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Biomedical subjects

J Kuikka

Publications and source records attributed to J Kuikka.

At least 19 recordsLinked to original sources

Analysis of left ventricular function from gated first-pass and multiple gated equilibrium acquisitions.

99mTechnetium-sestamibi is a new myocardial perfusion imaging agent that offers significant physical advantages over 201thallium for myocardial perfusion imaging. One of these advantages is that it can be used in the assessment of ventricular function by means of first-pass radionuclide angiography (FPRNA), acquired during the injection of the tracer. In this study we compared gated list mode first-pass acquisition with 99mTc-sestamibi (FP-MIBI) to multiple gated equilibrium radionuclide ventriculography (MUGA) with 99mTc-labelled red blood cells for the determination of global left ventricular ejection fraction (LVEF). The study population consisted of 20 patients (mean age 54 years) who were submitted to stress-rest perfusion imaging. Resting FPRNA was performed using 99mTc-sestamibi and the reference data were acquired within a week with the MUGA technique. A linear correlation between FP LVEF and MUGA LVEF gave an r = 0.974 (p < 0.01). Diastolic and systolic timing and velocity parameters had lower correlations between these two methods. We conclude that global LVEF can be precisely measured with 99mTc-sestamibi when compared to usually employed MUGA technique with 99mTc-labelled red blood cells.

Cardiac Output

Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine.

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P less than 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P less than 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.

3-Iodobenzylguanidine

Cardiotoxicity of epirubicin and doxorubicin: a double-blind randomized study.

24 patients with non-Hodgkin lymphoma were randomized into two multidrug regimens including either epirubicin (N = 12) or doxorubicin (N = 12) to establish the cardiotoxicity of each treatment modality. At cumulative doses of 400-500 mg/m2 left ventricular ejection fraction (LVEF) at rest determined by radionuclide angiocardiography decreased significantly more in the doxorubicin (-15 +/- 11%) than in the epirubicin group (0 +/- 13%, p less than 0.005). During epirubicin therapy no clinically significant cardiotoxicity developed, but a decrease larger than 10% in LVEF was seen in 4 of 12 patients at a mean cumulative level of 450 mg/m2. During doxorubicin therapy 1 patient developed a heart failure at a cumulative level of 200 mg/m2 and, altogether, in 7 patients LVEF decreased more than 10%. The monitoring of cardiac toxicity is imperative in patients treated with doxorubicin and is advisable if the patient is expected to receive epirubicin at more than 450 mg/m2.

Antineoplastic Combined Chemotherapy Protocols

Effect of hemodilution on maximal oxygen consumption, blood lactate response to exercise and cerebral blood flow in subjects with a high-affinity hemoglobin.

10 subjects with Hb Linköping (beta 36 Pro greater than Thr), a high-affinity hemoglobin variant, with a P50 of 2.2 kPa (16.5 mm Hg) were investigated before and 3-4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 +/- 13 (SD) to 146 +/- 15 g l-1 and the red cell volume from 2.77 +/- 0.83 to 2.23 +/- 0.67 l. Maximal oxygen consumption decreased slightly by 2.7 +/- 3.8 ml min-1 kg-1 and maximal exercise power by 11 +/- 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (-1.1 +/- 6.4 beats min-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 +/- 10.3 ml min-1 100 g-1 from before to after hemodilution. The results indicate that subjects with Hb Linköping have only limited benefit from their increased blood hemoglobin concentration.

Adult

Effect of early metoprolol injection followed by oral dosage on CK-MB release, and myocardial function in suspected acute myocardial infarction. A double-blind controlled study.

The effect of metoprolol on indices of infarct size and left ventricular function was compared with that of placebo in a double-blind randomized trial in patients with definite or suspected acute myocardial infarction. Intravenous metoprolol (15 mg) or placebo was given within 24 h of the onset of symptoms, and oral treatment (200 mg daily) was continued for 15 days. Thirty-five patients received metoprolol and 34 patients placebo. The mean (+/- SD) of maximal creatinine phosphokinase (CK)-MB activities was 142 +/- 110 IU/l in the placebo group and 74 +/- 72 IU/l in the metoprolol group (p less than 0.001). The ECG QRS score at discharge from hospital was 5.22 +/- 4.47 and 4.61 +/- 3.06 (NS), respectively. Global left ventricular ejection fraction at rest was 44 +/- 14 and 51 +/- 15% (p = 0.054), respectively, and no change occurred in either group from rest to peak exercise. Ventricular fibrillation occurred in 1 placebo patient during the first day in hospital and in 1 metoprolol patient on the 14th day. Holter monitoring revealed no significant difference in the occurrence of ventricular arrhythmias during the first 24 h. Smaller enzyme release and higher ejection fraction suggest myocardial protection by early metoprolol treatment in acute myocardial infarction.

Clinical Trials as Topic

Reversed left internal mammary artery graft for coronary bypass. Evaluation of function with digital subtraction angiography and radionuclide imaging.

Reversed left internal mammary artery grafting with retrograde flow to the left anterior descending coronary branch was used in five of 500 consecutive bypass operations. The indications were significant stenosis in the left subclavian artery (3 patients) or the proximal left internal mammary artery (1) and proximal damage to the left internal mammary artery during dissection from the thoracic wall (1). The postoperative clinical course was smooth in all five patients, with no evidence of myocardial ischemia. In follow-up averaging 14 months four patients were asymptomatic. The reversed internal mammary artery graft was visualized with digital subtraction angiography in four cases. Radionuclide imaging during exercise confirmed graft patency in all but the symptomatic patient, who was found to have an area of reversible ischemia anteriorly in the left ventricle.

Adult

Improvement of left ventricular function after starting insulin treatment in patients with non-insulin-dependent diabetes.

Left ventricular function was evaluated noninvasively before and three months after starting insulin treatment in nine patients (mean age 61.8 years, range 51-68 years) with non-insulin dependent diabetes showing an impaired insulin secretion capacity. After starting insulin treatment, fasting blood glucose decreased from 12.9 +/- 0.5 mmol/l (mean +/- SEM) to 9.8 +/- 1.2 mmol/l (p = 0.03), but the decrease of glycosylated haemoglobin Alc was not significant (9.0 +/- 0.4% vs. 8.3 +/- 0.6%). On systolic time intervals, PEP/LVET ratio improved from 0.44 +/- 0.03 to 0.37 +/- 0.02 (p = 0.03). On M-mode echocardiography, E-F slope became steeper (89 +/- 6 mm/sec vs. 103 +/- 8 mm/sec; p = 0.01) but no significant changes were observed in other variables reflecting diastolic or systolic function. On equilibrium radionuclide angiocardiography, the left ventricular ejection fraction at rest was similar before and after starting insulin treatment (48.6 +/- 3.2% vs. 49.2 +/- 2.8%) but during peak exercise the left ventricular ejection fraction improved significantly (51.0 +/- 5.3% vs. 59.9 +/- 4.7%; p = 0.02). The change of PEP/LVET ratio correlated significantly with the changes of blood glucose and glycosylated haemoglobin Alc levels, but the correlation between these metabolic variables and the change of left ventricular ejection fraction during exercise did not reach statistical significance. In conclusion, the left ventricular function improved concomitantly with improved metabolic control after starting insulin treatment in middle-aged patients with non-insulin-dependent diabetes having an impairment in insulin secretion capacity. This finding suggests that metabolic factors are involved in the left ventricular dysfunction observed in diabetes.

Blood Glucose

First-pass radionuclide ventriculography in conscious dogs.

Trained, chronically instrumented, conscious dogs were used to study the function of the left ventricle by first-pass radionuclide ventriculography (RNV). Six dogs were trained prior to a sterile left thoracotomy, where a left atrial catheter was implanted. After recovery of four days RNV was carried out by injecting a bolus of technetium-99m-DTPA via the catheter to the left atrium. The data was collected for 12 s to a computer by frame rate of 20 frames/s from left lateral view of the dog. The experiments were performed both in four-leg standing and in 60 degrees head-up tilted positions. The measurements were done with two injection volumes (0.25 and 1.0 ml/kg) to study the effect of volume on the results. The body position had effect on left ventricular end-diastolic and stroke volumes, whereas ejection fraction remained unchanged. In comparison of the two injection volumes a minor difference was found in left atrial emptying, while the differences in left ventricular function were non-significant. In spite of training and careful standardization of experimental procedures, relatively high individual variation between animals was found in most parameters studied. The first-pass RNV method proved to be promising for measuring the left ventricular function in conscious dogs. Although the left atrium has reflectory tachycardic potential to distension, the volumes used for RNV did not affect the results. The left ventricular adaptation to head-up tilting in conscious dogs seems to consist mainly of decrease in left ventricular volume without significant effect on ejection fraction.

Animals

Volumetric measurements in endotoxic shock using single photon emission tomography (SPET).

In 25 sheep organ volumes were determined using single photon emission tomography (SPET) prior to and during early endotoxic shock. The tracer used was in vitro 99Tcm-labelled red blood cells. The comparisons between the SPET volumes with the different lower threshold (LT) settings and the 'true' weighed organ volumes were done. The correlation coefficient of -0.87 was found between the LT and the 'true' liver volume and same for the spleen was -0.87. The LT-volume correction curves were used to determine the correct SPET volumes. Thus the accuracy of the liver volume lies within +/- 8%, the splenic volume within +/- 13% and that for the kidney volume +/- 19%. A highly significant decrease of the splenic volume was found 1 h after the induction of endotoxic shock, from 178 +/- 55 ml (mean +/- S.D.) to 101 +/- 25 ml. The kidney volume also decreased from 102 +/- 28 to 78 +/- 19 ml (p less than 0.05), whereas the liver volume remained nearly unchanged (796 +/- 219 versus 761 +/- 165 ml). The SPET study allows measurement of the organ volumes in vivo and the results are reliable when compared to the 'true' volumes. However, the proper LT-settings for organ contour are volume dependent and must be taken into account.

Animals

Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart.

Permeability-surface area products of the capillary wall, PSc, and the myocyte sarcolemma, PSpc, for D-glucose and 2-deoxy-D-glucose were estimated via the multiple indicator-dilution technique in isolated blood-perfused dog and Tyrode-perfused rabbit hearts. Aortic bolus injections contained 131I-albumin (intravascular reference), two of three glucoses: L-glucose (an extracellular reference solute), D-glucose, and 2-deoxy-D-glucose. Outflow dilution curves were sampled for 1-2.5 min without recirculation. The long duration sampling allowed accurate evaluation of PSpc by fitting the dilution curves with a multiregional axially distributed capillary-interstitial fluid-cell model accounting for the heterogeneity of regional flows (measured using microspheres and total heart sectioning). With average blood flow of 1.3 ml . g-1 . min-1, in the dog hearts the PSc for D-glucose was 0.72 +/- 0.17 ml . g-1 . min-1 (mean +/- SD; n = 11), and PSpc was 0.57 +/- 0.15 ml . g-1 . min-1. In the rabbit hearts with perfusate flow of 2.0 ml . g-1 . min-1 (n = 6), PSc was 1.2 +/- 0.1 and PSpc was 0.4 +/- 0.1 ml . g-1 . min-1. PSc for 2-deoxy-D-glucose was about 4% higher than for D-glucose and L-glucose in both preparations. Relative to L-glucose, there was no measurable transendothelial transport of either dextroglucose, indicating that transcapillary transport was by passive diffusion, presumably via the clefts between cells. The technique allows repeated measurements of D-glucose uptake at intervals of a few minutes; it may therefore be used to assess changes in transport rates occurring over intervals of several minutes.

Animals

A radionuclide model for studying changes in the regional blood volumes during early endotoxic shock: an experimental model.

Septic shock constitutes a great threat to patients undergoing major abdominal surgery and also to trauma patients. The current state of knowledge on pathophysiological mechanisms in septic shock is not fully known. The aim of this study was to develop an experimental model that resembled the clinical situation and allowed the exploration of central and peripheral vascular mechanisms in endotoxic shock. Seven anesthetized sheep (weighing 30-45 kg) were provoked to lethal endotoxic shock by intravenous injection of 3 mg/kg bodyweight Escherichia coli endotoxin. The arterial pressure was monitored. Serial radionuclide images of the chest and abdomen were recorded after injecting technetium-99m-labeled RBC's. The volumetric (blood) alterations of liver, spleen, kidney, heart, and lungs, as well as peripheral muscle were measured. Prior to injection of endotoxin base-line data were obtained. Two to 4 minutes after injection, spleen volume decreased by -36% (mean) followed by a slow restoration; the left ventricular volume and kidneys increased by a maximum of 10-15%, while the liver volume increased by 38% of initial volume.

Animals

Enalapril in chronic heart failure, a double-blind placebo-controlled study.

The efficacy of enalapril, a new angiotensin-converting enzyme inhibitor, was investigated in a double-blind placebo-controlled study in 24 patients with chronic heart failure. The patients belonging to NYHA functional class II-IV and treated with digoxin and diuretics were randomized to enalapril (12 patients) or placebo (12 patients) treatment for a 12-week period. Assessments were carried out at baseline and at 4 and 12 weeks during the treatment period. Complete data could be obtained on 10 patients receiving enalapril and on 11 patients receiving placebo. NYHA functional class improved by at least one class in 6 of 10 patients in the enalapril group, but only in 1 of 11 patients in the placebo group (chi 2 = 6.54; p less than 0.05). Duration of bicycle ergometer exercise increased significantly in the enalapril group from 8.8 +/- 3.4 to 11.3 +/- 4.2 (4 weeks) and to 11.2 +/- 3.6 min (12 weeks; p less than 0.05 for both), whereas it remained unchanged in the placebo group. Left ventricular ejection fraction by radionuclide ventriculography in the enalapril group increased significantly (baseline: 33.5 +/- 19.9%, 4 weeks: 40.0 +/- 20.0% (p less than 0.001), 12 weeks: 39.6 +/- 20.1% (p less than 0.01], whereas in the placebo group it did not change significantly from the baseline of 48.8 +/- 16.7%. The results indicate that enalapril induces a sustained relief of symptoms and improves exercise capacity in patients with heart failure. This subjective improvement appears to be accompanied by an increase in ejection fraction.

Adult

Assessment of cardiopulmonary alterations in endotoxic shock.

Using radionuclide first-pass technique, seven sheep were studied prior to and during endotoxic shock. In vitro labeled 99mTC red blood cells were used to measure right and left ventricular ejection fractions (RVEF and LVEF) and cardiopulmonary transit time (CPTT) prior to and at 1, 4, 30, and 60 minutes after the intravenous injection of endotoxin Escherichia coli, 3 mg/kg bodyweight. The LVEF decreased slightly from 51 to 42% but became normal four minutes later, while the RVEF remained decreased from 49 to 26% for 60 minutes. The CPTT was prolonged from 13 to 26 cardiac beats. The decrease in RVEF was well correlated with the prolongation of the CPTT.

Animals

Effect of induction of general anesthesia for cesarean section on intervillous blood flow.

Intervillous blood flow was measured by a new intravenous 133Xe method before and during induction of general anesthesia for cesarean section in 10 healthy mothers. The flow values showed a highly significant decrease (p less than 0.001) (35 per cent on an average) at the time of anesthesia compared with the control values. The impairment was observed in all the cases. The role of the maternal changes in hemodynamic parameters and acid-base balance as a background of this decrease is discussed.

Acid-Base Equilibrium

Quantitative radiocardiographic evaluation of cardiac dynamics in man at rest and during exercise.

113Inm radiocardiography in conjunction with a gamma camera and a digital computer is applied to measurements of cardiac output, stroke volume, ejection fraction, end-diastolic volume, pulmonary blood volume, pulmonary transfer time and dispersion both at rest and during muscular exercise. A modified gamma function is used in calculations of radiocardiographic curves. In twelve supine male subjects the maximal increase of cardiac output was 220%, stroke volume 30%, ejection fraction 15%, and pulmonary blood volume 30%. The present method provides a non-invasive tool for cardiovascular examinations during exercise.

Adult