Acute volume loading studied in cat myocardium with 31P nuclear magnetic resonance

To study the effects of acute volume loading on myocardial metabolic and mechanical function, seven cats were volume loaded via anastomosis of the abdominal aorta to the vena cava (AV shunt). Metabolic effects were evaluated with 31P nuclear magnetic resonance (NMR). Mechanical function was evaluated with heart rate X systolic blood pressure product (HR X SBP). Shunts were opened for 1-2 h during which time phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), and HR X SBP were monitored. High-energy phosphate energetics as determined by Pi/PCr and PCr/ATP ratios were correlated with HR X SBP. Opening of the AV shunts was associated with an increase (four cats) or a decrease (three cats) in HR X SBP. Pi/PCr ratios increased and PCr/ATP ratios decreased in cats with an increase in HR X SBP. In cats with a decrease in HR X SBP, Pi/PCr and PCr/ATP generally did not change significantly. In summary, acute volume loading could be associated with an increase or decrease in myocardial external work as evaluated by HR X SBP, accompanied by metabolic changes suggestive of appropriate induction of state 3 metabolism (active metabolic state: ADP + Pi----ATP) in those cats with increased mechanical work, and minimal change in bioenergetics in cats with no or minimal increase in mechanical work. These induced metabolic responses to myocardial mechanical loading can be evaluated with 31P NMR techniques and may provide insight into in vivo metabolic control mechanisms.     

Metabolic myopathy in canine muscle-type phosphofructokinase deficiency

In vivo 31phosphorus nuclear magnetic resonance spectroscopy (P-NMR) of the anterior tibialis muscle was used to investigate the metabolic myopathy of inherited muscle-type phosphofructokinase (PFK) deficiency in four (homozygous) dogs who had mild exercise intolerance, rare muscle cramps, increased serum creatine kinase activity, but no myoglobinuria. During isometric muscle work induced by indirect electrical stimulation, and subsequent recovery, changes in the ratio of phosphocreatine (PCr) and inorganic phosphates (Pi) were comparable in muscle of PFK-deficient and normal dogs and indicated a large capacity for arobic oxidative phosphorylation in canine muscle. The progressive accumulation of sugar phosphates (PME) during graded exercise clearly demonstrated the glycolytic block in PFK-deficient dogs. During a muscle contracture, induced by acute muscle stimulation, PFK-deficient muscle became completely depleted of PCr and ATP, accumulated large amounts of PME, and recovered very slowly. We conclude that PFK-deficient dogs have a metabolic myopathy that demonstrated some but not all the features recognized in the human disorder.     

Chemiluminescent measurement of increased free radical formation after ischemia/reperfusion

It has been proposed that xanthine oxidase-derived superoxide mediates reperfusion injury in the liver; however, there is a little direct evidence to support this hypothesis. In this paper we describe a model system to directly and noninvasively measure oxyradical formation and hepatic injury in isolated perfused rat liver. Using this sensitive chemiluminescent technique, we clearly demonstrate the theorized burst in oxygen radical production upon reperfusion of previously ischemic liver, without perturbing the system with chemical luminescence enhancers. This increase in chemiluminescence (CL) upon reperfusion was diminished by the free radical scavengers trolox and ascorbate, as well as N-2-mercaptoproprionyl-glycine (MPG), thereby confirming the oxyradical nature of this signal. Additionally, superoxide dismutase and the xanthine oxidase inhibitor allopurinol, but not catalase, attenuated the reperfusion effect, providing the most direct evidence so far that XOD derived superoxide anion is formed during liver reperfusion. Hepatic injury (AST release) did not appear to relate to increased CL, supporting the notion that the oxyradical flux may serve as a signal for other events leading to tissue injury. Further studies using this sensitive chemiluminescent technique should aid in delineating the detailed mechanism(s) of reperfusion injury.     

Expanding spectrum of pulmonary disease caused by nontuberculous mycobacteria

The clinical and radiographic features of 35 patients with nontuberculous mycobacterial (NTMB) pulmonary infections were reviewed. Radiographs of half the patients showed the pattern of cavitary upper-lobe infiltrates typical of reactivation tuberculosis; those of the other half had a radiographic pattern characterized by patchy, nodular infiltrates without an upper-lobe prevalence. Approximately half of the latter group showed multiple small cavities resembling those seen in bronchiectasis. These results suggest that studies in which the diagnosis of NTMB infection has been made primarily from sputum cultures may have been biased toward detecting cavitary disease. The spectrum of pulmonary disease caused by NTMB appears to be larger than previously appreciated. An enhanced awareness of alternate presentations of NTMB infections may result in earlier diagnosis.     

In vivo nuclear magnetic resonance imaging of lithium

Magnetic resonance imaging techniques have previously been applied to 1H, 23Na, 31P, and 19F nuclei. This is the first report of application of these techniques to 7Li. Lithium images of both aqueous phantoms and a rat abdomen are presented. Applications of this technique to humans are discussed.     

Autoanalgesia: opiate and non-opiate mechanisms

Autoanalgesia (behaviorally-activated antinociception) was elicited by lesion-induced hyperemotionality or the classical conditioning of fear to the environmental stimuli associated with measuring antinociception. Both hyperemotionality and antinociception exhibited parallel decline in septal-lesioned rats with daily handling and in VMH-lesioned rats following treatment with diazepam. Autoanalgesia elicited by conditioned fear was blocked by spinal cord transection but not by diazepam. Although opiate binding experiments suggested the involvement of endorphins as mediators of autoanalgesia, hypophysectomy, morphine tolerance or very high doses of opiate antagonists failed to reduce the antinociception. Electrolytic lesions of the nucleus raphe magnus, a descending serotonergic system, did cause a significant reduction in autoanalgesia. Therefore, endorphin systems may be activated by the stress involved in autoanalgesic paradigms as a parallel system, whose functional integrity is not necessary for the expression of behaviorally-induced antinociception.     

Pancreatic polypeptide from rat pancreas

Pancreatic polypeptide (PP) has been isolated from rat pancreas by gel filtration, ion exchange chromatography, and high performance liquid chromatography. The isolation was monitored with a RIA, using antibody to the carboxyl-terminal hexapeptide of bovine PP. Rat PP contains 36 amino acids and is similar in composition to PP from other mammalian sources. The single methionine residue in the peptide appears to oxidize easily to the sulfoxide, thereby giving rise to two immunoactive peaks on high performance liquid chromatography. Reduction to the native peptide can be accomplished with mercaptoethanol. The PP content of rat pancreas is about 2 mg/kg. The amino acid sequence of rat PP is Ala-Pro-Leu-Glu-Pro-Met-Tyr-Pro-Gly-Asp- Tyr-Ala-Thr-His-Glu-Gln-Arg-Ala-Gln-Tyr-Glu-Thr-Gln-Leu-Arg-Arg-Tyr-Ile- Asn-Thr-Leu-Thr-Arg-Pro-Arg-Tyr-NH2. This sequence preserves characteristics necessary for stabilization of the compact globular conformation found in avian PP.