Fall In Cardiac Output Research Articles

Myocardial alterations following traumatic hemorrhagic injury.

Cardiac dysfunction (CD) has emerged as a key contributor to delayed organ failure and late mortality in patients surviving the initial traumatic hemorrhagic response. Inflammatory processes are implicated in the initial stages of this CD; however, downstream pathways leading to a characteristic rapid fall in stroke volume and cardiac output are not yet fully defined. Currently, no cardioprotective treatments are available. We investigated the role of myocardial oxidative stress in the pathogenesis of CD associated to traumatic hemorrhagic injury, and its related metabolomic profile. Ex vivo tissue from a 3-hour murine model of pressure-controlled trauma hemorrhagic shock (THS) was analyzed. Animals were randomized to echocardiography-guided crystalloid fluid resuscitation or a control group (sham: cannulation and anesthesia only, or naïve: no intervention). Trauma hemorrhagic shock and naïve samples were assessed by immunohistochemistry for nuclear 8-hydroxy-2'-deoxyguanosine expression as a marker of oxidative stress. Metabolomic analysis of THS and sham group tissue was performed by LC-MS. 8-Hydroxy-2'-deoxyguanosine expression across the myocardium was significantly higher following THS injury compared to naïve group (33.01 ± 14.40% vs. 15.08 ± 3.96%, p < 0.05). Trauma hemorrhagic shock injury significantly increased lysine ( p = 0.022), and decreased aconitate ( p = 0.016) and glutamate ( p = 0.047) in the myocardium, indicating activation of a catabolic metabolism and oxidative stress response. We confirm the acute development of oxidative stress lesions and altered cardiac energy metabolism following traumatic hemorrhage injury, providing insight into the relationship between inflammatory damage and impaired cardiac contractility. These findings may provide targets for development of novel cardioprotective therapeutics aiming to decrease late mortality from trauma.

Utilidad del Integrated Pulmonary Index (IPI) en la Unidad de Reanimación Postanestésica (URPA)

Respiratory complications occur in 10-20% of patients in the immediate postoperative period and represent the most frequent perioperative complication. Patient-associated factors, such as age or comorbidities, and the anesthetic-surgical procedure, such as duration, type of surgery and degree of urgency, are associated with the appearance of these complications. From a pathophysiological point of view, the alteration of ventilatory mechanics in major surgery, the residual effect of medications used for anesthesia and other metabolic alterations, triggered by the state of disease or surgical aggression, may play a role in this process. Respiration aims to oxygenate the blood, while removing CO2 produced during aerobic metabolism. In the postoperative period, hypoxemia frequently occurs as a result of ventilation/perfusion changes, such as those that occur in the presence of atelectasis, which lead to shunt; while hypercapnia reflects a reduction in alveolar ventilation, commonly related to global hypoventilation in the context of sedation or residual neuromuscular blockade. Likewise, those situations in which there is an increase in the ventilation/perfusion ratio (dead space) will favor the appearance of hypercapnia if there is not enough compensatory increase in minute volume. In addition, it should be borne in mind that not only respiratory alterations can result in an increase in dead space, but the fall in cardiac output can favor the appearance of this effect due to the inability to provide adequate blood flow to all ventilated portions of the lung. Given the impact of complications on prognosis, early detection of these alterations through continuous monitoring can potentially improve clinical outcomes.

Evaluation of hemodynamic changes during laparoscopic cholecystectomy by transthoracic echocardiography

Background and Aims:The purpose of this study was to prospectively examine the effects of pneumoperitoneum and the reverse Trendelenburg position on cardiac hemodynamics during laparoscopic cholecystectomy using transthoracic echocardiography (TTE).Material and Methods:In this prospective observational study, after institutional review board clearance, forty patients of either sex of ASA I-II status undergoing laparoscopic cholecystectomy were enrolled in the study. Changes in cardiac output, stroke volume, and ejection fraction were recorded using TTE at different time intervals: Preoperatively, before creation of pneumoperitoneum, 5 min after creation of pneumoperitoneum, and 5 min after setting the operative reverse Trendelenburg position with legs at the level of the hips. All statistical analyses were performed using the statistical program SPSS version 16 and P value less than 0.05 was considered as statistically significant. Data were examined using mixed analysis of variance (ANOVA) followed by post hoc Bonferroni correction.Results:There was significant fall in cardiac output (CO) (45%, P < 0.001), stroke volume (SV) (42%, P < 0.001), and ejection fraction (EF) (31.8% change, P < 0.001) after creation of pneumoperitoneum with significant rise in MAP (11%, P < 0.001). But with reverse Trendelenburg position, there was a significant improvement of CO (30%), SV (28%), and EF (21% change) in comparison to values after pneumoperitoneum, but still remained below baseline. There was no change in heart rate at different time intervals. There was no significant difference in hemodynamics between ASA I and II patients.Conclusion:Patients undergoing laparoscopic cholecystectomy undergo significant hemodynamic changes after pneumoperitoneum and reverse Trendelenburg position.

Hemodynamic Patterns Before Inhospital Cardiac Arrest in Critically Ill Children: An Exploratory Study.

Exploratory retrospective analysis of arterial blood pressure and electrocardiogram waveforms. PICU and cardiac critical care unit in a tertiary-care children's hospital. Twenty-seven children with invasive blood pressure monitoring who suffered a total of 31 inhospital cardiac arrest events between June 2017 and June 2019. None. We assessed changes in cardiac output, systemic vascular resistance, stroke volume, and heart rate derived from arterial blood pressure waveforms using three previously described estimation methods. We observed substantial prearrest drops in cardiac output (population median declines of 65-84% depending on estimation method) in all patients in the 10 minutes preceding inhospital cardiac arrest. Most patients' mean arterial blood pressure also decreased, but this was not universal. We identified three hemodynamic patterns preceding inhospital cardiac arrest: subacute pulseless arrest (n = 18), acute pulseless arrest (n = 7), and bradycardic arrest (n = 6). Acute pulseless arrest events decompensated within seconds, whereas bradycardic and subacute pulseless arrest events deteriorated over several minutes. In the subacute and acute pulseless arrest groups, decreases in cardiac output were primarily due to declines in stroke volume, whereas in the bradycardic group, the decreases were primarily due to declines in heart rate. Critically ill children exhibit distinct physiologic behaviors prior to inhospital cardiac arrest. All events showed substantial declines in cardiac output shortly before inhospital cardiac arrest. We describe three distinct prearrest patterns with varying rates of decline and varying contributions of heart rate and stroke volume changes to the fall in cardiac output. Our findings suggest that monitoring changes in arterial blood pressure waveform-derived heart rate, pulse pressure, cardiac output, and systemic vascular resistance estimates could improve early detection of inhospital cardiac arrest by up to several minutes. Further study is necessary to verify the patterns witnessed in our cohort as a step toward patient rather than provider-centered definitions of inhospital cardiac arrest.

SARS-CoV-2 vaccination of people living with human T leukaemia virus type 1

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Taurine blunts doxorubicin cardiotoxicity: chronic and acute effects

Abstract Funding Acknowledgements Type of funding sources: None. Aim. To study the functional statement of the isolated heart inherent to doxorubicin cardiotoxicity under the chronic and acute action of taurine. Material and methods. Doxorubicin (Dx) cardiotoxicity manifested by heart failure development was reproduced classically by anthracycline i/p administration in rats in cumulative dose of 16 mg/kg (4 mg/kg four times during 2 weeks) – Dx series. Series with chronic action of taurine (Tr) included rats receiving this aminoacid daily per os during Dx administration (100 mg/kg) – Dx + Tr series. Rats of both series were sacrificed by euthanasia and the isolated heart was perfused by Krebs solution according to Langendorff (isovolumic heart) and Neely-Rovetto (working heart) methods in conditions of diverse hemodynamic and neuroendocrine efforts applying. Acute action of taurine was studied during its infusion in the perfusate of isolated hearts in final concentration of 40 µM. The hearts of intact rats constituted the control series. Results. Chronic action of taurine has identified certain important functional benefits, the most important being underlined beneath. The first, taurine reversed the negative inotropic effect of isolated heart on endothelin-1 (ET-1) action (10-7 M), detected in Dx series and manifested by both systolic pressure of left ventricle (LV) and cardiac output fall by about 9,1%. Taurine assured increase of these indices during ET-1 stimulation. The second, Tr notably improved both isovolumic relaxation and contraction of myocardium exhibited by significant enhancement of Veragut index (118,6 ± 9,6 vs 94,8 ± 6,5 1/sec), +dP/dPmax (8389 ± 445 vs 7216 ± 363 mm Hg/sec) and -dP/dTmax (7526 ± 378 vs 5684 ± 322 mm Hg/sec) during efforts with volume and resistance. The third, Tr significantly decreased LV end diastolic pressure (LVSDP) when coronary pressure of isovolumic heart elevated by 50% (from 80 up to 120 cm H20 column): 16,2 ± 1,2 vs 18,8 ± 1,4 mm Hg. Acute Tr action manifested by: (i) significant LVSDP diminution during 30 min of ischemia (52,4 ± 3,1 vs 63,7 ± 4,4 mm Hg) and on 45th min of reperfusion (18,3 ± 1,3 vs 22,8 ± 1,4 mm Hg), (ii) increased time of LV extrasystole appearance when the glucose content of Krebs solution was reduced by 50% (28,6 ± 2,8 vs 22,5 ± 2,4 min), and (iii) increased time of LV tachyarrhythmia appearance when the potassium content of Krebs solution raised up to 6,5 meq/L (9,2 ± 0,5 vs 6,9 ± 0,3 min). Conclusion. Taurine, a natural calcium modulator of the heart, notably improves functional reserves of the myocardium exposed to cardiotoxic action of Dx, and could be seen as a relevant remedy of primary and secondary prophylaxis of Dx induced heart failure in oncologic patients.

The Valsalva maneuver: an indispensable physiological tool to differentiate intra versus extracranial near-infrared signal.

Developing near-infrared spectroscopy (NIRS) parameter recovery techniques to more specifically resolve brain physiology from that of the overlying tissue is an important part of improving the clinical utility of the technology. The Valsalva maneuver (VM) involves forced expiration against a closed glottis causing widespread venous congestion within the context of a fall in cardiac output. Due to the specific anatomical confines and metabolic demands of the brain we believe a properly executed VM has the ability to separate haemodynamic activity of brain tissue from that of the overlying scalp as observed by NIRS, and confirmed by functional magnetic resonance imaging (fMRI). Healthy individuals performed a series of standing maximum effort VMs under separate observation by frequency domain near-infrared spectroscopy (FD-NIRS) and fMRI. Nine individuals completed the clinical protocol (6 males, age 21-40). During the VMs, brain and extracranial tissue targeted signal were significantly different (opposite direction of change) in both fMRI and NIRS (p=0.00025 and 0.00115 respectively), with robust cross correlation of parameters between modalities. Four of these individuals performed further VMs after infiltrating 2% xylocaine/1:100,000 epinephrine (vasoconstrictor) into scalp tissue beneath the probes. No significant difference in the cerebrally derived parameters was observed. The maximum effort VM has the ability to separate NIRS observable physiology of the brain from the overlying extracranial tissue. Observations made by this FD cerebral NIRS device are comparable with fMRI in this context.

Comparison of the Potency of Phenylephrine and Norepinephrine Bolus Doses Used to Treat Postspinal Hypotension During Elective Cesarean Section

(Int J Obst Anesth. 2019;38:25–31) Vasopressors to manage hypotension after spinal anesthesia are commonly used in obstetric patients. Phenylephrine has been considered the vasopressor of choice for many years, but it can result in reflex bradycardia and an associated fall in cardiac output. Norepinephrine is another potent vasopressor that has significant chronotropic effects that should limit bradycardia. However, there is little information about the preferred dose for managing postspinal hypotension in obstetric patients or its potency ratio compared with phenylephrine. This study aimed to calculate the 95% and 50% effective doses (ED95 and ED50) of both drugs and their potency ratio when administered as a bolus for the treatment of spinal-induced hypotension in women undergoing elective cesarean section.

Right Ventricular Failure Following Left Ventricular Assist Device Implantation

Left ventricular assist device (LVAD) is being used increasingly in recent years for end stage heart failure as a bridge to transplant (BTT) and also as a destination therapy (DT). Patients with end stage heart failure have some degree of elevated pulmonary capillary wedge pressure, causing right ventricular hypertrophy which in due course leads to decreased dilatation of the RV and fall in cardiac output & severe tricuspid regurgitation (TR) presenting with features of RV failure (RVF). Implantation of LVAD improves left heart function at the cost of right ventricular output with an incidence of 25%-30%. RVF may lead to impaired LVAD flow, difficulty in weaning from cardio-pulmonary bypass (CPB), decreased tissue perfusion and multi-organ failure. In this article we comprehended the pathophysiology leading to RVF post LVAD implantation and its preoperative predictors and the various treatment modalities for managing RVF post LVAD implantation.

Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section

BackgroundPhenylephrine, although considered the vasopressor of choice, can cause reflex bradycardia and a fall in cardiac output. Norepinephrine, due to its direct positive chronotropic and reflex negative chronotropic actions, is expected to overcome this problem. However, limited information about its effective dose for management of post-spinal hypotension, and its potency compared to phenylephrine, is available. MethodsOne hundred consecutive patients who developed post-spinal hypotension were treated with a predetermined dose of either phenylephrine or norepinephrine. Correction of hypotension after one minute was considered ‘success’. The starting dose for the first patient and testing interval (the incremental or decremental dosing) were 100 μg and 10 μg in the phenylephrine group, and 6 μg and 0.5 μg in the norepinephrine group. Doses for subsequent patients were determined by the responses of previous patients according to the Narayana rule for up-down sequential allocation. ED95 and ED50 of phenylephrine and norepinephrine boluses and their potency ratio were calculated. ResultsUsing Probit analysis, ED95 and ED50 values were 43.1 µg (95% CI 39.5 to 65.0 µg) and 33.2 µg (95% CI 5.1 to 37.0 µg) for phenylephrine, and 3.7 µg (95% CI 3.5 to 4.7 µg) and 3.2 µg (95% CI 1.8 to 3.4 µg) for norepinephrine. The relative potency ratio of norepinephrine and phenylephrine was 11.3 (95% CI 8.1 to 16.9). ConclusionBased on the results of this study, norepinephrine is about 11 times more potent than phenylephrine. When used as bolus doses for treatment of hypotension, 100 μg phenylephrine should be approximately equivalent to 9 μg norepinephrine.

The pathophysiology of the vasovagal response

In part I of this study, we found that the classical studies on vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. Since 1980, blood pressure and cardiac output have been measured continuously using noninvasive methods during tilt, mainly in patients with recurrent syncope, including women and the elderly. This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. The physiology responsible for each phase is discussed. Although the order of phases is consistent, the time spent in each phase may vary. In teenagers and young adults, progressive hypotension during phases 2 and 3 can be driven by vasodilatation or falling cardiac output. The fall in cardiac output is secondary to a progressive decrease in stroke volume because blood is pooled in the splanchnic veins. In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels.

Hemodynamic effects of lung recruitment maneuvers in acute respiratory distress syndrome

BackgroundClinical trials have, so far, failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of RMs on the cardiovascular system remain poorly understood.MethodsA computational model with highly integrated pulmonary and cardiovascular systems was configured to replicate static and dynamic cardio-pulmonary data from clinical trials. Recruitment maneuvers (RMs) were executed in 23 individual in-silico patients with varying levels of ARDS severity and initial cardiac output. Multiple clinical variables were recorded and analyzed, including arterial oxygenation, cardiac output, peripheral oxygen delivery and alveolar strain.ResultsThe maximal recruitment strategy (MRS) maneuver, which implements gradual increments of positive end expiratory pressure (PEEP) followed by PEEP titration, produced improvements in PF ratio, carbon dioxide elimination and dynamic strain in all 23 in-silico patients considered. Reduced cardiac output in the moderate and mild in silico ARDS patients produced significant drops in oxygen delivery during the RM (average decrease of 423 ml min−1 and 526 ml min−1, respectively). In the in-silico patients with severe ARDS, however, significantly improved gas-exchange led to an average increase of 89 ml min−1 in oxygen delivery during the RM, despite a simultaneous fall in cardiac output of more than 3 l min−1 on average. Post RM increases in oxygen delivery were observed only for the in silico patients with severe ARDS. In patients with high baseline cardiac outputs (>6.5 l min−1), oxygen delivery never fell below 700 ml min−1.ConclusionsOur results support the hypothesis that patients with severe ARDS and significant numbers of alveolar units available for recruitment may benefit more from RMs. Our results also indicate that a higher than normal initial cardiac output may provide protection against the potentially negative effects of high intrathoracic pressures associated with RMs on cardiac function. Results from in silico patients with mild or moderate ARDS suggest that the detrimental effects of RMs on cardiac output can potentially outweigh the positive effects of alveolar recruitment on oxygenation, resulting in overall reductions in tissue oxygen delivery.

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW - 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the Constant flow group and between the groups at cessation of the experiments. In hypothermic rat lungs perfused at constant flow, fluid filtration coefficient per gram PLW and B/P ratio increased more than 10-fold concerted by increased hemoconcentration, but the changes were less in hypothermic lungs perfused at constant PPA.

Cardiogenic syncope in therapeutic practice

Recent publications devoted to the etiology, diagnosis and treatment of cardiogenic syncope were reviewed. The analysis of the current state of views on a pathogenesis, classification and features of a clinical picture of syncope of cardiogenic etiology was performed. Cardiogenic syncope has a 20-30% mortality. The highest risk is characteristic for the age more than 45 years, heart failure, history of ventricular tachycardia, nonspecific changes on ECG. With three and more risk factors the probability of a sudden cardiac death within the next year can reach 80%. The cause of cardiogenic syncope is reduction of cerebral blood flow. Cardiogenic syncope can be caused by a fall in blood pressure, cardiac output and total peripheral vascular resistance. Cardiogenic syncope may be the result of bradycardia and asystole, supraventricular and ventricular tachycardia, pulmonary embolism, dissecting aortic aneurysm, structural defects and cardiac anomalies, presence of myxoma or mobile atrial clot, cardiac tamponade, constrictive pericarditis, acute myocardial ischemia, abnormalities of the coronary arteries, dysfunction of prosthetic valve and cardiac pacemakers. In the diagnosis of cardiogenic syncope anamnesis and data received on physical examination are important. Instrumental examination should include electrocardiography, detection of comorbid conditions, exercise stress tests such as cycle ergometry or treadmill test, Holter ECG monitor, echocardiography, and coronary angiography for suspected acute myocardial ischemia.

Neurohormonal activation in heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) develops when cardiac output falls as a result of cardiac injury. The most well-recognized of the compensatory homeostatic responses to a fall in cardiac output are activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS). In the short term, these 'neurohormonal' systems induce a number of changes in the heart, kidneys, and vasculature that are designed to maintain cardiovascular homeostasis. However, with chronic activation, these responses result in haemodynamic stress and exert deleterious effects on the heart and the circulation. Neurohormonal activation is now known to be one of the most important mechanisms underlying the progression of heart failure, and therapeutic antagonism of neurohormonal systems has become the cornerstone of contemporary pharmacotherapy for heart failure. In this Review, we discuss the effects of neurohormonal activation in HFrEF and highlight the mechanisms by which these systems contribute to disease progression.

2: Renal Haemodynamics and Acute Kidney Injury During Therapeutic Hypothermia and Re-Warming in Neonates with Hypoxic-Ischaemic Encephalopathy

Birth asphyxia is associated with acute kidney injury (AKI); severity may correspond with degree of hypoxia. Previous work by our group demonstrated lower cardiac output in neonates undergoing therapeutic hypothermia (TH). The relevance of these changes to AKI remains unknown. To describe longitudinal renal haemodynamic changes during TH and re-warming (RW) and evaluate their relationship with cardiac output in neonates with and without AKI. Prospective observational study of 18 term and near-term infants with hypoxic-ischaemic encephalopathy (HIE) who received TH. Doppler ultrasound was used to assess left ventricular output (LVO) and renal artery (RA) blood flow parameters – systolic and end-diastolic velocity (Vs and Vd), and resistive index (RI) during cooling [TH I (24 h) and II (72 h)] and post re-warming [RW I (12 h) and II (>24 h)]. AKI was defined as anuria/oliguria (100 mmol/L; or anuria/oliguria for >36 h; or any serum creatinine >125 mmol/L; or rising serum creatinine postnatally. There was no difference in baseline demographics or severity of HIE between neonates with (n=8) vs without (n=10) AKI. All 18 infants survived till discharge. Neonates who developed AKI had higher RA RI 24 h after TH was initiated [Table 1]. There was a temporal increase in LVO in both groups (P<0.01, two-way ANOVA), without intergroup difference. Neonates in the non-AKI group only showed an increase in RI (P=0.01) and a trend towards increase in RA Vs over time (P=0.05). Early changes in end-diastolic flow (EDF) were seen in both groups, which normalized over time. Elevated RA RI at 24 h after introduction of TH is associated with and predicts AKI. The fall in cardiac output and renal systolic flow after TH is not associated with AKI.

Role of angiotensin II type I (AT1 A1166C) receptor polymorphism in susceptibility of left ventricular dysfunction

BackgroundLeft ventricular dysfunction (LVD) with subsequent congestive heart failure (CHF) constitutes the final common pathway for a host of cardiac disorders. The impaired LV function develops in response to an ischemic insult followed by a fall in cardiac output that leads to activation of renin-angiotensin-system (RAS). Angiotensin II type I receptor (AT1), which mediate the vasoconstrictive and salt-conserving actions of the RAS, represent interesting candidate genes for cardiovascular diseases. Therefore, we conducted an association study between single nucleotide polymorphism (SNP) in AT1 gene and LVD in CAD patients. Methods and resultsThe present study recruited a total of 950 subjects including 720 angiography confirmed CAD patients and 230 healthy controls. Among 720 CAD patients, 229 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. The AT1 (A1166C, rs5186) polymorphism was determined by ARMS-PCR. Our results showed that the frequency of AT1 1166AC and CC genotypes were significantly higher in LVD patients in comparison to non-LVD (LVEF >45%) patients (p value = 0.003; OR = 1.81 and p value <0.001; OR = 4.33). Further analysis showed that AT1 A1166C polymorphism was significantly associated with LV end diastole (p-value = 0.031), end systole (p-value = 0.038) dimensions, and mean LVEF (p-value = 0.035). Moreover, on comparing the AT1 A1166C polymorphism in CAD patients with healthy controls, we did not find any association both at genotypic and allelic level (p value = 0.927; OR = 1.04 and p value = 0.219; OR = 0.83) respectively. ConclusionsOur study suggests that AT1 A1166C polymorphism may play significant role in conferring genetic susceptibility of LVD.

Hypometabolism in Endotoxic Shock Reflects a Thermoregulatory Response and Occurs Independently of Circulatory Hypoxia

Oxygen utilization (VO2) is thought to fall in the late stages of septic shock because of mitochondrial dysfunction, circulatory hypoxia or both. However, the applicability of this conceptual framework to early septic shock is unclear. We investigated this matter in a rat model of lipopolysaccharide (LPS)‐induced shock (endotoxic shock). A novel experimental preparation was devised to simultaneously monitor oxygen delivery (DO2) and VO2 in rats whose thermoregulation had not been disrupted by anesthetics. Using a β3‐adrenergic agonist known to activate brown adipocytes, we found no evidence of metabolic impairment between 20 and 150 min post‐LPS. In spite of that, VO2 fell early in the LPS‐challenged rats, and such a fall in VO2 seemed to be driving a decrease in body temperature. The fall in VO2 was not preceded by any fall in cardiac output or DO2. Furthermore, no imbalance between VO2 and DO2 were encountered, and an analysis of NAD+/NADH ratios provided no indication of tissue hypoxia. Only when hypometabolism and hypothermia were prevented by exposure to a warm environment did an imbalance in the DO2/VO2 ratio become evident, and such an imbalance was associated with tissue hypoxia (reduction in NAD+/NADH ratio). It is concluded that reduced VO2 in early endotoxic shock (i) results from neither metabolic failure nor circulatory hypoxia, (ii) reflects a thermoregulatory adjustment, and (iii) serves as preemptive strategy to avoid hypoxia. Clinical data and conduct should be reexamined in light of these new findings.FundingFAPESP, AHA &amp; CNPq.

Impaired Compensatory Responses to Hypovolemic Circulatory Stress in Women with Vasovagal Syncope

ObjectiveA fall in cardiac output (CO) due to a reduced venous return has been suggested as an important factor for the hemodynamic instability in vasovagal syncope (VVS). The aim was to investigate compensatory mechanisms to defend central blood volume during hypovolemic stress in women with VVS.Design and MethodsSingle (30 mmHg) and graded (20 to 70 mmHg) lower body negative pressure (LBNP) were used to create hypovolemic stress in 15 young women with VVS and 15 matched controls. Peripheral mobilization of venous blood from the arm (capacitance response), net fluid absorption and lower limb blood pooling were evaluated with volumetric technique. Hemodynamic responses and plasma norepinephrine (P‐NE) were measured.ResultsAlthough CO decreased in both groups during graded LBNP (P &lt; 0.05), VVS presented a significantly lower CO at LBNP of 40 mmHg (P = 0.045). Mobilization of capacitance blood from the peripheral circulation (ml/100 ml) was reduced in VVS (LBNP 40 mmHg, 0.194±0.02 vs. 0.299±0.02, P = 0.007; LBNP 50 mmHg, 0.172±0.01 vs. 0.314±0.04, P = 0.003), and net fluid absorption was ~40% lower (P = 0.019). VVS displayed a blunted percentage increase in P‐NE (P = 0.009) and a reduced maximal percentage increase in TPR (P = 0.041) during graded LBNP. Lower limb blood pooling was comparable in VVS and controls.ConclusionsImportant compensatory mechanisms to defend central blood volume during hypovolemic stress were impaired in VVS. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

The qualitative detection of decreases in cardiac output

BackgroundCardiac output is a major factor in the maintenance of physiological homeostasis and is difficult to measure with accuracy. This study describes an evidence-based technique, based on physiological changes, which may indicate small changes in cardiac output that cannot be measured by current techniques. MethodSynchronous changes in blood pressure, heart rate, pulse amplitude and end-tidal carbon dioxide are analysed using runs analysis and a normalisation technique. An evidence-based algorithm was used to detect possible changes in cardiac output and data extracts from 31 consenting patients are presented as examples. ResultsThe decrease in end-tidal carbon dioxide, during steady state ventilation, was greater in those events notified as hypovolaemia associated with a fall in cardiac output than those events notified as hypovolaemia alone. The difference in end-tidal carbon dioxide between the two groups was −0.25kPa (CI −0.42 to −0.09) p<0.003. DiscussionRuns analysis can detect trends in EtCO2 that during steady state ventilation may indicate a decrease in cardiac output. It is a safe technique; no additional hardware is required and the generated alerts only notify the clinician of the possibility of an adverse change. Determination of the rate of clinically significant false positives and negatives requires further work.