Back table outflow graft anastomosis technique for HeartWare HVAD implantation.

The management of concomitant aortic and aortic valve disease with left ventricular assist device (LVAD) implantation for patients with severe cardiomyopathy is challenging, and has not been established given the complexity of LVAD surgery with concomitant aortic interventions. A 45-year-old patient presented to our institution with end-stage heart failure symptoms and non-ischemic cardiomyopathy. The patient was found to have a bicuspid aortic valve, severe native aortic regurgitation, a significant ascending aortic aneurysm, and severely depressed left ventricular (LV) function requiring two inotropes. He underwent a successful hemiarch repair of the ascending aortic aneurysm using a back table outflow graft anastomosis technique, and subsequent placement of a HeartWare Ventricular Assist Device (HVAD) with concomitant aortic valve closure with a modified Park's stitch. The patient did well postoperatively and is currently listed for heart transplantation.

Sternal neoangiogenesis following internal mammary artery devascularization: an experimental model.

AIM: The use of bilateral internal thoracic arteries (BIMA) for coronary artery revascularization is associated with better long-term survival and longer freedom from reoperation. Concerns of deep sternal wound infections and mediastinitis have constantly emerged with the utilization of BIMA grafts on a routine basis, especially in diabetic patients. METHODS: We performed a quantitative evaluation of sternal bone healing and angiogenesis after left (LIMA) or bilateral internal mammary artery (BIMA) ligation two and four weeks after sternotomy in normal and diabetic Sprague-Dawley rats. RESULTS: The BIMA group showed a significant increase in neoangiogenesis two weeks after surgery compared to LIMA and control groups (control: 38.3 ± 5.1 vessels/mm², LIMA: 31.4 ± 3.6 vessels/mm², BIMA: 81.6 ± 7.7 vessels/mm²; P=0.047 and P=0.04, respectively). Four weeks after the procedure, bilateral devascularization was associated with lower microvessel formation when compared to LIMA or control groups (control: 50.4 ± 5.2 vessels/mm², LIMA: 64.6 ± 4.9 vessels/mm²; BIMA: 31.5 ± 4.4 vessels/mm²; P=0.006 and P=0.02, respectively). Diabetic animals showed similar results with lower four weeks microvessel formation. However, there were no significant differences when animals with induced diabetes were compared to the normal euglycemic groups for each procedure performed. CONCLUSION: BIMA ligation promotes an early increase in neoangiogenesis. Progressive sternal consolidation is associated with a significant lower level of capillaries and arterioles in the BIMA group four weeks after ligation. Diabetes did not influence the extent of neoangiogenesis between groups with similar procedures. More important clinical determinants could explain the increase incidence of sternal infection in this specific population.

RXR acts as a coregulator in the regulation of genes of the hypothalamo-pituitary axis by thyroid hormone receptors.

Thyroid hormone receptors (TRs) often modulate transcriptional activity of target genes by heterodimerization with the 9-cis retinoic acid receptor (RXR). On positive thyroid response elements (TREs), RXR favors binding of the TR-RXR complex to DNA and stimulates transcription. RXR action on negative TREs is unclear. Furthermore, the single half-site configuration of many negative TREs does not favor the binding of a classic TR-RXR heterodimer. In a comparative study using CV-1 cells (relatively RXR- and TR-deficient) and JEG-3 cells (relatively TR-deficient), we demonstrate the importance of RXR in the negative transcriptional regulation of genes of the hypothalamo-pituitary axis by tri-iodothyronine. While RXR has variable effects on ligand-independent activation produced by TRs, it was required for efficient ligand-dependent repression of the TRH gene for TRalpha1 and TRbeta1 and of the TSH genes by all TRs. Using different RXR constructs we also observed the importance of the C-terminus of RXR but not of the N-terminus nor the DNA-binding domain, in the potentiation of negative regulation. We thus suggest that, with regard to negative regulation of the TRH and TSH genes by thyroid hormones, RXR behaves more like a cofactor than a classic heterodimerization partner.

Cellular colocalization of dopamine D1 mRNA and D2 receptor in rat brain using a D2 dopamine receptor specific polyclonal antibody.

1. The main objective of this work was to investigate the extent of cellular colocalization of dopamine D1 and D2 receptors in the rat brain. A double labeling technique, that combined immunocytochemical labeling of the D2 receptor using polyclonal antibodies raised against the third intracellular loop of the short isoform of the human D2 receptor in combination with in situ hybridization detecting D1 mRNA expression, was designed to accomplish this goal. 2. The specificity of the antisera obtained was confirmed by immunoprecipitation assay, Western blot analysis, and immunocytochemistry on D2R transfected cells and murine brain tissue. Western blot using the D2 receptor antibody revealed a specific broad band centered at 67 kDa in transfected cells and a major protein of 88 kDa corresponding to D2R expressed in the caudate-putamen, to a lesser extent in the cortex, and not at all detected in the hypothalamic region. 3. The content of neurons double-labeled for D1/D2 receptors was observed at in differing intensities in the dorsal endopiroform nucleus, the intercalated nucleus of amygdala, the anterior part of the cortical nucleus amygdala, the nucleus of the lateral olfactory tract, the piriform cortex, the parabrachial nucleus, the supraoptic nucleus and the parabigeminal nucleus. All other regions of the brain revealed neurons expressing either D1 or D2 dopamine receptors but not both at that same time. 4. These results clearly demonstrated that specific neurons expressed both receptors D1 and D2, and that this colocalization was restricted to particular regions of the rat brain.

Regulation by chronic treatment with cabergoline of dopamine D1 and D2 receptor levels and their expression in the striatum of Parkinsonian-monkeys.

1. Chronic treatment for one month with the long-acting dopamine D2-like agonist cabergoline (0.25 mg/kg s.c. every 48 hours), had despite partial tolerance, sustained antiparkinsonian activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian monkeys (Macaca fascicularis). 2. Cabergoline treatment decreased by half striatal D2 receptor binding density measured by [3H]spiperone autoradiography versus untreated MPTP monkeys. No change in D2 mRNA measured by in situ hybridization and D2 receptor immunostaining was observed. 3. No change in either D1 receptor binding density or D1 receptor mRNA levels was observed in cabergoline-treated MPTP-monkeys compared to untreated MPTP-monkeys, suggesting receptor subfamily specificity of cabergoline. 4. The present results suggest that the cabergoline-induced behavioral partial tolerance is accompanied by a decrease in D2 receptor binding but not due to alterations in the steady state of D2 mRNA levels.

The neurogenic origin of hypertension in SHR may be mediated by angiotensin II through a receptor different from AT1 and AT2.

In spontaneously hypertensive rats (SHR) 15-18 weeks old, the intracerebroventricular (icv) administration of peptide angiotensin II (Ang) antagonists results in a short (30-60 min) decrease (15-25 mmHg) of blood pressure (BP). Both EXP-3174, a known metabolite of Losartan and AT1 selective, and PD-123177, a receptor AT2 specific compound, do not affect SHR BP following icv administration. The receptor AT1 selective non-peptide Ang antagonists, Losartan and L-158809, induce long-lived (days) significant BP reductions (< or = 40 mmHg) in SHR, but only 18 h after icv injection. The slow development of BP reduction and its persistence might be due to the formation of an active metabolite, different from EXP-3174, a Losartan metabolite. In older SHR (25-28 weeks), the hypotensive effect of Losartan and L-158809 is not significant. These results suggest that in the CNS of the young SHR, an active Renin-Ang-System is implicated in the establishment of the hypertensive state, and that the receptor for this function is different from AT1 and AT2, since it has a selectivity profile different from AT1 and AT2 receptor types.

The effect of citrate loading on exercise performance, acid-base balance and metabolism.

Nine subjects (VO2max 65 +/- 2 ml.kg-1.min-1, mean +/- SEM) were studied on two occasions following ingestion of 500 ml solution containing either sodium citrate (C, 0.300 g.kg-1 body mass) or a sodium chloride placebo (P, 0.045 g.kg-1 body mass). Exercise began 60 min later and consisted of cycle ergometer exercise performed continuously for 20 min each at power outputs corresponding to 33% and 66% VO2max, followed by exercise to exhaustion at 95% VO2max. Pre-exercise arterialized-venous [H+] was lower in C (36.2 +/- 0.5 nmol.l-1; pH 7.44) than P (39.4 +/- 0.4 nmol.l-1; pH 7.40); the plasma [H+] remained lower and [HCO3-] remained higher in C than P throughout exercise and recovery. Exercise time to exhaustion at 95% VO2max was similar in C (310 +/- 69 s) and P (313 +/- 74 s). Cardiorespiratory variables (ventilation, VO2, VCO2, heart rate) measured during exercise were similar in the two conditions. The plasma [citrate] was higher in C at rest (C, 195 +/- 19 mumol.l-1; P, 81 +/- 7 mumol.l-1) and throughout exercise and recovery. The plasma [lactate] and [free fatty acid] were not affected by citrate loading but the plasma [glycerol] was lower during exercise in C than P. In conclusion, sodium citrate ingestion had an alkalinizing effect in the plasma but did not improve endurance time during exercise at 95% VO2max. Furthermore, citrate loading may have prevented the stimulation of lipolysis normally observed with exercise and prevented the stimulation of glycolysis in muscle normally observed in bicarbonate-induced alkalosis.