Effects of environmental stress following myocardial infarction on behavioral measures and heart failure progression: The influence of isolated and group housing conditions.

BACKGROUND: Heart failure (HF) prognosis is negatively influenced by adverse environmental conditions associated with psychological distress and depression. The underlying mechanisms are not well understood because of insufficient experimental control in prior clinical and epidemiological studies. Using a validated animal model we examined whether distress-producing environmental manipulations (social isolation and crowding) increase HF progression following myocardial infarction (MI). METHODS: MI was induced using coronary artery ligation in 8-week old male Wistar rats (N=52) and results were compared to sham surgery (N=24). Housing conditions were randomly assigned at 5 days post MI or sham surgery (1/cage=isolation, 2/cage=standard reference condition, or 4/cage=crowding) and continued for 17 weeks until the end of observation. The open field test was used to test behavioral responses. Echocardiograms were obtained at weeks 8 and 16, and left ventricular (LV) weight at week 17. RESULTS: Housing conditions increased behavioral markers of distress (p=0.046) with the strongest effects for the isolated (1/cage) (p=0.022). MI did not increase distress-related behaviors compared to sham. MI-surgery resulted in characteristic HF indices (left ventricular ejection fraction (LVEF) at week 16=46 ± 12% vs. 80 ± 7% in sham, p<0.001). Housing condition was not related to LVEF or LV weight (p>0.10). CONCLUSIONS: Adverse environmental conditions, particularly isolated housing, produce increases in some of the behavioral indicators of distress. No effects of housing were found on post-MI progression of HF. The distress-HF associations observed in humans may therefore reflect common underlying factors rather than an independent causal pathway. Stronger environmental challenges may be needed in future animal research examining distress as related HF progression.

Three-dimensional 123I-meta-iodobenzylguanidine cardiac innervation maps to assess substrate and successful ablation sites for ventricular tachycardia: feasibility study for a novel paradigm of innervation imaging.

BACKGROUND: Innervation is a critical component of arrhythmogenesis and may present an important trigger/substrate modifier not used in current ventricular tachycardia (VT) ablation strategies. METHODS AND RESULTS: Fifteen patients referred for ischemic VT ablation underwent preprocedural cardiac (123)I- meta-iodobenzylguanidine ((123)I-mIBG) imaging, which was used to create 3-dimensional (3D) innervation models and registered to high-density voltage maps. 3D (123)I-mIBG innervation maps demonstrated areas of complete denervation and (123)I-mIBG transition zone in all patients, which corresponded to 0% to 31% and 32% to 52% uptake. (123)I-mIBG denervated areas were ≈2.5-fold larger than bipolar voltage-defined scar (median, 24.6% [Q1-Q3, 18.3%-34.4%] versus 10.6% [Q1-Q3, 3.9%-16.4%]; P<0.001) and included the inferior wall in all patients, with no difference in the transition/border zone (11.4% [Q1-Q3, 9.5%-13.2%] versus 16.6% [Q1-Q3, 12.0%-18.8%]; P=0.07). Bipolar/unipolar voltages varied widely within areas of denervation (0.8 mV [Q1-Q3, 0.3-1.7 mV] and 4.0 mV [Q1-Q3, 2.9-5.6 mV]) and (123)I-mIBG transition zones (0.8 mV [Q1-Q3, 0.4-1.8 mV] and 4.6 mV [Q1-Q3, 3.2-6.3 mV]). Bipolar voltages in denervated areas and (123)I-mIBG transition zones were <0.5 mV, 0.5 to 1.5 mV, and >1.5 mV in 35%, 36%, and 29%, as well as 35%, 35%, and 30%, respectively (P>0.05). Successful ablation sites were within bipolar voltage-defined scar (7%), border zone (57%), and areas of normal voltage (36%), but all ablation sites were abnormally innervated (denervation/(123)I-mIBG transition zone in 50% each). CONCLUSIONS: (123)I-mIBG innervation defects are larger than bipolar voltage-defined scar and cannot be detected with standard voltage criteria. Thirty-six percent of successful VT ablation sites demonstrated normal voltages (>1.5 mV), but all ablation sites were within the areas of abnormal innervation. (123)I-mIBG innervation maps may provide critical information about triggers/substrate modifiers and could improve understanding of VT substrate and facilitate VT ablation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01250912.

Differences in quantitative assessment of myocardial scar and gray zone by LGE-CMR imaging using established gray zone protocols.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard for myocardial scar evaluation. Heterogeneous areas of scar ('gray zone'), may serve as arrhythmogenic substrate. Various gray zone protocols have been correlated to clinical outcomes and ventricular tachycardia channels. This study assessed the quantitative differences in gray zone and scar core sizes as defined by previously validated signal intensity (SI) threshold algorithms. High quality LGE-CMR images performed in 41 cardiomyopathy patients [ischemic (33) or non-ischemic (8)] were analyzed using previously validated SI threshold methods [Full Width at Half Maximum (FWHM), n-standard deviation (NSD) and modified-FWHM]. Myocardial scar was defined as scar core and gray zone using SI thresholds based on these methods. Scar core, gray zone and total scar sizes were then computed and compared among these models. The median gray zone mass was 2-3 times larger with FWHM (15 g, IQR: 8-26 g) compared to NSD or modified-FWHM (5 g, IQR: 3-9 g; and 8 g. IQR: 6-12 g respectively, p < 0.001). Conversely, infarct core mass was 2.3 times larger with NSD (30 g, IQR: 17-53 g) versus FWHM and modified-FWHM (13 g, IQR: 7-23 g, p < 0.001). The gray zone extent (percentage of total scar that was gray zone) also varied significantly among the three methods, 51 % (IQR: 42-61 %), 17 % (IQR: 11-21 %) versus 38 % (IQR: 33-43 %) for FWHM, NSD and modified-FWHM respectively (p < 0.001). Considerable variability exists among the current methods for MRI defined gray zone and scar core. Infarct core and total myocardial scar mass also differ using these methods. Further evaluation of the most accurate quantification method is needed.

Effects of glucose ingestion on autonomic and cardiovascular measures during rest and mental challenge.

BACKGROUND: High levels of dietary sugar consumption may result in dysregulated glucose metabolism and lead to elevated cardiovascular disease risk via autonomic nervous system and cardiovascular dysfunction. Altered cardiovascular function can be examined using perturbation tasks such as mental challenge. This study examined the effects of controlled glucose intake on cardiovascular measures at rest and in responses to mental challenge in a laboratory setting. METHOD: Using a double blind within-subjects design, participants were monitored at baseline, following ingestion of a glucose or taste-control solution, during structured speech (SS), anger recall (AR) and recovery (N=24, 288 repeated measures; age = 21±2 years). Pre-ejection period (PEP), heart rate (HR), stroke index (SI), cardiac index (CI), blood pressure and total peripheral resistance (TPR) were measured throughout the protocol. RESULTS: Glucose resulted in sustained decreased PEP levels compared to control condition (Δ=11.98±9.52 vs. 3.27±7.65 m·s, P<.001) and transient increases in resting HR (P=.011), CI (P=.040) and systolic blood pressure (P=.009). Glucose did not result in increased cardiovascular reactivity to mental challenge tasks, but was associated with a delayed HR recovery following AR (P=.032). CONCLUSION: Glucose intake resulted in a drop in PEP indicating increased sympathetic nervous system activity. No evidence was found for glucose-related exaggerated cardiovascular responses to mental challenge. Dysregulated glucose metabolism may result in elevated cardiovascular disease risk as a result of repeated glucose-induced elevations of sympathetic nervous system activity.

Autonomic nervous system reactivity to positive and negative mood induction: the role of acute psychological responses and frontal electrocortical activity.

The differential effects of positive versus negative emotions on autonomic nervous system activity are insufficiently understood. This study examined the role of acute mood responses and central nervous system activity on heart rate variability (HRV) using 5-min event recall tasks (happiness and anger recall) and a 5-min Stroop Color Word Test (SCWT) in 20 healthy individuals (mean age 25 ± 4 years, 55% female). HRV was measured in high frequency (HF) and low frequency (LF) domains, and frontal brain activity using electroencephalography (EEG) in the alpha frequency band in F3 and F4. Happiness Recall resulted in increased LF-HRV (p = 0.005) but not HF-HRV (p=0.71). Anger Recall did not change HRV (p-values > 0.10). The SCWT produced decreases in HF-HRV (p = 0.001) as well as LF-HRV (p = 0.001). The magnitude of feeling "happy" during Happiness Recall was positively correlated with ΔHF-HRV (p = 0.050), whereas an incongruent mood state ("frustrated") was associated with smaller ΔHF-HRV (p = 0.070). Associations between frontal EEG activation and HRV responses were mostly non-significant, except for increased right frontal activation during Happiness Recall which was associated with a decrease in LF/HF ratio (p = 0.009). It is concluded that positive and negative mood induction result in differential HRV responses, which is related to both task valence and the intensity of task-induced emotions.

Depression in heart failure: biobehavioral mechanisms.

The etiology, predictive value, and biobehavioral aspects of depression in heart failure (HF) are described in this article. Clinically elevated levels of depressive symptoms are present in approximately 1 out of 5 patients with HF. Depression is associated with poor quality of life and a greater than 2-fold risk of clinical HF progression and mortality. The biobehavioral mechanisms accounting for these adverse outcomes include biological processes (elevated neurohormones, autonomic nervous system dysregulation, and inflammation) and adverse health behaviors (physical inactivity, medication nonadherence, poor dietary control, and smoking). Depression often remains undetected because of its partial overlap with HF-related symptoms and lack of systematic screening. Behavioral and pharmacologic antidepressive interventions commonly result in statistically significant but clinically modest improvements in depression and quality of life in HF, but not consistently better clinical HF or cardiovascular disease outcomes. Documentation of the biobehavioral pathways by which depression affects HF progression will be important to identify potential targets for novel integrative behavioral and pharmacologic interventions.

Cardiovascular and psychological reactivity and recovery from harassment in a biracial sample of high and low hostile men and women.

BACKGROUND: This study emphasizes the importance of studying the emotional, motivational, and cognitive characteristics accompanying and the potential hemodynamic mechanisms underlying cardiovascular reactivity to and recovery from interpersonal conflict. PURPOSE: The relation of dispositional hostility to cardiovascular reactivity during a frustrating anagram task and post-task recovery was investigated. METHODS: The sample was composed of 99 healthy participants (age, 18-30 years; 53% women; 51% Caucasian; 49% African American)-half randomly assigned to a harassment condition. High and low hostility groups were created by a median split specific to sex and race subgroup score distributions on the Cook-Medley Hostility Scale. It was hypothesized that hostility would interact with harassment such that harassed, high hostile individuals would display the greatest cardiovascular and emotional reactivity and slowest recovery of the four groups. Participants completed a 10-min baseline, a 6-min anagram task, and a 5-min recovery period with blood pressure, heart rate, pre-ejection period, stroke index, cardiac index, and total peripheral resistance index measured. RESULTS: Harassed participants displayed significantly greater cardiovascular responses and lower positive affect to the task and slower systolic blood pressure (SBP) recovery than did nonharassed participants. The high hostile group, irrespective of harassment, showed blunted cardiovascular responses during the task and delayed SBP recovery than the low hostile group. CONCLUSION: Although the predicted interaction between hostility and harassment was not supported in the context of cardiovascular responses, such an interaction was observed in the context of blame attributions, whereby harassed hostile participants were found to blame others for their task performance than the other subgroups.

Coping as a multisystem construct associated with pathways mediating HIV-relevant immune function and disease progression.

We review psychoneuroimmunological research linking coping with HIV disease progression and its indicators, as well as with viral and host factors that may mediate or contribute to HIV progression. Our perspective on coping broadly encompasses the attempts of multiple mental and biological systems to adapt to changing internal and environmental conditions and to reestablish homeostasis. Accordingly, we discuss studies within four dimensions of coping: cognitive (appraisals, expectancies, and explanatory style), emotional (the Type C coping pattern and related constructs), active-passive strategies and behavior patterns, and physiological (autonomic reactivity and recovery). Finally, we present a model that integrates key studies linking coping with HIV prognostic indicators and clinical disease progression. Based on empirical evidence, the model suggests plausible mechanisms by which coping may be connected to HIV progression/antiprogression factors and immunopathogenesis to affect HIV clinical progression.

Type C coping, alexithymia, and heart rate reactivity are associated independently and differentially with specific immune mechanisms linked to HIV progression.

The maladaptive Type C coping style has been linked to disease progression in HIV and other immunologically mediated disorders. We hypothesized that strong Type C coping, higher levels of alexithymia, and greater cardiovascular (particularly heart rate) responses to, and prolonged recovery from stress would be associated with poorer functioning of immune parameters previously linked to HIV pathogenesis and progression: (1) antigen-stimulated production of the beta (beta)-chemokines MIP-1 alpha and MIP-1 beta, which bind to the HIV co-receptor CCR5 and block HIV entry into CD4(+) lymphocytes; and (2) antigen-stimulated production of the proinflammatory cytokine interleukin-6 (IL-6), which synergizes immune activation associated with HIV replication. We examined relations among psychological, cardiovascular, and immune variables in a baseline sample of 200 HIV-infected, predominantly African American outpatients attending an HIV primary care clinic in inner-city Baltimore. In regression analyses adjusted for CD4(+) count and age, strong Type C coping was associated with significantly higher IL-6 production, as predicted. The theoretically related construct of alexithymia was correlated with significantly lower stimulated production of HIV-inhibiting MIP-1 alpha. Independent of alexithymia, greater heart rate reactivity, and poorer heart rate recovery in response to experimental stressors were also significantly associated with lower production of MIP-1 alpha, adjusted for cardiovascular medications, methadone use, CD4(+) count, and age. These findings support our primary set of hypotheses that maladaptive Type C coping, alexithymia, and heart rate reactivity/recovery are associated with disturbances in two key immune parameters implicated in HIV pathogenesis. Our secondary hypothesis, that dysregulated heart rate reactivity may mediate the connections between Type C coping and/or alexithymia and IL-6/ MIP-1 alpha was not confirmed. The finding that Type C coping, alexithymia, and heart rate reactivity/recovery are associated independently and differentially with specific aspects of relevant immune functioning may reflect distinct biobehavioral pathways that contribute to HIV progression.

Meal size of high-fat food is reliably greater than high-carbohydrate food across externally-evoked single-meal tests and long-term spontaneous feeding in rat.

A series of studies in rat using isoenergetic (kcal/ml) liquid diets differing in fat content has previously found dietary fat to dose-dependently increase daily caloric intake. In single-meal tests in which meal initiation was externally evoked in feeding-associated environments, the behavioral expression of this overeating was found to be larger meal intake. The present studies confirmed the ecological validity of this larger meal size of high-fat diet (HF) relative to high-carbohydrate diet (HC): meal size of HF>HC in home-cage testing (Experiment 1), and during undisturbed, spontaneous feeding in which ingestive behavior was continuously monitored (Experiments 2 and 3). These findings demonstrate that single-meal paradigms yield results consistent with spontaneous feeding of high-fat and high-carbohydrate liquid diets, thus supporting the use of single-meal studies to better understand the physiological bases of elevated caloric intake associated with chronic consumption of a high-fat diet.

Independent effects of diet palatability and fat content on bout size and daily intake in rats.

Although considerable evidence attests to the hyperphagic effects of high-fat (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density, and postingestive effects) which promote overeating is still unclear. The present studies investigated the independent effects of diet palatability and macronutrient composition on intake using the self-regulated intragastric infusion paradigm. In Experiment 1, rats were infused with either HF or high-carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily intake than HC; lick pattern analysis revealed that HF produced larger but not more frequent bouts. Test solution was not related to intake, possibly due to the relatively modest palatability manipulation. Experiment 2 provided a more sensitive test: The palatability manipulation was strengthened and diet infusion made optional by provision of chow. HF again elicited larger bout size and total daily intake (diet+chow) than HC. Rats given the more palatable solution significantly increased intake (via larger bouts) and thus the amount of diet infused, but chow intake decreased such that total kilocalorie intake was not significantly related to solution palatability. The reliable observation that HF promoted larger bout size and greater total kilocalorie intake than HC provides additional evidence that fat sends weaker feedback signals relevant to controls of both satiation (suppression of ongoing eating, behaviorally manifest in meal size) and satiety (suppression of subsequent intake, reflected in total daily intake).

Relation of cognitive appraisal to cardiovascular reactivity, affect, and task engagement.

The relation of primary cognitive appraisals to cardiovascular reactivity, affect, task engagement, and perceived stress was examined in 56 men (ages 18-29). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, preejection period, stroke index, cardiac index, and total peripheral resistance were assessed at rest and during performance of a computerized mental arithmetic task. Extending on prior investigations, threat and challenge appraisals were assessed independently from one another and from secondary appraisals. Positive and negative affect, task engagement, and levels of perceived stress were also assessed. Results indicated that threat (R2 =.08, p =.01), challenge (R2 =.14, p =.003), and their interaction (R2 =.11, p =.006) independently predicted DBP reactivity; DBP responses were greatest among participants with a high threat/low challenge pattern of appraisal. Threat appraisals predicted greater negative affect (R2 =.32) and perceived stress (R2 =.48), whereas challenge appraisals were related to greater positive affect (R2 =.44) and task engagement (R2 =.40, ps <.0001). Greater positive affect was correlated with increased SBP and DBP reactivity, and greater levels of task engagement with increased DBP response (ps < or = .002). Results suggest that primary cognitive appraisals are more potent predictors of affect and task engagement than cardiovascular reactivity.