Pre-transplant predictors of one yr weight gain after kidney transplantation.

Clinically useful predictors of weight gain could be used to reduce the epidemic of post-kidney transplant obesity and resulting co-morbidities. The purpose of this study was to identify predictors of weight gain at 12 months following kidney transplant in a cohort of 96 recipients. Demographic, clinical, and environmental data were obtained at transplant and 12 months. Descriptive, correlational, and Bayesian network analysis were used to identify predictors. For the 52 (55.9%) recipients who gained weight, the average amount gained was 9.18 ± 6.59 kg. From the 15 baseline factors that met inclusion criteria, Bayesian network modeling identified four baseline predictors for weight gain: younger age, higher carbohydrate consumption, higher trunk fat percentage, and higher perception of mental health quality of life. Three are modifiable through either pre- or immediate post-transplant clinical intervention programs.

Local opiate receptors in the sinoatrial node moderate vagal bradycardia.

Met-enkephalin-arg-phe (MEAP) interrupts vagal bradycardia when infused into the systemic circulation. This study was designed to locate the opiate receptors functionally responsible for this inhibition. Previous observations suggested that the receptors were most likely located in either intracardiac parasympathetic ganglia or the pre-junctional nerve terminals innervating the sinoatrial node. In this study 10 dogs were instrumented with a microdialysis probe inserted into the sinoatrial node. The functional position of the probe was tested by briefly introducing norepinephrine into the probe producing an increase in heart rate of more than 30 beats/min. Vagal stimulations were conducted at 0.5, 1.2 and 4 Hz during vehicle infusion (saline ascorbate). Cardiovascular responses during vagal stimulation were recorded on-line. MEAP was infused directly into the sinoatrial node via the microdialysis probe. The evaluation of vagal bradycardia was repeated during the nodal application of MEAP, diprenorphine (opiate antagonist), and diprenorphine co-infused with MEAP. MEAP introduced into the sinoatrial node via the microdialysis probe reduced vagal bradycardia by more than half. Simultaneous local nodal blockade of these receptors with the opiate antagonist, diprenorphine, eliminated the effect of MEAP demonstrating the participation by opiate receptors. Systemic infusions of MEAP produced a reduction in vagal bradycardia nearly identical to that observed during nodal administration. When local nodal opiate receptors were blocked with diprenorphine, the systemic effect of MEAP was eliminated. These data lead us to suggest that the opiate receptors responsible for the inhibition of vagal bradycardia are located within the sinoatrial node with few, if any, participating extra-nodal or ganglionic receptors.

Transient arterial occlusion raises enkephalin in the canine sinoatrial node and improves vagal bradycardia.

The C-terminal proenkephalin sequence, Methionine-enkephalin-arginine-phenylalanine (MEAP), is abundant in the myocardium and when delivered into the sinoatrial (SA) node by microdialysis, the peptide had significant vagolytic activity. The study that follows was conducted to determine if an increase in endogenous nodal MEAP could be demonstrated during reduced nodal blood flow and was endogenous MEAP similarly vagolytic. Microdialysis probes were placed in the canine SA node and perfused at 5 microl per min. The SA node artery was occluded and released four times at 10-min intervals. The intermittent occlusions were followed by one or two prolonged occlusions (30 min). Vagally mediated bradycardia was compared before, during, and after occlusion of the artery. An increase in recovered MEAP (70-220 fmol) was recorded during each of the initial 10-min occlusions. MEAP returned to baseline during each subsequent 10-min reperfusion. There was a sustained increase in MEAP (110-150 fmol) during longer occlusions. Contrary to the hypothesis, the increased MEAP during arterial occlusion was coincident with improved vagal bradycardia. The improvement in vagally mediated bradycardia was highly reproducible and was observed again during a second 30-min occlusion. The improved vagal function was reversed or reduced, respectively, when naltrindole or glibenclamide was included in the microdialysis inflow during arterial occlusion. Although these observations suggested that opioid receptors and ATP-sensitive K+ channels might have been involved, only a single dose of each agent was practical. Therefore, the specificity of these two responses remains to be confirmed. In summary, the recovery of endogenous opioids from the sinoatrial node increased during reduced arterial perfusion of the node. Contrary to expectations, the increase in recovered endogenous opioids was accompanied byimproved rather than impaired vagal bradycardia.

Delta opioid receptors inhibit vagal bradycardia in the sinoatrial node.

BACKGROUND: Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP. METHODS AND RESULTS: Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 microL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/microL and a half-maximal response near 0.1 nmoles/microL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/microL with the half-maximal response near 0.1 nmoles/microL, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the delta opiate receptor antagonist, naltrindole. Selected mu (endomorphin, super DALDA) and kappa (dynorphin, U50488) receptor agonists and mu (CTAP) and kappa (norBNI) receptor antagonists were completely ineffective in this system. CONCLUSIONS: These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.

Autonomic control of heart rate in dogs treated chronically with morphine.

The vagotonic effect of chronic morphine on the parasympathetic control of the heart was examined in dogs treated with morphine for 2 wk. Because normal vagal function is critical to myocardial stability, the study was conducted to evaluate for potential impairments following chronic vagal stimulation. The hypothesis that persistent vagal outflow would result in a loss of vagal reserve and reduced vagal control of heart rate was tested. Heart rate and the high-frequency variation in heart rate (power spectral analysis) declined shortly after initiation of subcutaneous morphine infusion. A progressive bradycardia correlated well with the rising plasma morphine. The resting bradycardia (57 beats/min) was maintained through day 2 and was accompanied by a significant parallel increase in vagal effect and a decline in the intrinsic heart rate (160 vs. 182 beats/min). A compensatory increase in the ambient sympathetic control of heart rate was evident on day 2 and was supported by an increase in circulating catecholamines. The lowered intrinsic heart rate and elevated sympathetic activity were maintained through day 10 despite a return of the resting heart rate and plasma catecholamines to pretreatment values. These observations suggested that chronic morphine alters either the intrinsic function of the sinoatrial node or reduces the postvagal tachycardia normally attributed to nonadrenergic, noncholinergic agents. Both acute and chronic morphine depressed the rate of development of bradycardia during direct vagal nerve stimulation without altering the rate of recovery afterward. This last observation suggests that acute morphine reduces the rate of acetylcholine release. Results provide insight into the mechanisms that maintain vagal responsiveness. The results are also relevant clinically because opiates are increasingly prescribed for chronic pain and opiate abuse is currently in resurgence.