Search

Objectives: To ascertain the impact of skin-to-skin care between parents and infants on cardiac function and cerebral blood flow in preterm infants. Study design: We undertook a prospective study of 40 self-ventilating preterm infants at a quaternary center and assessed cardiac performance and cerebral blood flow. Assessments were carried out two hours before skin-to-skin care and then 60 minutes after skin-to-skin care (with the infant still on parent and turned supine). Result(s): Infants were 30.5 +/- 0.6 weeks' gestational age and 1378 +/- 133 g birthweight. Axillary temperature noted a nonsignificant increase during skin-to-skin care from 36.7 +/- 0.07degreeC to 36.9 +/- 0.07degreeC (P =.07). Cardiac contractility (right ventricular fractional area change [26.5% +/- 0.3% vs 27.8% +/- 0.4; P <.001] and tricuspid annular plane systolic excursion [0.73 +/- 0.03 cm vs 0.77 +/- 0.03 cm; P =.02]) increased significantly, coincident with decreased measures of pulmonary vascular resistance. An increase in systemic cardiac output was associated with increased cerebral blood flow and reduced middle cerebral artery resistive index (0.81 +/- 0.02 vs 0.74 +/- 0.02; P =.0001). Conclusion(s): We documented a significant circulatory beneficial adaptation to a common neonatal practice. These findings align with previously documented physiologic benefits in cardiorespiratory stability and cardiac rhythm in preterm infants, and may be mediated through modulation of the autonomic nervous system.Copyright © 2020 Elsevier Inc.

Objectives: To ascertain the impact of skin-to-skin care between parents and infants on cardiac function and cerebral blood flow in preterm infants. Study design: We undertook a prospective study of 40 self-ventilating preterm infants at a quaternary center and assessed cardiac performance and cerebral blood flow. Assessments were carried out two hours before skin-to-skin care and then 60 minutes after skin-to-skin care (with the infant still on parent and turned supine). Result(s): Infants were 30.5 +/- 0.6 weeks' gestational age and 1378 +/- 133 g birthweight. Axillary temperature noted a nonsignificant increase during skin-to-skin care from 36.7 +/- 0.07degreeC to 36.9 +/- 0.07degreeC (P =.07). Cardiac contractility (right ventricular fractional area change [26.5% +/- 0.3% vs 27.8% +/- 0.4; P <.001] and tricuspid annular plane systolic excursion [0.73 +/- 0.03 cm vs 0.77 +/- 0.03 cm; P =.02]) increased significantly, coincident with decreased measures of pulmonary vascular resistance. An increase in systemic cardiac output was associated with increased cerebral blood flow and reduced middle cerebral artery resistive index (0.81 +/- 0.02 vs 0.74 +/- 0.02; P =.0001). Conclusion(s): We documented a significant circulatory beneficial adaptation to a common neonatal practice. These findings align with previously documented physiologic benefits in cardiorespiratory stability and cardiac rhythm in preterm infants, and may be mediated through modulation of the autonomic nervous system.Copyright © 2020 Elsevier Inc.

Subchronic intoxications induced in male rats by repeated intraperitoneal injections of lead acetate and cadmium chloride, administered either alone or in combination, are shown to affect the biochemical, cytological and morphometric parameters of blood, liver, heart and kidneys. The single twitch parameters of myocardial trabecular and papillary muscle preparations were measured in the isometric regime to identify changes in the heterometric (length-force) and chronoinotropic (frequency-force) contractility regulation systems. Differences in the responses of these systems in trabecules and papillary muscles to the above intoxications are shown. A number of myocardium mechanical characteristics changing in rats under the effect of a combined lead-cadmium intoxication and increased proportion of α-myosin heavy chains were observed to normalize fully or partially if such intoxication was induced against background administration of a proposed bioprotective complex. Based on the experimental results and literature data, some assumptions are suggested concerning the mechanisms of the cardiotoxic effects produced by lead and cadmium. © 2020

Length-dependent activation (LDA) of contraction is an important mechanism of proper myocardial function that is often blunted in diseases accompanied by deficient contractility and impaired calcium homeostasis. We evaluated how the extent of LDA is related to the decreased force in healthy rat myocardium under negative inotropic conditions that affect the calcium cycle. The length-dependent effects on auxotonic twitch and Ca-transient were compared in isolated rat ventricular cardiomyocytes at room temperature (“25C”) and near-physiological temperature (“35C”) in normal Tyrode and at 25°C with thapsigargin-depleted sarcoplasmic reticulum (“25C + Thap”). At the slack length, a similar negative inotropy in “35C” and “25C + Thap” was accompanied by totally different changes in Ca-transient amplitude, time-to-peak, and time-to-decline from peak to 50% amplitude. End-systolic/end-diastolic tension-sarcomere length relationships were obtained for each individual cell, and the ratio of their slopes, the dimensionless Frank-Starling Gain index, was 2.32 ± 0.16, 1.78 ± 0.09, and 1.37 ± 0.06 in “25C,” “35C” and “25C + Thap,” respectively (mean ± S.E.M.). Ca-transient diastolic level and amplitude did not differ between “25C” and “35C” at any SL, but in “35C” it developed and declined significantly faster. In contrast, thapsigargin-induced depletion of SERCA2a significantly attenuated and retarded Ca-transient. The relative amount of Ca2+ utilized by troponin C, evaluated by the integral magnitude of a short-lived component of Ca-transient decline (“bump”), increased by ~25% per each 0.05 μm increase in SL in all groups. The kinetics of the Ca-TnC dissociation, evaluated by the bump time-to-peak, was significantly faster in “35C” and slower in “25C + Thap” vs. “25C” (respectively, 63.7 ± 5.3 and 253.6 ± 8.3% of the value in “25C,” mean ± S.E.M.). In conclusion, a similar inotropic effect can be observed in rat ventricular myocardium under totally different kinetics of free cy

Background: A large body of evidence suggests a low-fat diet is an essential element of primary prevention in cardiovascular disease and heart failure (HF). Current HF guidelines do not have an endorsed dietary fat advice for patients with established HF; therefore most clinicians apply the same restricted fat diet for prevention of atherosclerotic disease to HF patients. Objective(s): To determine the current evidence of effectiveness and a review of a low-fat diet in HF. Method(s): This review was performed by a comprehensive literature searching in PubMed and Embase in a range of subjects from basic to clinical studies, addressing the role of dietary fat in myocardial contractility and clinical outcomes in both animal and human models. We selected 13 studies (8 human and 5 animal) satisfying the eligibility and the out-comes of interest. Result(s): There were 51874 human and 102 animal subjects included in this review. Substantial role of fatty acids (FA) as the primary source of energy for the myocardium is well established. Several animal-based laboratory studies suggested high FA improves cardiac contractility and prolongs survival in rodents with HF. Evidence shows a low concentration of low-density lipoprotein in plasma is associated with a poor prognosis in HF patients. (Fig. 1) [Figure Presented]. Conclusion(s): This review has identified a deficiency in current dietary fat advice in HF clinical guidelines, particularly those with severely reduced LV ejection fraction. Need for a large randomised clinical trial to assess the cause-effect of fat diet on myocardial function and long-term prognosis in this subset is highly demanded.

The slow force response (SFR) of a cardiac muscle to a sudden stretch is thought to be important in the regulatory adaptation of myocardial contraction. Autocrine-paracrine regulation pathways which involve angiotensin II are participating in this mechanism. On the other hand, renin-angiotensin-aldosterone system (RAS) is altered in hypertrophic or failing myocardium. We compared the effects of sudden stretch to SFR as well as to twitch and Ca2+ transient characteristics in rat myocardium with monocrotaline-induced heart failure with those in normal rat myocardium without and with inhibition of angiotensin II type-1 (AT1) receptors. Our findings indicate that the myocardium of rats with monocrotaline-induced right ventricular failure is deficient with activation of local RAS and therefore expresses blunted SFR, very similar to the depression of SFR observed in normal myocardium under inhibition of AT1 receptors. The "failing" myocardium does not further respond to the "putative" inhibition of AT1 receptors by losartan. In conclusion, SFR is related to autocrine-paracrine regulation of myocardial contraction in normal rat myocardium and that the involvement of RAS into stretch-induced modulation of contractility may be significantly altered in failing heart. © 2018 Slovak Academy of Sciences. All rights reserved.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.Copyright © 2015 The British Pharmacological Society.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.Copyright © 2015 The British Pharmacological Society.

Objective: Pulmonary hypertension and right ventricular performance and not left sided dysfunction are highlighted in the cardiovascular effects of bronchopulmonary dysplasia (BPD). Our study objective was to assess left sided vascular and cardiac indices which may reflect elevated systemic afterload and resultant pulmonary venous back pressure and consider possible therapeutic options. Method(s): Vascular biophysical and cardiac parameters were measured by ultrasonography in 20 infants with severe BPD and 20 healthy term infants. Result(s): Maximum aortic thickness was greater in BPD infants (827.5+/-163 vs 657.5+/-67.8 m, p<0.0001). Biophysical arterial markers [stiffness index (3.4+/- 0.6 vs 2.3+/-0.4, p<0.0001), input impedance (574.4+/-127.4 vs 328.1+/-113.2 dynes.s/cm5, p<0.0001) and circumferential wall tension (23126.8+/-2395 vs 20613.8+/-2242.4 d/cm, p=0.001)] were elevated. Left ventricular diastolic dysfunction [(elevated E/A ratio (0.9+/-0.09 vs 1.07+/-0.07, p<0.0001), prolonged E wave deceleration time (60.4+/-7 vs 75.6+/-7.9ms, p<0.0001), Isovolumic relaxation time (54 (49, 57) vs 68 (67, 71.7) ms, p<0.0001) and reduced pulmonary venousflow(VTI, 8.2+/-0.3 vs 5.4+/-0.4cm, p<0.0001) were noted. Themeanvelocity of circumferential fibre shortening (3+/-0.64 vs 1.7+/-0.42 circ/sec, p<0.0001) and Tei index (0.27+/-0.05 vs 0.33+/-0.05, p=0.001) was altered. Conclusion(s): Increased downstream stiffness, reduced myocardial contractility and elevated atrial/pulmonary venous back pressure may lead to pulmonary venous congestion and continued need for respiratory support. Systemic afterload reduction as a therapeutic option merits prospective analysis.

Objective: Pulmonary hypertension and right ventricular performance and not left sided dysfunction are highlighted in the cardiovascular effects of bronchopulmonary dysplasia (BPD). Our study objective was to assess left sided vascular and cardiac indices which may reflect elevated systemic afterload and resultant pulmonary venous back pressure and consider possible therapeutic options. Method(s): Vascular biophysical and cardiac parameters were measured by ultrasonography in 20 infants with severe BPD and 20 healthy term infants. Result(s): Maximum aortic thickness was greater in BPD infants (827.5+/-163 vs 657.5+/-67.8 m, p<0.0001). Biophysical arterial markers [stiffness index (3.4+/- 0.6 vs 2.3+/-0.4, p<0.0001), input impedance (574.4+/-127.4 vs 328.1+/-113.2 dynes.s/cm5, p<0.0001) and circumferential wall tension (23126.8+/-2395 vs 20613.8+/-2242.4 d/cm, p=0.001)] were elevated. Left ventricular diastolic dysfunction [(elevated E/A ratio (0.9+/-0.09 vs 1.07+/-0.07, p<0.0001), prolonged E wave deceleration time (60.4+/-7 vs 75.6+/-7.9ms, p<0.0001), Isovolumic relaxation time (54 (49, 57) vs 68 (67, 71.7) ms, p<0.0001) and reduced pulmonary venousflow(VTI, 8.2+/-0.3 vs 5.4+/-0.4cm, p<0.0001) were noted. Themeanvelocity of circumferential fibre shortening (3+/-0.64 vs 1.7+/-0.42 circ/sec, p<0.0001) and Tei index (0.27+/-0.05 vs 0.33+/-0.05, p=0.001) was altered. Conclusion(s): Increased downstream stiffness, reduced myocardial contractility and elevated atrial/pulmonary venous back pressure may lead to pulmonary venous congestion and continued need for respiratory support. Systemic afterload reduction as a therapeutic option merits prospective analysis.

AimsWe explored the use of highly purified murine and human pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) to generate functional bioartificial cardiac tissue (BCT) and investigated the role of fibroblasts, ascorbic acid (AA), and mechanical stimuli on tissue formation, maturation, and functionality.Methods and resultsMurine and human embryonic/induced PSC-derived CMs were genetically enriched to generate three-dimensional CM aggregates, termed cardiac bodies (CBs). Addressing the critical limitation of major CM loss after single-cell dissociation, non-dissociated CBs were used for BCT generation, which resulted in a structurally and functionally homogenous syncytium. Continuous in situ characterization of BCTs, for 21 days, revealed that three critical factors cooperatively improve BCT formation and function: both (i) addition of fibroblasts and (ii) ascorbic acid supplementation support extracellular matrix remodelling and CB fusion, and (iii) increasing static stretch supports sarcomere alignment and CM coupling. All factors together considerably enhanced the contractility of murine and human BCTs, leading to a so far unparalleled active tension of 4.4 mN/mm2 in human BCTs using optimized conditions. Finally, advanced protocols were implemented for the generation of human PSC-derived cardiac tissue using a defined animal-free matrix composition.ConclusionBCT with contractile forces comparable with native myocardium can be generated from enriched, PSC-derived CMs, based on a novel concept of tissue formation from non-dissociated cardiac cell aggregates. In combination with the successful generation of tissue using a defined animal-free matrix, this represents a major step towards clinical applicability of stem cell-based heart tissue for myocardial repair. © 2013 The Author.

Birth is accompanied by a series of rapid adaptations of the cardiovascular system, one of the most notable being a doubling of left ventricular (LV) stroke volume. What makes this increase in LV stroke volume remarkable is that before birth the heart functions at a maximal level that cannot easily be increased with acute interventions such as volume infusion. Although changes in heart rate, contractility and afterload contribute to the adaptations of birth they do not adequately explain the doubling of LV stroke volume. Early studies obscured the role that ventricular preload plays in controlling fetal and newborn cardiac function by focusing on these other mechanisms and by failing to appreciate fully the significance of ventricular constraint in limiting heart function. Recent evidence suggests that ventricular constraint, arising from the tissues that surround the heart (chest wall, lungs and pericardium), limits fetal ventricular preload and thus determines the limits of fetal cardiac function. Relief of this constraint at birth, with aeration of the lungs and clearance of the lung liquid associated with the fetal lungs, may be the key mechanism that increases LV preload and thus increases LV stroke volume in the newborn.

Inflammation plays an important role in mediating and exacerbating myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, facilitates inflammation and modulates metabolism. However, the role of MIF in mediating local inflammation subsequent to ischemic myocardial injury has not been established. We hypothesized that genetic deletion of MIF protects the heart against severe I/R injury by suppressing inflammation and/or modulating energy metabolism. We showed in the mouse I/R model that duration of both ischemia and reperfusion is a determinant for the degree of regional inflammation and tissue damage. Following a prolonged cardiac I/R (60 min/24 h) MIF KO mice had a significant reduction in both infarct size (26 +/- 3% vs 45 +/- 4%, P< 0.05) and cardiomyocyte apoptosis (1.4 +/- 0.2% vs 5.4 +/- 0.4%, P< 0.05) and preserved contractile function compared with WT. MIF KO mice with I/R had reduced expression of various inflammatory cytokines and mediators (P< 0.05), suppressed infiltration of neutrophils (- 40%) and macrophages (- 33%, both P< 0.05), and increased macrophage apoptosis (14.4 +/- 1.4% vs 5.2 +/- 0.6%, P< 0.05). Expression of toll-like receptor-4 (TLR-4), phosphorylation of c-Jun N-terminal kinase (JNK), and nuclear fraction of NF-kappaB p65 were also significantly lower in MIF KO hearts with I/R. Further, MIF KO mice exhibited a lower glucose uptake but higher fatty acid oxidation rate than that in WT (both P< 0.05). In conclusion, MIF deficiency protected the heart from prolonged/severe I/R injury by suppressing inflammatory responses. We have identified a critical role of MIF in mediating severe I/R injury. Thus, MIF inhibitory therapy may be a novel strategy to protect the heart against severe I/R injury. © 2011 Elsevier Ltd.

Background: Current clinical heart preservation is still limited to 6 hours. A suitable heart transplantation model to rapidly screen the effectiveness of new solutions is essential. This study examines a new screening test-a modification of the conventional abdominal rat heart transplantation model that overcomes its serious limitation of lack of quantitative evaluation of function. Method(s): Rat hearts, with an externalized intraventricular balloon-tipped catheter, were transplanted immediately (controls) or flushed and stored in colloid-free University of Wisconsin solution in ice for 6, 9, or 12 hours before transplantation. One and 7 days later this catheter was connected to a pressure transducer and a calibrated syringe. Heart rate, maximum developed pressure, and maximum rate of left ventricular pressure rise were determined. Grafts were prepared for histologic study on day 7. Result(s): All preserved hearts commenced beating within 2 minutes (controls beat within 20 seconds). On day 1 the heart rate and chamber stiffness (DELTAP/DELTAt) were similar in all groups. The 9- and 12- hour-preserved hearts had significantly (p < 0.05) diminished developed pressure and contractility. On day 7 contractility and developed pressure improved in 9- and 12-hour-preserved grafts. There was extensive muscular atrophy and necrosis, with extensive cellular infiltrate in the 9- and 12- hour-preserved grafts; other grafts showed no damage. Conclusion(s): This quantitative model provides an ischemia-related gradation of function and greater discrimination than conventional methods. It has refuted previous studies suggesting effective preservation for 20 hours and demonstrated that functional testing is essential in evaluating preservation regimens.

Birth is accompanied by a series of rapid adaptations of the cardiovascular system, one of the most notable being a doubling of left ventricular (LV) stroke volume. What makes this increase in LV stroke volume remarkable is that before birth the heart functions at a maximal level that cannot easily be increased with acute interventions such as volume infusion. Although changes in heart rate, contractility and afterload contribute to the adaptations of birth they do not adequately explain the doubling of LV stroke volume. Early studies obscured the role that ventricular preload plays in controlling fetal and newborn cardiac function by focusing on these other mechanisms and by failing to appreciate fully the significance of ventricular constraint in limiting heart function. Recent evidence suggests that ventricular constraint, arising from the tissues that surround the heart (chest wall, lungs and pericardium), limits fetal ventricular preload and thus determines the limits of fetal cardiac function. Relief of this constraint at birth, with aeration of the lungs and clearance of the lung liquid associated with the fetal lungs, may be the key mechanism that increases LV preload and thus increases LV stroke volume in the newborn.

Inflammation plays an important role in mediating and exacerbating myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, facilitates inflammation and modulates metabolism. However, the role of MIF in mediating local inflammation subsequent to ischemic myocardial injury has not been established. We hypothesized that genetic deletion of MIF protects the heart against severe I/R injury by suppressing inflammation and/or modulating energy metabolism. We showed in the mouse I/R model that duration of both ischemia and reperfusion is a determinant for the degree of regional inflammation and tissue damage. Following a prolonged cardiac I/R (60 min/24 h) MIF KO mice had a significant reduction in both infarct size (26 +/- 3% vs 45 +/- 4%, P< 0.05) and cardiomyocyte apoptosis (1.4 +/- 0.2% vs 5.4 +/- 0.4%, P< 0.05) and preserved contractile function compared with WT. MIF KO mice with I/R had reduced expression of various inflammatory cytokines and mediators (P< 0.05), suppressed infiltration of neutrophils (- 40%) and macrophages (- 33%, both P< 0.05), and increased macrophage apoptosis (14.4 +/- 1.4% vs 5.2 +/- 0.6%, P< 0.05). Expression of toll-like receptor-4 (TLR-4), phosphorylation of c-Jun N-terminal kinase (JNK), and nuclear fraction of NF-kappaB p65 were also significantly lower in MIF KO hearts with I/R. Further, MIF KO mice exhibited a lower glucose uptake but higher fatty acid oxidation rate than that in WT (both P< 0.05). In conclusion, MIF deficiency protected the heart from prolonged/severe I/R injury by suppressing inflammatory responses. We have identified a critical role of MIF in mediating severe I/R injury. Thus, MIF inhibitory therapy may be a novel strategy to protect the heart against severe I/R injury. © 2011 Elsevier Ltd.

Background: Current clinical heart preservation is still limited to 6 hours. A suitable heart transplantation model to rapidly screen the effectiveness of new solutions is essential. This study examines a new screening test-a modification of the conventional abdominal rat heart transplantation model that overcomes its serious limitation of lack of quantitative evaluation of function. Method(s): Rat hearts, with an externalized intraventricular balloon-tipped catheter, were transplanted immediately (controls) or flushed and stored in colloid-free University of Wisconsin solution in ice for 6, 9, or 12 hours before transplantation. One and 7 days later this catheter was connected to a pressure transducer and a calibrated syringe. Heart rate, maximum developed pressure, and maximum rate of left ventricular pressure rise were determined. Grafts were prepared for histologic study on day 7. Result(s): All preserved hearts commenced beating within 2 minutes (controls beat within 20 seconds). On day 1 the heart rate and chamber stiffness (DELTAP/DELTAt) were similar in all groups. The 9- and 12- hour-preserved hearts had significantly (p < 0.05) diminished developed pressure and contractility. On day 7 contractility and developed pressure improved in 9- and 12-hour-preserved grafts. There was extensive muscular atrophy and necrosis, with extensive cellular infiltrate in the 9- and 12- hour-preserved grafts; other grafts showed no damage. Conclusion(s): This quantitative model provides an ischemia-related gradation of function and greater discrimination than conventional methods. It has refuted previous studies suggesting effective preservation for 20 hours and demonstrated that functional testing is essential in evaluating preservation regimens.

Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood.

[No abstract available]

[No abstract available]

[No abstract available]

[No abstract available]

The influence of therapeutic doses of guanethidine (1 mg/kg of body weight) and double this dose, on the contractile activity and ultrastructure of the myocardium and on catecholamine content in cardiac muscle and adrenal glands was studied using rabbits. A 0.1% solution of the drug was administered subcutaneously for 14 days. It was established that a 2 wk period of guanethidine administration resulted in weakening of the contractile activity of the left ventricle, and decrease of epiniphrine and norepinephrine content in the myocardium. Electron microscopy of the myocardium showed changes in ultrastructure of muscle cells, intracellular deposits of glycogen, increase of lipid content and some mitochondrial destruction. The data obtained reveal disorders of energy metabolism in muscle cells due to guanethidine.

[No abstract available]

[No abstract available]

[No abstract available]

[No abstract available]

[No abstract available]

[No abstract available]

[No abstract available]