Heart Mass Research Articles

Quantitative Analyses of the Left Ventricle Volume and Cardiac Function in Normal and Infarcted Yucatan Minipigs.

(1) Background: The accuracy of the left ventricular volume (LVV) and contractility measurements with cardiac magnetic resonance imaging (CMRI) is decreased if the papillary muscles are abnormally enlarged, such as in hypertrophic cardiomyopathy in human patients or in pig models of human diseases. The purpose of this work was to establish the best method of LVV quantification with CMRI in pigs. (2) Methods: The LVV in 29 Yucatan minipig hearts was measured using two different techniques: the “standard method”, which uses smooth contouring along the endocardial surface and adds the papillary volume to the ventricular cavity volume, and the “detailed method”, which traces the papillary muscles and trabeculations and adds them to the ventricular mass. (3) Results: Papillary muscles add 21% to the LV mass in normal and infarcted hearts of Yucatan minipigs. The inclusion or exclusion of these from the CMRI analysis significantly affected the study results. In the normal pig hearts, the biggest differences were found in measurements of the LVV, ejection fraction (EF), LV mass and indices derived from the LV mass (p < 0.001). The EF measurement in the normal pig heart was 11% higher with the detailed method, and 19% higher in the infarcted pig hearts (p < 0.0001). The detailed method of endocardium tracing with CMRI closely represented the LV mass measured ex vivo. (4) Conclusions: The detailed method, which accounts for the large volume of the papillary muscles in the pig heart, provides better accuracy and interobserver consistency in the assessment of LV mass and ejection fraction, and might therefore be preferable for these analyses.

Improving the metrics for donor heart sizing.

Predicted heart mass matches donor and recipient sizing for heart transplantation. Physiologic considerations further refines matching and can allow for safe use of undersized and sex mismatched organs.

Embryonic Thermal Manipulation Affects Ventilation, Metabolism, Thermal Control and Central Dopamine in Newly Hatched and Juvenile Chicks.

The first third of incubation is critical for embryonic development, and environmental changes during this phase can affect the physiology and survival of the embryos. We evaluated the effects of low (LT), control (CT), and high (HT) temperatures during the first 5 days of incubation on ventilation (E), body temperature (Tb), oxygen consumption (O2), respiratory equivalent (E/O2), and brain monoamines on 3-days-old (3d) and 14-days-old (14d) male and female chickens. The body mass of LT animals of both ages and sexes was higher compared to HT and CT animals (except for 3d males). The heart mass of 14d HT animals was higher than that of CT animals. Thermal manipulation did not affect E, O2 or E/O2 of 3d animals in normoxia, except for 3d LT males E, which was lower than CT. Regarding 14d animals, the HT females showed a decrease in E and O2 compared to CT and LT groups, while the HT males displayed a lower O2 compared to CT males, but no changes in E/O2. Both sexes of 14d HT chickens presented a greater Tb compared to CT animals. Thermal manipulations increased the dopamine turnover in the brainstem of 3d females. No differences were observed in ventilatory and metabolic parameters in the 3d animals of either sexes, and 14d males under 7% CO2. The hypercapnic hyperventilation was attenuated in the 14d HT females due to changes in O2, without alterations in E. The 14d LT males showed a lower E, during hypercapnia, compared to CT, without changes in O2, resulting in an attenuation in E/O2. During hypoxia, 3d LT females showed an attenuated hyperventilation, modulated by a higher O2. In 14d LT and HT females, the increase in E was greater and the hypometabolic response was attenuated, compared to CT females, which resulted in no change in the E/O2. In conclusion, thermal manipulations affect hypercapnia-induced hyperventilation more so than hypoxic challenge, and at both ages, females are more affected by thermal manipulation than males.

Diet-induced Obesity Differentially Modulates Cardiac Inflammatory Status in the C57 and FVB Mouse Strains.

Cardiovascular diseases correspond to the highest risk of sudden death worldwide, and obesity is largely related to be an increased risk factor. There is a higher prevalence of arterial hypertension in obese individuals, including the presence of cardiac hypertrophy. It is already known the role of toll-like receptors [TLR], mainly 2 and 4 in heart cells, as fundamental to the process of cardiac hypertrophy. Obesity has been studied as an activator of damage-associated molecular patterns [DAMPs], which use the TLR signaling pathway to increase the nuclear factor of inflammation, NF-kB, increasing cytokine expression in heart tissue. It's already known that FVB/N and C57BL/6 mouse strains have different behaviors in relation to metabolism, but the difference in cardiac tropism and innate immune system modulation are not clear. The present study aimed to evaluate the contribution of innate immune factors to cardiac hypertrophy induced by an experimental model of obesity comparing two mouse strains: C57BL/6 and FVB/N. Both strains were submitted to a high-fat diet containing 23% protein, 35.5% carbohydrate, and 35.9% fat for 68 days. Hearts were collected, weighed, and submitted to RT-qPCR, and the serum was analyzed by Bioplex. We observed an increase in heart mass after 68 days in both strains. This was followed by an increase of α-actin only in C57BL/6 while ANF was increased in FVB/N. Gene expression of innate immune components and inflammatory cytokines were only increased in C57BL/6, but not in FVB/N. Based on the results obtained, we verified that C57BL/6 mice had a more robust action of innate immune system then FVB/N.

Pre-transplant amiodarone use does not affect long-term heart transplant survival.

Effect of pre-transplant amiodarone use on post-heart transplant (HT) survival is not well established. We therefore sought to examine the effect of amiodarone use on post-HT survival. We stratified adults who underwent HT between January 2000 and August 2018 in the Scientific Registry of Transplant Recipients according to pre-transplant amiodarone use and used recipient and donor characteristics to calculate propensity scores. We then used overlap propensity score weighting to construct Cox proportional hazards regression models (adjusted for Index for Mortality Prediction After Cardiac Transplantation [IMPACT] score and donor/recipient predicted heart mass [PHM] ratio) for mortality outcomes. Logistic regression was used to compare the odds of primary graft failure and drug-treated rejection. 25,394 adult HT recipients were included; median (inter-quartile range) age was 55 (46, 62) years and 75.5% were men. Compared with nonusers, amiodarone users had a significantly higher prevalence of hypertension (46.7% vs. 50.2%; p<0.0001), left ventricular assist device (LVAD) use (24.5% vs. 31.3%; p<0.0001), and ventilator support (2.5% vs. 3.6%; p<0.0001), respectively. The 10-year post-HT mortality rate in the overall population was 32.0%. Amiodarone use was associated with higher post-transplant 30-day (hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.11-1.41) and 1-year mortality (HR 1.13, 1.04-1.22), but similar 5-year (HR 1.01, 95% CI 0.96-1.07) and 10-year mortality (HR 1.05, 95% CI 0.98-1.13). Amiodarone use increased primary graft failure risk (odds ratio (OR) 1.30, 95% CI 1.07-1.57) but decreased drug-treated rejection (OR 0.81, 95% CI 0.70-0.93). Although pre-transplant amiodarone was associated with higher short-term mortality, its use did not affect long-term survival. Whether the short-term outcomes are related to greater graft failure risk is unclear.

Oversized donor heart transplantation-clinical experience with an underestimated problem.

Heart transplantation is the definitive treatment for end-stage heart failure. With respect to donor-recipient size matching, the problems with undersized heart transplantation have been widely discussed, but there is a paucity of information on oversized transplants due to the presumed advantage of large hearts. We intend to share our center's experience with oversized heart transplantation and its associated problems which would help to expand the knowledge on oversized cardiac allografts. Patients who underwent isolated heart transplantation at our hospital between March 1, 2008, and March 1, 2020, were included. For adults, a donor-recipient predicted heart mass percentage difference exceeding 30% and for children, a donor-recipient weight ratio < 0.8 and > 2.0 was considered a mismatch. We collected data from the in-patient medical records and analyzed the in-hospital outcomes and survival post-transplant among various other parameters. Out of the 43 patients included in this study, 32 (74.4%) patients received a matched heart and 11 (25.6%) patients received oversized hearts. None of the patients received an undersized heart. The in-hospital mortality rate of oversized transplants was 18.2% whereas that of matched transplants was 9.4% (p = 0.432). The post-operative characteristics and 1-year survival were comparable between the groups. We encountered problems specific to oversizing in 5 of the 11 patients (45.4%) which are discussed. With the liberalization of donor criteria to overcome organ shortage, oversized heart transplantation poses certain unique challenges, which when efficiently managed offers acceptable outcomes.

Assessing predicted heart mass size matching in obese heart transplant recipients

Predicted heart mass (PHM) is currently the most reliable metric for donor-recipient size matching in heart transplantation. Undersizing PHM donor-recipient match more than 20% independently predicts reduced survival. However, it is unclear if this is the case in obese recipients, in whom size matching can be challenging. We examined the use of PHM undersized hearts in obese recipients and assessed its impact on survival. The United Network for Organ Sharing database was queried for adult patients undergoing heart transplantation from 1995 to 2020. Obese recipients (BMI ≥ 30) were categorized based on donor-recipient PHM match ≤-20% (undersized) or >-20% (size-matched). Nearest-neighbor propensity score matching was performed to adjust for baseline differences between cohorts. Temporal outcomes were compared by Kaplan-Meier survival analysis. A total of 13,668 obese recipients met inclusion criteria, with 9.6% receiving undersized and 90.4% receiving size-matched hearts. The proportion of undersized donor hearts in obese recipients significantly decreased over the study period (16.2% [1995] to 7.4% [2019], NP-trend < 0.001). Propensity-score matching resulted in 984 well-matched pairs of undersized and size-matched obese recipients. Recipients of undersized hearts saw similar 30-day mortality (5.5% vs 6.0%, p= 0.11) and re-transplantation rates (1.2% vs 1.2%, p=1.00) as size-matched recipients. Survival at 1 year (88.4% vs 87.9%, p=0.14), and 15 years (35.1% vs 31.0%, p=0.12) was similar across cohorts. A decreasing proportion of PHM undersized hearts are being utilized in obese recipients. However, utilizing PHM undersized hearts in obese recipients was not associated with a detriment in survival.

N-acetylcysteine+nimesulide: An association strategy aiming to prevent nimesulide-induced hepatotoxicity

Introduction: Nimesulide is a potent anti-inflammatorywith rapid and long-lasting effects, but also with a high riskof hepatotoxicity. Objective: This work aimed to preventnimesulide-induced hepatotoxicity through the associationof nimesulide with a hepatoprotective agent. Materials andMethods: First, we tested three hepatoprotective agents:N-acetylcysteine, L-carnitine, and Gingko biloba extract inan in vitro hepatic cell model. Both N-acetylcysteine and G.biloba showed promisor results. We selected N-acetylcysteineto continue the studies in an animal model. In vivo study wasperformed using male Wistar rats divided in 4 groups: control,nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) +N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone(100mg/kg/day). Treatments were given by gavage, daily, for15 days. Results: Animals receiving nimesulide alone showedlower body weight gain compared to control. Body weightgain in the nimesulide + N-acetylcysteine group was higherthan nimesulide alone, evidencing lower toxicity. However,the body weight gain of the nimesulide + N-acetylcysteinegroup was still lower than the control animals. Animals treatedwith nimesulide alone presented an increased relative mass ofheart, liver, and spleen and significant hepatic damage seen inmicroscopy when compared to other groups. N-acetylcysteineco-administered with nimesulide prevented the increasedheart mass, but the same was not true with liver and spleen.Conclusions: This work evidence partial protection elicitedby the association of N-acetylcysteine and nimesulide againstnimesulide-induced hepatotoxicity.

Does Succinic Acid Treatment Improve Metabolic Health in a Murine Model of Early Aging?

Aging is associated with a decline in metabolic health, specifically increased body weight, adiposity, mitochondrial dysfunction, and impaired insulin-stimulated glucose transport contributing to greater incidence of type II diabetes, even in early aging. Previously, we have documented that succinic acid (SA) improves mitochondrial function likely through increased mitochondrial biogenesis; however, the effects of SA on age-related metabolic health are unknown. Therefore, we sought to determine the effect of SA treatment on metabolic health in an early aging mouse model. Methods Metabolic health was measured in 43 mice (24 young (YG) vehicle, 19 aged (16 months); aged mice were randomized to vehicle (n=8) or succinic acid (n=11, 0.75 mg/ml in drinking water), respectively). After 6 weeks of treatment, insulin, glucose, and pyruvate tolerance tests were completed, and physical activity (PA), via spontaneous wheel running, was assessed for both the young and aged mice. Body weight (BW), epididymal white adipose tissue (EWAT) and heart mass measurements were obtained to assess possible effects on obesity, adiposity, and heart health. Results The aged mice had significantly increased BW (YG 27 ± 4 vs. Aged 38 ± 3g), heart weight (YG 0.13 ± 0.01 vs. Aged 0.17 ± 0.01 g), and EWAT mass (YG 0.51 ± 0.08 vs. Aged 1.4 ± 0.38 g) (all, p<0.05). Aged also had reduced pyruvate tolerance (YG 25470 ± 1206 vs. Aged 31883 ± 4348 area under the curve, AUC, p<0.05), though glucose (YG 47119 ± 3460 vs. Aged 43979 ± 8750 AUC) and insulin tolerance (YG 15425 ± 4364 vs. Aged 14928 ± 1762 AUC) were not affected by age (both, p>0.05). PA tended to be ~50% lower in the aged (YG 8778 ± 5774 vs. Aged 4132±1523 rev) mice, while aged mice treated with SA increased PA by 48% (6118 ± 2203 rev). SA treatment had no effect on BW (Aged 37.8 ± 2.7 vs. Aged-SA 37.7 ± 3.2 g), EWAT mass (Aged 1.4 ± 0.4 vs. Aged-SA 1.3 ± 0.4g), nor heart mass (Aged 0.17 ± 0.01 vs. Aged-SA 0.19 ± 0.04g) (all, p>0.05). Despite no significant age difference in glucose tolerance, SA treatment seemed to reduce the AUC in the aged animals (Aged 43979 ± 8750 vs. Age-SA 37181 ± 5383 AUC, p= 0.11); however, no such effect for SA was found with insulin or pyruvate tolerance. Conclusion In a murine model of early aging, despite elevated body weight, adiposity, and heart weight, we found no age-associated impact on glucose or insulin tolerance, though the impaired pyruvate tolerance is suggestive of greater gluconeogenesis in this model of early aging. Treatment with SA had no significant effect on body weight or adiposity, but we did find tendencies for improved glucose tolerance and physical activity. Further work is needed to determine if treatment with succinic acid, an FDA-approved compound, might improve metabolic health with aging.

Velvet Antler Ameliorates Cardiac Function by Restoring Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats With Heart Failure After Myocardial Infarction.

Objective: Velvet antler (VA; cornu cervi pantotrichum), a well-known traditional Chinese medicine, has been shown to exert cardioprotective effects. The purpose of this study was to investigate the effect of VA on heart failure (HF) caused by ischemia-reperfusion, and explore its possible mechanism from the regulation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 alpha (SERCA2a). Methods: A rat model of HF was established by ligating the left anterior descending coronary artery of male Sprague–Dawley rats (n = 88). One week after surgery, VA (200, 400, or 800 mg/[kg day−1]) or enalapril (1 mg/[kg day−1]) was administered daily for the next 4 weeks. Heart function was detected by echocardiography and histopathological analysis. The serum BNP level was measured by ELISA, and the expression of SERCA2a, PLB, PLB-Ser16, and PKA was determined by western blotting. SERCA2a and PLB mRNA levels were determined by real-time quantitative PCR. Results: Compared with the sham group, cardiac function in the HF group, including the serum BNP level, heart mass index, myocardial collagen deposition, and left ventricular ejection fraction, was markedly reduced; however, these changes could be reversed by VA treatment. In addition, VA (200 mg/[kg·d−1]) inhibited the decrease of SERCA2a and PLB mRNA levels and SERCA2a, PLB, PLB-Ser16, and PKA protein expression and restored the activity of SERCA2a and PKA. Enalapril affected only PLB protein expression. Conclusion: VA can improve myocardial fibrosis and ventricular remodeling in rats, thereby helping to restore cardiac function. The underlying mechanism may be related to the upregulation of the expression and activation of PKA and PLB and the restoration of the expression and activity of SERCA2a.

Морфометричні показники міокарда щурів при дії загальної гіпотермії

Hypothermia is a situation in which the internal body temperature drops below 35 degrees Celsius. The article presents the relevance, theoretical aspects and features of the action of general hypothermia on the heart in general and cardiomyocytes in particular. The purpose of the study was to study the changes in the myocardium under the action of general hypothermia at different levels of structural organization. The object of the study were the hearts of laboratory adult rats. The study involved 20 animals. The longitudinal section shows that the right ventricle is much thinner than the left and its cavity is presented in the form of a crescent. The interventricular septum is thicker than the wall of the right ventricle and goes into its cavity. Results. To establish the shape of the heart and track the dynamic changes at the organ level, we calculated an index showing the ratio of the width of the heart to its length. In 80% of cases, the heart shape of intact rats was conical, the index averaged 55%, only 20% elliptical, the index was more than 65%. We did not observe other forms of heart in the group of intact rats. In the experimental groups, a spherical heart shape appeared. The thickness of the anterior wall of the left ventricle for 10 days from the beginning of the experiment was 3.15±0.11 mm, the side wall 3.1±0.11 mm, the posterior wall 2.45±0.04 mm, interventricular septum 2.95±0.09 mm. In the right ventricle, the thickness of the anterior wall is 1.04±0.03 mm, the posterior wall is 1.36±0.04 mm. On the 30th day from the beginning of the experiment, the thickness of the anterior wall of the left ventricle was 3.21±0.11 mm, the side wall 2.65±0.06 mm, the posterior wall 3.27±0.09 mm, the interventricular septum 3.14±0.13 mm. In the right ventricle, the thickness of the anterior wall is 1.09±0.04 mm, the posterior wall is 1.38±0.03 mm. Conclusions. The increase in heart mass, change in its shape due to changes in the middle third of the heart wall of both the left and right ventricles. The highest rates were in the middle third of the heart (zone "B"): In all layers of the myocardium there is an increase in the diameter of cardiomyocytes, a decrease in the distance between individual cardiomyocytes and their groups. The distance between adjacent cardiomyocytes in the left ventricle is: in the outer layer 1/8 of the diameter of the cardiomyocyte, between groups of cardiomyocytes 1/4 of the diameter of the cardiomyocyt

Trans-ovo permethrin exposure affects growth, brain morphology and cardiac development in quail.

Permethrin is a commonly used, highly effective pesticide in poultry agriculture, and has recently been trialed in conservation efforts to protect Galápagos finch hatchlings from an invasive ectoparasite. Although permethrin is considered safe for adults, pesticides can have health consequences when animals are exposed during early life stages. The few studies that have examined permethrin's effects in embryonic chicks and rats have shown hydrocephaly, anencephaly, reduced cellular energy conversion, and disruption of developing heart muscle. To test whether trans-ovo exposure of permethrin affects early development in birds, we exposed Japanese quail (Coturnix japonica) eggs to cotton treated with 1% permethrin that was incorporated into nests in two amounts (0.2, 0.8 g), each with a paired untreated cotton control group. When measured on incubation Day 15, we found permethrin-treated developing birds were smaller and showed signs of microcephaly, although mortality rates were the same. Despite no difference in heart mass, ventricular tissue was less compact, cardiac arteries were reduced and heart rates were slower in permethrin-treated birds. Differences in heart development were also observed at 5 days of incubation, indicating that abnormalities are present from early in cardiac development. Future studies are needed to examine permethrin's effects on developmental pathways and to determine if these effects persist after hatching to affect offspring health. This study provides evidence that permethrin can cross the eggshell to cause non-lethal but adverse effects on embryonic development, and studies should look beyond hatching when monitoring the efficacy of permethrin on wild bird populations.

Establishing a model for studying the effects of maternal hyperthyroidism in utero.

Thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), play a critical role in growth and maintenance in all organ systems. Research suggests that maternal hyperthyroidism is a risk factor for craniosynostosis (CS in infants). CS is characterized by the premature fusion of the cranial sutures, which leads to debilitating side effects. The mechanism of TH-induced CS is obscure. The overall objective of this study is to enhance the knowledge about in utero thyroid-related mechanisms and how they relate to the development of CS. However, a model for study must first be established. It is hypothesized that a dose of T4 between 50 pg and 0.5 ug will induce thyrotoxicosis in an avian model. Fertilized chicken eggs were injected beneath the chorioallantoic membrane with saline and 50pg, 0.5ng, 5.0ng, 50ng and 0.5ug T4. Embryos (N=4-6 per group) were collected at E19. In addition to viability, body and heart mass were recorded. Hyperthyroidism is known to cause a decrease in body mass. Results showed a significant decrease in body mass with 50ng T4 (p&lt;0.001) while maintaining viability (92%). Hyperthyroidism is also known to cause cardiac hypertrophy. Results showed a significant increase in heart to body mass ratio with 50ng T4 (p&lt;0.001). In conclusion, the 50ng T4 is the appropriate dose to maintain viability with accompanied phenotypic changes indicative of thyrotoxicosis. Determining an effective dosage regimen is important for establishing a model for studying the mechanisms of hyperthyroid-induced CS. Supported by the NASA West Virginia Space Grant Consortium (80NSSC20M0055).

RETURN OF NERVE FUNCTION FOLLOWING RENAL DENERVATION IN THE PRESENCE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITION IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Regrowth of renal nerves and functional restoration occurs following renal denervation (RDN). There is little information regarding the impact of concomitant anti-hypertensive therapies on the extent of reinnervation following RDN. Angiotensin-II has previously been shown to promote renal vessel innervation. We hypothesised that angiotensin-converting enzyme inhibition (ACEi) prolongs the antihypertensive effects of RDN by delaying renal nerve regrowth. The aim of this study was to examine the effect of ACEi treatment on the return of nerve function at 12-weeks post-RDN in spontaneously hypertensive rats (SHR). Design and method: Male SHRs (∼12 weeks of age, n &gt; 7/group) were implanted with a radiotelemetry probe to record mean arterial pressure (MAP). Rats were infused with enalapril (1 mg/kg/day s.c.) or vehicle for two weeks. Rats then underwent sham or surgical RDN procedures and ACEi/vehicle infusion continued for an additional 12 weeks following RDN. Vascular contraction to perivascular nerve stimulation in renal lobar arteries was assessed using wire myography to determine the extent of renal nerve function return. Results: ACEi and RDN independently caused an immediate and sustained reduction in MAP (ACEi: -12 ± 3 mmHg, RDN: -19 ± 4 mmHg, both P &lt; 0.05) across the 12-week period compared to untreated counterparts. However, the blood pressure-lowering effect of RDN was not enhanced by concomitant ACEi. Heart mass was ∼16% less in ACEi-RDN rats compared to untreated counterparts. Return of neurovascular function was observed in RDN-treated rats, but levels were only partially restored to that of untreated rats (P &lt; 0.001). ACEi alone attenuated the response to perivascular nerve stimulation (P &lt; 0.05) but the effects of ACEi in combination with RDN were not additive. Conclusions: Here we show partial functional reinnervation is evident 12 weeks following RDN in the SHR. This may account for the sustained reduction in MAP following RDN. ACEi infusion alone attenuated neurovascular function, but ACEi combined with RDN did not affect the return of renal neurovascular function. These findings suggest that RDN and ACEi effectively lower blood pressure in the long term and may confer cardioprotective benefits despite the return of nerve function. However, ACE inhibition does not provide additive benefits to delaying renal reinnervation.

Cardioprotective effects of severe calorie restriction from birth in adult ovariectomized rats

AimsMenopause is a female condition induced by a reduction of ovarian hormone and is related to an increase in cardiovascular diseases in women. We have shown that severe calorie restriction (SCR) from birth reduces the cardiometabolic risk in adult male Wistar rats. In this study, we investigated the effects of SCR from birth to adulthood on cardiovascular function of ovariectomized rats. Main methodsFrom birth to adulthood, rats were daily fed ad libitum (control group - C) or with 50% of the amount consumed by the control group (calorie-restricted group - R). At 90 days, half of the rats in each group underwent bilateral ovariectomy (OVX), totaling 4 groups: C-Sham, C-OVX, R-Sham, R-OVX. Systolic blood pressure (SBP), heart rate (HR) and, double product (DP) index were recorded by tail-cuff plethysmography. Cardiac function was analyzed by the Langendorff technique and cardiomyocyte diameter was accessed by histologic analysis. Additionally, cardiac SERCA2 content and redox status were evaluated. Key findingsC-OVX rats exhibited reduced cardiac function and cardiac non-enzymatic total antioxidant capacity (TAC). R-Sham animals showed reduced SBP, DP, HR, improved cardiac function, reduced cardiac protein carbonyl derivatives and increased TAC, catalase, and superoxide dismutase activities. R-OVX rats maintained reduced SBP, DP, HR, and increased contractility and relaxation indexes. R-Sham and R-OVX rats exhibited preserved heart mass and reduced cardiomyocyte diameter. Cardiac SERCA2 content did not differ between the groups. SignificanceTaken together, our findings show cardioprotective effects of SCR from birth in adult ovariectomized rats.

Use of water-alcohols treatment of medicinal plants under conditions modeling intoxication by lead and cadmium

The results of studying the effects of water-alcohol infusions of medicinal plants - rhizomes of thick-leafed incense (Bergenia crasslifolia L. Fritsch), dioica nettle leaves (Urtica dioca L.), burdock roots (Arctium lappa L.), and mother-and-leaf leaves - are presented. ordinary machichi (Tussilago farfara L.) on the organism of laboratory rats under conditions of short-term intoxication with heavy metals in doses of 25 mg of lead and 2.5 mg of cadmium per 1 kg of live weight. In the course of studies it was found that the effect of heavy metals on the body of laboratory animals is selective - the main “depot” of lead was bone tissue, and cadmium - the kidneys and liver. The addition of 1 ml of water-alcohol infusions from medicinal raw materials to the diet of rats as detoxicants caused a decrease in the level of lead in the animal organism to 6.32 times, cadmium to 3.46 times. The greatest detoxification ability was shown by infusions of the roots of burdock and leaves of nettle dioecious. Under the influence of elevated doses of lead and cadmium in laboratory animals there was an increase in heart mass by 40.34 % and spleen by 89.91 %, a decrease in the content of alkaline phosphatase in blood serum by 25.81 %. Water-alcohol infusions normalized the biochemical parameters of rat blood serum. Studies have shown that the infusions of rhizomes of thick-leafed frangipani, burdock roots, dioecious nettles and coltsfoot leaves with antioxidant properties can be the basis for the development of an effective herbal preparation used for the prevention and treatment of animals from intoxication with salts of heavy metals.

Evaluating Matching by Predicted Heart Mass in Adolescent Heart Transplantation: Analysis of the United Network for Organ Sharing Database

<h3>Purpose</h3> Predicted Heart Mass (PHM) has emerged as an attractive size matching metric in adult cardiac transplantation. However, since PHM was derived from a healthy adult cohort, its generalizability to the pediatric population is unclear. We hypothesize that PHM can be extended to older adolescents, and potentially broaden the donor pool available to this group. <h3>Methods</h3> The United Network for Organ Sharing database was retrospectively analyzed for patients aged 13-18 undergoing heart transplantation. Recipients were divided into quintiles (Q1-Q5) based on donor-to-recipient predicted heart mass ratios (PHMR). Primary endpoint was graft survival at five years. <h3>Results</h3> 1727 adolescent heart transplant recipients between January 1994 and September 2019 were retrospectively analyzed. The median PHMR's for each quintile was 0.85 (0.60 to 0.92), 0.98 (0.92 to 1.03), 1.08 (1.03 to 1.14), 1.22 (1.14 to 1.31), and 1.44 (1.31 to 2.3). Kaplan-Meier survival curves demonstrated comparable survival across all quintiles of PHMR (p=0.9). Multivariate Cox regression showed no significant difference in graft failure of the outer quintiles when compared to the middle quintile (Q1: 0.98 HR, p=0.93; Q2: 0.93 HR, p=0.69; Q4: 1.14 HR, p=0.46; Q5: 1.05 HR, p=0.79). Significant covariates included transplant year (HR: 0.95, p<0.0001), serum bilirubin (HR: 1.06, p=0.002), ECMO at transplantation (HR: 1.89, p=0.035), recipient age (HR: 1.14, p=0.0013), number of previous transplantations (HR: 1.59, p=0.007), and underlying diagnosis of congenital heart disease (vs. dilated cardiomyopathy, HR: 1.69, p=0.0005). Ischemic time in hours (HR: 1.08, p=0.17) and mechanical circulatory support at transplantation (HR: 0.91, p=0.49) were not significant. <h3>Conclusion</h3> Matching by PHM is not associated with survival or risk in adolescent heart transplant recipients. Our results underscore the ongoing need to develop an improved size-matching method in pediatric heart transplantation.

Recipient Morbid Obesity Worsens Post Heart Transplantation Survival

PurposeMorbid obesity (body mass index (BMI) ≥ 35kg/m2) is a relative contraindication for a heart transplant (HT). However, the clinical outcome of these HT recipients is not well established. This study examined the clinical outcome of morbidly obese patients who underwent HT in The United States.MethodsWe included adult patients who underwent HT between 2000 and 2018 in the Scientific Registry of Transplant Recipients with available BMI information. We compared 30-day, 1-, 5-, and 10-year survival of those with a BMI≥ 35 kg/m2 and BMI = 18.5-34.99 kg/m2. Cox proportional hazards regression models then determined the influence of BMI category on survival adjusting for known recipient and donor risk factors, including Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score and predicted heart mass ratio.Results36,115 adult HT recipients were included: 2638 (7.3%) morbidly obese. The median (inter-quartile range) age was 55 (46, 62) years, 24.7% were female, and follow-up was 4.1 (1.1, 8.3) years. Morbidly obese patients had more hypertension (p<0.0001), diabetes (p<0.0001), and VAD use (p<0.0001). Survival among morbidly obese compared to other group was lower at 30-day, 1-, 5- , and 10-years. After adjustment for known risks, morbid obesity was associated with higher post-transplant 30-day (HR 1.64, 95% CI 1.37-1.97), 1-year (HR 1.50, 1.33-1.69), 5-year (HR 1.36, 1.24-1.49), and 10-year mortality risk (HR 1.28, 1.19-1.39).ConclusionSurvival following HT was significantly lower in recipients with morbid obesity. The risk associated with BMI≥ 35kg/m2 should be considered at the time of transplant assessment. Morbid obesity (body mass index (BMI) ≥ 35kg/m2) is a relative contraindication for a heart transplant (HT). However, the clinical outcome of these HT recipients is not well established. This study examined the clinical outcome of morbidly obese patients who underwent HT in The United States. We included adult patients who underwent HT between 2000 and 2018 in the Scientific Registry of Transplant Recipients with available BMI information. We compared 30-day, 1-, 5-, and 10-year survival of those with a BMI≥ 35 kg/m2 and BMI = 18.5-34.99 kg/m2. Cox proportional hazards regression models then determined the influence of BMI category on survival adjusting for known recipient and donor risk factors, including Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score and predicted heart mass ratio. 36,115 adult HT recipients were included: 2638 (7.3%) morbidly obese. The median (inter-quartile range) age was 55 (46, 62) years, 24.7% were female, and follow-up was 4.1 (1.1, 8.3) years. Morbidly obese patients had more hypertension (p<0.0001), diabetes (p<0.0001), and VAD use (p<0.0001). Survival among morbidly obese compared to other group was lower at 30-day, 1-, 5- , and 10-years. After adjustment for known risks, morbid obesity was associated with higher post-transplant 30-day (HR 1.64, 95% CI 1.37-1.97), 1-year (HR 1.50, 1.33-1.69), 5-year (HR 1.36, 1.24-1.49), and 10-year mortality risk (HR 1.28, 1.19-1.39). Survival following HT was significantly lower in recipients with morbid obesity. The risk associated with BMI≥ 35kg/m2 should be considered at the time of transplant assessment.

Size Matching and Combined Heart Kidney Transplantation - UNOS Registry Analysis

<h3>Purpose</h3> Optimal size-matching metrics for prediction of outcomes after combined heart-kidney transplantation (HKT) are unknown. <h3>Methods</h3> Combined HKTs performed between January 2000 and April 2019 were analyzed using United Network of Organ Sharing registry. Size metrics (weight, height, body mass index (BMI) and predicted heart mass (PHM)) were divided into seven equally sized groups using donor-to-recipient ratio. Kaplan-Meier survival and Cox proportional hazard analyses were performed to assess composite risk of mortality or re-transplantation at 1-year. <h3>Results</h3> A total of 1,290 recipients were analyzed; 155 events occurred (n=153 deaths; n=4 re-transplants). Compared to a well-matched cohort, severe under-sizing by either PHM (0.56 to 0.85; hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.02-3.08, p=0.042) or weight (0.50 to 0.80; HR 2.00, 95% CI 1.14-3.52, p=0.015), but not BMI and height, was associated with an increased risk of events. Upon categorizing recipients into 4 groups based on presence or absence of severe under-sizing by either PHM or weight ratio, those whose donors were severely undersized for both were at significantly higher risk of poor outcomes (HR 2.74, 95% CI 1.78-4.19, p<0.001) compared to those whose donors were severely undersized by either (PHM alone: HR 0.84, 95% CI 0.42-1.67, p=0.623; weight ratio alone: HR 0.86, 95% CI 0.42-1.78, p=0.692) or none (reference category). <h3>Conclusion</h3> Recipients of combined HKT whose donors were severely undersized based on both weight ratio and PHM had significantly worse outcomes compared to those whose donors were severely undersized by either parameter alone or not at all.

Severe Recipient Obesity Decreases Post Heart Transplant Survival

<h3>Purpose</h3> Severe obesity, defined as body mass index (BMI) ≥ 40 kg/m², is a contraindication for a heart transplant (HT). However, practice varies across transplant centers. This study examined the post-transplant survival of these patients who underwent HT in the United States. <h3>Methods</h3> We included adult patients who underwent HT between 2000 and 2018 in the Scientific Registry of Transplant Recipients with available BMI information. We compared 30-day, 1-, 5- and 10-year survival of those with a BMI≥ 40 kg/m² with BMI = 18.5-39.99 kg/m² using the Kaplan-Meier method. Cox proportional hazards regression models then determined the influence of BMI category on survival adjusting for known recipient and donor risk factors, including Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score and predicted heart mass ratio. <h3>Results</h3> 36,115 adult HT recipients were included: 275 (0.8%) severely obese. The median (inter-quartile range) age was 55 (46, 62) years, and 25.4% were female. Severely obese patients had more hypertension (p=0.0019), diabetes (p<0.0001), and VAD use (p<0.0001). During a median follow-up of 4.1 (1.1, 8.3) years, 11,219 (30.3%) recipients died. Survival among severely obese compared to other groups was lower at 30-day, 1-, 5-, and 10-years (Figure; p<0.0001 for all). After adjustment for known risks, morbid obesity was associated with significantly higher post-transplant 30-day (HR 1.75, 95% CI 1.28-2.73; p=0.0125), 1-year (HR 1.44, 1.04-1.99; p=0.0260), 5-year (HR 1.27, 1.00-1.61; p=0.0541), and 10-year mortality risk (HR 1.31, 1.07-1.60; p=0.0094). <h3>Conclusion</h3> Survival following HT was significantly lower in recipients with severe obesity. Severe obesity should be addressed before HT is considered.