Background: Human engineered heart tissue (EHT) transplantation represents a potential regenerative strategy for heart failure patients and has been successful in preclinical models. Clinical application requires upscaling, adaptation to good manufacturing practices (GMP) and determination of the effective dose. Methods: Cardiomyocytes were differentiated from three different human induced pluripotent stem cell (hiPSC) lines including one reprogrammed under GMP conditions. Protocols for hiPSC expansion, cardiomyocyte differentiation and EHT generation were adapted to substances available in GMP quality. EHT geometry was modified to generate patches suitable for transplantation in a small animal model and perspectively humans. Repair efficacy was evaluated at 3 doses in a cryo-injury guinea pig model. Human-scale patches were epicardially transplanted onto healthy hearts in pigs to assess technical feasibility. Results: We created mesh structured tissue patches for transplantation in guinea pigs (1.5x2.5 cm, 9-15x10 6 cardiomyocytes) and pigs (5x7 cm, 450 x10 6 cardiomyocytes). EHT patches coherently beat in culture and developed high force (mean 4.6 mN). Cardiomyocytes matured, aligned along the force lines, and demonstrated advanced sarcomeric structure and action potential characteristics closely resembling human ventricular tissue. EHT patches containing ~4.5, 8.5, 12x10 6 or no cells were transplanted 7 days after cryo-injury (n=18-19 per group). EHT transplantation resulted in a dose-dependent remuscularization (graft size: 0-12% of the scar). Only high-dose patches improved left-ventricular function (+8% absolute, +24% relative increase). The grafts showed time-dependent cardiomyocyte proliferation. While standard EHT patches did not withstand transplantation in pigs, the human-scale patch enabled successful patch transplantation. Conclusions: EHT patch transplantation resulted in a partial remuscularization of the injured heart and improved left-ventricular function in a dose-dependent manner in a guinea pig injury model. Human scale patches were successfully transplanted in pigs in a proof-of-principle study.

NCT02319083.

Despite a higher risk profile in the ViV group, early mortality rates were not different compared with those of surgery. Although ViV resulted in elevated transvalvular gradients and therefore a lower rate of device success, mortality rates were similar to those with redo-SAVR. At present, both techniques serve as complementary approaches, and allow individualized patient care with excellent outcomes.

SummaryThe results of treatment with frusemide in 105 patients with established acute renal failure admitted during the past six years were reviewed and compared with control groups. Daily doses of2,000 mg of frusemide administered from the day of admission onwards produced a significant increase in the number of patients who attained a diuresis and decreased the duration of oliguria.The reduction in the time spent in hospital and in the number of dialyses required suggests that the use of frusemide in these large doses is indicated in patients with severe established acute renal failure.

Normal pregnant women and rats undergo a volume expansion. Atrial natriuretic peptide (ANP) is involved in volume homeostasis and is stimulated in response to volume expansion in nonpregnant animals, resulting in natriuresis and diuresis. The conscious, chronically catheterized rat was used to measure mean arterial blood pressure (MABP) and renal responses to administered ANP (160 ng.kg-1.min-1 i.v.) to determine if the actions of ANP are altered by pregnancy. These experiments examined virgin (n = 7) and pregnant rats, studied on gestational days 7-9 (n = 9) and 15-17 (n = 7). Renal clearance studies (with inulin and p-aminohippurate) were conducted in control conditions and during 60 min of ANP infusion. After the ANP infusion, plasma ANP concentrations were measured in virgin and pregnant rats. MABP fell with ANP infusion to similar absolute values in virgins (112 +/- 2 to 80 +/- 6 mmHg), 7- to 9-day pregnant (114 +/- 2 to 91 +/- 3 mmHg), and 15- to 17-day pregnant (107 +/- 2 to 88 +/- 4 mmHg) rats although the percent decline in MABP in 15- to 17-day pregnant rats was less than in virgins. Plasma ANP concentrations were similar in all groups. ANP had no effect on glomerular filtration rate, renal plasma flow, or renal vascular resistance in virgin or pregnant rats. ANP increased sodium excretion in virgins and in 7- to 9-day pregnant rats (+102 +/- 27 and +135 +/- 47%, respectively) but not in 15- to 17-day pregnant animals (+23 +/- 22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Este estudo descritivo, de natureza quantitativa, visou: identificar o tempo médio de assistência de enfermagem despendido e requerido pelos Recém-Nascidos (RN) internados na Unidade Neonatal do Hospital Universitário da Universidade de São Paulo; calcular o custo do tempo médio de assistência de enfermagem despendido e requerido por RN; verificar o montante financeiro da adequação do quadro de profissionais de enfermagem requerido para assistir os RN. O tempo médio de assistência despendido pela equipe de enfermagem e requerido pelos RN foi calculado por meio de equações disponíveis na literatura e aplicação do Nursing Activities Score. O custo do tempo médio de assistência e do montante financeiro da adequação do quadro de profissionais foi calculado com base no custo/hora dos enfermeiros e dos técnicos de enfermagem. O impacto financeiro da adequação quantitativa de profissionais de enfermagem correspondeu a um acréscimo de 30% no custo do quadro existente.

IntroductionWe investigated whether treatment with terlipressin during recovery from hypotension due to haemorrhagic shock (HS) is effective in restoring cerebral perfusion pressure (CPP) and brain tissue markers of water balance, oxidative stress and apoptosis.MethodsIn this randomised controlled study, animals undergoing HS (target mean arterial pressure (MAP) 40 mmHg for 30 minutes) were randomised to receive lactated Ringer’s solution (LR group; n =14; volume equal to three times the volume bled), terlipressin (TERLI group; n =14; 2-mg bolus), no treatment (HAEMO group; n =12) or sham (n =6). CPP, systemic haemodynamics (thermodilution technique) and blood gas analyses were registered at baseline, shock and 5, 30, 60 (T60), 90 and 120 minutes after treatment (T120). After the animals were killed, brain tissue samples were obtained to measure markers of water balance (aquaporin-4 (AQP4)), Na+-K+-2Cl− co-transporter (NKCC1)), oxidative stress (thiobarbituric acid reactive substances (TBARS) and manganese superoxide dismutase (MnSOD)) and apoptotic damage (Bcl-x and Bax).ResultsDespite the HS-induced decrease in cardiac output (CO) and hyperlactataemia, resuscitation with terlipressin recovered MAP and resulted in restoration of CPP and in cerebral protection expressed by normalisation of AQP4, NKCC1, TBARS and MnSOD expression and Bcl-x/Bax ratio at T60 and T120 compared with sham animals. In the LR group, CO and blood lactate levels were recovered, but the CPP and MAP were significantly decreased and TBARS levels and AQP4, NKCC1 and MnSOD expression and Bcl-x/Bax ratio were significantly increased at T60 and T120 compared with the sham group.ConclusionsDuring recovery from HS-induced hypotension, terlipressin was effective in normalising CPP and cerebral markers of water balance, oxidative damage and apoptosis. The role of this pressor agent on brain perfusion in HS requires further investigation.

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