Impact of changes in heart rate and stroke volume on the cross sectional flow velocity distribution of diastolic mitral blood flow

The effect of changes in stroke volume on the cross sectional velocity distribution in the mitral orifice during passive mitral inflow was studied in six patients with total atrioventricular block, atrial fibrillation and VVI pacemakers during periods with different heart rates. The time velocity integrals recorded both in the left ventricular outflow tract and at the mitral orifice decreased significantly as the heart rate was increased from 60 to 80 and from 80 to 100 beats per minute. Instantaneous cross sectional flow velocity profiles were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital ultrasound maps. Each patient had a characteristic cross sectional flow velocity profile in the mitral orifice recorded at the level of the leaflet tips in a four chamber view. The velocity profiles varied between the patients. With increase in heart rate only minimal changes in the flow profiles from individual patients were seen. The maximum velocity through the mitral orifice overestimated the cross sectional mean velocity at the same time by a factor of 1.4–1.9. The maximum time velocity integral overestimated the cross sectional mean by a factor of 1.4–1.8. The observed cross sectional skew varied between patients but did not change significantly with increasing heart rate and decrease in stroke volume.     

Experimental application of thermosensitive paramagnetic liposomes for monitoring magnetic resonance imaging guided thermal ablation.

The use of a liposomal paramagnetic agent with a T(1)-relaxivity that increases markedly at temperatures above the phase transition temperature (T(m)) of the liposomal membrane was evaluated during magnetic resonance imaging (MRI) guided hyperthermia ablation. A neodymium-yttrium aluminum garnet (Nd-YAG) laser unit and a radiofrequency ablation system were used for tissue ablation in eight rabbit livers in vivo. One ablation was made in each animal prior to administration of the liposomal agent. Liposomes with a T(m) of 57 degrees C containing gadodiamide (GdDTPA-BMA) were injected iv, and two additional ablations were performed. T(1)-weighted scans were performed in heated tissue, after tissue temperature had normalized, and 15-20 min after normalization of tissue temperature. Increase in signal intensity (DeltaSI) for ablations prior to injection of the agent was 13.0% (SD = 5.7) for the laser group and 9.1% (SD = 7.9) for the radiofrequency group. Signal intensity after administration of the agent unrelated to heating was not statistically significant (DeltaSI = 1.4%, P = 0.35). For ablations made after injection of the agent, a significant increase was found in the laser (DeltaSI = 34.5%, SD = 11.9) and radiofrequency group (DeltaSI = 21.6%, SD = 22.7). The persistent signal enhancement found in areas exposed to a temperature above the threshold temperature above T(m) allows thermal monitoring of MRI guided thermal ablation.     

Phase I trial of parenteral 6-thioguanine given on 5 consecutive days

For almost 30 years, 6-thioguanine (6-TG) has been administered p.o. for treatment of various human cancers, especially leukemias, even though the systemic availability of the drug given p.o. is known to be low and highly variable. Parenterally administered 6-TG has been studied in detail in humans only on a single-day intermittent schedule, although multiple-day intermittent schedules are known to produce maximal cytotoxic effects in several animal species. To develop a multiple-day regimen for parenteral 6-TG therapy, we carried out a dose-seeking and pharmacokinetic study of the drug given i.v. daily for 5 days in patients with various refractory advanced solid tumors. Dose-limiting myelosuppression without other significant toxicity occurred at 55-65 mg/m2 daily for 5 days. After i.v. administration at 65 mg/m2, the mean peak plasma concentration of 6-TG ranged from 6-10 microM. These concentrations are 8-300 times greater than peak plasma concentrations of 6-TG in plasma reported to occur after p.o. administration at 100 mg/m2. We suggest that the antitumor activity of 6-TG be reassessed against human cancers in regimens of i.v. administration on multiple-day intermittent schedules.     

Modelling seasonal and weather dependency of cardiac arrests using the covariate order method

A data set concerning cardiac arrests treated by the Emergency Medical Service in Trondheim during a nine year period is analysed. The relationship between the occurrence of cardiac arrest and covariates related to weather and season is examined. The covariate order method is used in the analysis of the data. It is explained how this method can be extended to recurrent event data, and the practical usefulness and flexibility of the method is demonstrated in these analyses. In the analyses a significant relationship between outdoor air temperature, or factors closely related to outdoor air temperature, and the occurrence of cardiac arrest is found. The incidence of cardiac arrest decreases with increasing temperature. Further a significant effect of snowfall is also found, with increased intensity of cardiac arrest on days with snowfall. A more borderline significant effect of precipitation is also identified.     

Comparing a novel automatic 3D method for LGE-CMR quantification of scar size with established methods

Current methods for the estimation of infarct size by late-enhanced cardiac magnetic imaging are based upon 2D analysis that first determines the size of the infarction in each slice, and thereafter adds the infarct sizes from each slice to generate a volume. We present a novel, automatic 3D method that estimates infarct size by a simultaneous analysis of all pixels from all slices. In a population of 54 patients with ischemic scars, the infarct size estimated by the automatic 3D method was compared with four established 2D methods. The new 3D method defined scar as the sum of all pixels with signal intensity (SI) ≥35 % of max SI from the complete myocardium, border zone: SI 35–50 % of max SI and core as SI ≥50 % of max SI. The 3D method yielded smaller infarct size (?2.8 ± 2.3 %) and core size (?3.0 ± 1.7 %) than the 2D method most similar to ours. There was no difference in the size of the border zone (0.2 ± 1.4 %). The 3D method demonstrated stronger correlations between scar size and left ventricular (LV) remodelling parameters (LV ejection fraction: r = ?0.71, p < 0.0005, LV end-diastolic index: r = 0.54, p < 0.0005, and LV end-systolic index: r = 0.59, p < 0.0005) compared with conventional 2D methods. Infarct size estimation by our novel 3D automatic method is without the need for manual demarcation of the scar; it is less time-consuming and has a stronger correlation with remodelling parameters compared with existing methods.     

Glucose-Insulin-Potassium Reduces Infarct Size When Administered During Reperfusion

Coronary reperfusion improves ventricular function and survival after infarction, but the metabolic conditions at this time may not be optimal to protect the heart. The objective of this study was to evaluate if metabolic support with glucose-insulin-potassium (GIK) administered at the time of coronary reperfusion could elicit the same cardioprotection as GIK infusion during the entire ischemia/reperfusion period. Three groups of anesthetized, open-chest rats were subjected to 30 minutes of regional ischemia and 180 minutes of reperfusion. Groups 1 (controls) and 2 (GIK_IR) received saline or GIK, respectively, throughout the whole experimental period, whereas a third group (GIK_R) received GIK from the onset of reperfusion only. Infarct size was significantly reduced in the GIK-treated groups, compared with controls (GIK_IR 44 ± 5% and GIK_R 45 ± 5% vs. control 66 ± 4%; P < 0.05). Postischemic recovery of cardiac function improved when GIK was only administered during the reperfusion phase. Furthermore, infusion of GIK resulted in reduced plasma concentrations of free fatty acids and increased plasma glucose (both P < 0.05) compared with controls. This study demonstrates that glucose-insulin-potassium administration at the onset of the postischemic reperfusion period is as cardioprotective as administration of GIK during the entire ischemia/reperfusion period.     

RAMP2 and RAMP3 mRNA levels are increased in failing rat cardiomyocytes and associated with increased responsiveness to adrenomedullin

Adrenomedullin (AM) is a potent vasorelaxing peptide with natriuretic and diuretic actions. Recent data indicate that AM may function as an endogenous regulator of cardiac function. We investigated to what extent AM, the AM receptor subtypes, and AM receptor-associated proteins were regulated in cardiomyocytes and non-cardiomyocytes of rats with congestive heart failure (CHF), and whether such regulation was paralleled by corresponding alterations of functional responses to AM. Cardiomyocytes and non-cardiomyocytes were isolated from myocardial tissue of rats 7 days after induction of myocardial infarction or sham operation. AM immunoreactivity was found in cardiomyocytes, endothelial cells, and fibroblasts. Robust increase of AM mRNA levels was observed both in the cardiomyocytes and in the non-cardiomyocytes of CHF rats compared to that of sham-operated rats (2.7-fold and 3.7-fold, respectively, P <0.05). Fairly high mRNA levels and immunoreactivity against the AM receptor chaperone receptor activity-modifying protein-2 (RAMP2) were also detected in the cardiomyocytes and non-cardiomyocytes. However, induction of RAMP2 mRNA expression was restricted to cardiomyocytes (1.8-fold increase in cardiomyocytes from CHF rats vs. sham rats; P <0.05). In contrast, very low levels of RAMP3 mRNA were observed. RAMP3 mRNA levels, however, were elevated in both cardiomyocytes and non-cardiomyocytes from CHF rats (6.5-fold and 2.4-fold increase vs. sham rats, respectively; P <0.05). Parallel increases of specific AM receptor binding sites and of AM-stimulated adenylyl cyclase activities were observed in failing cardiomyocytes compared to cardiomyocytes from sham rats (fivefold and sixfold increase, respectively; P <0.05). Thus, this study demonstrates that AM mRNA levels, AM receptor binding sites, and AM-stimulated adenylyl cyclase activities are increased in cardiomyocytes from failing rat hearts. Furthermore, our data suggest that induction of RAMP2 and RAMP3 contributes to the increased responsiveness to AM in failing cardiomyocytes.     

Varus Femoral Osteotomy Improves Sphericity of the Femoral Head in Older Children With Severe Form of Legg-Calvé-Perthes Disease

Background  

In the Norwegian prospective study on Legg-Calvé-Perthes disease (LCPD), we found varus femoral osteotomy gave better femoral head sphericity at a mean of 5 years postoperative than physiotherapy in children older than 6.0 years at diagnosis with femoral head necrosis of more than 50%. That study did not include separate analyses for hips with 100% necrosis and those with a percentage of necrosis between 50% and 100%.