bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bolus ghrelin administration ameliorates the inflamatory response and oxidative stress during precutaneous cardiopulmonary support in a rat model
Authors: SUKUMARAN VIJAYAKUMAR , Fujii Yutaka , Tsuchimochi Hirotsugu , Shirai Mikiyasu , Tatsumi Eisuke , Pearson James T 
Published: November 2023

BackgroundPercutaneous cardiopulmonary support (PCPS) induced inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately leads to multiple organ failure. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. We investigated the protective effects of ghrelin against the PCPS‐induced inflammatory reactions, oxidative stress and acute organ damage.MethodsAdult male Sprague Dawley rats were subjected to PCPS for 4 hours and randomly received vehicle (n=6) or a bolus of ghrelin (150μg/kg, sc, n=6). Rats were euthanized and heart, lung, kidney and brain samples were harvested for further histopathological analysis. Blood samples were taken before starting, after 2 hrs and 4 hrs of PCPS. We measured the plasma cytokine levels of (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6), catecholamines (norepinephrine, epinephrine and dopamine) and organ damage markers (lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Oxidative stress markers (3‐nitrotyrosine) were measured by western blot.ResultsPCPS‐induced leucocytosis and increased plasma levels of TNF‐α, IL‐6 indicating an inflammatory response. In addition, organ damage markers and catecholamines were also elevated. Ghrelin treatment attenuated the inflammatory response, as evidenced by reduced inflammatory cytokines, organ damage markers and protein levels of 3‐nitrotyrosin. Importantly, ghrelin dramatically suppressed the plasma catecholamines concentration when compared to the PCPS group.ConclusionsThese results suggest that ghrelin inhibits the inflammatory response and oxidative stress. One bolus of ghrelin might provide an effective approach for reducing widespread PCPS‐induced organ injury.Support or Funding InformationJapan society for the promotion of science
Effects of Sanguinate™ on Systemic and Microcirculatory Variables in a Model of Prolonged Ischemic Shock
Authors: Nugent William H , Cestero Ramon F , Jubin Ronald , Abuchowski Abe , Song Bjorn K 
Published: November 2023

Hemorrhage after trauma is the leading cause of preventable death in young adults. In cases of severe blood loss, outcomes are dependent on prompt hemorrhage control and restoration of volume and oxygen carrying capacity. There is a dire need for oxygen carrying resuscitants that overcome the perishability, compatibility, and bioreactivity issues of blood.To study the effects of prolonged hypoxia and the effects of resuscitative fluids, a new model of prolonged ischemic shock (PIS) was developed by subjecting 17 male Sprague Dawley rats to a controlled, stepwise blood withdrawal (45% by volume), which mimicked conditions of post‐injury progressive hemorrhage control. Animals were then maintained in a state of untreated ischemic shock for at least 60 minutes and then received a 20% hypovolemic resuscitation with one of three test solutions: a crystalloid (Lactated Ringer's Solution; LRS), a colloid (Hextend™), or a novel PEGylated carboxyhemoglobin‐based oxygen carrier (Sanguinate™). Measurements of post‐resuscitative survival, spinotrapezius muscle interstitial oxygenation (PISFO2), arteriolar diameters, and systemic cardiovascular parameters were obtained throughout the experimental time course.The PIS hemorrhage protocol produced peripheral tissue hypoxia as measured by phosphorescence quenching microscopy and was lethal in sham (untreated) animals after 90 min. Survival was significantly different among treatment groups (p < 0.01), where LRS, Hextend™ and Sanguinate™‐treated animals survived 16 ± 3.4, 76 ± 11.1 and 193 ± 33.4 mins, respectively. Only Sanguinate™ produced a significant rise in tissue PISFO2 by two hours post‐resuscitation (p < 0.01). Mean arterial pressure (MAP) was significantly increased in Sanguinate™ versus LRS (p < 0.05) post‐resuscitation, and higher than Hextend™ by 60 min post‐resuscitation (p < 0.0001). Post‐resuscitative increases in MAP and PISFO2 correlated with increased survival times.We present a new model of evaluating prolonged tissue ischemia in the setting of hemorrhagic shock. Using this PIS model, we have shown that resuscitation with a carboxyhemoglobin‐based oxygen carrier (Sanguinate™) results in improved survival compared to standard resuscitation fluids. The PIS model provides a platform to investigate outcomes due to prolonged ischemia as opposed to acute hemorrhagic shock, and may therefore be more clinically applicable to current resuscitation protocols. Additionally, the PIS model may be useful in studies of reperfusion injury.Support or Funding InformationSupport: Song Biotechnologies, LLC & Prolong Pharmaceuticals, LLC
Taurine Supplementation Improves Cardiac Ischemia/Reperfusion Injury by Inhibiting Intra‐Cardiac Renin‐Angiotensin System Overactivity in Adult Female Rats Perinatally Depleted of Taurine
Authors: Kulthinee Supaporn , Navar L. Gabriel , Roysommuti Sanya 
Published: November 2023

Perinatal taurine depletion particularly followed by a high sugar diet exacerbates cardiac injury, sympathoexcitation, and arterial pressure dysregulation after ischemia/reperfusion (IR) in adult male rats, while taurine treatment before and after cardiac IR prevents or reduces the adverse effects of IR. This study tested the hypothesis that in adult female rats perinatally depleted of taurine followed by a high sugar diet, taurine supplementation mitigates the cardiac IR injury by inhibiting intra‐cardiac renin‐angiotensin system overactivity. Female Sprague‐Dawley rats were fed normal rat chow with tap water alone (control, C) or tap water containing 3% beta‐alanine (taurine depletion, TD) from conception to weaning. Female offspring were fed the normal rat chow and drank 5% glucose in tap water (CG and TDG) or tap water alone (TDW and CW) throughout the study. One week before surgery, half of the rats in each treatment were supplemented with 3% taurine in tap water (CW+T, CG+T, TDW+T, and TDG+T). At 7–8 weeks of age, cardiac angiotensin II content and plasma cardiac injury markers were studied in anesthetized rats after cardiac IR induction and in untreated Sham control rats. Body, heart, and heart to body weight ratios were not significantly different among the nine groups. While plasma cardiac injury markers significantly increased in all IR groups compared to Sham control, the marked cardiac damage was observed in the TDG group (creatine kinase MB: Sham 211 ± 2 u/l, CW 300 ± 7 u/l, CW+T 245 ± 5 u/l, CG 313 ± 7 u/l, CG+T 251 ± 9 u/l, TDW 330 ± 6 u/l, TDW+T 318 ± 7 u/l, TDG 367 ± 3 u/l, TDG+T 334 ± 8 u/l; cardiac troponin C: TDG 0.9 ± 0.1 ng/ml, TDG+T 0.4 ± 0.1 ng/ml, other groups < 0.01 ng/ml; N‐terminal prohormone brain natriuretic peptide: TDG 8.8 ± 0.3 pg/ml, TDG+T 6.3 ± 0.2 pg/ml, other groups < 5.0 pg/ml). Further, cardiac angiotensin II levels significantly increased in CG, TDW, and TDG compared to Sham and CW groups (Sham 32.3 ± 1.5 pg/ml, CW 43.6 ± 3.0 pg/ml, CW+T 43.3 ± 2.6 pg/ml, CG 75.9 ± 8.41 pg/ml, CG+T 46.3 ± 2.5 pg/ml, TDW 80.3 ± 5.7 pg/ml, TDW+T 53.2 ± 2.4 pg/ml, TDG 139.0 ± 8.1 pg/ml, TDG+T 82.4 ± 3.7 pg/ml). The adverse effects of IR on cardiac injury and angiotensin II content were similarly attenuated, at least in part, by taurine supplementation. The present study demonstrates that perinatal taurine depletion particularly followed by a high sugar diet exacerbates cardiac IR injury via intra‐cardiac renin‐angiotensin system overactivity in adult female rats, and this adverse effect can be reduced by short‐term taurine supplementation.Support or Funding InformationThis work was supported by Khon Kaen University, Khon Kaen, Thailand.
Cardioprotective Role of Regulator of G Protein Signaling 6 in the Ischemic Heart
Authors: Rorabaugh Boyd R. , Chakravarti Bandana , Seeley Sarah L. , Bui Albert D. , Yang Jianqi , Watts Stephanie W , Neubig Richard R. , Fisher Rory A 
Published: November 2023

Gαi‐coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In the present study, we investigated the impact of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6−/−) and wildtype (RGS6+/+) mice were subjected to 30 min ischemia and 2 hr reperfusion on a Langendorff heart apparatus. Infarcts in RGS6−/− hearts were significantly larger than infarcts in RGS6+/+ hearts. RGS6−/− hearts also exhibited increased phosphorylation of β2‐adrenergic receptors, ERK, and GRK2. Mitochondrial GRK2 as well as caspase‐3 cleavage were increased significantly in RGS6−/− hearts compared to RGS6+/+ hearts following ischemia. Chronic propranolol treatment of mice prevented the observed increases in ischemic injury and phosphorylation of ERK and GRK2 observed in RGS6−/− hearts. Our findings suggest that loss of RGS6 predisposes the ventricle to pro‐death signaling through the β2AR‐ERK‐GRK2 signaling axis and provide evidence for a protective role of RGS6 in the ischemic heart. Individuals expressing genetic polymorphisms that suppress the activity of RGS6 may be at increased risk of cardiac ischemic injury. Furthermore, the development of agents that increase RGS6 expression or activity might provide a novel strategy for the treatment of ischemic heart disease.Support or Funding InformationThis work was supported by the National Institute of General Medicine [GM39561 to RRN], National Cancer institute [CA161882 to RAF], the American Heart Association [14GRNT20460208 to RAF], and an Ohio Northern University Bower and Bennet Endowment Award to BRR
Effect of arterial stiffness on hemodynamic responses to the cold pressor test in men and women
Authors: Tucker Matthew A. , Looney Jacob , Lyon Matthew , Layman Lawrence C. , Pollock David M. , Harris Ryan A. 
Published: November 2023

Differences in arterial stiffness between men and women have been described and may partly explain the sex‐related disparity in cardiovascular disease risk. Sex differences in the hemodynamic response to a cold pressor test (CPT) have also been described. However, it is unknown if arterial stiffness influences the hemodynamic response to a CPT and whether sex differences in this relationship exist.PURPOSETo investigate the relationship between arterial stiffness and hemodynamic responses to CPT in healthy men and women.METHODS18 men (age 29 ± 6 y, BMI = 26.4 ± 4.8 kg/m2) and 10 women (age 28 ± 6 y, BMI = 24.9 ± 5.1 kg/m2) participated in this study. Arterial stiffness was assessed via automated analyses of brachial and estimated aortic pressure waveforms to determine AIx75 (an indirect marker of arterial stiffness, corrected for a heart rate of 75 bpm). The CPT protocol consisted of a 5 min baseline followed by immersion of the right hand up to the wrist in ice water (~2°C) for 3 min. Hemodynamic parameters including total peripheral resistance index (TPRI), cardiac index (CI), and diastolic/systolic blood pressure (DBP/SBP) were measured throughout the protocol using beat‐to‐beat monitoring of the ‐ finger arterial pressure (Finapres NOVA).RESULTSBaseline measures of AIx75, TPRI, CI, DBP, and SBP were not statistically different between sexes (all p>0.05). Independent of sex, TPRI, CI, DBP, and SBP all increased in response to CPT (all p<0.001). Overall, AIx75 was significantly correlated with the change (Δ) in TPRI (r=0.406, p=0.032) and ΔCI (r=−0.438, p=0.020). However, AIx75 was positively associated with ΔTPRI in men (r=0.536, p=0.022) but not women (r=0.092, p=0.801). Similarly, there was a trend towards significance in the relationship between AIx75 and ΔCI (r=−0.462, p=0.054) and ΔSBP (r=0.401, p=0.099) in men, but not in women (r=−0.456, p=0.186 and r=−0.402, p=0.249, respectively).CONCLUSIONThese data suggest that arterial stiffness is associated with an increased vascular resistance response to CPT in men but not women. The sex‐dependent disparity in the observed relationships between arterial stiffness and ΔTPRI suggests that basal arterial stiffness influences the hemodynamic response to sympathoexcitation differently between sexes. Further evaluation of the exact mechanisms are warranted.Support or Funding InformationNIH/NHLBI P01HL06999 (R.A.H.)
IMPACT OF ANGIOTENSIN CONVERTING ENZYME (ACE) GENE LEVELS ON BAROREFLEX IMPAIRMENT AND SYMPATHETIC HYPERACTIVITY AFTER A HIGH FRUCTOSE DIET
Authors: Moraes‐Silva Ivana C , de Souza Leandro E , Casarini Dulce E. , Irigoyen Maria‐Claudia 
Published: November 2023

ACE gene polymorphism may influence in pathologically‐induced adaptations. We investigated whether mice harbouring 1, 2 or 3 copies of the ACE gene are distinctly impaired after a high fructose diet (F) regarding cardiovascular autonomic control, vascular reactivity, and metabolic parameters.Male mice received F (100g/l) or tap water (C) for 8 weeks. Glucose tolerance (0–120 min after glucose load=1.5 g/Kg ip), total cholesterol and triglycerides were measured. Blood pressure (BP) was directly recorded (Windaq, 4kHz) and baroreflex sensitivity was evaluated by heart rate (HR) responses to vasoactive drugs. HR and BP variabilities were analyzed in frequency domain by FFT. Mesenteric resistance artery reactivity to noradrenaline (Nor;0.1nM‐1μM), and acetylcholine (Ach;1nM‐10μM) was studied in an isometric myograph (DMT,620M). Results in mean±SEM, statistical analysis: ANOVA, p<0.05.No differences were found among C. F induced glucose intolerance vs. C (1 copy: 100±3 vs. F=198±5; 2 copies: 121±4 vs. F=201±8; 3 copies: 86±4 vs. F=212±5 mg/dl at 120th min) without differences among F mice. Total cholesterol and triglycerides were not significantly altered. Systolic BP increased after F vs. C with an additional augment in 3‐copy mice (15±1mmHg vs. 1copy:6±1; 2copies:9±1; mean C:112±2 mmHg), while diastolic BP increased ~8±1mmHg in all F‐fed groups vs. C (mean C:80±2mmHg). Bradycardic responses reduced 40%, 44% and 56% in F‐fed 1, 2 and 3‐copy mice, respectively, as well as tachycardic responses (decreases of 50%, 37% and 60%, respectively). Once more, 3‐copy mice was the most impaired (p<0.05 vs. 1 and 2). While sympathovagal balance increased ~40% in 1 and 2‐copy mice, it increased 130% in 3‐ copy. Similarly, BP variability was higher in 3‐copy (+33%) vs. other groups (p<0.05), and its sympathetic component (LF) had a more pronounced augment in 3‐copy vs. 1 and 2‐copy (31±3; 11±2 and 20±5 %, respectively, p<0.05). Moreover, F‐fed 3‐copy mice arterial reactivity to Nor was superior than the others (mean C:102±4; F:1 copy:170±5; 2 copies:190±7; 3 copies:214±10 %) while Ach‐induced relaxation was more reduced in 3‐copy mice than 1 and 2 copies (mean C:76±5; F:1 copy:58±8, 2 copies:47±6, 3 copies:36±5 %). A negative correlation was observed between BP variability and Ach‐induced maximal relaxation (r2=0.75), and a positive correlation was seen for Nor‐induced maximal constriction (r2=0.78). Similarly, LF component of BP was negatively correlated with Ach maximal relaxation (r2=0.75), and positively correlated with Nor maximal constriction (r2=0.72).Concluding, the F‐induced magnitude of autonomic and vascular dysfunctions are modulated by ACE gene levels. The association of these mechanisms can respond for BP increase and for a more increased cardiovascular risk in 3‐copy mice.Support or Funding InformationFAPESP and PNPD‐CAPES
Identification of open‐loop baroreflex gain from continuous arterial pressure monitoring
Authors: Mannoji Hiroshi , Saku Keita , Nishikawa Takuya , Tohyama Takeshi , Oga Yasuhiro , Abe Kiyokazu , Kishi Takuya , Tsutsui Hiroyuki , Sunagawa Kenji 
Published: November 2023

BackgroundAlthough the importance of arterial baroreflex function in cardiovascular disease is well established, the lack of practical methods to identify the open‐loop baroreflex transfer function (H) makes it difficult to serve as a clinical tool. We repeatedly demonstrated that the H approximates a first‐order low pass filter with the corner frequency of 0.05 Hz in rats. In theory, a feedback system with H attenuates disturbance (D) to D/(1+H). We hypothesized that the baroreflex attenuates the power spectrum density (PSD) of arterial pressure (AP) in its operating frequency range (<0.1Hz), thereby H can be identified from the attenuation of PSD as long as D remains unchanged irrespective of baroreflex function.MethodsWe used 9 Wister‐Kyoto rats. We created graded baroreflex dysfunction by sinoaortic denervation (SAD) (partial: denervation only in right side, n=3 and total: bilateral denervation). One week after SAD, we calculated PSD from continuous AP recording (telemetry, 12hours). To estimate the baroreflex gain, we took the ratio of PSD at 2 frequencies (0.01 Hz/0.1 Hz) and normalized the value by PSD of total SAD. At the end of each experiment, we isolated baroreceptors and measured the open‐loop baroreflex gain.ResultsPartial SAD increased the lability (standard deviation of AP), and total SAD increased more (sham: 6.41 ± 0.79, partial SAD: 9.16 ± 0.58, total SAD: 20.1 ± 5.00 mmHg, p<0.001). SAD increased PSD below 0.1Hz, whereas did not affect above 0.1 Hz indicating that D remains unchanged regardless of SAD (Fig. 1). Estimated open loop baroreflex gain linearly correlated with that experimentally determined (y = 0.24x + 0.11, R2 = 0.87) (Fig. 2).ConclusionPower spectrum anaysis of AP time series allows us to identify broreflex function. The proposed framework may faclitate the noninvasive estimation of baroreflex function in clinial setting.
Wavelet Analysis of Cardiac Baroreflex Sensitivity during Stepwise Blood Pressure Changes
Authors: Tarumi Takashi , Tian Fenghua , Xing Chang‐Yang , Turner Marcel , Repshas Justin , Zhang Rong 
Published: November 2023

BackgroundCardiac baroreflex regulates short‐term fluctuations in blood pressure (BP) via controlling heart rate (HR). The objective of this study was to determine the effect of steady‐state BP changes on cardiac baroreflex sensitivity (BRS) using wavelet analysis.MethodsThirteen subjects (67±7 years, 8 women) were tested during intravenous infusions of sodium nitroprusside (SNP) and phenylephrine (PE). Drug dosage was increased stepwise after achieving steady‐state BP in each stage. BRS was calculated from the beat‐by‐beat changes in systolic BP and RR interval within the frequency band of 0.02–0.20 Hz. Linear mixed model was used to analyze the effect of steady‐state BP changes on BRS.ResultsSNP infusion decreased mean arterial pressure (MAP) by 15% and increased HR by 12%. In contrast, PE infusion increased MAP by 23% and decreased HR by 3%. Representative wavelet map of BRS estimation during drug infusions is shown below. During SNP and PE infusions, there was a positive association between changes in steady‐state MAP and BRS (P<0.001). Furthermore, the slope of BRS reduction with decreasing MAP during SNP infusion was greater than that during PE infusion (0.085±0.014 vs. 0.042±0.011 ms/mmHg per 1 mmHg change in MAP, P=0.004).ConclusionsSteady‐state decrease in BP is associated with elevation of HR and marked reduction of BRS. These findings suggest that dynamic short‐term regulation of BP during hypotension may be impaired and elevate the risk of fall or syncope.Support or Funding InformationThis study was supported by the NIH (R01AG033106 and K99HL133449) and the Americann Heart Association (14POST20140013).
Gonadal Hormone Receptors Underlie The Resistance Of Female Rats To Cardiovascular Complications Of Endotoxemia
Authors: El‐Lakany Mohammed A , El‐Gowelli Hanan M , Fouda Mohamed A , El‐Gowilly Sahar M , El‐Mas Mahmoud M 
Published: November 2023

Gender differences exist in the immunological and cardiovascular complications of sepsis, with the male gender being more vulnerable to these conditions. The current study tested the hypotheses that female rats are protected against the endotoxemia‐evoked hypotension and cardiac autonomic dysfunction, and that the presence of functional gonadal hormone receptors is a prerequisite for such protection. Changes in blood pressure (BP), heart rate (HR) and cardiac sympathovagal balance, as indexed by the analysis of heart rate variability (HRV), caused by a single i.v. dose of lipopolysaccharide (LPS, 10 mg/kg) were determined in conscious male and female rats. In male rats, LPS caused significant falls in BP and increases in HR. The spectral index of the cardiac sympathovagal balance (low‐frequency/high‐frequency ratio (LF/HF) of interbeat intervals was reduced by LPS, suggesting a shift in cardiac autonomic control towards parasympathetic dominance. Remarkably, none of the above cardiovascular effects of LPS was evident in female rats. We also report that pretreatment of female rats with fulvestrant (nonselective estrogen receptor blocker), PHTPP (estrogen receptor‐β blocker), mifepristone (progesterone receptor blocker) or formestane (aromatase inhibitor) uncovered clear hypotensive and tachycardic responses to LPS. Moreover, these female rats, unlike their male counterparts, exhibited increases, rather than decreases, in LF/HF ratio in response to LPS. Alternatively, LPS failed to modify the cardiovascular function in female rats pretreated with MPP, a selective blocker of estrogen receptor‐α. These findings highlight important roles for estrogen receptor‐β and progesterone receptors in guarding against cardiovascular derangements caused by endotoxemia in female rats.Support or Funding InformationSupported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)