Positive and negative affect is related to experiencing chest pain during exercise-induced myocardial ischemia

© 2017 by the American Psychosomatic Society. Objective: Silent myocardial ischemia is thought to be associated with worse cardiovascular outcomes due to a lack of perception of pain cues that initiate treatment seeking. Negative affect (NA) has been associated with increased pain reporting and positive affect (PA) with decreased pain reporting, but these psychological factors have not been examined within the context of myocardial ischemia. This study evaluated the associations between PA, NA, and chest pain reporting in patients with and without ischemia during exercise testing. Methods: A total of 246 patients referred for myocardial perfusion single-photon emission computed tomography exercise stress testing completed the positive and negative affect schedule-expanded version, a measure of PA and NA. Presence of chest pain and myocardial ischemia were evaluated using standardized protocols. Results: Logistic regression analyses revealed that for every 1-point increase in NA, there was a 13% higher chance for ischemic patients (odds ratio [OR] = 1.13; 95 % confidence interval [CI] = 1.02 to 1.26) and an 11% higher chance in nonischemic patients (OR = 1.11; 95% CI = 1.03 to 1.19) to report chest pain. A significant interaction of PA and NA on chest pain reporting (ß = 0.02; 95% CI = 0.002 to 0.031) was also observed; nonischemic patients with high NA and PA reported more chest pain (57%) versus patients with low NA and low PA (13%), with high NA and low PA (17%), and with high PA and low NA (7%). Conclusions: Patients who experience higher NA are more likely to report experiencing chest pain. In patients without ischemia, high NA and PA was also associated with a higher likelihood of reporting chest pain. Results suggest that high levels of PA as well as NA may increase the experience and/or reporting of chest pain

Expression of Phosphoinositide-Specific Phospholipase C Isoforms in Native Endothelial Cells

<div><p>Phospholipase C (PLC) comprises a superfamily of enzymes that play a key role in a wide array of intracellular signalling pathways, including protein kinase C and intracellular calcium. Thirteen different mammalian PLC isoforms have been identified and classified into 6 families (PLC-β, γ, δ, ε, ζ and η) based on their biochemical properties. Although the expression of PLC isoforms is tissue-specific, concomitant expression of different PLC has been reported, suggesting that PLC family is involved in multiple cellular functions. Despite their critical role, the PLC isoforms expressed in native endothelial cells (ECs) remains undetermined. A conventional PCR approach was initially used to elucidate the mRNA expression pattern of PLC isoforms in 3 distinct murine vascular beds: mesenteric (MA), pulmonary (PA) and middle cerebral arteries (MCA). mRNA encoding for most PLC isoforms was detected in MA, MCA and PA with the exception of η2 and β2 (only expressed in PA), δ4 (only expressed in MCA), η1 (expressed in all but MA) and ζ (not detected in any vascular beds tested). The endothelial-specific PLC expression was then sought in freshly isolated ECs. Interestingly, the PLC expression profile appears to differ across the investigated arterial beds. While mRNA for 8 of the 13 PLC isoforms was detected in ECs from MA, two additional PLC isoforms were detected in ECs from PA and MCA. Co-expression of multiple PLC isoforms in ECs suggests an elaborate network of signalling pathways: PLC isoforms may contribute to the complexity or diversity of signalling by their selective localization in cellular microdomains. However in situ immunofluorescence revealed a homogeneous distribution for all PLC isoforms probed (β3, γ2 and δ1) in intact endothelium. Although PLC isoforms play a crucial role in endothelial signal transduction, subcellular localization alone does not appear to be sufficient to determine the role of PLC in the signalling microdomains found in the native endothelium.</p></div

Summary of mRNA expression for phospholipase C isoforms.

<p><i>MAECs</i>, <i>mesenteric arteries endothelial cells; PAECs</i>, <i>pulmonary arteries endothelial cells; MCAECs</i>, <i>middle cerebral arteries endothelial cells; MA</i>, <i>mesenteric arteries; PA</i>, <i>pulmonary arteries; MCA</i>, <i>middle cerebral arteries</i>.</p><p>Summary of mRNA expression for phospholipase C isoforms.</p

Characterization of phospholipase C β isoforms in native arteries.

<p><b>A.</b> The presence of mRNA for phospholipase C (PLC) β isoforms was determined in mesenteric arteries (MA), pulmonary arteries (PA) and middle cerebral arteries (MCA) by PCR. Typical agarose gel electrophoresis of the PCR products showed the expression profile in different vascular beds. Brain and blood were used as positive control tissues. n = 3. <b>B.</b> Quantitative real time PCR analysis of mRNA expression levels of PLCβ isoforms in MA and freshly isolated endothelial cells (ECs) from MA, PA and MCA. Bar graphs show the expression profile of PLCβ1 (a), β2 (b), β3 (c) and β4 (d) isoforms in MAECs, PAECs, MCAECs, MA and blood as control for β2. n = 3. * P<0.05 between MAECs and MCAECs; # P<0.05 between PAECs and MCAECs; † P<0.05 between MCAECs and MAs; ‡ P<0.05 between control tissue and MA. <b>C.</b> (a) Representative immunoblots of murine MA and brain that were obtained using the primary antibody anti-PLC β3 (Abcam #ab52199). GAPDH was used as reference protein. Relevant molecular weight markers are indicated on the left. n = 3. (b) Intracellular distribution of PLCβ3 immunoreactivity in ECs. (Left) Typical image showing labelling of PLC β3 in red and nuclei in blue; scale = 10 μm. (Right) Labelling of PLC β3 (red) overlay with internal elastic lamina (IEL; green) where voids correspond to potential myoendothelial projections; nucleus in blue; scale = 10 μm; n = 4.</p

Characterization of phospholipase C γ isoforms in native arteries.

<p><b>A.</b> The presence or mRNA for phospholipase C (PLC) γ isoforms was determined in mesenteric arteries (MA), pulmonary arteries (PA) and middle cerebral arteries (MCA) by PCR. Typical agarose gel electrophoresis of the PCR products showed the expression profile in the different vascular beds and brain was used as control tissue. n = 3. <b>B.</b> Quantitative real time PCR analysis of mRNA expression levels of PLCγ isoforms in MA and freshly isolated endothelial cells (ECs) from MA, PA and MCA. Bar graphs show the expression profile of PLCγ1 (a) and γ2 (b) isoforms in MAECs, PAECs, MCAECs and MA. n = 3. <b>C.</b> (a) Representative immunoblots of murine MA and brain that were analyzed using the primary antibody anti-PLC γ2 (Abcam #ab18983). GAPDH was used as reference protein. Relevant molecular weight markers are indicated on the left. n = 3. (b) Intracellular distribution of PLCγ2 immunoreactivity in ECs. (Left) Typical image showing labelling of PLCγ2 in red and nuclei in blue; scale = 10 μm. (Right) Labelling of PLCγ2 (red) overlay with internal elastic lamina (IEL; green) where voids correspond to potential myoendothelial projections; nucleus in blue; scale = 10 μm; n = 4.</p

Characterization of phospholipase C ε, ζ and η isoforms in native arteries.

<p><b>A.</b> The presence of mRNA for phospholipase C (PLC) ε, ζ, η1 and η2 isoforms was determined in mesenteric arteries (MA), pulmonary arteries (PA) and middle cerebral arteries (MCA) by PCR. Typical agarose gel electrophoresis of the PCR products showed the expression profile of PLCε, ζ, η1 and η2 isoforms in the different vascular beds and brain or testis were used as control tissue. n = 3. <b>B.</b> Quantitative real time PCR analysis of mRNA expression levels of PLCε, ζ, η1 and η2 isoforms in MA and freshly isolated endothelial cells (ECs) from MA, PA and MCA. Bar graphs show the expression of PLCε (a), ζ (b), η1 (c) and η2 (d) isoforms in MAECs, PAECs, MCAECs, MA and testis as positive control for ζ. n = 3. * P<0.05 between MAECs and MCAECs; # P<0.05 between PAECs and MCAECs; † P<0.05 between MCAECs and MA.</p

Table_1_Thirty-year trends and outcome of isolated versus combined group 2 pulmonary hypertension after cardiac transplantation.DOCX

AimTo investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years.MethodsPatients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test.ResultsThe prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term  mortality  were  not  significantly  associated  with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively).ConclusionOver 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.</p

Table_2_Thirty-year trends and outcome of isolated versus combined group 2 pulmonary hypertension after cardiac transplantation.DOCX

AimTo investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years.MethodsPatients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test.ResultsThe prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term  mortality  were  not  significantly  associated  with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively).ConclusionOver 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.</p