Molecular and cellular biochemistry
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Mol. Cell. Biochem. · Mar 1998
Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury.
In a previous report, we have demonstrated that simultaneous inhibition of nucleoside transport and adenosine deaminase accumulates endogenous adenosine and protects the myocardium against stunning. The differential cardioprotective effects of erythro-9(2-hydroxy-3-nonyl)-adenine (EHNA), a potent inhibitor of adenosine deamination but not transport, and p-nitrobenzylthioinosine (NBMPR), a selective blocker of adenosine and inosine transport, are not known. Thirty-seven anaesthetized adult dogs were instrumented to monitor left ventricular performance using sonomicrometery. ⋯ Superior myocardial protection was observed with inhibition of nucleoside transport by NBMPR alone or in combination with inhibition of adenosine deaminase by EHNA. Selective blockade of nucleoside transport by NBMPR is more cardioprotective than inhibition of adenosine deaminase alone in attenuating myocardial stunning. It is not known why EHNA partially inhibit adenosine deaminase, in vivo.
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Mol. Cell. Biochem. · Mar 1998
Role of nucleoside transport and purine release in a rabbit model of myocardial stunning.
Previously, we have demonstrated the role of nucleoside transport and purine release in post-ischemic reperfusion injury (myocardial stunning) in several canine models of ischemia. Since rabbits are deficient of xanthine oxidase, it is not known whether selective blockade of purine release is beneficial in a rabbit model of coronary artery occlusion and reperfusion (stunning). Therefore, we determined the hemodynamic and metabolic correlates in response to myocardial stunning in the presence or absence of selective nucleoside transport blocker (p-nitrobenzylthioinosine, NBMPR) and adenosine deaminase inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine, EHNA). ⋯ AMP was higher in the LAD compared to the CFX segment. Significant accumulation of adenosine was observed in the treated group compared to the control group. It is concluded that EHNA/NBMPR induced site specific entrapment of adenosine of nucleoside transport in the rabbit heart, in vivo.
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Mol. Cell. Biochem. · Feb 1998
ReviewRespiratory muscle dysfunction in mechanically-ventilated patients.
The interaction between a patient and a ventilator is the major determinant of the amount of respiratory muscle rest achieved by the machine. We are beginning to acquire a better understanding of the mechanisms that underlie this complex interaction, but this information has yet to be integrated into the routine clinical management of ventilator-supported patients. To achieve that goal, we need better techniques of detecting and monitoring patient-ventilation asynchrony, and the development of simple algorithms that can minimize its occurrence. Finally, research is needed to determine the occurrence and importance of respiratory muscle fatigue during failed weaning attempts so as to better guide the timing and pace of the weaning process in problematic patients.
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Mol. Cell. Biochem. · Nov 1997
Ischemic preconditioning is not additive to preservation with hypothermia or crystalloid cardioplegia in the globally ischemic rat heart.
The aim of this study was to evaluate the additive protective efficiency of ischemic preconditioning when used in combination with conventional clinically relevant cardioprotective methods of hypothermia or hypothermic cardioplegia during sustained global ischemia. Isolated rat hearts were aorta-perfused with Krebs-Henseleit buffer and were divided into six groups (n = 10 each). Group I: Ischemia at 34 degrees C for 60 min; Group PC + I: preconditioned (PC) ischemia at 34 degrees C, 2 episodes of 5 min ischemia and 10 min reperfusion at 34 degrees C followed by I; Group HI: hypothermic ischemia at 10 degrees C for 60 min; Group PC + HI: preconditioned (PC) hypothermic ischemia, 2 episodes of 5 min ischemia and 10 min reperfusion at 34 degrees C followed by HI; Group CPL + HI: single dose of 'Plegisol' cardioplegia followed by HI; Group PC + CPL + HI: preconditioned hypothermic cardioplegia, followed by CPL + HI. ⋯ This protective effect of preconditioning was possibly mediated by the reduction in the breakdown of purine metabolites. Hypothermia alone or in combination with crystalloid cardioplegia prevented the irreversibility of the ischemic injury but produced contractile and vascular stunning which was not improved by ischemic preconditioning. The results of this study indicate that preconditioning when combined with hypothermia or hypothermic cardioplegia offered no significant additional protection.
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Mol. Cell. Biochem. · Sep 1997
High resolution respirometry of permeabilized skeletal muscle fibers in the diagnosis of neuromuscular disorders.
High resolution respirometry in combination with the skinned fiber technique offers the possibility to study mitochondrial function routinely in small amounts of human muscle. During a period of 2 years, we investigated mitochondrial function in skeletal muscle tissue of 13 patients (average age = 5.8 years). In all of them, an open muscle biopsy was performed for diagnosis of their neuromuscular disorder. ⋯ Also in the 3 patients with Duchenne muscular dystrophy (DMD) decreased oxidation rates (42 +/- 5%) were detected. In addition a low RCI (1.2) indicated a loose coupling of oxidative phosphorylation in the mitochondria of these patients. It is concluded that investigation of mitochondrial function in saponin skinned muscle fibers using high resolution respirometry in combination with multiple substrate titration offers a valuable tool for evaluation of mitochondrial alterations in muscle biopsies of children suffering from neuromuscular disorders.