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The cardiac pumping mechanics can be characterized by both the maximal systolic elastance (Emax) and theoretical maximum flow (Qmax), which are generated using an elastance–resistance model. The signals required to fit the elastance–resistance model are the simultaneously recorded left ventricular (LV) pressure and aortic flow (Qm), followed by the isovolumic LV pressure. In this study, we evaluated a single-beat estimation technique for determining the Emax and Qmax by using the elastance–resistance model based solely on the measured LV pressure and cardiac output. The isovolumic LV pressure was estimated from the measured LV pressure by using a non-linear least-squares approximation technique. The measured Qm was approximated by an unknown triangular flow (Qtri), which was generated by using a fourth-order derivative of the LV pressure. The Qtri scale was calibrated using the cardiac output. Values of EmaxtriQ and QmaxtriQ obtained using Qtri were compared with those of EmaxmQ and QmaxmQ obtained from the measured Qm. Healthy rats and rats with chronic kidney disease or diabetes mellitus were examined. We found that the LV Emax and Qmax can be approximately calculated using the assumed Qtri, and they strongly correlated with the corresponding values derived from Qm (P

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.

// Chih-Hsien Wang 1, 2 , Ru-Wen Chang 3 , Chun-Yi Chang 4 , Ming-Shiou Wu 5 , Hsien-Li Kao 5 , Liang-Chuan Lai 3 , Tai-Horng Young 6 , Hsi-Yu Yu 1 , Yih-Sharng Chen 1 and Kuo-Chu Chang 3 1 Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan 2 Department of Surgery, National Taiwan University Hospital, Hsinchu Branch, Hsinchu 300, Taiwan 3 Department of Physiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan 4 Department of Emergency Medicine, Taipei Veterans General Hospital, Chu-Tung Branch, Hsinchu 310, Taiwan 5 Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan 6 Institute of Biomedical Engineering, College of Medicine and Engineering, National Taiwan University, Taipei 100, Taiwan Correspondence to: Kuo-Chu Chang, email: kcchang1008@ntu.edu.tw Keywords: cardiac contractility; pressure-ejected volume curve; end-systolic elastance; left ventricular pressure; triangular aortic flow Received: June 20, 2017 Accepted: September 23, 2017 Published: October 10, 2017 ABSTRACT To quantitate the contractile mechanics of the heart, the ventricle is considered an elastic chamber with known end-systolic elastance ( E es ). E es can be calculated from a single pressure-ejected volume curve, which requires simultaneous records of left ventricular (LV) pressure and the aortic flow ( Q m ). In clinical settings, it is helpful to evaluate patients’ cardiac contractile status by using a minimally invasive approach to physiological signal monitoring, wherever possible, such as by using LV pressure alone. In this study, we evaluated a method for determining E es on the basis of the measured LV pressure and an assumed aortic flow with a triangular wave shape ( Q tri ). Q tri was derived using a fourth-order derivative of the LV pressure to approximate its corresponding Q m . Values of E es triQ obtained using Q tri were compared with those of E es mQ obtained from the measured Q m . Healthy rats (NC; n = 28) and rats with type 1 diabetes (DM; n = 26) and chronic kidney disease (CKD; n = 20) were examined. The cardiodynamic conditions in both the DM and CKD groups were characterized by a decline in E es mQ and E es triQ . A significant regression line for E es was observed ( P < 0.0001): E es triQ = 2.6214 + 1.0209 × E es mQ ( r 2 = 0.9870; n = 74). Our finding indicates that the systolic pumping mechanics of the heart can be derived from a single LV pressure recording together with the assumed Q tri .

Extracorporeal life support (ECLS) is a world-famous life-saving method. Until now, changes in arterial wave properties due to ECLS have remained unexamined. In this study, we determined the effects of ECLS on arterial wave properties and ventricular/arterial coupling in male Wistar rats with the measured aortic pressure alone. Ascending aortic pressure signals were measured before ECLS and at 30, 60, and 90 min after weaned off. The aortic pressure signal then calculated by fourth-order derivative to obtain an assumed triangular flow wave. The ratio of mean systolic pressure to mean diastolic pressure (Pms/Pmd), a parameter for evaluating the matching condition between myocardial oxygen demand and supply, was significantly higher after ECLS. The magnitude of forward pressure (|Pf|) augmented by ECLS prevailed over the backward pressure (|Pb|), leading to a decline in wave reflection factor. Pms/Pmd was positively linearly correlated with |Pf| (Pms/Pmd = 0.9177 + 0.0078 × |Pf|, r = 0.8677; P Pf| was a predominant factor responsible for the mismatch between the myocardial oxygen demand and supply in rats after ECLS phase of experiment.

Arterial wave transit time (τw) in the lower body circulation is an effective biomarker of cardiovascular risk that substantially affects systolic workload imposed on the heart. This study evaluated a method for determining τw from the vascular impulse response on the basis of the measured aortic pressure and an assumed triangular flow (Qtri). The base of the unknown Qtri was constructed with a duration set equal to ejection time. The timing of the peak triangle was derived using a fourth-order derivative of the pressure waveform. Values of τws obtained using Qtri were compared with those obtained from the measure aortic flow wave (Qm). Healthy rats (n = 27), rats with chronic kidney disease (CKD; n = 22), and rats with type 1 (n = 22) or type 2 (n = 11) diabetes were analyzed. The cardiovascular conditions in the CKD rats and both diabetic groups were characterized by a decrease in τws. The following significant relation was observed (P τwtriQ = −1.5709 + 1.0604 × τwmQ (r2 = 0.9641). Our finding indicates that aortic impulse response can be an effective method for the estimation of arterial τw by using a single pressure recording together with the assumed Qtri.

Ion variable measurements before and after ECLS. (DOCX 64Â kb)

Body weight, arterial blood gas, hematocrit, and hemodynamic variables showed in sham group (n = 2). (DOCX 71 kb)

New Findings What is the central question of this study? This study aimed to investigate the hypothesis that pyridoxamine, one of the three natural forms of vitamin B6, can protect against myocardial relaxation of senescent animals by targeting arterial stiffening and contractile dysfunction of the left ventricle. What is the main finding and its importance? We found that treating the senescent rats with pyridoxamine for 5 months might improve myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor. Our team demonstrated in the past that pyridoxamine attenuated arterial stiffening by targeting the pathogenic formation of glycated collagen cross-links in aged rats. Herein, we examined whether pyridoxamine therapy can protect against mechanical defects in myocardial relaxation by improving arterial wave properties and cardiac contractile performance in senescent animals. Fifteen-month-old male Fisher 344 rats were treated daily with pyridoxamine (1 g l−1 in drinking water) for 5 months and compared with age-matched untreated control animals (20 months old). Arterial wave properties were characterized by wave transit time (τw) and wave reflection factor (Rf). We measured the contractile status of the myocardium in an intact heart as the left ventricular (LV) end-systolic elastance (Ees). Myocardial relaxation was described according to the time constant of the LV isovolumic pressure decay (τe). Pyridoxamine therapy prevented the age-associated prolongation in LV τe and the diminished Ees in senescent rats. The drug also attenuated the age-related augmentation in afterload imposed on the heart, as evidenced by the increased τw and decreased Rf. We found that the LV τe was significantly influenced by both the arterial τw and Rf (τe = 16.3902 + 8.3123 × Rf − 0.4739 × τw; r = 0.7048, P

Background Extracorporeal life support (ECLS) systems are life-saving devices used for treating patients with severe cardiopulmonary failure. In this study, we implemented a rat model of ECLS without the administration of inotropes or vasopressors. Methods The rats underwent 5 min of untreated asphyxial cardiac arrest and were resuscitated by ECLS for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the ECLS outflow and inflow, respectively. Thereafter, ECLS was terminated, wounds were closed, and mechanical ventilation was provided for another 90 min. Subsequently, blood gas and hemodynamic analyses were performed. The plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured 120 min after reperfusion. Results The metabolic rate of lactate in the group of asphyxial cardiac arrest rescued by ECLS was slow; therefore, the pH at 120 min after reperfusion was significantly lower in this group than that in the group of normal rats treated with ECLS. The hemodynamic data showed no between-group differences. The plasma levels of CRP, IL-6, IL-10, and TNF-α increased after ECLS treatment. Conclusions We successfully established a rodent ECLS model, which might be a useful approach for studying the pathophysiology induced by ECLS under clinical conditions. Electronic supplementary material The online version of this article (doi:10.1186/s12872-017-0558-6) contains supplementary material, which is available to authorized users.

Left ventricular (LV) relaxation is influenced by vascular loads imposed on the heart. The current study investigated the influence of the timing and magnitude of arterial wave reflection on LV isovolumic pressure relaxation, with a specific focus on the aging process. Fisher 344 rats aged 6, 18, and 24 months were anesthetized and thoracotomized. Arterial wave reflection was characterized by wave transit time ( τ w ) and wave reflection factor ( R f ) using the impulse response of the filtered aortic input impedance spectra. Indices of LV pressure relaxation included peak – dP LV / dt and the isovolumic relaxation time constant ( τ e ). The vascular dynamic condition in the rats was characterized by (1) a progressive increase in R f and decrease in τ w associated with age, especially at 24 months; and (2) a decline in aortic compliance ( C m ). Changes in LV relaxation consisted of a fall in peak – dP LV / dt and a rise in LV τ e with age. Taking LV τ e as the dependent variable and arterial R f and τ w as the two independent variables, multiple linear regression was employed to fit the data. The correlation among the three parameters reached significance ( τ e = 11.885 + 5.350 × R f − 0.213 × τ w ; r = 0.5823, p τ w shortened and arterial R f was augmented with age, LV τ e became more prolonged and late pressure relaxation slowed. Thus, the heavy reflection intensity with early return of the pulse wave reflection might account for the age-related deterioration in LV isovolumic pressure decay.

The accurate measurement of arterial wave properties in terms of arterial wave transit time (τw) and wave reflection factor (Rf) requires simultaneous records of aortic pressure and flow signals. However, in clinical practice, it will be helpful to describe the pulsatile ventricular afterload using less-invasive parameters if possible. We investigated the possibility of systolic aortic pressure-time area (PTAs), calculated from the measured aortic pressure alone, acting as systolic workload imposed on the rat diabetic heart. Arterial wave reflections were derived using the impulse response function of the filtered aortic input impedance spectra. The cardiovascular condition in the rats with either type 1 or type 2 diabetes was characterized by (1) an elevation in PTAs; and (2) an increase in Rf and decrease in τw. We found that an inverse linear correlation between PTAs and arterial τw reached significance (τw = 38.5462 − 0.0022 × PTAs; r = 0.7708, P PTAs increased, the reflection intensity increased: Rf = –0.5439 + 0.0002 × PTAs; r = 0.8701; P PTAs might act as a useful index describing the diabetes-related deterioration in systolic ventricular workload.

It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg(-1) d(-1)) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg(-1) d(-1)) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max), using the elastance-resistance model. Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in E max associated with the increased Q max in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased E max, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Q max, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal resistance, possibly through its ability to reduce the aforementioned myocardial depressant substances. However, since our results were obtained in anesthetized open-chest rats, extrapolation to what may occur in conscious intact animals should be done with caution.

The goal of this research was to design thermosensitive drug vehicles for glaucoma therapy. Thermosensitive ophthalmic drop was prepared by mixing linear poly(N-isopropylacrylamide-g-2-hydroxyethyl methacrylate) (PNIPAAm-g-PHEMA), PNIPAAm-g-PHEMA gel particles and antiglaucoma drug. This produced polymeric eyedrop containing the drug epinephrine was a clear solution at room temperature which became a soft film after contacting the surface of cornea. The drug entrapped within the tangled polymer chains was therefore released progressively after topical application. Evaluation of the drug release responded as a function of crosslinking density and PHEMA macromer contents. The in vivo studies indicated that the intraocular pressure (IOP)-lowering effect for a polymeric eyedrop lasted for 26 h, which is significantly better than the effect of traditional eyedrop (8 h). Hence our investigations successfully prove that the thermosensitive polymeric eyedrop with ability of controlled drug release exhibits a greater potential for glaucoma therapy.

Introduction Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. In this study, we investigated whether low-dose atorvastatin exerts any beneficial effect on vascular dynamics in streptozotocin (STZ)-induced diabetes in male Wistar rats. Methods Diabetes was induced using a single tail-vein injection of STZ at 55 mg kg−1. The diabetic rats were treated daily with atorvastatin (10 mg kg−1 by oral gavage) for 6 weeks. They were also compared with untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. A thiobarbituric acid reactive substances measurement was used to estimate the malondialdehyde content. Results The high plasma level of total cholesterol in the diabetic rats did not change in response to this low-dose treatment with atorvastatin. Atorvastatin resulted in a significant increase of 15.4% in wave transit time and a decrease of 33.5% in wave reflection factor, suggesting that atorvastatin may attenuate the diabetes-induced deterioration in systolic loads imposed on the heart. This was in parallel with its lowering of malondialdehyde content in plasma and aortic walls in diabetes. Atorvastatin therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the diminished ratio of left ventricular weight to body weight. Conclusion These findings indicate that low-dose atorvastatin might protect diabetic vasculature against diabetes-associated deterioration in aorta stiffness and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived malondialdehyde.

INTRODUCTION: In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship. METHODS: Diabetes was induced by a single tail vein injection of 55 mg kg(-1) streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L(-1) in drinking water) or oxfenicine (150 mg kg(-1) by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max). Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. RESULTS: When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max. Acetyl-l-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q max corresponded to an increase in total vascular resistance when treated with oxfenicine. CONCLUSIONS: Acetyl-l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility associated with unaltered LV internal resistance.