The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo.

Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NER(plaque) (determined on inversion-recovery fast spin echo images) remained high (∼2) until 48 h after injection of CB2-R targeted micelles, whereas NER(plaque) decreased after 36 h in the control group. The inter-scan variability and relation between NER(plaque) and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NER(plaque) correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NER(plaque) can be best evaluated at 36-48 h post-injection. Because NER(plaque) was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NER(plaque) values is recommended.

Does physical training increase insulin sensitivity in chronic heart failure patients?

To determine the effect of training on insulin sensitivity (IS) and how this relates to peak V(.)O(2) (peak oxygen uptake) in CHF (chronic heart failure), 77 CHF patients (New York Heart Association class, II/III; men/women, 59/18; age, 60+/-9 years; body mass index, 26.7+/-3.9 kg/m(2); left ventricular ejection fraction, 26.9+/-8.1%; expressed as means+/-S.D.) participated in the study. Patients were randomly assigned to a training or control group (TrG or CG respectively). Sixty-one patients completed the study. Patients participated in training (combined strength and endurance exercises) four times per week, two times supervised and two times at home. Before and after intervention, anthropometry, IS (euglycaemic hyperinsulinaemic clamp) and peak V(.)O(2) (incremental cycle ergometry) were assessed. Intervention did not affect IS significantly, even though IS increased by 20% in TrG and 11% in CG (not significant). Peak V(.)O(2) increased as a result of training (6% increase in TrG; 2% decrease in CG; P <0.05). In both groups (TrG and CG), the change in IS correlated positively with the change in peak V(.)O(2) ( r =0.30, P <0.05). Training resulted in an increase in peak V(.)O(2), but not in IS. Whether physical training actually increases IS in CHF patients remains unclear.

Response to exercise of patients with idiopathic hyper-CK-emia.

Patients with an idiopathic increase in serum creatine kinase (CK) levels (hyper-CK-emia) have a benign prognosis, but symptoms may be disabling in daily life. Previous studies have suggested that physical exercise increases the severity of complaints in these patients. We studied whether maximal and submaximal bouts of exercise on a cycle ergometer are harmful for patients with idiopathic hyper-CK-emia. Such dynamic exercise did not lead to larger increases in serum CK activity or more complaints in 11 patients with idiopathic hyper-CK-emia, compared with 11 age-matched healthy controls. Our data suggest that exercise does not result in more extensive muscle damage in patients with idiopathic hyper-CK-emia than in healthy subjects.

Brain death-induced alterations in myocardial workload and high-energy phosphates: a phosphorus 31 magnetic resonance spectroscopy study in the cat.

BACKGROUND: Hemodynamic deterioration resulting from brain death-induced myocardial left ventricular dysfunction may preclude heart donation. A reduced myocardial high-energy phosphate content, assessed by biopsy specimens, has been suggested to be responsible for this phenomenon. By applying phosphorus 31 magnetic resonance spectroscopy, in vivo myocardial high-energy phosphate metabolism can be studied continuously. METHODS: Twelve cats were sedated, intubated, ventilated, and studied for 240 minutes. Heart rate, arterial blood pressure, and arterial blood gases were monitored. Central venous pressure was kept constant. Myocardial work was expressed as rate-pressure product (RPP=heart rate x systolic arterial blood pressure). After sternotomy a radio frequency surface coil was positioned onto the left ventricle. A parietal trephine hole was drilled, and an inflatable balloon was inserted. The animal was placed into a 4.7 T horizontal 40 cm bore magnet interfaced to a spectrometer. Brain death (n=6) was induced by rapid inflation of the balloon; the six other cats served as a sham-operated control group. 31P spectra were obtained in 30 seconds, with ventilation and arterial blood pressure curve triggering. The phosphocreatine/to/adenosine triphosphate ratio, as an estimator of energy metabolism, was calculated. RESULTS: Brain death was established within 30 seconds after inflation of the balloon. Changes in RPP were characterized by a triphasic profile with a maximum increase from 19.3+/-1.4 x 10(3) to 87.5+/-8.1 x 10(3) mm Hg x min(-1) (p < .0001 vs control group) at 2 minutes after inflation of the balloon. Subsequently, RPP decreased and was normalized at 15 minutes after inflation. The third phase was characterized by hemodynamic deterioration, which became significant at 180 minutes and resulted in mean arterial pressure of 71+/-12 mm Hg (p < .05 vs control group) at the end of the experimental period. RPP deteriorated to 14.6+/-2.0 x 10(3) mm Hg x min(-1) (p < .05 vs control group) at 240 minutes. Because the heart rate remained constant during the third phase, the decrease in RPP was caused by a decrease in systolic arterial blood pressure. The initial phosphocreatine/adenosine triphosphate ratio of 1.65+/-0.16 varied to 1.52+/-0.06 at 2 minutes, and to 1.73 +/-0.17 (all values NS vs control group and vs initial ratio) at 240 minutes. CONCLUSIONS: The energy status of the heart is not affected by brain death. Therefore brain death-induced hemodynamic deterioration is not caused by impaired myocardial high-energy phosphate metabolism.