The Ambiguous Cue Task: Measurement reliability of an experimental paradigm for the assessment of interpretation bias and associations with mental health.

Interpretation biases in the processing of ambiguous affective information are assumed to play an important role in the onset and maintenance of emotional disorders. Reports of low reliability for experimental measures of cognitive biases have called into question previous findings on the association of these measures with markers of mental health and demonstrated the need to systematically evaluate measurement reliability for measures of cognitive biases. We evaluated reliability and correlations with self-report measures of mental health for interpretation bias scores derived from the Ambiguous Cue Task (ACT), an experimental paradigm for the assessment of approach-avoidance behavior towards ambiguous affective stimuli. For a non-clinical sample, the measurement of an interpretation bias with the ACT showed high internal consistency (rSB = .91 - .96, N = 354) and acceptable 2-week test-retest correlations (rPearson = .61 - .65, n = 109). Correlations between the ACT interpretation bias scores and mental health-related self-report measures of personality and well-being were generally small (r ≤ |.11|) and statistically not significant when correcting for multiple comparisons. These findings suggest that in non-clinical populations, individual differences in the interpretation of ambiguous affective information as assessed with the ACT do not show a clear association with self-report markers of mental health. However, in allowing for a highly reliable measurement of interpretation bias, the ACT provides a valuable tool for studies considering potentially small effect sizes in non-clinical populations by studying bigger samples as well as for work on clinical populations, for which potentially greater effects can be expected.

Heightened response to positive facial cues as a potential marker of resilience following childhood adversity.

Background: Childhood maltreatment profoundly influences social and emotional development, increasing psychiatric risk. Alterations in the implicit processing of threat-related cues following early abuse and neglect represent a marker of mental health vulnerability. Less is known about how early adversity influences the perception of positive social cues, despite their central role in establishing and maintaining social interactions and their association with better mental health outcomes.Methods: The sample consisted of 42 children and adolescents with substantiated childhood maltreatment experiences and 32 peers (mean age 13.3), matched on age, pubertal status, gender, socioeconomic status, ethnicity, and cognitive ability. A computerised experimental task assessed the perceived emotional intensity of positive (happy) and negative (fearful) facial expressions. Mental health symptoms were measured via self- and parental reports, and perceived social support was self-reported.Results: The experience of abuse and neglect was associated with heightened perceived intensity of positive facial cues. Cross-sectional post-hoc moderation and mediation analyses, employing a model-building approach, revealed that in maltreatment-exposed participants: (i) their increased response to positive facial cues was associated with lower symptoms; (ii) the presence of social support accounted for their heightened perceived intensity of positive facial cues; (iii) the presence of social support putatively contributed to lower symptoms by increasing the perceived intensity of positive facial cues. No group differences in perceived intensity of negative expressions were observed.Conclusions: These findings provide fresh insight into how positive faces are processed following maltreatment experience in childhood. Maltreatment experience was found to be associated with heightened perceived intensity of happy faces, which in turn was associated with better mental health and greater levels of social support. This suggests that heightened saliency of positive emotions acts protectively in children with maltreatment experience.

The impact of childhood maltreatment on perceiving positive social cues, especially explicit emotional intensity appraisal, is less understood compared to the extensive focus on its role in processing threat-related cues and psychiatric risk.In this study, we found that maltreatment experience was associated with heightened perceived intensity of happy faces, which in turn was associated with better mental health and greater levels of social support.These findings suggest that heightened saliency of positive emotions may act protectively in children with maltreatment experience.

Atypical Interpersonal Problem-Solving and Resting-state Functional Connectivity in Adolescents with Maltreatment Experience.

BACKGROUND: Childhood maltreatment is associated with altered neurocognitive functioning, which is thought to reflect, in part, adaptation to early adverse environmental experiences. However, we continue to lack a precise mechanistic understanding linking atypical neurocognitive processing with social functioning and psychiatric outcomes following early adversity. OBJECTIVE: The present work investigated interpersonal problem-solving, resting-state functional connectivity (rsFC), and mental health symptoms in adolescents with documented maltreatment experience and explored whether altered neural function contributes in part to poorer social functioning. METHODS: Forty adolescents (aged 12-17) with documented experiences of abuse or neglect and a carefully matched group of 42 non-maltreated peers participated in this study that measured task-based interpersonal problem-solving skills and rsFC. RESULTS: Adolescents with maltreatment experience showed poorer interpersonal problem-solving performance, which partly accounted for their elevated mental health symptoms. Resting-state seed-based analyses revealed that adolescents with maltreatment experience showed a significant increase in rsFC between medial Default Mode Network (DMN) hubs, the medial prefrontal cortex (mPFC), with a posterior cluster, including the posterior cingulate cortex (PCC), precuneus (PCu), retrosplenial cortex (RSC), and lingual gyrus (LG). Moderation analyses revealed that maltreatment-related increased DMN rsFC partly accounted for poorer performance in interpersonal problem-solving. CONCLUSION: Poorer interpersonal problem-solving, partly accounted for by atypical coupling between DMN medial hubs, was associated with maltreatment exposure. Interventions tailored to enhance interpersonal problem-solving represents a promising avenue to promote resilience and reduce the likelihood of mental health disorder following maltreatment experience.

Altered reward and effort processing in children with maltreatment experience: a potential indicator of mental health vulnerability.

In this longitudinal study of children and adolescents with a documented history of maltreatment, we investigated the impact of maltreatment on behavioral and neural indices of effort-based decision making for reward and examined their associations with future internalizing symptoms. Thirty-seven children with a documented history of maltreatment (MT group) and a carefully matched group of 33 non-maltreated children (NMT group) aged 10-16, completed an effort-based decision-making task during functional magnetic resonance imaging (fMRI). Internalizing symptoms were assessed at baseline and again 18 months later. Computational models were implemented to extract individual estimates of reward and effort sensitivity, and neural signals during decision-making about different levels of reward and effort were analyzed. These were used to predict internalizing symptoms at follow-up. We identified lower effort-related activation in the anterior cingulate cortex (ACC), a prespecified region-of-interest, in the MT relative to the NMT group. No group differences were observed in the striatum, or in behavioral indices of reward and effort processing. Lower effort-related ACC activation significantly predicted elevated internalizing symptoms at follow-up in the MT group. These findings suggest that disrupted effort-related activation may index latent vulnerability to mental illness in children who have experienced maltreatment.

Brain Signal Variability Differentially Affects Cognitive Flexibility and Cognitive Stability.

Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory, albeit this holds only for tasks requiring cognitive flexibility. However, cognitive stability, i.e., the ability to maintain a task goal in the face of irrelevant distractors, should suffer under high levels of brain signal variability. To directly test this prediction, we studied both behavioral and brain signal variability during cognitive flexibility (i.e., task switching) and cognitive stability (i.e., distractor inhibition) in a sample of healthy human subjects and developed an efficient and easy-to-implement analysis approach to assess BOLD-signal variability in event-related fMRI task paradigms. Results show a general positive effect of neural variability on task performance as assessed by accuracy measures. However, higher levels of BOLD-signal variability in the left inferior frontal junction area result in reduced error rate costs during task switching and thus facilitate cognitive flexibility. In contrast, variability in the same area has a detrimental effect on cognitive stability, as shown in a negative effect of variability on response time costs during distractor inhibition. This pattern was mirrored at the behavioral level, with higher behavioral variability predicting better task switching but worse distractor inhibition performance. Our data extend previous results on brain signal variability by showing a differential effect of brain signal variability that depends on task context, in line with predictions from computational theories. SIGNIFICANCE STATEMENT: Recent neuroscientific research showed that the human brain signal is intrinsically variable and suggested that this variability improves performance. Computational models of prefrontal neural networks predict differential effects of variability for different behavioral situations requiring either cognitive flexibility or stability. However, this hypothesis has so far not been put to an empirical test. In this study, we assessed cognitive flexibility and cognitive stability, and, besides a generally positive effect of neural variability on accuracy measures, we show that neural variability in a prefrontal brain area at the inferior frontal junction is differentially associated with performance: higher levels of variability are beneficial for the effectiveness of task switching (cognitive flexibility) but detrimental for the efficiency of distractor inhibition (cognitive stability).

Stochastic Dynamics Underlying Cognitive Stability and Flexibility.

Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task switching (flexibility) and distractor inhibition (stability) in a paradigm specifically designed to probe both functions. We develop a physiologically plausible, explicit model of neural networks that maintain the currently active task rule in working memory and implement the decision process. We simplify the four-choice decision network to a nonlinear drift-diffusion process that we canonically derive from a generic winner-take-all network model. By fitting our model to the behavioral data of individual subjects, we can reproduce their full behavior in terms of decisions and reaction time distributions in baseline as well as distractor inhibition and switch conditions. Furthermore, we predict the individual hemodynamic response timecourse of the rule-representing network and localize it to a frontoparietal network including the inferior frontal junction area and the intraparietal sulcus, using functional magnetic resonance imaging. This refines the understanding of task-switch-related frontoparietal brain activity as reflecting attractor-like working memory representations of task rules. Finally, we estimate the subject-specific stability of the rule-representing attractor states in terms of the minimal action associated with a transition between different rule states in the phase-space of the fitted models. This stability measure correlates with switching-specific thalamocorticostriatal activation, i.e., with a system associated with flexible working memory updating and dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences.

Touchscreen-paradigm for mice reveals cross-species evidence for an antagonistic relationship of cognitive flexibility and stability.

The abilities to either flexibly adjust behavior according to changing demands (cognitive flexibility) or to maintain it in the face of potential distractors (cognitive stability) are critical for adaptive behavior in many situations. Recently, a novel human paradigm has found individual differences of cognitive flexibility and stability to be related to common prefrontal networks. The aims of the present study were, first, to translate this paradigm from humans to mice and, second, to test conceptual predictions of a computational model of prefrontal working memory mechanisms, the Dual State Theory, which assumes an antagonistic relation between cognitive flexibility and stability. Mice were trained in a touchscreen-paradigm to discriminate visual cues. The task involved "ongoing" and cued "switch" trials. In addition distractor cues were interspersed to test the ability to resist distraction, and an ambiguous condition assessed the spontaneous switching between two possible responses without explicit cues. While response times did not differ substantially between conditions, error rates (ER) increased from the "ongoing" baseline condition to the most complex condition, where subjects were required to switch between two responses in the presence of a distracting cue. Importantly, subjects switching more often spontaneously were found to be more distractible by task irrelevant cues, but also more flexible in situations, where switching was required. These results support a dichotomy of cognitive flexibility and stability as predicted by the Dual State Theory. Furthermore, they replicate critical aspects of the human paradigm, which indicates the translational potential of the testing procedure and supports the use of touchscreen procedures in preclinical animal research.

Prefrontal cortical mechanisms underlying individual differences in cognitive flexibility and stability.

The pFC is critical for cognitive flexibility (i.e., our ability to flexibly adjust behavior to changing environmental demands), but also for cognitive stability (i.e., our ability to follow behavioral plans in the face of distraction). Behavioral research suggests that individuals differ in their cognitive flexibility and stability, and neurocomputational theories of working memory relate this variability to the concept of attractor stability in recurrently connected neural networks. We introduce a novel task paradigm to simultaneously assess flexible switching between task rules (cognitive flexibility) and task performance in the presence of irrelevant distractors (cognitive stability) and to furthermore assess the individual "spontaneous switching rate" in response to ambiguous stimuli to quantify the individual dispositional cognitive flexibility in a theoretically motivated way (i.e., as a proxy for attractor stability). Using fMRI in healthy human participants, a common network consisting of parietal and frontal areas was found for task switching and distractor inhibition. More flexible persons showed reduced activation and reduced functional coupling in frontal areas, including the inferior frontal junction, during task switching. Most importantly, the individual spontaneous switching rate antagonistically affected the functional coupling between inferior frontal junction and the superior frontal gyrus during task switching and distractor inhibition, respectively, indicating that individual differences in cognitive flexibility and stability are indeed related to a common prefrontal neural mechanism. We suggest that the concept of attractor stability of prefrontal working memory networks is a meaningful model for individual differences in cognitive stability versus flexibility.

Similarity between brain activity at encoding and retrieval predicts successful realization of delayed intentions.

Remembering delayed intentions can be highly demanding. Accuracy in laboratory paradigms assessing prospective memory (PM) is typically well below ceiling, and failure to remember intended behaviors after a delay is a common occurrence in everyday life. However, relatively little is known of the potential differences in brain activity that distinguish successful versus unsuccessful PM. In this fMRI study, participants repeatedly encoded, stored, and then had the opportunity to retrieve intended behaviors while engaged in a distracting ongoing task. This yielded a success rate of approximately two thirds. Overall levels of brain activity distinguished successful versus unsuccessful trials at all three stages (encoding, storage, and retrieval), suggesting multiple neural determinants of PM success. In addition, the voxelwise similarity between patterns of brain activity at encoding and retrieval was greater for successful than unsuccessful trials. This was true even in posterior cingulate, which showed opposite patterns of signal change between encoding and retrieval. Thus, successful realization of delayed intentions may be associated with reinstatement of encoding context at the time of retrieval.

Nutritional implications in vascular endothelial cell metabolism.

Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular function. Numerous physiologic and pathophysiologic stimuli are often mediated by nutrients that can contribute to the overall functions of endothelial cells in the regulation of vascular tone, coagulation, cellular growth, immune and inflammatory responses. Therefore, nutrient-mediated functional changes of the endothelium and the underlying tissues may be significantly involved in disease processes such as atherosclerosis. There is evidence that individual nutrients or nutrient derivatives may either provoke or prevent metabolic and physiologic perturbations of the vascular endothelium. Diets high in fat and/or calories are considered a risk factor for the development of atherosclerosis. Our research has shown that certain diet-derived lipids and their derivatives can disrupt normal endothelial integrity, thus reducing the ability of the endothelium to act as a selectively permeable barrier to blood components. Mechanisms underlying fatty acid-mediated endothelial cell dysfunction may be related to changes in fatty acid composition as well as to an increase in cellular oxidative stress. Selective lipid accumulation and fatty acid changes in endothelial cells can modulate membrane fluidity, proteoglycan metabolism and signal transduction mechanisms. Most importantly, dietary fats rich in certain unsaturated fatty acids, may be atherogenic by enhancing the formation of reactive oxygen intermediates. A subsequent imbalance in cellular oxidative stress/antioxidant status can activate oxidative stress-responsive transcription factors, which in turn may promote cytokine production, expression of adhesion molecules on the surface of endothelial cells, and thus intensify an inflammatory response in atherosclerosis. Our data also suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, can protect endothelial cells by interfering with lipid/cytokine-mediated endothelial cell dysfunction. These findings contribute to the understanding of the interactive role of dietary fats with inflammatory components, as well as with nutrients that exhibit antiatherogenic properties, in the development of atherosclerosis.

Hypoxemia and elevated tachykinins in rat monocrotaline pneumotoxicity.

This study was performed to test whether monocrotaline (MCT)-induced early airway dysfunction and gas exchange abnormalities result in arterial hypoxemia. Thirty young male Sprague-Dawley rats were divided into four groups: control, MCT1, MCT2, and MCT3. Each of the control animals was injected (subcutaneously) with saline; each of the MCT rats was injected with MCT (60 mg/kg, subcutaneously). The rats were tested 1 (MCT1), 2 (MCT2), or 3 (MCT3) weeks after MCT injection. Two days before each animal was tested, it was anesthetized with sodium pentobarbital, and its carotid artery was chronically cannulated. Blood was sampled from the arterial catheter of the conscious rat, and blood gases and pH were measured. Pulmonary arterial pressure (Ppa) was determined in the anesthetized, open chest animal. Heart weight was measured and a weight ratio obtained of right ventricle (RV) to left ventricle plus septum (LV+S). The amount of lung substance P and airway neutral endopeptidase (NEP) activity were also measured. MCT significantly decreased arterial oxygen tension (Pao2) and increased the RV/(LV+S) weight ratio 2 and 3 weeks after administration, whereas it did not significantly increase Ppa until 3 weeks after injection. MCT significantly increased lung substance P levels and decreased airway NEP activities 1-3 weeks after administration. These data suggest that tachykinins cause hypoxemia and RV hypertrophy; then hypoxia may augment the development of pulmonary hypertension.

delta Opioid extends hypothermic preservation time of the lung.

To test the hypothesis that a delta opioid, DADLE ([D-Ala2, D-Leu5]-enkephalin), could protect tissue from ischemic damage during hypothermic lung preservation, we studied three groups of rats. In group 1 (n = 8), lung function was studied immediately after harvesting. In group 2 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution and preserved for 24 hours. In group 3 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution plus DADLE (1 mg/kg) and preserved for 24 hours. Lung function was studied by using a living rat perfusion model. Venous blood from the host rat perfused the pulmonary artery of the isolated lung. Blood from the isolated lung was returned to the carotid artery of the host rat with a roller pump. Severe pulmonary edema, hemorrhage, and occlusive pulmonary artery resistance occurred in group 2 within 30 minutes of perfusion. Perfusion studies were carried out for more than 60 minutes in groups 1 and 3. Pulmonary blood flow was lower in group 2 than in either group 1 or group 3. Pulmonary vascular resistance was much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway pressure and airway resistance were much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway resistance was also higher in group 3 than in group 1 after 20 minutes of perfusion (p < 0.05). Oxygen tensions from the pulmonary vein of the isolated lung in group 2 were lower than those in groups 1 and 3 (p < 0.05). Alveolar-arterial oxygen difference was much higher in group 2 than in groups 1 and 3 (p < 0.05). Lung tissue wet/dry weight ratio after perfusion was much higher in group 2 than in groups 1 and 3. The results clearly show, for the first time, that DADLE can effectively enhance hypothermic lung preservation in rats.

Cardiovascular responses to cigarette smoke exposure in restrained conscious rats.

The effect of exposure to cigarette smoke on cardiovascular function was examined in conscious, restrained Sprague-Dawley rats. Rats were exposed to 3, 6 and 9 puffs of either air or cigarette smoke during the "break in" period and to 10 puffs on the day of the experiment (day 4). HR, cardiac output and mean arterial pressure were recorded continuously throughout the experimental period. Rats exposed previously to cigarette smoke generated from either low-nicotine (0.16 mg/cig.) or high-nicotine (2.45 mg/cig.) cigarettes showed a dose-related decrease in HR in response to restraint stress. In addition, exposure to cigarette smoke produced a further decrease in HR and cardiac output and an increase in mean arterial pressure. This effect by cigarette smoke was dose-dependent (dependent on the cigarette nicotine content) and was antagonized by intra-arterial pretreatment with the nicotinic antagonists mecamylamine and hexamethonium and also with the ganglionic blocker chlorisondamine. Intra-arterial pretreatment with atropine methyl bromide blocked the bradycardia in response to both restraint stress and cigarette smoke. Furthermore, pretreatment with an arginine vasopressin antagonist, d(CH2)5Tyr(Me)arginine vasopressin, significantly attenuated the increase in mean arterial pressure and total peripheral resistance and the decrease in HR and cardiac output due to cigarette smoke. On the other hand, pretreatment with the opioid receptor antagonist naloxone had no effect on cardiovascular parameters in response parameters in response to cigarette smoke. These results implicate arginine vasopressin, in addition to the activation of both sympathetic and parasympathetic systems, in mediating cardiovascular responses to cigarette smoke.

Influence of nutrients and cytokines on endothelial cell metabolism.

The vascular endothelium plays an active role in physiological processes such as hemostasis, regulation of vessel tone and vascular permeability. Cell injury, or any event which disrupts endothelial integrity and thus endothelial permeability properties, may be involved in the early events leading to atherosclerotic lesion formation. Because of its constant exposure to blood components, including prooxidants, diet-derived fats and their derivatives, the endothelium is susceptible to oxidative stress and to injury mediated by blood lipid components. It is likely that these events potentiate the overall inflammatory response to injury by increasing cytokine release in proximity to the endothelium, which then could further disrupt endothelial barrier function. Even though mechanisms associated with lipid/cytokine-mediated endothelial cell dysfunction are unclear, our data suggest that they may be both oxidative and non-oxidative in nature. We suggest that dietary fats, rich in certain unsaturated fatty acids are atherogenic by enhancing the formation of reactive oxygen intermediates. These intermediates can activate oxidative stress-responsive transcription factors, such as NF-kappa B, which in turn may promote cytokine production, adhesion molecule expression and ultimately endothelial barrier dysfunction. The resulting disturbances in endothelial integrity possibly allow increased penetration of cholesterol-rich lipoprotein remnants into the arterial wall, a critical event in the etiology of atherosclerosis. Data suggest that certain nutrients, which have antioxidant and/or membrane stabilizing properties, protect endothelial cells by interfering with the above proposed mechanisms of endothelial cell dysfunction.

Nitroglycerin (exogenous nitric oxide) substitutes for endothelium-derived nitric oxide in potentiating vasorelaxations and cyclic AMP elevations induced by calcitonin gene-related peptide (CGRP) in rat aorta.

Rat calcitonin gene-related peptide (rCGRP) causes endothelium-dependent vasorelaxations via a dual signal transduction mechanism involving elevations of both cyclic AMP and cyclic GMP levels in rat aorta. These responses are all dependent on de novo synthesis of nitric oxide (NO) in endothelial cells and appear to involve a mechanistic link between cyclic GMP and cyclic AMP responses in smooth muscle cells. The present study determined whether NO from an exogenous source (i.e. added nitroglycerin) could substitute for endogenous NO in rCGRP-induced responses in endothelium-denuded aorta. Nitroglycerin (1 microM) significantly elevated cyclic GMP levels by 20-fold and 3.3-fold and cyclic AMP levels by 26% and 22% at 1 and 2 min, respectively. By itself, rCGRP (100 nM) did not significantly elevate cyclic AMP levels. In combination, however, nitroglycerin and rCGRP caused more-than-additive cyclic AMP elevations (41% above basal at 1 and 2 min). Nitroglycerin also potentiated rCGRP-induced vasorelaxations in endothelium-denuded rings, thus uncovering a direct (endothelium-independent) relaxant effect of rCGRP in rat aorta. The data indicate that exogenous NO can substitute for endogenous NO in rCGRP-induced relaxant and cyclic AMP responses in aorta. This nitroglycerin-induced potentiation of CGRP effects likely involves inhibition of cyclic-GMP-inhibited-phosphodiesterase in smooth muscle cells, thus allowing cyclic AMP to accumulate and mediate the direct vasodilator effects of rCGRP.

N omega-nitro-L-arginine inhibits vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta induced by calcitonin gene-related peptide (CGRP).

Our previous studies showed that vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta induced by rat calcitonin gene-related peptide (rCGRP) are inhibited by hemoglobin and methylene blue, blockers of the endothelium-derived relaxant factor (EDRF, now recognized as nitric oxide [NO]). In the present study, we used N omega-nitro-L-arginine (L-NNA), a selective inhibitor of nitric oxide synthase, to test whether rCGRP-induced relaxations and cyclic AMP and cyclic GMP responses in rat aorta require de novo synthesis of NO. L-NNA (30 microM, 15 min) inhibited by 84, 76 and 73% the relaxations induced by rCGRP at 1, 10 and 100 nM, respectively. D-NNA (30 microM), which does not inhibit nitric oxide synthase, did not block rCGRP-induced vasorelaxations. Addition of L-arginine (3 mM) 5 min before L-NNA completely prevented the L-NNA-inhibition of CGRP-induced relaxations. L-NNA (30 microM, 15 min) also inhibited the elevations of both cyclic AMP and cyclic GMP levels caused by CGRP (100 nM). The data suggest that de novo synthesis of nitric oxide from its precursor L-arginine is required for rCGRP to induce vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta.

Autoperfused heart-lung preparation: one reason for unsuccessful lung preservation.

Normothermic autoperfused heart-lung preparation has the advantages of avoiding ischemic time and allowing continuous monitoring of organ function during preservation. When this technique is used, the lungs deteriorate quickly, but the reasons for this deterioration have not been investigated. This study was designed to explore the possible cause of rapid lung deterioration. Three groups of mongrel dogs were used. In Group 1 (N = 5), a buffer bag was used in the heart-lung preparation. In Group 2 (N = 6), a 20 mu filter was incorporated between the buffer bag and the right atrium. In Group 3 (N = 5), no buffer bag was used. Average survival time was 15.0 +/- 3.1 hours in Group 1, 13.5 +/- 0.7 hours in Group 2, and 21.6 +/- 2.3 hours in Group 3. Heart function was comparable among the three groups, but the arterial pulse pressure was lower and the heart rate higher in Group 3. Both white blood cell and platelet counts decreased contonuously during the preservation period. Examination of the filters in Group 2 revealed numerous aggregates consisting of platelets, white blood cells, red blood cells, and fibrin. Small thrombi were also found in the lungs in Groups 1 and 2. The results indicated that one important reason for quick lung deterioration was numerous aggregates, which were formed in the buffer bag, returned from the venous line, and trapped in the lungs. Removal of the buffer bag reduced the production of aggregates but tended to de-stabilize the hemodynamics of the preparation.