Bassam Soussi

Impairment of Cardiac Function and Bioenergetics in Adult Transgenic Mice Overexpressing the Bovine Growth Hormone Gene1

Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.

Growth hormone improves bioenergetics and decreases catecholamines in postinfarct rat hearts.

The aims of this study were to examine, in vivo, the effects of GH treatment on myocardial energy metabolism, function, morphology, and neurohormonal status in rats during the early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague Dawley rats. Three different groups were studied: MI rats treated with saline (n 5 7), MI rats treated with GH (MI 1 GH; n 5 11; 3 mg/kgzday), and sham-operated rats (sham; n 5 8). All rats were investigated with 31 P magnetic resonance spectroscopy and echocardiography at 3 days after MI and 3 weeks later. After 3 weeks treatment with GH, the phosphocreatine/ATP ratio increased significantly, compared with the control group (MI 5 1.69 6 0.09 vs. MI 1 GH 5 2.42 6 0.05, P , 0.001; sham 5 2.34 6 0.08). Treatment with GH significantly attenuated an increase in left ventricular end systolic volume and end diastolic volume. A decrease in ejection fraction was prevented in GH-treated rats (P , 0.05 vs. MI). Myocardial and plasma noradrenaline levels were significantly lower in MI rats treated with GH. These effects were accompanied by normalization of plasma brain natriuretic peptide levels (sham 5 124.1 6 8.4; MI 5 203.9 6 34.7; MI 1 GH 5 118.3 6 8.4 ng/ml; P , 0.05 vs. MI). In conclusion, GH improves myocardial energy reserve, preserves left ventricular function, and attenuates pathologic postinfarct remodeling in the absence of induction of left ventricular hypertrophy in postinfarct rats. The marked decrease in myocardial content of noradrenaline, after GH treatment, may protect myocardium from adverse effects of catecholamines during postinfarct remodeling. (Endocrinology 141: 4592‐ 4599, 2000)

Harmful Singlet Oxygen can be helpful

Highly reactive harmful singlet oxygen O2(1delta(g)) can be helpful while relaxing to its triplet ground state O2(3sigma(g)-). The energy emitted during this relaxation from the excited energy state is discernable at 634 nm. We report here on the effect of this energy as photon illumination and as energy transfer in air on the production of reactive oxygen species (ROS) by human monocytes, measured as isoluminol-enhanced chemiluminescence. We demonstrate up to 60% decrease in the secretion of ROS after 2-min illumination of the monocytes stimulated with phorbol myristate acetate (PMA). The results provide in vitro documentation of the utility of singlet oxygen energy in modifying cellular behaviour.

Preservation of rat skeletal muscle energy metabolism by illumination

Skeletal muscle viability is crucially dependent on the tissue levels of its high energy phosphates. In this study we investigated the effect of the preservation medium Perfadex and illumination with Singlet Oxygen Energy (SOE). Singlet oxygen can be produced photochemically by energy transfer from an excited photosensitizer. The energy emitted from singlet oxygen upon relaxation to its triplet state is captured as photons at 634 nm and is here referred to as SOE. Rat hind limb rectus femoris muscles were preserved for five hours at 22 degrees C in Perfadex, saline, SOE illuminated Perfadex or SOE illuminated saline. Extracts of the muscles were analysed by 31P NMR. Data were analysed using two-way analysis of variance and are given as mean values micromol/g dry weight) +/- SEM. The ATP concentration was higher (p = 0.006) in saline groups (4.52) compared with Perfadex groups (2.82). There was no statistically significant difference in PCr between the saline groups (1.25) and Perfadex groups (0.82). However, there were higher (p = 0.003) ATP in the SOE illuminated groups (4.61) compared with the non-illuminated groups (2.73). The PCr was also higher (p < 0.0001) in the SOE illuminated groups (1.89) compared with the non-illuminated groups (0.18). In conclusion, Perfadex in this experimental model was incapable of preserving the high energy phosphates in skeletal muscle during 5 hours of ischemia. Illumination with SOE at 634 nm improved the preservation potential, in terms of a positive effect on the energy status of the muscle cell.

Energy metabolism during microsurgical transfer of human skeletal muscle assessed by high-pressure liquid chromatography and by 31P-nuclear magnetic resonance.

The effect of ischaemia and reperfusion on human skeletal muscle was studied during free vascularised muscle transfer. Muscle biopsy specimens were taken from patients having microsurgical muscle transfer, 18 cases (17 patients; 12 men, 5 women). The biopsies were taken three times: before transfer of the muscle (control), at maximum ischaemic time, and one hour after revascularisation. The biopsy specimens were analysed for purine nucleotides, by high-pressure liquid chromatography (HPLC), and by nuclear magnetic resonance (NMR) at 500 MHz. Phosphocreatine (PCr) recovered only partially (79%) and adenosine triphosphate (ATP) did not differ significantly from normal control after revascularisation and a mean ischaemic time of 114 minutes. NMR measurements showed an accumulation of glucose-6-phosphate (G-6-P) during the ischaemic period, indicating anaerobic metabolism. After three hours of ischaemia and one hour of reperfusion the PCr recovery was less than 60% ( r = 0.7). The results confirm those of previous animal studies, which set three hours normothermic ischaemia as a safe limit for tissue preservation when transferring skeletal muscle. Longer ischaemic times may cause serious postoperative healing problems and reduced muscle function.

Purine Metabolism During Microsurgical Transfer of Human Skeletal Muscle

The effect of ischaemia followed by reperfusion on energy metabolism was studied in human skeletal muscle after microsurgical free transfer. Muscle biopsy specimens from 11 patients treated by free muscle transfer for facial palsy, injury to an extremity, or scalp defect were studied. The biopsy specimens were taken during ischaemia and after one hour of reperfusion, respectively. They were analysed for ATP to uric acid and creatine phosphate by high pressure liquid chromatography. Ischaemia lasting one or two hours affected the energy metabolism of the muscle cell as evidenced by a 50% reduction in creatine phosphate; a 20% reduction in ATP and in the energy charge; a 100% increase in inosine monophosphate, and a 700% increase in hypoxanthine and xanthine. Reperfusion for one hour improved these figures somewhat, and induced the production of uric acid. Skeletal muscle can therefore tolerate ischaemia for up to two hours in the clinical situation without permanent damage to the tissues.

Brain and skull

It is well established that the anatomical correlations between brain and skull are very poor and so variable as to made precise topometry difficult and doubtful. Thus, all exact topographical measurement of brain structures requires a careful choice of reliable anatomical reference points. Therefore, any precise topographical analysis of brain structures ought to be performed according to judicious and definite cerebral reference lines based on cutaneous, cranial as well as brain landmarks (Tamraz and Comair).

Spine and cord

Magnetic Resonance Imaging is the modality of choice for studying the spine and more particularly the spinal cord, which benefits a direct evaluation without any need of administration of contrast media intrathecally. Major developments have been acquired with respect to surface coils as well as new pulse sequences, improving images and contrast resolution. Basic principles and strategies in MRI technique need to be preserved and used in spinal imaging.

Skull base and face

The neuro-ocular plane (N.O.P.) remains the most accurate cephalic orientation for the investigation and biometrical study as well as for follow-up of diseases of the eyes and the optic nerves in the axial or in the coronal planes. The same applies to the screening and exploration of diseases involving the face and skull base, due to the close parallelism of NOP to the Frankfurt-Virchow anthropological baseline. Several works demonstrated these widely adopted results.

Selective beta‐1 blockade improves left ventricular energy status, systolic and diastolic function in the rats with postinfarct heart failure

Background: The mechanisms for the beneficial effects of beta-blockade in heart failure are incompletely understood. The aim of this study was to investigate the effects of betal-blockade on cardiac bioenergetics and function in rats during early postinfarct remodeling phase. Methods: Large myocardial infarction (MI) was induced in male Sprague-Dawley rats. Two different groups were studied: rats with MI treated with metoprolol (5 mg!kg/b; n = 9) during 4 weeks and rats with MI placebo treated (n = 9). All rats were investigated with 31P MRS and transthoracic echocardiography (ECHO) 3 days after induction of MI and 4 weeks later. Volume-selective 31P MRS was performed on 2.35 T Bruker Biospec magnet. Results: Trentrnent with metoprolol increased myocardial PCr/ATP ratio indicating improved myocardial energy reserve which was associated with improvement in systolic and diastolic function.