In vivo R1-enhancement mapping of canine myocardium using ceMRI with Gd(ABE-DTTA) in an acute ischemia-reperfusion model.

PURPOSE: To demonstrate the usefulness of normalized DeltaR1 (DeltaR1(n)) mapping in myocardial tissue following the administration of the contrast agent (CA) Gd(ABE-DTTA). MATERIALS AND METHODS: Ischemia-reperfusion experiments were carried out in 11 dogs. The method exploited the relatively long tissue lifetime of Gd(ABE-DTTA), and thus no fast R1 measurement technique was needed. Myocardial perfusion was determined with colored microspheres (MP). RESULTS: With varying extent of ischemia, impaired wall motion (WM) and lower DeltaR1(n) values were detected in the ischemic sectors, as opposed to the nonischemic sectors where normal WM and higher DeltaR1(n) were observed. Based on the DeltaR1(n), data from the myocardial perfusion assay and the DeltaR1(n) maps were compared in the ischemic sectors. A correlation analysis of these two parameters demonstrated a significant correlation (R = 0.694, P < 0.005), validating the DeltaR1(n)-mapping method for the quantitation of ischemia. Similarly, pairwise correlations were found for the MP, DeltaR1(n), and wall thickening (WT) values in the same areas. Based on the correlation between DeltaR1(n) and MP, DeltaR1(n) maps calculated with a pixel-by-pixel resolution can be converted to similarly high-resolution myocardial perfusion maps. CONCLUSION: These results suggest that the extent of the severity of ischemia can be quantitatively represented by DeltaR1(n) maps obtained in the presence of our CA.

Morphological and functional differences in cardiac parameters between power and endurance athletes: a magnetic resonance imaging study.

The present study compared morphological and functional parameters of the left ventricle by magnetic resonance imaging (MRI) in competitive athletes engaged in endurance and power activities and sedentary control subjects. Twenty male subjects, 7 endurance-trained athletes (ETA) (age 23.8+/-3.5 yr), 7 strength-trained athletes (STA) (age 22.8+/-4.0 yr), and 6 sedentary controls (age 24.1+/-2.2 yr) were studied by MRI. In the ETA group body size related left ventricular mass (rel.LVM) was significantly higher than that in the STA group (71.0+/-9.2 vs 57.4+/-15.7 g/m3). The difference between their size related left ventricular wall thickness (rel.LVWT) values (9.37+/-1.0 vs 8.37+/-1.8 mm/m) was near to the level of significance (p=0.057). Relative left ventricular internal diameter (rel.LVID) was significantly higher in the ETA group compared to the STA group (42.3+/-1.0 vs 40.1+/-2.5 mm/m, p<0.05). The muscular quotient (MQ=LVWT/LVID) of the ETA group was not significantly higher compared to the strength athletes. Relative left ventricular end-diastolic volume (LVEDV) was also higher in the ETA group than in the STA group (69.5+/-6.7 vs 59.9+/-8.2 ml/m3, p<0.05) and the controls (53.6+/-3.7, p<0.001). Significantly higher relative stroke volume (SV) was measured in the ETA group compared to the STA group and the controls (41.0+/-5.7; 32.6+/-6.9; 32.0+/-3.2 ml/m3). According to the present data, the strongest impact on LV cavity size and wall thickness is caused by long-term high intensity endurance training. Intense strength training does not necessarily induce wall thickening.

The effects of the NMR shift-reagents Dy(PPP)2, Dy(TTHA) and Tm(DOTP) on developed pressure in isolated perfused rat hearts. The role of shift-reagent calcium complexes.

The 23Na NMR shift-reagent complexes (Dy(PPP)2, Dy(TTHA), and Tm(DOTP)) bind stoichiometric amounts of Ca2+. Thus, in perfused rat heart systems, a supplementation of Ca2+ is required to maintain the requisite extracellular free calcium concentration ([Ca(o)]f) and to approximate a physiological level of contractile function. The amount of reagent-bound Ca2+ in a heart perfusate that contains a shift-reagent depends on: (1) Ca2+ binding by excess ligand used during the preparation of the shift-reagent; and (2) the Ca2+ binding affinity of the shift-reagent. To address point 1), we introduced a 1H and 31P NMR spectroscopic titration method to quantify directly the concentration of the excess ligand. We also used this method to minimize the amount of excess ligand (L) and thus the amount of Ca*L complex. To address point (2), we determined the stepwise Kd (microm) values of the Ca complexes of the three shift-reagents.: Dy(PPP)2, Kd=0.09, Kd2=7.9; Dy(TTHA), Kd1=10.66, Kd2=10.12; and Tm(DOTP), K(d1)=0.502, Kd2=4.98. The Kd values of the Ca complexes of the phosphonate and triphosphate based shift-reagents, Tm(DOTP) and Dy(PPP)2, respectively, are lower than those of the polyaminocarboxylate-based Dy(TTHA), indicating stronger Ca binding affinities for the former two types of complexes. We have also shown a positive correlation between [Ca(o)]f and left ventricular developed pressure (LVDP) in perfused rat hearts. Dy(TTHA) has shown no effect on LVDP v[Ca(o)]f. The LVDP values in the presence of the phosphonate and triphosphate based shift-reagents, however, were significantly higher than expected from the [Ca(o)]f levels alone. Thus a positive inotropic effect, independent of [Ca(o)]f, is evident in the presence of Tm(DOTP) or Dy(PPP)2.

23Na NMR shift reagents enhance cardiac staircase effect in isolated perfused rat hearts.

The effects of the currently used (23)Na NMR shift reagents, dysprosium bis-triphosphate [Dy(PPP)(2)], dysprosium triethylenetriamine hexaacetate [Dy(TTHA)] and thulium 1,4,7, 10-tetraazacyclododecane-N,N',N",N"'-tetra(methylenephosphonate) [Tm(DOTP)] were studied in the rat heart cardiac staircase model. Rat hearts were perfused with low or normal extracellular free calcium ([Ca(o)](f)). At low [Ca(o)](f) (0.34 +/- 0.05 mM), hearts were perfused with Dy(PPP)(2) (group I), Dy(TTHA) (group II) or no shift reagent (group III), while at normal [Ca(o)](f) (1.25 +/- 0.15 mM), hearts were perfused with Tm(DOTP) (group IV), Dy(TTHA) (group V) or no shift reagent (group VI). Left ventricular developed pressure (LVDP) values in group I were significantly higher than in groups II and III (p < 0.01), while no significant differences were found between groups II and III. LVDP values in group IV were significantly higher than in groups V and VI (p < 0.05), while the LVDP values in groups V and VI were almost identical. Also, a positive correlation between pacing rate and intracellular sodium ([Na(i)]) was evident. The [Na(i)] values at high [Ca(o)](f) were significantly lower than at low [Ca(o)](f) at each pacing level (p <0.01), indicating a negative correlation between [Na(i)] and [Ca(o)](f). No statistical differences were found in [Na(i)] between groups I vs II and IV vs V, showing that determination of [Na(i)] is not affected by any of these shift reagents. Thus the different LVDP responses in groups I vs II and IV vs V were not mirrored in [Na(i)] changes. We hypothesize that a direct, sarcolemmal Ca-Dy(PPP)(2)-, or Ca-Tm(DOTP)-induced positive inotropic effect could be responsible for these Na(i)-independent LVDP increases in groups I and IV.

Synthesis and in vivo evaluation of new contrast agents for cardiac MRI.

Analogues 2-6 of N(3),N(6)-bis(2'-myristoyloxyethyl)-1, 8-dioxotriethylenetetraamine-N,N,N',N'-tetraacetic acid (BME-DTTA) (1), which like 1 are also based on the DTTA structure but contain shorter fatty acyl chains, were synthesized to improve the water solubility of the corresponding gadolinium complexes. The gadolinium complexes of 1 and 3-5 have very low solubility in water. Thus liposomal preparations are necessary for their in vivo MRI application. These liposomal preparations retain high in vitro relaxivities (27.1, 21.57, 20.32, 23.1 s(-1) mM(-1), respectively) and induce sustained MRI signal intensity enhancements (67.2, 38.4, 52.1, 41.7 in arbitrary units, respectively). The gadolinium complex of 2 is quite soluble in water. Its lifetime in the blood stream, however, is short. The gadolinium complex of analogue 6, N-(2-butyryloxyethyl)-N'-(2-ethyloxyethyl)-N,N'-bis[N' ',N' '-bis(carboxymethyl)acetamido]-1,2-ethanediamine (ABE-DTTA), has demonstrated its potential as a water-soluble, cardiac-specific, MRI contrast agent. It is completely soluble in water at a 25 mM concentration, allowing the preparation of an injectable dose. The in vitro relaxivity of the complex is 16.24 s(-1) mM(-1). The agent shows a specific accumulation in the heart tissue reaching its maximum within 15 min after administration, inducing a sustained MRI signal intensity enhancement of 43.6%. This enhancement lasts for at least 3 h, thus indicating a reasonably long lifetime of this contrast agent in the myocardium without deleterious effects on heart function parameters.

Lateralization of human temporal lobe epilepsy by 31P NMR spectroscopic imaging at 4.1 T.

OBJECTIVE: To compare the phosphorous metabolite ratios in the mesial temporal lobe of healthy volunteers (n = 20) with the corresponding ratios in patients with temporal lobe epilepsy (n = 30) using 31P NMR spectroscopic imaging and to lateralize the seizure focus in temporal lobe epilepsy patients using various phosphorous metabolite ratios-phosphocreatine to inorganic phosphate (PCr/Pi), PCr to adenosine triphosphate (PCr/gamma-ATP), and (gamma-ATP/Pi)--and to compare with clinical lateralization results. METHODS: All 31P NMR spectroscopic imaging studies were performed on a high-field, 4.1 T, whole-body NMR spectroscopic imaging system using a 31P/1H double-tuned volume coil. RESULTS: We found an average reduction of 15% in the PCr/Pi and gamma-ATP/Pi ratios compared with the corresponding ratios in healthy volunteers in the entire mesial temporal lobe, and more than a 30% reduction in these two ratios in the anterior region of the epileptogenic mesial temporal lobe. These ratios were also reduced significantly in the ipsilateral lobe when compared with their corresponding values in the contralateral lobe. In patients we lateralized the seizure focus, based on these 31P NMR data, and compared the results with the clinical lateralization. The lateralization based on either the PCr/Pi or the gamma-ATP/Pi ratio yielded a correspondence of 70 to 73% with the final clinical lateralization. In the subgroup of patients (n = 9) that needed intracranial EEG for the presurgical lateralization because of inconclusive results from the noninvasive methods, a 78% correspondence was found with the 31P NMR-based lateralization, whereas MRI provided a correspondence of only 33%, and scalp EEG provided a correspondence of only 56%. CONCLUSIONS: These results suggest the utility of adding the 31P NMR method to the group of noninvasive modalities used for presurgical decision making in temporal lobe epilepsy patients.

The modulation of pacing-induced changes in intracellular sodium levels by extracellular Ca2+ in isolated perfused rat hearts.

This study demonstrates the inverse relationship between extracellular free calcium ([Ca(o)]f) and intracellular sodium ([Na(i)]) in isolated perfused rat hearts and thus supports the role of [Na(i)] in the "calcium paradox". It also shows that the extent of the increase in [Na(i)] (delta[Na(i)]), and the extent of the decrease in left ventricular developed pressure (deltaLVDP) in isolated perfused rat hearts, induced by pacing, is modulated by [Ca(o)]f. At low (0.24 mM) as well as normal (1.15 mM) [Ca(o)]f, [Na(i)] increased with pacing, progressively and significantly (P<0.01 and P<0.05, respectively), reaching a maximum of 12.56 +/- 0.46 and 9.22 +/- 0.16 mM at 500 beats/min, respectively. At high [Ca(o)]f (2.2 mM), however, no pacing-induced increase in [Na(i)] was observed. Simultaneously, within the pacing range of 250-500 beats/min, the interval-force relationship was negative for all [Ca(o)]f. With decreasing [Ca(o)]f, a gradually increasing delta[Na(i)] was induced. We hypothesise that a [Ca(o)]f-dependent Na-Ca exchanger activity modulates Na+ uptake, and thus baseline [Na(i)]. During incremental pacing, the increase in pacing rate induces a [Ca(o)]f-dependent delta[Na(i)], which may interact further with the sarcolemmal Na-Ca exchanger activity. As a result, both baseline [Na(i)] and the pacing-induced, [Ca(o)]f-dependent delta[Na(i)] modulate the net Ca2+ uptake, and thus SR Ca, in a manner that results in a modulated left ventricular force development.

In vivo characterization of Gd(BME-DTTA), a myocardial MRI contrast agent: tissue distribution of its MRI intensity enhancement, and its effect on heart function.

We have determined an LD50 of 0.56 +/- 0.05 mmol/kg for liposomal Gd(BME-DTTA) in mice and also shown that liposomal Gd(BME-DTTA) has no deleterious effects on heart rate, blood pressure, left ventricular force and AV conductance in ferret hearts in vivo at the magnetic resonance imaging (MRI)-effective dose of 0.05 mmol/kg body weight. In MRI images, a 1H signal intensity enhancement is observed in the following organs in decreasing order of the effect: heart approximately spleen > kidney > liver. This enhancement is stable for over 3 h in all organs. The results of 1H MRI and electron micrographs indicate that the lipophilic fatty acyl groups in the ligand BME structure and the particle sizes of liposomal Gd(BME-DTTA) are two important factors for tissue specificity of liposomal Gd(BME-DTTA) in the intensity enhancement. In vitro relaxivity of a liposomal Gd(BME-DTTA) sample, stored at 4 degrees C, remained stable for over 4 months of observation, but a significant decrease in relaxivity was observed in a sample stored at room temperature, most likely reflecting some deterioration in liposome chemistry.

In vivo MRI visualization of acute myocardial ischemia and reperfusion in ferrets by the persistent action of the contrast agent Gd (BME-DTTA).

BACKGROUND: Contrast agent-enhanced magnetic resonance imaging (MRI) has the potential to visualize myocardial ischemia. To date, however, no agent has been found that has a sustained effect that allows MRI detection for the entire duration of ischemia and reperfusion and thus is useful in conjunction with stress test MRI. In this article, we introduce the gadolinium complex of N3,N6-bis(2'-myrisotyloxyethyl)-1,8-dioxo-triethylene- tetraamine-N,N,N1,N1-tetraacetic acid [Gd(BME-DTTA)], an agent potentially useful for such a purpose. METHODS AND RESULTS: Four protocols were carried out. ECG-triggered, partially T1-weighted, spin-echo MRI was used in protocols A through C. In protocol A, in nonischemic ferrets, 50 mumol/kg Gd(BME-DTTA) induced a 70 +/- 5% intensity enhancement lasting 3 hours. In protocol B, the left anterior descending coronary artery was occluded, and a 99mTc-sestamibi-induced autoradiographic contrast verified (r = .87, P < .01) a Gd(BME-DTTA)-induced (n = 5) or Gd(DTPA)-induced (n = 4) MRI contrast. In the Gd(BME-DTTA) group a sustained contrast and in the Gd(DTPA) group a short-lived contrast were observed. In protocol C (n = 11), during ischemia, a 31 +/- 3.3% (P < .02) contrast was evident between the ischemic and nonischemic myocardial regions. Upon reperfusion, a contrast of 19 +/- 3% (P < .05) and 13 +/- 4.5% (P < .05) persisted for 5 and 15 minutes, respectively. Beyond 15 minutes, the contrast continued to diminish gradually. Nonradioactive microspheres verified (r = .87, P < .05) ischemia and reperfusion in this model. In protocol D (n = 4), blood delta R1 data showed that the blood pool retained Gd(BME-DTTA) for the entire time frame of the experiment at high enough concentration to provide an appropriate wash-in effect during the initial contrast enhancement and during reperfusion. CONCLUSIONS: This study demonstrates that Gd(BME-DTTA) induces a sustained MRI contrast between regions of normal versus ischemic myocardium, showing the potential of this agent for the diagnosis of ischemic heart disease in conjunction with stress tests.

Cardiac staircase and NMR-determined intracellular sodium in beating rat hearts.

Isolated, perfused rat hearts (30 degrees C, n = 13) were paced from 218 +/- 4 beats/min to 433 +/- 4 beats/min while systolic and diastolic pressure were recorded and intracellular Na+ concentration ([Na+]i) was monitored by 23Na nuclear magnetic resonance (NMR) spectroscopy. [Na+]i increased progressively with increasing stimulation frequency. In seven hearts (group I) an initial, progressive increase in systolic pressure was observed followed by a decrease in pressure with further increase in frequency. From the onset, a progressive decrease in systolic pressure was observed in group II (n = 6) in response to increased frequency. In group I an [Na+]i increase of up to 134 +/- 7% of control (P < 0.001) was observed, whereas in group II the gain in [Na+]i with increasing pacing rate was attenuated, reaching a maximum of 120 +/- 3% of control (P < 0.02). The differential pressure response between group I and group II hearts may reflect an enhanced sensitivity of rat hearts to the shortening of the restitution period of the sarcoplasmic reticulum, outweighing the positive inotropic effect induced by an increased [Na+]i. Only in rat hearts whose [Na+]i-induced increase in pressure outweights the restitution deficit would a complete positive inotropic effect be anticipated.

[Complications from physiological and rate responsive pacemaker implantations]. / Fiziológiás és frekvenciaválaszos pacemaker implantációk szövödményei.

One hundred eighteen surgical complications of 209 patients underwent 249 physiological and rate responsive pacemaker implantations are discussed. In 27.9% of total complications represented the dislodgement of atrial leads occurred particularly in the early period of the observation time which decreased significantly later in the second period of the survey. This high complication rate of bifocal pacemakers was found due to a high incidence of the generator preerosion beside the dislodgment of the atrial electrodes. Complication rate could be reduced by the improvement of surgical technics, and with the implantations of new types of leads and smaller generators, however the number of complications remained higher compared to the pacemaker systems with one lead. The implantation procedure of ventricular rate responsive pacemakers is simple, and significant improvement in working capacity could be observed by the restoration of the chronotropic capacity during exercise. Physiological and atrial rate responsive pacemakers provide many advantages in the hemodynamic state even at rest which exceed all disadvantage of the expected complications, which might occur.

Attenuation of the cardiac effects of cocaine by dizocilpine.

Cocaine abuse causes autonomic and cardiovascular effects that may be life threatening. Attenuation of cocaine-induced seizures has been produced by the noncompetitive antagonist of the N-methyl-D-aspartate receptor channel complex, dizocilpine. The purpose of the present study was, first, to determine effects of dizocilpine on the incidence of pacing-induced ventricular arrhythmias and, second, to evaluate the effects of dizocilpine on cocaine-induced depression of sympathetic efferent activity to the heart. Adult dogs were anesthetized and instrumented for blood pressure and an electrocardiogram. After vagotomy and thoracotomy, electrodes and strain gauges were sutured onto the right atrium and ventricle. A left thoracic sympathetic efferent nerve was isolated and stimulated for analysis of the innervation pattern. Arrhythmias were induced with programmed electrical stimulation of the heart before and during left cardiac sympathetic efferent nerve stimulation. The control incidence of induced arrhythmias was only 2%, which increased to 21% during left sympathetic stimulation. Cocaine (2 mg/kg iv) significantly increased these to 11 and 42%, respectively. Dizocilpine (0.5 mg/kg iv) reduced the incidence of induced ventricular arrhythmias to 2% with cocaine (P < 0.05) and to 19% with cocaine and left sympathetic stimulation (P < 0.01). One or two sympathetic efferent cardiac nerves were stimulated to evaluate innervation patterns. These nerves were severed and prepared for recording multifiber efferent neurograms. Nerve traffic was analyzed by counting positive spikes for 15 s. Control activities were normalized at 100%. Within 6 min, cocaine (2 mg/kg iv) reduced the sympathetic efferent activity to 83 +/- 4% of control (n = 14 nerves).(ABSTRACT TRUNCATED AT 250 WORDS)

A selective inversion recovery method for the improvement of 23Na NMR spectral resolution in isolated perfused rat hearts.

Shift-reagent-aided 23Na NMR spectroscopy allows differentiation of the intracellular (Na(i)) and extracellular sodium (Na(o)) signals. The goal of the present study has been to develop a 23Na NMR spectroscopic method to minimize the intensity of the shift-reagent-shifted Na(o) signal and thus increase Na(i) resolution. This is achieved by a selective inversion recovery (SIR) method which enhances the resolution between the Na(i) and Na(o) peaks in shift-reagent-aided 23Na NMR spectroscopy. The application of SIR with Dy(TTHA), Tm(DOTP), or with low concentrations of Dy(PPP)2 results in both good spectral resolution and physiologically acceptable contractile function in the isolated, perfused rat heart model.

[Multistep prognosis in acute myocardial infarction using the PRIMA method (Pattern Recognition by Independent Multicategory Analysis)]. / Friss myocardialis infarctusban szenvedö betegek többlépcsös prognosztizálása PRIMA módszerrel.

Authors analysed the possibilities of in-hospital prognosis made of patients with acute myocardial infarction by using information obtained during admission. Eighty eight patients with transmural myocardial infarction (not older than 70 years and the prehospital delay shorter than 24 hours) were analysed. On the basis of the hospital events they were divided into 3 classes: (a) uneventful (16), (b) complicated (55) and (c) lethal (17). The initial 26 data available in the first hour were analysed by PRIMA pattern recognition method adapted to ROSY--80B microcomputer. 3 days later the 3 class distances of the initial PRIMA analysis together with the 21 new data of the remaining 79 patients were analysed again. The third analysis (66 patients) was made between the 4th and 6th days after a successful mobilization. The last analysis (44 patients) was performed just before the discharge of the patients, who were able to carry out the low-level and submaximal ergometric tests. The average effectiveness of the method gradually improved during hospitalization from 80% to 91%. The recognition ability of each class respectively was 57% for (a) uneventful, 82% for (b) complicated, and 95% for (c) lethal initially, and it has improved finally: 82% for uneventful, 94% for complicated cases.

[Hemorheologic parameters during the 6 months following myocardial infarct]. / Haemorheologiai paraméterek alakulása a myocardialis infarctust követö fél évben.

It is verified that rheological factors play a role in the pathomechanism of ischemic heart disease (IHD) and acute myocardial infarction (AMI). The changes of the rheological parameters (whole blood and plasma viscosity, fibrinogen level, hematocrit) of 17 patients (mean age: 59 years) were studied in the first six months after AMI. The measurements were carried out after the admission, before the discharge from the hospital and at the control examinations after one and six months. A slight increase of hematocrit and whole blood viscosity was found during the six months follow up period which was statistically significant concerning the hematocrit (p less than 0.05). As the part of the control examination exercise stress test was performed. Among the rheological parameters hematocrit and whole blood viscosity of those who showed myocardial ischemia during the test were significantly worse (p less than 0.05) comparing to the non ischemic group. These results underline the role of hemorheological parameters as risk factors in these diseases.

[Hemorrheologic parameters in myocardial infarct during the hospitalization phase]. / Haemorheologiai paraméterek alakulása a myocardialis infarctus hospitális szakában.

The changes of the rheological parameters (whole blood and plasma viscosity, fibrinogen level, red cell count, hematocrit) of 22 AMI patients (mean age: 59 years) were studied during the hospital phase of acute myocardial infarction. The measurements were carried out after the admission, after the beginning of the mobilization and before the discharge from the hospital. Looking at the results of all of the patients they could not find any statistically significant change, although in the first phase improving hemorheological parameters were measured and this way the discharge values were similar to the admission ones. In men significantly worse starting values were found than in women and the deterioration of these parameters in their group was also expressed. The deliberate use of diuretics and the administration of high dose nitroglycerin may be one part of the less worsening rheological parameters in comparison with the literature.

Epicardial ECG signals following global myocardial ischaemia.

Experiments were performed on 10 dog hearts undergone 15 to 90-minute normothermic arrests and 60-minute reperfusion in a special heart-lung model. The purpose of the experiments was to characterize the global ischaemic effects recorded on epicardial electrograms. The duration of QRS complexes and of RR intervals, the integral of ST segment shifts (sigma ST), the number of points showed ST segment displacements (NoST) and the ST segment isopotential map obtained by computer control were evaluated. Only a minor ST segment deviation, a small increase in duration of QRS complexes and of RR intervals with bradycardia and a tendency to electrical stability were found after global ischaemic influences. These observations indicate that pathological electrical manifestations occurring after a global ischaemia are less serious than those occurring after a focal ischaemia.