findings, it is concluded that the lung is a suitable home for hepatocytes. However, the hepatocytes survived only in cases of acute hepatic failure with some remaining vital liver parenchyma.

Differential therapy with calcium antagonists in pulmonary hypertension secondary to COPD. Hemodynamic effects of nifedipine, diltiazem, and verapamil.

In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long-term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension.

Prognostic significance of postinfarction arrhythmias and biventricular dysfunction under stress.

The prognostic relevance on mortality of right ventricular dysfunction in comparison with left ventricular function during stress, complex arrhythmias detected by Holter monitoring, and variables of exercise performance, was evaluated via a retrospective follow-up of more than four years for cardiac mortality of all patients in the chronic stage after myocardial infarction who were referred serially during a one-year period to stress radionuclide-ventriculography and 24-h Holter monitoring. A sample of 47% (213) of all patients admitted after myocardial infarction to the rehabilitation center during 1983 was investigated by scintigraphic stress testing and Holter monitoring and were followed up. Subsequent medication and invasive therapeutic interventions were documented. The mortality during a mean follow-up period of 3.9 years in 213 patients (mean age, 56 years) was 14.6%. Significantly decreased values of left and right ventricular ejection fractions during stress scintigraphy (38 +/- 14 versus 50 +/- 15%, p = 0.000 and 45 +/- 13 versus 54 +/- 11%, p = 0.001, respectively) were revealed in the cardiac deceased patient cohort compared with the remainder. Complex arrhythmias during Holter monitoring occurred twice as often (62 vs. 34%, p = 0.0059) in later deceased patients. Lifetable analysis demonstrated that patients with biventricular stress dysfunction had a significantly worse survival prognosis than those with monoventricular dysfunction. Multivariate nonlinear Cox survival analysis revealed that left and right ventricular ejection fraction during stress and arrhythmias were of independent prognostic significance compared with multiple clinical variables including those of exercise performance. Thus, apart from left ventricular dysfunction and arrhythmias, scintigraphically assessed right ventricular stress dysfunction is a further marker of poor prognosis after myocardial infarction. This reflects the previously neglected pathophysiologic significance of right ventricular performance in patients after myocardial infarction.

Correlation between heart disorders and concentrations of directly measured atrial natriuretic peptide in plasma.

We used new commercially available direct radioimmunoassay to measure human atrial natriuretic peptide (h-ANP) in plasma from 48 individuals who were being evaluated for left and right ventricular function. For 13 healthy individuals with normal ventricular function these concentrations ranged up to 54 ng/L. Measurements of h-ANP clearly differentiated between normal subjects, patients with coronary artery disease, and patients who had undergone orthotopic heart transplantation (ANOVA P less than 0.0001, significant differences between all groups)--all showing normal ventricular function at rest. There was a strong negative correlation (r = -0.64, P less than 0.001) between left ventricular ejection fraction and h-ANP concentrations in plasma of patients with proven coronary artery disease, patients with cardiomyopathy, and healthy individuals. Results by the present method and methods involving extraction of the sample correlated well. Evidently the direct assay of h-ANP in plasma yields information that could be used to help evaluate heart disorders and other pathophysiological conditions causing increased h-ANP concentrations in plasma.