Aortic Flow Signals Research Articles

Monitoring of cardiovascular physiology augmented by a patient-specific biomechanical model during general anesthesia. A proof of concept study.

During general anesthesia (GA), direct analysis of arterial pressure or aortic flow waveforms may be inconclusive in complex situations. Patient-specific biomechanical models, based on data obtained during GA and capable to perform fast simulations of cardiac cycles, have the potential to augment hemodynamic monitoring. Such models allow to simulate Pressure-Volume (PV) loops and estimate functional indicators of cardiovascular (CV) system, e.g. ventricular-arterial coupling (Vva), cardiac efficiency (CE) or myocardial contractility, evolving throughout GA. In this prospective observational study, we created patient-specific biomechanical models of heart and vasculature of a reduced geometric complexity for n = 45 patients undergoing GA, while using transthoracic echocardiography and aortic pressure and flow signals acquired in the beginning of GA (baseline condition). If intraoperative hypotension (IOH) appeared, diluted norepinephrine (NOR) was administered and the model readjusted according to the measured aortic pressure and flow signals. Such patients were a posteriori assigned into a so-called hypotensive group. The accuracy of simulated mean aortic pressure (MAP) and stroke volume (SV) at baseline were in accordance with the guidelines for the validation of new devices or reference measurement methods in all patients. After NOR administration in the hypotensive group, the percentage of concordance with 10% exclusion zone between measurement and simulation was >95% for both MAP and SV. The modeling results showed a decreased Vva (0.64±0.37 vs 0.88±0.43; p = 0.039) and an increased CE (0.8±0.1 vs 0.73±0.11; p = 0.042) in hypotensive vs normotensive patients. Furthermore, Vva increased by 92±101%, CE decreased by 13±11% (p < 0.001 for both) and contractility increased by 14±11% (p = 0.002) in the hypotensive group post-NOR administration. In this work we demonstrated the application of fast-running patient-specific biophysical models to estimate PV loops and functional indicators of CV system using clinical data available during GA. The work paves the way for model-augmented hemodynamic monitoring at operating theatres or intensive care units to enhance the information on patient-specific physiology.

Defects in Vascular Mechanics Due to Aging in Rats: Studies on Arterial Wave Properties from a Single Aortic Pressure Pulse.

Changes in vascular mechanics due to aging include elevated vascular impedance, diminished aorta distensibility, and an accelerated return of pulse wave reflection, which may increase the systolic workload on the heart. Classically, the accurate measurement of vascular mechanics requires the simultaneous recording of aortic pressure and flow signals. In practice, it is feasible to estimate arterial wave properties in terms of wave transit time (τw) and wave reflection index (RI) by using aortic pressure signal alone. In this study, we determined the τw and magnitudes of the forward (∣Pf∣) and backward (∣Pb∣) pressure waves in Long–Evans male rats aged 4 (n = 14), 6 (n = 17), 12 (n = 17), and 18 (n = 24) months, based on the measured aortic pressure and an assumed triangular flow (Qtri). The pulsatile pressure wave was the only signal recorded in the ascending aorta by using a high-fidelity pressure sensor. The base of the unknown Qtri was constructed using a duration, which equals to the ejection time. The timing at the peak of the triangle was derived using the fourth-order derivative of the aortic pressure waveform. In the 18-month-old rats, the ratio of τw to left ventricular ejection time (LVET) decreased, indicating a decline in the distensibility of the aorta. The increased ∣Pb∣ associated with unaltered ∣Pf∣ enhanced the RI in the older rats. The augmentation index (AI) also increased significantly with age. A significant negative correlation between the AI and τw/LVET was observed: AI = −0.7424 − 0.9026 × (τw/LVET) (r = 0.4901; P < 0.0001). By contrast, RI was positively linearly correlated with the AI as follows: AI = −0.4844 + 2.3634 × RI (r = 0.8423; P < 0.0001). Both the decreased τw/LVET and increased RI suggested that the aging process may increase the AI, thereby increasing the systolic hydraulic load on the heart. The novelty of the study is that Qtri is constructed using the measured aortic pressure wave to approximate its corresponding flow signal, and that calibration of Qtri is not essential in the analysis.

Systolic aortic pressure-time area is a useful index describing arterial wave properties in rats with diabetes.

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 < 0.0001). By contrast, as the PTAs increased, the reflection intensity increased: Rf = –0.5439 + 0.0002 × PTAs; r = 0.8701; P <0 .0001. All these findings suggested that as diabetes stiffened aortas, the augmented aortic PTAs might act as a useful index describing the diabetes-related deterioration in systolic ventricular workload.

Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats.

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 (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, 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.

0368 : Aortic impedance in older subjects: MR and applanation tonometry study by wave intensity analysis

Central pressure waveform can be decomposed into pressure transmission and reflection waves. Zc, characteristic impedance of aorta can be measured through the recording of pulse pressure and aortic flow signals and reflects structural and functional properties of elastic central and peripheral muscular arteries. This study proposes a novel method using wave intensity analysis to assess reflected waves by decomposition of magnetic resonance imaging central aortic flow and central aortic pressure waveform measured by tonometry in 30 older subjects allowing to obtain the aortic characteristic impedance in the time domain and reflection index (IR) and reflection magnitude (MR). Elderly patients were mean aged of 75.25±5.85 years (14 female, 16 male). Mean Zc value was 424.34±94.41 DSC for the whole aging population. We found a strong negative association between Zc and LVET (r=–0.53, p=0.004). We found also a trend of negative association between Zc and aortic diameter, at the aortic root, (r=–0.36, p=0.05), and pressure augmentation (r=–0.36, p=0.06), and also with Aix (r = –0.32, p=0.09). Zc was positively associated with PPA (r = 0.41, p=0.02), and also strongly with HR (r= 0.54, p=0.003). Association between RM and IR were positively significant with aorta length measure by MRI, respectively (r=0.41, p=0.03) for RM and (r=0.42, p=0.03) for IR. RM associated positively with thoracic aorta length (r2 = 0.15, p=0.04) after adjustment to age and height, IR also associated positively with thoracic aorta length (r2 = 0.16, p=0.04) after adjustment to age and height. This automatic signal treatment of aortic flow and pulse pressure waveform is a good method for assessment of wave reflections in older subjects allowing obtaining reflection magnitude. Aortic characteristic impedance is inversely correlated to left ventricular ejection time and aortic diameter as new insights suggest.

Acetyl-l-Carnitine and Oxfenicine on Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetes in Male Wistar Rats

IntroductionIn 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.MethodsDiabetes 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.ResultsWhen 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.ConclusionsAcetyl-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.

Vascular Dysfunction in Hypertension Revealed by Fourier Analysis of Aortic Blood Flow

Impedance measurements have been used to quantify changes in vascular function associated with hypertension. Fourier analysis based solely on the arterial flow wave may provide a useful alternative to traditional techniques. Therefore the utility of blood flow frequency analysis in differentiating vascular changes in hypertension is tested. A frequency-based method was developed to evaluate the aortic pulse wave under conditions of spontaneous hypertension, sodium nitroprusside (SNP) induced normotension in spontaneously hypertensive rats (SHR), and phenylephrine (PE) induced hypertension in Wistar–Kyoto rats (WKY). Under anesthesia, animals were instrumented and signals were digitized for measurement of arterial blood pressure, aortic blood flow, and electrocardiogram. Hemodynamic parameters were extracted and the aortic flow signal was processed via Fourier analysis to produce a fingerprint of pulse transmission. Results demonstrated significant fingerprint differences between SHR and WKY at baseline pressures. Fingerprint differences are simulated by PE-induced hypertension, however, they did not match the SHR fingerprint despite similar flow-based biomarkers. Conversely, administration of SNP to the SHR creates differences in the fingerprint, however, SNP did not approximate the WKY fingerprint despite similar hemodynamics. Furthermore, characteristic fingerprint differences between SHR and WKY vasculature are maintained regardless of the intervention. In conclusion, results suggest Fourier analysis can be used to reveal functional vascular states regardless of pressure. Data presented demonstrates functional differences in the hypertensive vasculature that cannot be ameliorated with SNP, or reproduced with PE in normotensive vasculature. This may be useful clinically, to identify vascular dysfunction prior to overt hypertension.

Estimation of cardiac output and peripheral resistance using square-wave-approximated aortic flow signal

This paper presents a model-based approach to estimation of cardiac output (CO) and total peripheral resistance (TPR). In the proposed approach, the response of cardiovascular system (CVS), described by the windkessel model, is tuned to the measurements of systolic, diastolic and mean arterial blood pressures (BP) so as to yield optimal individual- and time-specific system time constant that is used to estimate CO and TPR. Unique aspects of the proposed approach are that it approximates the aortic flow as a train of square waves and that it also assumes pressure-dependent arterial compliance, as opposed to the traditional windkessel model in which aortic flow is approximated as a train of impulses and constant arterial compliance is assumed. It was shown that the proposed model encompasses the standard windkessel model as a limiting case, and that it also yields more realistic BP waveform response than the standard windkessel model. The proposed approach has potential to outperform its standard counterpart by treating systolic, diastolic, and mean BP as independent features in estimating CO and TPR, rather than solely resorting to pulse pressure as in the case of the standard windkessel model. Experimental results from in-vivo data collected from a number of animal subjects supports the viability of the proposed approach in that it could achieve approximately 29% and 24% reduction in CO and TPR errors when compared with its standard counterpart.

Editorial: engineering approaches to study cardiovascular physiology: modeling, estimation, and signal processing

EDITORIAL article Front. Physiol., 05 November 2012Sec. Computational Physiology and Medicine Volume 3 - 2012 | https://doi.org/10.3389/fphys.2012.00425

Pyridoxamine prevents age-related aortic stiffening and vascular resistance in association with reduced collagen glycation

An increase in oxidative chemical modifications of tissue proteins by advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs) has been implicated in normal aging. Pyridoxamine (PM), one of the three natural forms of vitamin B 6, has been identified as an inhibitor of AGE/ALE products formed during the autoxidation of carbohydrates and peroxidation of lipids. The current study seeks to determine whether PM intervention could prevent the age-related aortic stiffening and vascular resistance through its ability to inhibit the pathogenic cross-linking of glycated collagen. Male Fisher 344 rats at 15 months were treated daily with PM (1 g l − 1 in drinking water) for 5 months and compared with the age-matched, untreated controls at 20 months. Pulsatile aortic pressure and flow signals were measured to perform the vascular impedance analysis. The anti-AGE antibody 6D12 was used to detect glycation-derived modification of aortic collagen, using protein blotting analysis. PM therapy attenuated the age-related increase in total peripheral resistance. An increase in wave transit time and aortic compliance by PM indicated that the drug improved aortic distensibility of the aged vasculature. This paralleled its reduction of AGE-collagen cross-links on aortas. Treatment of the old animals with PM also prevented the age-induced augmentation in vascular load imposed on the heart, as evidenced by an increased wave transit time and a decreased wave reflection factor. These findings suggest a partial role of PM in improving arterial mechanics by targeting the pathogenic formation of AGE-induced aortic collagen cross-links in old rats.

How much of the intraaortic balloon volume is displaced toward the coronary circulation?

ObjectiveDuring intraaortic balloon inflation, blood volume is displaced toward the heart (Vtip), traveling retrograde in the descending aorta, passing by the arch vessels, reaching the aortic root (Vroot), and eventually perfusing the coronary circulation (Vcor). Vcor leads to coronary flow augmentation, one of the main benefits of the intraaortic balloon pump. The aim of this study was to assess Vroot and Vcor in vivo and in vitro, respectively.MethodsDuring intraaortic balloon inflation, Vroot was obtained by integrating over time the aortic root flow signals measured in 10 patients with intraaortic balloon assistance frequencies of 1:1 and 1:2. In a mock circulation system, flow measurements were recorded simultaneously upstream of the intraaortic balloon tip and at each of the arch and coronary branches of a silicone aorta during 1:1 and 1:2 intraaortic balloon support. Integration over time of the flow signals during inflation yielded Vcor and the distribution of Vtip.ResultsIn patients, Vroot was 6.4% ± 4.8% of the intraaortic balloon volume during 1:1 assistance and 10.0% ± 5.0% during 1:2 assistance. In vitro and with an artificial heart simulating the native heart, Vcor was smaller, 3.7% and 3.8%, respectively. The distribution of Vtip in vitro varied, with less volume displaced toward the arch and coronary branches and more volume stored in the compliant aortic wall when the artificial heart was not operating.ConclusionThe blood volume displaced toward the coronary circulation as the result of intraaortic balloon inflation is a small percentage of the nominal intraaortic balloon volume. Although small, this percentage is still a significant fraction of baseline coronary flow.

Blind Identification of Two-Channel IIR Systems With Application to Central Cardiovascular Monitoring

This paper presents a new approach to blind identification of a class of two-channel infinite impulse response (IIR) systems with applicability to clinical cardiovascular monitoring. Specifically, this paper deals with a class of two-channel IIR systems describing wave propagation dynamics. For this class of systems, this paper first derives a blind identifiability condition and develops a blind identification algorithm, which is able to determine both the numerator and denominator polynomials of the channel dynamics uniquely. This paper also develops a new input signal deconvolution algorithm that can reconstruct the input signal from the identified two-channel dynamics and the associated two-channel measurements. These methods are applied to identify the pressure wave propagation dynamics in the cardiovascular system and reconstruct the aortic blood pressure and flow signals from blood pressure measurements taken at two distinct extremity locations. Persistent excitation, model identifiability, and asymptotic variance are analyzed to quantify the method’s validity, accuracy, and reliability without employing direct measurement of the aortic blood pressure and flow signals. The experimental results based on 83 data segments obtained from a swine subject illustrate how the cardiovascular dynamics can be identified accurately and reliably, and the aortic blood pressure and flow signals can be stably reconstructed from two distinct peripheral blood pressure signals under diverse physiologic conditions.

P-1 Remodeling of Myocardial Gap Junctions and its Correlation with Cardiac Contractility in Diabetic Rats

not available at time of printing. Poster Sessions 1: Heart Failure/Myocardial Diseases P-1 Remodeling of Myocardial Gap Junctions and its Correlation with Cardiac Contractility in Diabetic Rats Dong-Feng Yeih1, Pen-Chih Liao1, Ho-Tsung Hsin1, Kuo-Chin Chen1, Ai-Hsian Li1, Yung-Zu Tseng2. 1Department of Cardiology, Far-Eastern Memorial Hospital, Taiwan, 2Department of Cardiology, National Taiwan University, Taiwan Introduction: Gap junctions play an essential role in coupling adjacent cardiomyocytes, ensuring organized propagation of action potential and synchronizing beating in cardiomyocytes. However, it remains unclear that temporal remodeling of myocardial gap junctions and its relation to cardiac contractility in diabetic rats. Methods: Male Wistar rats, weighing 250 to 300 grams, were randomized to injection with either vehicle or streptozotocin (50mg, IP). Invasive hemodynamic studies with simultaneous recordings of left ventricular pressure and aortic flow signals were done at 4, 8 and 12 weeks after injection. Maximal systolic elastance (Emax) and maximum theoretical flow (Qmax) were assessed by curve fitting techniques; protein expression of non-phosphorylated Cx43 (P0) and total amount of Cx43 (T) in the left ventricle by western blotting analysis. Results: Emax was significantly lower in diabetic rats than in controls and Emax was significantly depressed with time in diabetic groups. On the other hand, Qmax was preserved and cardiac output was maintained in diabetic rats. Protein expression of total Cx43 was persistently attenuated in diabetic groups, while P0 was enhanced at 8 and 12 weeks after injection. The ratio of P0 to T was significantly increased with time, which correlated well with the declines in Emax in diabetic rats. Conclusions: Temporal remodeling of myocardial gap junctions, with persistently lower total Cx43 and gradually increased non-phosphorylated Cx43 and the ratio of P0 to T, occurred in the evolution of systolic dysfunction in diabetic rats. P-2 Quantification of Left Ventricular Diastolic Dynamics in Normal and Diseased Myocardium by Speckle-Tracking Echocardiography Kaoru Dohi1, Katsuya Onishi2, Takeshi Takamura1, Emiyo Sugiura1, Hiroshi Nakajima1, Kazuhide Ichikawa1, Masaki Tanabe1, Hiroya Tamada1, Masatoshi Miyahara1, Mashio Nakamura1, Masaaki Ito1. 1Department of Cardiology, Mie University Graduate School of Medicine, Japan, 2Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Japan Background: The present study aimed to quantify left ventricular (LV) diastolic dynamics and to elucidate their relations to systolic properties in normal and diseased myocardium. Methods: 50 patients with hypertensive LV hypertrophy (LVH: EF 61±8%, QRS 96±16ms), 50 patients with dilated cardiomyopathy (DCM: EF 31±10%, QRS 121±32ms), and 50 normal controls (Control: EF 5±6%, QRS 89±9ms) had echo-study with speckle-tracking strain and strain rate imaging. To quantify LV diastolic relaxation and segmental synchrony, global peak relaxation rate (PRR) during early diastole and standard deviation (SD) of the 18 segmental time-to-PRR (TPRR-SD) were calculated from apical 4-, 2-, and long axis views. To elucidate the relations between diastolic and systolic properties, global peak systolic strain (PSS) and SD of the segmental time-to-peak PSS (TPSS-SD) were also evaluated. Results: LV relaxation and diastolic synchrony were significantly impaired in LVH and was more prominent in DCM (PRR: 0.8±0.3* 1/s in LVH, 0.5±0.2*# 1/s in DCM, and 1.2±0.3 1/s in Control, TPRR-SD: 55±16*ms in LVH, 79±35*# ms in DCM, and 42±13ms in Control, *p < 0.05 vs. Control and #p < 0.05 vs. LVH, respectively). There were strong correlations between PSS and PRR, and TPRR-SD and TPSS-SD (r = 0.83 and r = 0.83, p < 0.05, respectively). Conclusion: Speckle-tracking echocardiography quantified LV diastolic dynamics and exhibited the strong relation to systolic properties.

DYNAMIC EFFECTS OF RESPIRATION ON AORTIC BLOOD FLOW AND ITS AUTONOMIC CONTROL IN RATS

1. Respiratory related arterial pressure variability may reflect body fluid status and/or cardiac sympathetic function. The underlying mechanism is not clear. 2. In the present study, we used an electromagnetic blood flow meter to measure ascending aortic blood flow, from which stroke volume was integrated, to study respiration-stroke volume coupling and its underlying neural regulation. Experiments were performed on male Sprague-Dawley rats that were anaesthetized with pentobarbital sodium, paralysed with pancuronium and under mechanical ventilation. 3. Programmed irregular ventilation evoked significant variability in arterial pressure, aortic flow and stroke volume signals. Good coupling was noted between lung volume and aortic flow, as well as between lung volume and stroke volume; this coupling persisted under all experimental conditions. The aortic flow power and stroke volume variability and the transfer magnitude of the lung volume-aortic flow and lung volume-stroke volume couplings were suppressed by 1 mg/kg propranolol, but not by 0.3 mg/kg atropine or a combination of 0.3 mg/kg atropine and 2.5 mg/kg phentolamine. 4. These results suggest that respiratory related variability in aortic flow and stroke volume, which ultimately contributes to arterial pressure variability, is primarily under cardiac sympathetic control via beta-adrenoceptors in anaesthetized and mechanically ventilated rats.

Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide‐induced type 2 diabetes

Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max)). After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and 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. Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG. AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes.

Aminoguanidine prevents fructose‐induced deterioration in left ventricular–arterial coupling in Wistar rats

Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties. Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature. There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.

Validation of pulse contour derived stroke volume variation during modifications of cardiac afterload

Left ventricular stroke volume variation (SVV) or its surrogates are useful tools to assess fluid responsiveness in mechanically ventilated patients. So far it is unknown, how changes in cardiac afterload affect SVV. Therefore, this study compared left ventricular SVV derived by pulse contour analysis with SVV measured using an ultrasonic flow probe and investigated the influence of cardiac afterload on left ventricular SVV. In 13 anaesthetized, mechanically ventilated pigs [31(SD 6) kg], we compared cardiac output (CO), stroke volume (SV), and SVV determined by pulse contour analysis and by an ultrasonic aortic flow signal (Bland-Altman analysis). After obtaining baseline measurements, cardiac afterload was increased using phenylephrine and decreased using adenosine (both continuously administered). Measurements were performed with a constant tidal volume (12 ml kg-1) without PEEP. Neither increasing mean arterial pressure (MAP) [from 59 (7) to 116 (19)] nor decreasing MAP [from 63 (7) to 39 (4)] affected CO, SV, and SVV (both methods). Method comparison revealed a bias for SVV of 0.1% [standard error of the mean (SE) 0.8] at baseline, -1.2% (SE 0.8) during decreased and 4.0% (SE 0.7) during increased afterload, the latter being significantly different from the others (P<0.05). Thereby, pulse contour analysis tended to underestimate SVV during decreased afterload and to overestimate SVV during increased afterload. Limits of agreement were approximately 6% for all points of measurement. Left ventricular SVV is not affected by changes in cardiac afterload. There is a good agreement of pulse contour with flow derived SVV. The agreement decreases, if afterload is extensively augmented.

Arterial stiffening and cardiac hypertrophy in a new rat model of type 2 diabetes

We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg(-1) of NA, 30 min before an intravenous injection of 50 mg kg(-1) STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1.49 +/- 0.33 (mean +/- SD) to 1.95 +/- 0.28 mmHg s mL(-1) (P < 0.05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor (0.46 +/- 0.09 vs. 0.61 +/- 0.13, P < 0.05) and decreased wave transit time (25.8 +/- 3.8 vs. 20.6 +/- 2.8 ms, P < 0.05). Ratio of the left ventricular weight to body weight was also enhanced in the 8-week STZ-NA diabetic rats. The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration.

Effects of diabetes and gender on mechanical properties of the arterial system in rats: aortic impedance analysis.

We determined the effects of diabetes and gender on the physical properties of the vasculature in streptozotocin (STZ)-treated rats based on the aortic input impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured and were then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. Male but not female diabetic rats exhibited an increase in cardiac output in the absence of any significant changes in arterial blood pressure, resulting in a decline in total peripheral resistance. However, in each gender group, diabetes contributed to an increase in wave reflection factor, from 0.47 +/- 0.04 to 0.84 +/- 0.03 in males and from 0.46 +/- 0.03 to 0.81 +/- 0.03 in females. Diabetic rats had reduced wave transit time, at 18.82 +/- 0.60 vs 21.34 +/- 0.51 msec in males and at 19.63 +/- 0.37 vs 22.74 +/- 0.57 msec in females. Changes in wave transit time and reflection factor indicate that diabetes can modify the timing and magnitude of the wave reflection in the rat arterial system. Meanwhile, diabetes produced a fall in aortic characteristic impedance from 0.023 +/- 0.002 to 0.009 +/- 0.001 mmHg/min/kg/ml in males and from 0.028 +/- 0.002 to 0.014 +/- 0.001 mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished aortic characteristic impedance and wave transit time suggest that the muscle inactivation in diabetes may occur in aortas and large arteries and may cause a detriment to the aortic distensibility in rats with either sex. We conclude that only rats with male gender diabetes produce a detriment to the physical properties of the resistance arterioles. In spite of male or female gender, diabetes decreases the aortic distensibility and impairs the wave reflection phenomenon in the rat arterial system.

Systolic elastance and resistance in the regulation of cardiac pumping function in early streptozotocin-diabetic rats.

We determined the roles of maximal systolic elastance (E(max)) and theoretical maximum flow ((max)) in the regulation of cardiac pumping function in early streptozotocin (STZ)-diabetic rats. Physically, E(max) can reflect the intrinsic contractility of the myocardium as an intact heart, and (max) has an inverse relation to the systolic resistance of the left ventricle. Rats given STZ 65 mg/kg i.v. (n = 17) were divided into two groups, 1 week and 4 weeks after induction of diabetes, and compared with untreated age-matched controls (n = 15). Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and (max), using the elastance-resistance model. After 1 or 4 weeks, STZ-diabetic animals show an increase in effective LV end-diastolic volume (V(eed)), no significant change in peak isovolumic pressure (P(iso)(max)), and a decline in effective arterial volume elastance (E(a)). The maximal systolic elastance E(max) is reduced from 751.5 +/- 23.1 mmHg/ml in controls to 514.1 +/- 22.4 mmHg/ml in 1- and 538.4 +/- 33.8 mmHg/ml in 4-week diabetic rats. Since E(max) equals P(iso)(max)/V(eed), an increase in V(eed) with unaltered P(iso)(max) may primarily act to diminish E(max) so that the intrinsic contractility of the diabetic heart is impaired. By contrast, STZ-diabetic rats have higher theoretical maximum flow (max) (40.9 +/- 2.8 ml/s in 1- and 44.5 +/- 3.8 ml/s in 4-week diabetic rats) than do controls (30.7 +/- 1.7 ml/s). There exists an inverse relation between (max) and E(a) when a linear regression of (max) on E(a) is performed over all animals studied (r = 0.65, p < 0.01). The enhanced (max) is indicative of the decline in systolic resistance of the diabetic rat heart. The opposing effects of enhanced (max) and reduced E(max) may negate each other, and then the cardiac pumping function of the early STZ-diabetic rat heart could be preserved before cardiac failure occurs.