Clinical utility of intravascular ultrasound in the assessment of coronary allograft vasculopathy: a review.

Coronary artery vasculopathy (CAV) is one of the major factors that limit the long-term survival of heart transplant recipients. It is difficult to diagnose CAV, especially in the early stages. Traditional coronary angiography has been used for the diagnosis of CAV, but this method has limitations. Current literature suggests that intravascular ultrasound (IVUS) is a safe imaging technique that is beneficial for the early diagnosis of CAV; in comparison, IVUS with virtual histology (IVUS-VH) is an even more promising diagnostic utility. Despite its advantages, IVUS is currently not routinely utilized as the primary diagnostic modality for CAV in heart transplant recipients. In this review, we evaluate and summarize the clinical utility of IVUS in the early diagnosis of CAV, including its utility for assessing vessel remodeling, plaque composition, and prognostic value; morphometric analysis; and guiding therapy. After reviewing the relevant published literature, it is our recommendation that the use of IVUS be considered in all post-transplant CAV screening.

Neurological and brain MRS findings in patients with Gaucher disease type 1.

Gaucher disease type 1 (GD1) is an autosomal recessive lysosomal storage disorder, characterised by accumulation of glycosphingolipids in visceral organs. Although considered non-neuronopathic neurological involvement has been reported in single cases. The aim of our study was to investigate central and peripheral nervous system involvement in patients with GD1. We investigated nine unrelated patients with GD1 by three-dimensional cerebral 1H-magnetic resonance spectroscopic imaging and clinical and neurophysiological tests. We found an increased choline level on MRS in four patients. One of these patients had mixed axonal neuropathy and subclinical involvement of the central somatosensory tract as well as monoclonal gammopathy. One patient with normal cerebral choline levels had evidence of bilateral carpal tunnel syndrome upon neurophysiological exam. The N370S mutation was found in 11 out of 18 alleles. Three patients were compound heterozygous for the L444P mutation. There was no correlation between increased cerebral choline levels and type of mutations. MRS findings suggest that in patients with classical non-neuronopathic GD1, the brain is involved at a subclinical level in some patients.

Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors.

The mechanism of extracellular ATP-triggered vagal depressor reflex was further studied in a closed-chest canine model. Adenosine and ATP were administered individually in equimolar doses (0.01-1.0 mumol/kg) into the right coronary artery (RCA) and left circumflex coronary artery (LCA). When administered into the RCA, adenosine and ATP exerted an identical and relatively small negative chronotropic effect on sinus node automaticity; the time to peak negative chronotropic effect was >/=7 s. When administered into the LCA, adenosine had no effect on sinus node automaticity, whereas ATP markedly suppressed sinus node automaticity. This effect of ATP 1) reached its peak in <2 s after its administration, 2) was short lasting, and 3) was completely abolished by either intravenous administration of the muscarinic cholinergic blocker atropine (0.2 mg/kg) or intra-LCA administration of 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), a potent P2X(2/3) purinergic receptor (P2X(2/3)R) antagonist, but not by diinosine pentaphosphate (Ip(5)I), a potent inhibitor of P2X(1)R and P2X(3)R. Repetitive administrations of ATP were not associated with reduced effects, indicative of receptor desensitization, thereby excluding the involvement of the rapidly desensitized P2X(1)R in the action of ATP. It was concluded that ATP triggers a cardio-cardiac vagal depressor reflex by activating P2X(2/3)R located on vagal sensory nerve terminals localized in the left ventricle. Because these terminals mediate vasovagal syncope, these data could suggest a mechanistic role of extracellular ATP in this syndrome and, in addition, give further support to the hypothesis that endogenous ATP released from ischemic myocytes is a mediator of atropine-sensitive bradyarrhythmias associated with left ventricular myocardial infarction.

Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase.

The F(o)F(1)-ATPase, a multisubunit protein complex of the inner mitochondrial membrane, produces most of the ATP in mammalian cells. Mitochondrial diseases as a result of a dysfunction of ATPase can be caused by mutations in mitochondrial DNA-encoded ATPase subunit a or rarely by an ATPase defect of nuclear origin. Here we present a detailed functional and immunochemical analysis of a new case of selective and generalized ATPase deficiency found in an Austrian patient. The defect manifested with developmental delay, muscle hypotonia, failure to thrive, ptosis, and varying lactic acidemia (up to 12 mmol/L) beginning from the neonatal period. A low-degree dilated cardiomyopathy of the left ventricle developed between the age of 1 and 2 y. A >90% decrease in oligomycin-sensitive ATPase activity and an 86% decrease in the content of the ATPase complex was found in muscle mitochondria. It was associated with a significant decrease of ADP-stimulated respiration of succinate (1.5-fold) and respiratory control with ADP (1.7-fold) in permeabilized muscle fibers, and with a slight decrease of the respiratory chain complex I and compensatory increase in the content of complexes III and IV. The same ATPase deficiency without an increase in respiratory chain complexes was found in fibroblasts, suggesting a generalized defect with tissue-specific manifestation. Absence of any mutations in mitochondrial ATP6 and ATP8 genes indicates a nuclear origin of the defect.