Myocardial Perfusion Pressure Research Articles

Eccentric exercise improves myocardial oxygen supply/demand balance with decelerating aortic diastolic pressure decay: The acute and chronic studies

ABSTRACT Both eccentric (ECC) and concentric (CON) exercises improve energy expenditure and blood lipid profile. Although ECC exercise has a more beneficial effect on these factors than CON exercise, its benefits on vital organs are still unclear. This study investigated the mode-of-action-dependent effects on myocardial perfusion index. Seventeen healthy men (age: 26 ± 5 years) were randomly enrolled in CON (n = 9) and ECC (n = 8) groups. Transient exercise and regular training (three-day a week for 4-week) included bicep curl comprising 5-set of 10-repetition, each using 75% one-repetition maximum concentric loading. The ECC group performed one-repetition of ECC for 3-s and CON for 1-s, while the CON group performed one-repetition of CON for 3-s and ECC for 1-s. All participants were assessed for subendocardial viability ratio (SEVR, myocardial perfusion index) and aortic diastolic pressure decay. Before study, these were found to be same for both groups. Transient (ΔSEVR: 20.3 ± 13.3%, p = 0.01; Δdecay: −0.07 ± 0.02 s−1, p < .001) and regular (ΔSEVR: 18.5 ± 12.8%, p = .001; Δdecay: −0.06 ± 0.05 s−1, p = .004) ECC (but not CON) exercises significantly increased SEVR and decelerated decay. Increased SEVR with ECC exercise was associated with decelerated decay (transient ECC: r2 = 0.56, 95% confidence interval [CI] = −0.95 to −0.10, p = .03; regular ECC: r2 = 0.53, 95% CI = −0.95 to −0.05, p = .04). These findings suggest that ECC exercise improves myocardial perfusion and diastolic pressure contour is involved in physiological mechanisms.

Use of an end-tidal carbon dioxide-guided algorithm during cardiopulmonary resuscitation improves short-term survival in paediatric swine

AimTo evaluate an algorithm that uses an end-tidal carbon dioxide (ETCO2) target of ≥ 30 torr to guide specific changes in chest compression rate and epinephrine administration during cardiopulmonary resuscitation (CPR) in paediatric swine. MethodsSwine underwent asphyxial cardiac arrest followed by resuscitation with either standard or ETCO2-guided algorithm CPR. The standard group received chest compressions at a rate of 100/min and epinephrine every 4 min during advanced life support consistent with the American Heart Association paediatric resuscitation guidelines. In the ETCO2-guided algorithm group, chest compression rate was increased by 10 compressions/min for every minute that the ETCO2 was < 30 torr, and the epinephrine administration interval was decreased to every 2 min if the ETCO2 remained < 30 torr. Short-term survival and physiologic data during active resuscitation were compared. ResultsShort-term survival was significantly greater in the ETCO2-guided algorithm CPR group than in the standard CPR group (16/28 [57.1%] versus 4/28 [14.3%]; p = 0.002). Additionally, the algorithm group had higher predicted mean ETCO2, chest compression rate, diastolic and mean arterial pressure, and myocardial perfusion pressure throughout resuscitation. Swine in the algorithm group also exhibited significantly greater improvement in diastolic and mean arterial pressure and cerebral perfusion pressure after the first dose of epinephrine than did those in the standard group. Incidence of resuscitation-related injuries was similar in the two groups. ConclusionsUse of a resuscitation algorithm with stepwise guidance for changes in the chest compression rate and epinephrine administration interval based on a goal ETCO2 level improved survival and intra-arrest hemodynamics in this porcine cardiac arrest model.

Abstract 249: Association of Diastolic Blood Pressure and Myocardial Perfusion Pressure with Survival During Pediatric Cardiopulmonary Resuscitation

Introduction: Myocardial perfusion pressure (MPP), defined as the aortic diastolic pressure minus the central venous diastolic pressure, is an important determinant of return of spontaneous circulation (ROSC) in cardiac arrest. However, measuring MPP requires both arterial and venous catheters and is often not possible. When only invasive arterial monitoring is available, diastolic blood pressure (DBP) is suggested as a surrogate for MPP during resuscitation and is also associated with survival after cardiac arrest. Hypothesis: We hypothesized that DBP measured during chest compression delivery would mirror MPP during resuscitation and both would be associated with survival. Methods: We performed a retrospective, secondary analysis of 102 swine resuscitations. Pediatric swine underwent asphyxial cardiac arrest and were resuscitated with predefined periods of basic and advanced life support (BLS and ALS). MPP and DBP were recorded every 30 s during chest compression delivery. Results: For both survivors and non-survivors, DBP mirrored MPP throughout resuscitation ( Figure 1A, B ). During BLS, both MPP and DBP were significantly greater in survivors (MPP: 8.5 0.6 vs. 1.1 0.5 mmHg; p &lt; 0.0001; DBP 17.3 0.6 vs. 8.7 0.5 mmHg; p &lt; 0.0001). During ALS, MPP and DBP were greater in survivors than non-survivors (MPP: 20.5 1.0 vs. 0.7 0.3 mmHg; p &lt; 0.0001; DBP 32.3 0.9 vs. 8.8 0.2 mmHg; p &lt; 0.0001). During ALS, the magnitude of change in both MPP and DBP after the first epinephrine administration in survivors was greater than in non-survivors (MPP: 24.4 3.3 vs. 4.8 0.9 mmHg; p &lt; 0.0001; DBP: 24.5 3.1 vs. 5.4 0.8 mmHg; p &lt; 0.0001). Conclusion: These observations confirm that both DBP and MPP are associated with survival in cardiac arrest and validate the use of DBP as a surrogate for MPP. Figure 1: Myocardial perfusion pressure (MPP) and diastolic blood pressure (DBP) during BLS and ALS in survivors (A) and non-survivors (B). Arrows indicate administration of epinephrine during ALS.

Abstract 300: End-Tidal CO 2 -Guided Chest Compression Delivery Improves Survival in a Pediatric Model of Respiratory Failure and Cardiac Arrest

Introduction: The American Heart Association (AHA) recommends the use of end-tidal CO 2 (ETCO 2 ) to evaluate the quality of chest compression delivery during CPR. In a pediatric model of asphyxial cardiac arrest, ETCO 2 -guided chest compression delivery improved survival over standard CPR. Since the most common cause of pediatric cardiac arrest is respiratory failure, we investigated whether this observed survival benefit persisted in a model of respiratory failure preceding cardiac arrest. Methods: Prior to a 17-min asphyxial cardiac arrest, peak inspiratory pressures were adjusted to a goal PaCO 2 of 80 torr to mimic pre-arrest respiratory failure. Male swine (3-4 kg) were randomized to receive either ETCO 2 -guided or standard CPR for 10 min of BLS followed by 10 min of ALS. In the ETCO 2 -guided group, chest compression rate and depth were adjusted to obtain a maximal ETCO 2 level. In the standard group, chest compressions were delivered per AHA guidelines. Hemodynamic parameters were recorded every 30 seconds, and resuscitation was continued for 20 min or until ROSC. Results: Twenty swine underwent asphyxial cardiac arrest. After adjustment of ventilation prior to asphyxia, pH and PaCO 2 were 7.15 and 79 torr in the ETCO 2 -guided group and 7.14 and 78 torr in the standard group. Survival was greater in the ETCO 2 -guided group than in the standard group (7/10 versus 1/10; p=0.02). During resuscitation, mean ETCO 2 and chest compression rate were higher in the ETCO 2 -guided group (38.6 ± 1.2 versus 22.9 ± 1.2, p=0.01; 154.4 ± 1.2 versus 100.5 ± 0.1, p&lt;0.001, respectively). During resuscitation, diastolic blood pressure, myocardial perfusion pressure, systemic perfusion pressure, and cerebral perfusion pressure were higher in the ETCO 2 -guided group ( Figure 1 ) Conclusions: ETCO 2 -guided chest compression delivery improves survival and resuscitation hemodynamics over standard CPR in a pediatric model of respiratory failure and cardiac arrest.

Impact of aortic stiffness on myocardial ischaemia in non-obstructive coronary artery disease

ObjectiveHigh aortic stiffness may reduce myocardial perfusion pressure and contribute to development of myocardial ischaemia. Whether high aortic stiffness is associated with myocardial ischaemia in patients with stable angina and...

Pilot Study to Compare the Use of End‐Tidal Carbon Dioxide–Guided and Diastolic Blood Pressure–Guided Chest Compression Delivery in a Swine Model of Neonatal Asphyxial Cardiac Arrest

BackgroundThe American Heart Association recommends use of physiologic feedback when available to optimize chest compression delivery. We compared hemodynamic parameters during cardiopulmonary resuscitation in which either end‐tidal carbon dioxide (ETCO 2) or diastolic blood pressure (DBP) levels were used to guide chest compression delivery after asphyxial cardiac arrest.Methods and ResultsOne‐ to 2‐week‐old swine underwent a 17‐minute asphyxial‐fibrillatory cardiac arrest followed by alternating 2‐minute periods of ETCO 2‐guided and DBP‐guided chest compressions during 10 minutes of basic life support and 10 minutes of advanced life support. Ten animals underwent resuscitation. We found significant changes to ETCO 2 and DBP levels within 30 s of switching chest compression delivery methods. The overall mean ETCO 2 level was greater during ETCO 2‐guided cardiopulmonary resuscitation (26.4±5.6 versus 22.5±5.2 mm Hg; P=0.003), whereas the overall mean DBP was greater during DBP‐guided cardiopulmonary resuscitation (13.9±2.3 versus 9.4±2.6 mm Hg; P=0.003). ETCO 2‐guided chest compressions resulted in a faster compression rate (149±3 versus 120±5 compressions/min; P=0.0001) and a higher intracranial pressure (21.7±2.3 versus 16.0±1.1 mm Hg; P=0.002). DBP‐guided chest compressions were associated with a higher myocardial perfusion pressure (6.0±2.8 versus 2.4±3.2; P=0.02) and cerebral perfusion pressure (9.0±3.0 versus 5.5±4.3; P=0.047).ConclusionsUsing the ETCO 2 or DBP level to optimize chest compression delivery results in physiologic changes that are method‐specific and occur within 30 s. Additional studies are needed to develop protocols for the use of these potentially conflicting physiologic targets to improve outcomes of prolonged cardiopulmonary resuscitation.

Left Versus Biventricular Assist Devices in Cardiac Arrest.

Maintaining adequate organ perfusion during cardiac arrest remains a challenge, and various assist techniques have been evaluated. We assessed whether a right ventricular impeller assist device (RVAD) in adjunct to a left ventricular impeller assist device (LVAD) is beneficial. Twenty anesthetized pigs were randomized to maximized circulatory support by percutaneously implanted left- or biventricular assist device(s) during 30 minutes of electrically induced ventricular fibrillation followed by three attempts of cardioversion. Continuous hemodynamic variables were recorded. Cardiac output and myocardial, cerebral, renal, and ileum mucosa tissue perfusion were measured with fluorescent microspheres, and repeated blood gas analyses were obtained. With biventricular support, an increased LVAD output was found compared with left ventricular (LV) support; 3.2 ± 0.2 (SEM) vs. 2.0 ± 0. 2 L/minute just after start of ventricular fibrillation, 3.2 ± 0.1 vs. 2.0 ± 0.1 L/minute after 15 minutes, and 3.0 ± 0.1 vs. 2.1 ± 0.1 L/minute after 30 minutes of cardiac arrest (pg < 0.001). Biventricular support also increased aortic and LV pressure, in addition to end-tidal CO2. Tissue blood flow rates were increased for most organs with biventricular support. Blood gas analyses showed improved oxygenation and lower s-lactate values. However, myocardial perfusion was degraded with biventricular support and return of spontaneous circulation less frequent (5/10 vs. 10/10; p = 0.033). Biventricular support was associated with high intraventricular pressure and decreased myocardial perfusion pressure, correlating significantly with flow rates in the LV wall. A transmural flow gradient was observed for both support modes, with better maintained subepicardial than midmyocardial and subendocardial perfusion.

P24: DUAL EFFECT OF PHENYLEPHRINE TO IMPROVE CORONARY PERFUSION DURING ANAPHYLAXIS MANAGEMENT

Adrenaline, the drug of choice in anaphylaxis may produce side effects like tachycardia resulting in impaired coronary perfusion in the setting of severe hypotension. In this situation, Phenylephrine was used to improve coronary perfusion by Increasing coronary flow time from reflex bradycardia and an increase in coronary perfusion pressure resulting from an overall increase in systemic blood pressure. We describe a situation where at the end of an elective high anterior resection for colovesical fistula, immediately after administering reversal agents (Neostigmine and glycopyrrolate), there was severe hypotension with systolic blood pressure of 40m mmHg unresponsive to Ephedrine and Metaraminol. Adrenaline boluses resulted in tachycardia with marked ST segment elevation and slight increase in blood pressure. Intravenous Phenylephrine 100 mcg bolus was given and repeated twice over a period of 15 minutes which reduced the heart rate from 130 to 100 beats/minute as well as increased the blood pressure with ST segment returning to baseline. ANZAAG guidelines were followed to maximise management and team efficiency during and after the crisis and resulted in an uneventful recovery. A 10 fold increase in serum Tryptase confirmed anaphylaxis. Anaphylaxis to reversal agents (Neostigmine and Glycopyrrolate) is rare1 and in this situation it was complicated by ECG evidence of tachycardia induced ST segment elevation after administration of 2 doses of 100 mcg increments of adrenaline with only small increase in blood pressure. Phenylephrine improved the myocardial perfusion and blood pressure. We recommend that Phenylephrine should be considered in the presence of Adrenaline induced tachycardia to improve myocardial perfusion during anaphylaxis management. 1. McNicholas JJ, Harban FM. Anaphylaxis caused by neostigmine. Anaesthesia 2000; 55: 1039.

Ventricular-arterial coupling assessment using gated single-photon emission computed tomography: relationship with reserve pulse pressure and repolarization abnormalities.

In patients with normal myocardial perfusion, ST-segment depression and reserve pulse pressure (rPP) can identify patients at higher risk of cardiovascular events. We aimed to explore the prevalence of impaired ventricular-arterial coupling (VAc) in patients with normal myocardial perfusion imaging and its relationship with ST-segment depression and rPP. The present study included consecutive patients with normal myocardial perfusion imaging by single-photon emission computed tomography and ST-segment depression. Stroke volume, end-systolic pressure, arterial elastance (Ea), ventricular elastance (Ev), and VAc (Ea/Ev) were estimated both at rest and during stress. The difference between stress and rest (ΔVAc) was calculated. A positive ΔVAc was considered an impaired ΔVAc (iVAc). A total of 92 patients were prospectively included. iVAc was identified in 44 (59%) patients with ST-segment depression compared with 3 (16%) patients with normal repolarization (P=0.001). A higher incidence of abnormal rPP was identified in patients with ST-segment depression compared with the control group (61 vs. 16%, P=0.0001). ST-segment depression was identified as the only independent predictor of iVAc (adjusted OR 7.5; 95% CI 1.9-30.0, P=0.004). Noninvasive assessment of VAc is feasible with gated single-photon emission computed tomography and appears to be related to ST-segment depression and reserve rPP.

Increased wave reflection and ejection duration in women with chest pain and nonobstructive coronary artery disease: ancillary study from the Women's Ischemia Syndrome Evaluation.

Wave reflections augment central aortic SBP and increase systolic pressure time integral (SPTI) thereby increasing left ventricular (LV) afterload and myocardial oxygen (MVO2) demand. When increased, such changes may contribute to myocardial ischemia and angina pectoris, especially when aortic diastolic time is decreased and myocardial perfusion pressure jeopardized. Accordingly, we examined pulse wave reflection characteristics and diastolic timing in a subgroup of women with chest pain (Women's Ischemia Syndrome Evaluation, WISE) and no obstructive coronary artery disease (CAD). Radial artery BP waveforms were recorded by applanation tonometry, and aortic BP waveforms derived. Data from WISE participants were compared with data from asymptomatic women (reference group) without chest pain matched for age, height, BMI, mean arterial BP, and heart rate. Compared with the reference group, WISE participants had higher aortic SBP and pulse BP and ejection duration. These differences were associated with increased augmentation index and reflected pressure wave systolic duration. These modifications in wave reflection characteristics were associated with increased SPTI and wasted LV energy (Ew) and a decrease in pulse pressure amplification, myocardial viability ratio, and diastolic pressure time fraction. WISE participants with no obstructive CAD have changes in systolic wave reflections and diastolic timing that increase LV afterload, MVO2 demand, and Ew with the potential to reduce coronary artery perfusion. These alterations in cardiovascular function contribute to an undesirable mismatch in the MVO2 supply/demand that promotes ischemia and chest pain and may contribute to, or increase the severity of, future adverse cardiovascular events.

Non-invasively estimated end-systolic elastance in patients with resistant hypertension and type 2 diabetes mellitus

Ventriculo-arterial coupling (VAC) has been shown to be impaired in patients with type 2 diabetes mellitus (type 2 DM) and hypertension, and to improve with antihypertensive treatment. We examined if VAC in patients with type 2 DM and hypertension improved after a period of intensified antihypertensive treatment. VAC was estimated as the ratio of effective arterial elastance (E A) to end-systolic elastance (E ES) using pressure and flow curves obtained non-invasively (applanation tonometry and echocardiography). Left ventricular (LV) systolic and diastolic functions were evaluated using LV volumes, ejection fraction (EF), mitral inflow pattern, and Doppler tissue mitral annulus velocities. In total, 180 patients were included and for 100 patients the data met the quality criteria. Patients were categorized as having controlled (CH, n = 34), uncontrolled (UH, n = 32) or resistant (RH, n = 34) hypertension. In patients with RH, EF at follow-up was reduced from 48 to 42% (p = 0.005) and E ES from 2.18 mmHg/ml to 1.47 mmHg/ml (p = 0.003). EES, however, was also reduced in patients with CH and UH (CH 2.41-2.26, p = 0.05, UH 2.51-2.04, p = 0.05). In the present study, intensified antihypertensive treatment did not improve VAC or LV function in patients with hypertension and type 2 DM despite better control of BP. We speculate whether this is due to a reduction in myocardial perfusion pressure or to a gradual progression of diabetic cardiomyopathy.

Myocardial perfusion pressure in patients with hypertension and coronary artery disease

The target blood pressure (BP) in patients with hypertension and coronary artery disease (CAD) has been controversial. Whether patients with both diabetes mellitus and CAD should follow targets for either diabetes mellitus or CAD is uncertain. Focusing only on one determinant of coronary blood flow (CBF) - myocardial perfusion pressure (MPP) - coronary BP in patients with hypertension was used to estimate the impact of setting BP targets. A consecutive series of 101 patients referred for coronary angiography for stable angina pectoris or possible CAD had BP measurements proximal and distal to coronary artery stenosis. Fractional flow reserve (FFR) was measured from adenosine-induced maximal hyperemia. DBP after the coronary stenosis was the MPP. The most severe coronary lesion for each person was selected. Of 101 patients, 65.0 ± 10.6 years (mean ± SD), there were 69 with hypertension and 33 with diabetes mellitus of whom 25 had diabetes mellitus along with hypertension. In hypertension, FFR was 0.83 ± 0.08, range from 0.49 to 0.97, with 40% having FFR less than 0.8. There was a significant linear relationship between systemic DBP and MPP. CBF approximates zero with MMP of 50 mmHg under resting conditions and 40 mmHg with coronary vasodilatation. On the basis of our findings in hypertension, if DBP were 80, 70, 65 and 60 mmHg, 1.4, 7.1, 15.7 and 54.3%, respectively, of patients would have an MPP of less than 50 mmHg. The values were similar for patients with diabetes mellitus. In our patient group with moderate coronary artery stenosis, a target DBP of 60 mmHg or less would be associated with unacceptably low MPPs. In patients with diabetes mellitus, the presence and severity of CAD stenosis may be more important factor in setting BP targets for treatment of hypertension. Because the degree of coronary stenosis is unknown in most patients with hypertension and CAD, guideline recommendations should consider cautioning clinicians about the potential for myocardial ischaemia at low DBP.

Acute aortocaval fistula: role of low perfusion pressure and subendocardial remodeling on left ventricular function

The experimental model of aortocaval fistula is a useful model of cardiac hypertrophy in response to volume overload. In the present study it has been used to investigate the pathologic subendocardial remodeling associated with the development of heart failure during the early phases (day 1, 3, and 7) following volume overload. Compared with sham treated rats, aortocaval fistula rats showed lower systemic blood pressure and higher left ventricular end-diastolic pressure This resulted in lower coronary driving pressure and left ventricular systolic and diastolic dysfunction. Signs of myocyte necrosis, leukocyte cell infiltration, fibroplasia and collagen deposition appeared sequentially in the subendocardium where remodeling was more prominent than in the non-subendocardium. Accordingly, increased levels of TNF-alpha, IL-1 beta, and IL-6, and enhanced MMP-2 activity were all found in the subendocardium of rats with coronary driving pressure ≤ 60 mmHg. The coronary driving pressure was inversely correlated with MMP-2 activity in subendocardium in all time-points studied, and blood flow in this region showed positive correlation with systolic and diastolic function at day 7. Thus the predominant subendocardial remodeling that occurs in response to low myocardial perfusion pressure during the acute phases of aortocaval fistula contributes to early left ventricular dysfunction.

Contributions of central command and exercise pressor reflex on myocardial perfusion during exercise in rats

To examine how myocardial perfusion is controlled by a feedforward (termed “central command”) and feedback (exercise pressor reflex) neural mechanisms during exercise, left ventricular (LV) myocardial perfusion was measured during either electrical stimulation of subthalamic locomotor region (SLR), the electrical or chemical stimulation of which is known to elicit coordinated locomotion and concomitant cardiorespiratory responses, or electrical stimulation of tibial nerve in either anesthetized or decerebrated rats. Changes in LV myocardial perfusion and muscle blood flow to the right gastrocnemius muscle were measured by a Laser‐Doppler flowmetry. Arterial pressure and heart rate (HR) were also measured. Stimulation of SLR rapidly increased both LV myocardial perfusion and mean arterial pressure (MAP) in a stimulus intensity‐dependent manner. Stimulation of SLR also increased gastrocnemius muscle blood flow gradually throughout the stimulus period. Beta‐adrenergic blockade attenuated the rapid increase in myocardial perfusion evoked by SLR stimulation. Tibial nerve stimulation also rapidly increased LV myocardial perfusion and MAP. These results suggest that both feedforward and feedback control of the myocardial perfusion play an important role in meeting myocardial demands for adequate blood supply.

499 Myocardial Perfusion Pressure in Patients With Coronary Artery Disease and Hypertension With and Without Diabetes Mellitus: Implications for Diastolic Blood Pressure Targets in Hypertension Management

vasculopathy characterized by enhanced pulmonary artery smooth muscle cells (PASMC) proliferation and suppressed apoptosis. This results in both increase in pulmonary arterial pressure and pulmonary vascular remodeling. Recent studies have shown the implication of different transcription factors and proteins such as signal of transducer and activator of transcription 3 (STAT3), bone morphogenetic protein receptor 2 (BMPR2) and peroxisome proliferatoractivated receptor gamma (PPARa) in the etiology of PAH. Indeed, the activation of STAT3 induces BMPR2 downregulation contributing to the decrease in PPARa activity. In chondrocytes, the activation of this axis has been attributed to the advanced glycation endproducts receptor (RAGE). In a PAH proteomic study, RAGE has been demonstrated as one of the most upregulated protein in the PAH patients’ lungs. Thus, we hypothesized that by activating STAT3, RAGE induces BMPR2 and PPARa downregulation promoting PAH-PASMC proliferation and resistance to apoptosis in PAH. METHODS/RESULTS: We confirmed on human PAH lung biopsies that RAGE is overexpressed (n 5; qRT-PCR). In vitro, using PASMC isolated from PAH and healthy patients (n 3), we demonstrated that RAGE is overexpressed in PAH-PASMC compare to healthy PASMC. Its upregulation induces STAT3 activation and BMPR2 and PPARa decrease (qRT-PCR; western blot). The activation of the RAGE/STAT3/BMPR2/PPARa axis promotes PAHPASMC proliferation (Ki67) and suppresses apoptosis (TUNEL). This phenotype was totally reversed upon RAGE inhibition (by siRNA) or PPARa activation (by rosiglitazone). Furthermore, control cells treated with a RAGE agonist (S100A4 peptide) or with a PPARa antagonist (W9662) have a proliferative phenotype, mimicking the pathology. The S100A4 proliferative phenotype is reversed when PPARa is activated and we also demonstrated that PPARa is a downstream target of RAGE. In vivo, RAGE inhibition (siRNA nebulization i.t.) in rats with monocrotaline and sugen-induced PAH had decreased mean PA pressure (catheterization and Doppler echography) and right ventricular hypertrophy (M-mode ultrasound, n 8 per group). This decrease in PAH was associated with a significant improvement in lung perfusion measured by CT-angiogram and decreased PA wall thickness. Decrease in PA remodeling is associated with a decrease in both proliferation (Ki67) and resistance to apoptosis (TUNEL), associated with RAGE/STAT3/BMPR2/PPARa axis deregulation. Thus, we demonstrated for the first time that RAGE is an upstream regulator of PPARa and that Sugen-induced PAH could be reversed by protein inhibition. CONCLUSION: We demonstrated the implication of RAGE in the etiology of PAH. Moreover, we showed that RAGE constitutes a new and attractive therapeutic target for PAH. Featured Research

Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.

We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H(2)O(2))-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H(2)O(2) (600 micromol L(-1)) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H(2)O(2) exposure. Benidipine at 1 nmol L(-1) and nifedipine at 10 nmol L(-1) decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L(-1)) significantly reduced the H(2)O(2)-induced myocardial damage. Nifedipine (10 nmol L(-1)) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H(2)O(2). The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.

Right Ventricular Failure Resulting from Pressure Overload: Role of Intra-Aortic Balloon Counterpulsation and Vasopressor Therapy

Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure.

The Optimization Study on Time Sequence of Enhanced External Counter-Pulsation in AEI-CPR

To improve the aortic pressure and myocardial perfusion pressure during cardiac arrest, this study is designed to optimize sequence of Enhanced External Counter- Pulsation (EECP) for a cardiopulmonary resuscitation (CPR) technique — Active Compression-Decompression CPR coupled with EECP and Inspiratory Impedance Threshold Valve (AEI-CPR). EECP is lower-limbs compression equipment for AEI-CPR that enhanced blood regurgitation during chest decompression. Different occasion for EECP performance would bring different hemodynamic effect. A mathematical model of human circulatory system used to research AEI-CPR has been established. And then the AEI-CPR hemodynamic effect to the blood circulatory system is performed on the model. A genetic algorithm (GA) that used to find optimum sequence of the EECP is performed on the model when other parameters of external force for AEI-CPR are definite. At first, set the maximum strength of chest compression, chest decompression and lower-limbs compression at 400Nt, 160Nt and 300mmHg, respectively. Set the frequency of CPR at 100min-1 and the ratio of chest compression compared to LLCP at 1:1. Then, after genetic algorithm is performed on the established model, fifty groups of optimal results are obtained. The maximum coronary perfusion pressure (CPP) takes place when the EECP begin its compression at 0.2s and the interval among crural, femoral and iliac compression is 0.05s. By applying the optimization algorithm on the CPR mathematical model, the optimum sequence of the EECP could be found. And the experiment results indicate that obvious hemodynamic effect is attained when the EECP began compression at the end of chest compression.

Influence of orientation of bi-leaflet valve prostheses on coronary perfusion pressure in humans

Orientation of a bi-leaflet prosthesis (BLP) might influence coronary perfusion. The aim of this study was to investigate the influence of the orientation on coronary perfusion pressure during hyperemia and adrenergic stimulation. During hyperemia perfusion pressure determines coronary blood flow. Fourteen patients with normal coronary angiogram underwent aortic valve replacement (AVR) by a BLP, and seven received a bio-prosthesis. Patients receiving a BLP were randomized to either orientation A (hinge mechanism perpendicular to a line drawn between the coronary ostia) or B (hinge mechanism parallel to the line between the ostia). Six months after surgery all patients underwent cardiac catheterization. Pressures were measured during resting conditions, during maximum hyperemia, and during maximum adrenergic stimulation with a guiding catheter in the aortic arch (P(ao)), simultaneously with a sensor tipped guide wire in the coronary artery (P(cor)) and in the aortic root (P(root)). P(ao)-P(root) described a flow-induced pressure drop in the aortic root (Venturi effect) and the gradient P(root)-P(cor) described coronary ostium abnormalities. Only small non-significant differences in myocardial perfusion pressure were found between different orientations of a bi-leaflet prosthesis or between bi-leaflet prostheses and bio-prostheses in P(ao)-P(root) and P(root)-P(cor).

The effect of 4-week chilli supplementation on metabolic and arterial function in humans

To investigate the effects of regular chilli ingestion on some indicators of metabolic and vascular function. A randomized cross-over dietary intervention study. Launceston, Australia. Healthy free-living individuals. Thirty-six participants (22 women and 14 men), aged 46+/-12 (mean+/-s.d.) years; BMI 26.4+/-4.8 kg/m(2), consumed 30 g/day of a chilli blend (55% cayenne chilli) with their normal diet (chilli diet), and a bland diet (chilli-free) for 4 weeks each. Metabolic and vascular parameters, including plasma glucose, serum lipids and lipoproteins, insulin, basal metabolic rate, blood pressure, heart rate, augmentation index (AIx; an indicator of arterial stiffness), and subendocardial-viability ratio (SEVR; a measure of myocardial perfusion), were measured at the end of each diet. In a sub-study, during week 3 of each dietary period, the vascular responses of 15 subjects to glyceryl-trinitrate (GTN) and salbutamol were also studied. For the whole group, there were no significant differences between any of the measured parameters when compared at the end of the two dietary periods. When analysed separately, men had a lower resting heart rate (P=0.02) and higher SEVR (P=0.05) at the end of the chilli diet than the bland diet. In the sub-study, baseline AIx on the chilli diet was lower (P<0.001) than on the bland diet, but there was no difference in the effects of GTN and salbutamol between the two diets. Four weeks of regular chilli consumption has no obvious beneficial or harmful effects on metabolic parameters but may reduce resting heart rate and increase effective myocardial perfusion pressure time in men.