Significant Reduction In Cardiac Output Research Articles

Even periconceptional alcohol consumption can have long-term consequences on heart health in the offspring.

Even periconceptional alcohol consumption can have long-term consequences on heart health in the offspring.

Mechanical circulatory support in ventricular arrhythmias.

In atrial and ventricular tachyarrhythmias, reduced time for ventricular filling and loss of atrial contribution lead to a significant reduction in cardiac output, resulting in cardiogenic shock. This may also occur during catheter ablation in 11% of overall procedures and is associated with increased mortality. Managing cardiogenic shock and (supra) ventricular arrhythmias is particularly challenging. Inotropic support may exacerbate tachyarrhythmias or accelerate heart rate; antiarrhythmic drugs often come with negative inotropic effects, and electrical reconversions may risk worsening circulatory failure or even cardiac arrest. The drop in native cardiac output during an arrhythmic storm can be partly covered by the insertion of percutaneous mechanical circulatory support (MCS) devices guaranteeing end-organ perfusion. This provides physicians a time window of stability to investigate the underlying cause of arrhythmia and allow proper therapeutic interventions (e.g., percutaneous coronary intervention and catheter ablation). Temporary MCS can be used in the case of overt hemodynamic decompensation or as a “preemptive strategy” to avoid circulatory instability during interventional cardiology procedures in high-risk patients. Despite the increasing use of MCS in cardiogenic shock and during catheter ablation procedures, the recommendation level is still low, considering the lack of large observational studies and randomized clinical trials. Therefore, the evidence on the timing and the kinds of MCS devices has also scarcely been investigated. In the current review, we discuss the available evidence in the literature and gaps in knowledge on the use of MCS devices in the setting of ventricular arrhythmias and arrhythmic storms, including a specific focus on pathophysiology and related therapies.

Echocardiographic assessment of felines sedated with dexmedetomidine or xylazine associated with butorphanol

This prospective cohort study aimed to evaluate by echocardiogram the cardiovascular effects of α2 agents associated with butorphanol in cats. A group of 18 mixed-breed cats with a mean weight of 3.65 + 0.7 kg, with an approximate age of 6 months. The cats were assigned in three groups, XB (Xylazine/butorphanol group) sedation with 0.5 mg/kg of xylazine and 0.5 mg/kg of butorphanol IM; DB (Dexmedetomidine/butorphanol group): sedation with 20 µg/kg of dexmedetomidine and 0.5 mg/kg of butorphanol IM; C: control group which received saline solution in volume approximated to those used in the other groups, IM. Echocardiographic variables as ejection fraction (Simpson's method and M-mode) and left ventricular shortening fraction (M-mode), ejection volume, end-systolic volume and cardiac output (Teichholz), tissue Doppler E' and A' wave velocities and cardiac index were evaluated. There was a reduction in echocardiographic variables compared with the control group, being statistically significant for heart rate, ejection fraction (% by Simpson), shortening fraction (% in M-mode) and end-systolic volume in XB and DB groups, and tissue Doppler E' and A' wave velocity (m/s), E'/A' ratio, cardiac output and cardiac index only in XB group. When compared to each other, XB and DB differed significantly in the tissue Doppler E' and A' wave velocity (m/s), and E'/A' ratio. Xylazine was more deleterious than dexmedetomidine in most of the variables evaluated, leading to a significant reduction in cardiac output and cardiac index at the doses used in this study.

Maternal hemodynamics and computerized cardiotocography during labor with epidural analgesia

PurposeTo analyze the mechanisms involved in the fetal heart rate (FHR) abnormalities after the epidural analgesia in labor.MethodsA prospective unblinded single-center observational study on 55 term singleton pregnant women with spontaneous labor. All women recruited underwent serial bedside measurements of the main hemodynamic parameters using a non-invasive ultrasound system (USCOM-1A). Total vascular resistances (TVR), heart rate (HR), stroke volume (SV), cardiac output (CO) and arterial blood pressure were measured before epidural administration (T0), after 5 min 5 (T1) from epidural bolus and at the end of the first stage of labor (T2). FHR was continuously recorded through computerized cardiotocography before and after the procedure.ResultsThe starting CO was significantly higher in a subgroup of women with low TVR than in women with high-TVR group. After the bolus of epidural analgesia in the low-TVR group there was a significant reduction in CO and then increased again at the end of the first stage, in the high-TVR group the CO increased insignificantly after the anesthesia bolus, while it increased significantly in the remaining part of the first stage of labor. On the other hand, CO was inversely correlated with the number of decelerations detected on cCTG in the 1 hour after the epidural bolus while the short-term variation was significantly lower in the group with high-TVR.ConclusionMaternal hemodynamic status at the onset of labor can make a difference in fetal response to the administration of epidural analgesia.

Exposure to Doxorubicin Modulates the Cardiac Response to Isoproterenol in a Sex‐Dependent Manner

IntroductionSubclinical cardiotoxicity occurs in cancer patients who receive low doses of anthracyclines such as doxorubicin (DOX), which can develop into overt cardiomyopathy when triggered by other cardiovascular stressors. Female rodents are protected from DOX‐induced cardiac dysfunction in experimental studies. However, the sex‐related differences in DOX‐induced increased susceptibility to later‐onset cardiovascular stressors are yet to be determined. Therefore, in the present study, we determined the effects of a low dose of DOX on the cardiac response to catecholamine stress induced by isoproterenol (ISO) in male and female mice. Since sex hormones are believed to mediate the sexually dimorphic response to DOX, we determined whether gonadectomy is able to reverse the observed response.MethodsFive‐week old intact and gonadectomized male and female C57Bl/6 mice were administered saline or DOX (4 mg/kg/week for 5 weeks by intraperitoneal injections). After a 5‐week recovery period, mice were administered daily subcutaneous injections of ISO (10 mg/kg) or saline for 14 days. Cardiac function was measured by echocardiography before, immediately after the first dose of ISO (stress echo), and following 14 days of daily ISO injections. Hearts were harvested and weighed at the end of the experiment.ResultsStress echo shows that the positive chronotropic effect of ISO was blunted in DOX‐treated male and female mice, while the positive inotropic effect is maintained. Following 14 days of daily ISO injections, saline‐treated male mice exhibited a hypertrophic response to ISO, indicated by an increase in the heart weight‐to‐tibia length, while DOX‐treated male mice did not. In addition, ISO caused more reduction of cardiac output in DOX‐treated male mice than that in saline‐treated male mice. On the other hand, both saline‐treated and DOX‐treated female groups exhibited a hypertrophic response to ISO. ISO treatment for 14 days did not cause significant reduction in cardiac output in either saline‐treated or DOX‐treated female mice. Similar experiments were performed in a cohort of gonadectomized male and female mice. Intriguingly, sexually dimorphic responses are observed in gonadectomized mice similar to those observed in intact mice.ConclusionExposure to DOX modulates the cardiac response to isoproterenol in a sex‐dependent manner. DOX treatment abrogates the adaptive hypertrophic response to ISO in male mice, making them more susceptible to declining cardiac output. Deprivation of sex hormones by gonadectomy did not reverse this sexual dimorphism, suggesting that other mechanisms are implicated. Further research is warranted to determine the mechanisms of this sexual dimorphism.

Adenosine, lidocaine, and magnesium for attenuating ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta in a porcine model.

Minimally invasive resuscitative endovascular balloon occlusion of the aorta (REBOA) following noncompressible hemorrhage results in significant ischemia reperfusion injury (IRI). Adverse outcomes from IRI include organ dysfunction and can result in profound hemodynamic and molecular compromise. We hypothesized that adenosine, lidocaine, and magnesium (ALM) attenuates organ injury and inflammation responses following REBOA IRI in a porcine model of hemorrhage. Animals underwent a 20% controlled hemorrhage followed by 45 minutes of supraceliac balloon occlusion. They were randomized into two groups: control (n = 9) and ALM intervention (n = 9) to include a posthemorrhage, pre-REBOA bolus (200 mL of 3% NaCl ALM) followed by a continuous drip (2 mL/kg per hour of 0.9% NaCl ALM) during the 4-hour resuscitative period. Primary outcomes included hemodynamic parameters, gene expression of inflammatory signaling molecules, and plasma concentrations of select cytokines and chemokines. The ALM cohort demonstrated a significant reduction in cardiac output and cardiac index. Plasma concentrations of interleukin 2 and interleukin 10 were significantly lower 3 hours post-REBOA in animals treated with ALM versus vehicle. Interleukin 4 levels in plasma were also lower with ALM at 3 and 4 hours post-REBOA (p < 0.05). Liver expression of IL1RN, MTOR, and LAMP3 messenger RNA was significantly lower with ALM as compared with the vehicle. No significant difference in large bowel gene expression was observed between treatments. In a porcine model of hemorrhage, ALM treatment mitigated inflammatory responses early during post-REBOA resuscitation. Our findings suggest that ALM use with trauma may reduce inflammatory injury and improve outcomes related to REBOA utilization.

Hemodynamics of different volumes of red blood cell transfusion in preterm infants.

Although many controversies exist regarding the risk of red blood cell (RBC) transfusions, half of preterm infants born at <32weeks of gestational age receive such transfusions because of anemia of prematurity. Because of the costs and risks associated with multiple transfusions, it has been suggested that a large transfusion volume reduces the number of transfusions. However, there have been persistent concerns that RBC transfusion might lead to volume overload. We examined the impacts of large (20mL/kg) compared to standard volume (15mL/kg) transfusions on the hemodynamic variables of stable, electively transfused, preterm infants, by serially measuring echocardiographic parameters and plasma B-type natriuretic peptide levels. A total of 39 infants born at <34weeks of gestation and aged >2weeks at the time of enrollment were randomly allocated to either a standard volume (15mL/kg) or a large volume (20mL/kg) group. Significant reductions in cardiac output and transient increases in plasma B-type natriuretic peptide levels were found after RBC transfusion in both the standard and large volume (20mL/kg) groups. However, these changes were not significantly different between the two groups. Large-volume transfusions could be tolerable in stable preterm infants with anemia.

Effects of an Innovative Head-Up Tilt Protocol on Blood Pressure and Arterial Stiffness Changes.

The objective of our study was to identify blood pressure (BP) and pulse wave velocity (PWV) changes during orthostatic loading, using a new the head-up tilt test (HUTT), which incorporates the usage of a standardized hydrostatic column height. Methods: 40 healthy subjects 20–32 years performed HUTT, which was standardized to a height of the hydrostatic column at 133 cm. Exposure time was 10 min in each of 3 positions: horizontal supine 1, HUTT, and horizontal supine 2. The individual tilt up angle made it possible to set the standard value of the hydrostatic column. Hemodynamic parameters were recorded beat to beat using “Task Force Monitor 3040 i”, pulse-wave velocity (PWV) was measured with a sphygmograph–sphygmomanometer VaSera VS1500N. Results: Orthostatic loading caused a significant increase in heart rate (HR) and a decrease in stroke volume (SV) (p < 0.05) but no significant reductions in cardiac output, changes in total vascular resistance (TVR), or BP. An analysis of personalized data on systolic blood pressure (SBP) changes in tilt up position as compared to horizontal position (ΔSBP) revealed non-significant changes in this index in 48% of subjects (orthostatic normotension group), in 32% there was a significant decrease in it (orthostatic hypotension group) and in 20% there was a significant increase in it (orthostatic hypertension group). These orthostatic changes were not accompanied by any clinical symptoms and/or syncope. During HUTT, all subjects had in the PWV a significant increase of approximately 27% (p < 0.001). Conclusion: The new test protocol involving HUTT standardized to a height of hydrostatic column at 133 cm causes typical hemodynamics responses during orthostatic loading. Individual analysis of the subjects revealed subclinical orthostatic disorders (OSD) in up to 52% of the test persons. During HUTT, all test subjects showed a significant increase in PWV. The new innovative HUTT protocol can be applied in multi-center studies in healthy subjects to detect preclinical forms of orthostatic disorders under standard gravity load conditions.

Administration of apo A-I (Milano) nanoparticles reverses pathological remodelling, cardiac dysfunction, and heart failure in a murine model of HFpEF associated with hypertension

Therapeutic interventions with proven efficacy in heart failure with reduced ejection fraction (HFrEF) have been unsuccessful in heart failure with preserved ejection fraction (HFpEF). The modifiable risk factor with the greatest impact on the development of HFpEF is hypertension. The objectives of this study were to establish a murine model of HFpEF associated with hypertension and to evaluate the effect of apo A-IMilano nanoparticles (MDCO-216) on established HFpEF in this model. Subcutaneous infusion of angiotensin II in combination with 1% NaCl in the drinking water was started at the age of 12 weeks in male C57BL/6 N mice and continued for the entire duration of the experiment. Treatment with MDCO-216 partially reversed established cardiac hypertrophy, cardiomyocyte hypertrophy, capillary rarefaction, and perivascular fibrosis in this model. Pressure-volume loop analysis was consistent with HFpEF in hypertension mice as evidenced by the preserved ejection fraction and a significant reduction of cardiac output (7.78 ± 0.56 ml/min versus 10.5 ± 0.7 ml/min; p < 0.01) and of the peak filling rate (p < 0.05). MDCO-216 completely reversed cardiac dysfunction and abolished heart failure as evidenced by the normal lung weight and normal biomarkers of heart failure. In conclusion, apo A-IMilano nanoparticles constitute an effective treatment for established hypertension-associated HFpEF.

Abstract WP374: High Frequency Blood Pressure Monitoring in the Acute Phase of Large Vessel Occlusion Ischemic Stroke

Introduction: Decreases in blood pressure (BP) during endovascular therapy (EVT) have been associated with infarct progression and worse outcome after large vessel occlusion (LVO) stroke. However, BP trajectories in the acute phase prior to EVT have not been well characterized. We thus used high-frequency BP and hemodynamic monitoring to create a continuous BP time trend and to determine timing of BP reductions. Methods: We prospectively enrolled patients with LVO stroke undergoing EVT. BP and cardiac hemodynamic variables were recorded every 20 seconds from emergency room admission until end of EVT using non-invasive finger plethysmography. Time trends of BP recordings were categorized into 4 windows: admission to imaging; imaging to EVT; EVT to groin puncture and groin puncture to recanalization. Episodes of hypotension (mean arterial pressure ≤ 70 mmHg) were correlated with administered medications and other potentially related interventions. Time trends in hemodynamic variables were analyzed using generalized estimating equations. Results: 25 patients underwent continuous BP monitoring (age 74±18; 68% female; mean NIHSS 12, monitoring time 8.34±2 hrs). Aggregated time series data revealed a marked BP reduction around time of imaging from which patients recovered (mean SBP 33 mmHg, duration 18 min, Fig A). A sustained decrease in BP was observed after groin puncture without return to baseline BP levels. In 62% of cases, reductions in BP were associated with BP lowering medications. A significant reduction in cardiac output (p=0.003) and increase in stroke volume variation (p=0.022) was seen across predetermined time points (Fig B &amp; C). Conclusion: In patients with LVO, marked and frequently iatrogenic BP reductions occur around time of initial imaging and may present a potential target for intervention. Changes in cardiac hemodynamic variables throughout acute stroke period suggest a potential role for fluid resuscitation for hemodynamic optimization.

Effects of different doses of magnesium sulfate on pneumoperitoneum-related hemodynamic changes in patients undergoing gastrointestinal laparoscopy: a randomized, double-blind, controlled trial

BackgroundThe infusion of magnesium sulfate is well known to reduce arterial pressure and attenuate hemodynamic response to pneumoperitoneum. This study aimed to investigate whether different doses of magnesium sulfate can effectively attenuate the pneumoperitoneum-related hemodynamic changes and the release of vasopressin in patients undergoing laparoscopic gastrointestinal surgery.MethodsSixty-nine patients undergoing laparoscopic partial gastrectomy were randomized into three groups: group L received magnesium sulfate 30 mg/kg loading dose and 15 mg/kg/h continuous maintenance infusion for 1 h; group H received magnesium sulfate 50 mg/kg followed by 30 mg/kg/h for 1 h; and group S (control group) received same volume 0.9% saline infusion, immediately before the induction of pneumoperitoneum. Systemic vascular resistance (SVR), cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum vasopressin and magnesium concentrations were measured. The extubation time, visual analogue scale were also assessed. The primary outcome is the difference in SVR between different groups. The secondary outcome is the differences of other indicators between groups, such as CO, MAP, HR, CVP, vasopressin and postoperative pain score.ResultsPneumoperitoneum instantly resulted in a significant reduction of cardiac output and an increase in mean arterial pressure, systemic vascular resistance, central venous pressure and heart rate in the control group (P < 0.01). The mean arterial pressure (T2 – T4), systemic vascular resistance (T2 – T3), central venous pressure(T3-T5) and the level of serum vasopressin were significantly lower (P < 0.05) and the cardiac output (T2 – T3) was significantly higher (P < 0.05) in group H than those in the control group. The mean arterial pressure (T4), systemic vascular resistance (T2), and central venous pressure(T3-T4) were significantly lower in group H than those in group L (P < 0.05). Furthermore, the visual analog scales at 5 min and 20 min, the level of vasopressin, and the dose of remifentanil were significantly decreased in group H compared to the control group and group L (P < 0.01).ConclusionMagnesium sulfate could safely and effectively attenuate the pneumoperitoneum-related hemodynamic instability during gastrointestinal laparoscopy and improve postoperative pain at serum magnesium concentrations above 2 mmol/L.Trial registrationThe study was retrospectively registered at Chinese Clinical Trial Registry; the registration number is ChiCTR-IPD-17011145, principal investigator: D.Y. Q., date of registration: April 13, 2017.

Abstract 330: LDK378 Attenuates Macro and Microcirculation in a Sepsis Rat Model Induced by Cecal Ligation and Puncture

Background: Sepsis is a systemic inflammatory response syndrome caused by severe infections. Myocardial dysfunction has been associated with increased mortality in septic patients. Previous studies have demonstrated that LDK378, a second-generation ALK inhibitor, is a potential anti-inflammatory mediator. We investigated the effects of LDK378 on macro and microcirculation in a rat model of cecal ligation and puncture (CLP) induced sepsis. Hypothesis: LDK378 attenuates the deleterious effects of sepsis on macro- and micro- circulation in CLP induced septic rats. Method: Fifteen male rats weighing between 450-550g were randomized into three groups: Sham, CLP, and CLP+LDK378. Our rat sepsis model was induced by 50% cecum ligation and two punctures with a 20-gauge needle. LDK378 (20mg/kg) was administered intraperitoneal (IP) to animals at 0h, 24h and 48 hours after CLP operation in the CLP+LDK378 group. Cardiac output (CO), mean arterial pressure (MAP); sublingual microcirculation including perfused small vessel density (PVD) and microcirculatory flow index (MFI) were measured at 6h, 30h and 54h after CLP. Results: Significant reduction in CO, MAP, MFI and PVD were observed in both CLP and CLP+LDK378 groups at 6h, 30h and 54h. However, the levels of CO, MAP, MFI and PVD reduction were significantly better in the CLP+LDK378 group when compared with the CLP group at 30h and 54h after CLP. Conclusion: LDK378 attenuates macro and microcirculation parameters in our rat model of sepsis.

Abstract 17077: Acute Hemodynamic Effects of Oral Nitrite in Pulmonary Hypertension Related to Heart Failure With Preserved Ejection Fraction (PH-HFpEF)

Introduction: Pulmonary hypertension (PH) occurs in 35-83% of patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse outcomes. There are no effective therapeutic options for these patients. Oral nitrite has demonstrated promise in pre-clinical models of PH-HFpEF. Recently, a phase 2 clinical trial showed that a single dose of inhaled nitrite significantly lowered pulmonary, right atrial, and pulmonary artery wedge pressures and substantially increased pulmonary artery compliance in patients with PH-HFpEF. We are currently evaluating the efficacy of chronic oral nitrite as a novel therapeutic agent in PH-HFpEF. We report, for the first time, our initial findings of the acute hemodynamic effects of a single dose of oral nitrite. Methods: This is part of an ongoing blinded 10-week cross-over treatment trial of oral nitrite in PH-HFpEF (NCT03015402). Patients were defined as having PH-HFpEF based on an ejection fraction &gt; 40% and right heart catheterization (RHC) with a mPAP≥ 25 mmHg, PAWP ≥15 mmHg and TPG ≥ 12 mmHg. Patients who met criteria based on a screening RHC were given a single open label dose of 40 mg of sodium nitrite. Cardiopulmonary hemodynamics were obtained by RHC at baseline and after a single dose of oral nitrite. We are actively enrolling patients with the intent to provide open label oral sodium nitrite to ten patients. Results: Eight patients have currently been enrolled in the cross-over trial, of which four have required a screening RHC and have been given open label oral nitrite. Oral nitrite was well tolerated in all patients without any adverse events. Acute cardiopulmonary hemodynamic are presented in Figure 1. Conclusion: Administration of oral nitrite acutely results in an improvement of right ventricular and left ventricular filling pressures without any significant reduction in cardiac output, cardiac index, or mean arterial pressure. Oral nitrite may be a novel therapeutic agent for patients with PH-HFpEF.

Lithotomy versus jack-knife position on haemodynamic parameters assessed by impedance cardiography during anorectal surgery under low dose spinal anaesthesia: a randomized controlled trial.

BackgroundAlthough the prone position providing better exposure for anorectal surgery is required it can cause a reduction of cardiac output and cardiac index. The goal was to compare haemodynamic changes assessed by impedance cardiography during anorectal surgery under low-dose spinal anaesthesia in lithotomy and jack-knife position.MethodsThe prospective randomized controlled study included 104, ASA I-II adult patients admitted for elective minor anorectal surgery, assigned to be performed in lithotomy (groupL, n = 52) or jack-knife position (groupJ, n = 52). After arrival to operating room the standard monitoring, impedance cardiography device was connected to the patient, and the following variables were recorded: cardiac output, cardiac index, systemic vascular resistance, stroke index at times of arrival to operating room, placement for, start and end of surgery and placement to bed. Spinal block was made in the sitting position with 4 mg of 0.5% hyperbaric bupivacaine and 10 μg of Fentanyl injected over 2 min. Comparison was based on haemodynamic changes between and inside groups over time. Student’s t, chi square tests were used for statistical analysis with p < 0.05 regarded as statistically significant.ResultsThe reduction of cardiac output was statistically significant after placement of the patient into the prone position: from baseline 7.4+/−1.6 to 4.9+/−1.2 after placement for and 4.7+/−1.2 at the start and end of surgery (mean +/−SD l/min). The difference of cardiac output between groups was 2.0 l/min after positioning for and the start of surgery and 1.5 l/min at the end of surgery (p < 0.05). Mean cardiac index reduced from baseline 3.9+/−0.8 to 2.6+/−0.7 and 2.4+/−0.6 (mean+/−SD l/min/m2) in groupJ and between groups: by 1.0 l/min/m2 after placement for, 1.1 at the start and 0.8 at the end of surgery (p < 0.05). Systemic vascular resistance increased from baseline 1080+/−338 to 1483+/−479 after placement for, 1523+/−481 at the start and 1525+/−545 at the end of surgery in groupJ (mean+/−SD dynes/sec/cm−5, p < 0.05).ConclusionsAccording to impedance cardiography, jack-knife position after low-dose spinal anaesthesia produces transitory, but statistically significant reduction of cardiac output and cardiac index with increase of systemic vascular resistance, compared to insignificant changes in lithotomy position.Trial registrationClinical Trials NCT02115178.

Bleeding, hypothermia, acidosis and the normal ROTEM®

shock (HS) and acute pancreatitis (AP) is associated with multiple organ dysfunction syndrome (MODS) and death. Most common in MODS are cardiac and pulmonary dysfunction.The ‘gut-lymphhypothesis’ states thatMODSisdue to the releaseof toxic factors fromthe intestine intomesenteric lymph (ML). Significant composition changes to ML are associated with acute pancreatitis and other CI’s. ML is delivered to the systemic circulation via the thoracic duct and en route bypasses the liver avoidingpotential detoxification, beforefirst encountering the heart and then lungs. The aim of this study was to determine the effect of HS and AP conditioned ML on cardiac function and the effect of external drainage of ML. Methods: Groups (n=8 / group) of normal rats and those with taurocholate induced severe AP, a model of critical illness, had either no lymphatic intervention or thoracic duct (TD) ligation with external ML drainage (to protect the hearts from exposure to ML). After 6 hours the heart was removed from both groups for ex vivo functional measurements, including cardiac output and ventricular contractility (+dP/dt), relaxation (-dP/dt). In a separate experiment ML was collected from normal rats and those with HS and AP and infused into ex vivo perfused working hearts from donor normal rats to assess the impact on cardiac function. Results: Significant cardiac dysfunction was found in the hearts removed from rats with established AP alone (no lymphatic intervention) compared to the control group (p<0.05). Strikingly this dysfunction did not occur in rats with established AP and TD ligation with ML drainage. In the second experiment infusion of HS and AP conditioned ML resulted in an immediate, similar and significant reduction of cardiac output (p< 0.05) with corresponding significant reductions in the measures of cardiac contractility and relaxation (p<0.05) compared with normal lymph. Discussion:HS and AP conditioned ML causes significant cardiac dysfunction which can be prevented by TD ligation and external ML drainage. This cardio-depressant effect is likely to be important in other CI’s. The nature of the mediators in ML is still speculative but likely to be gut and pancreas derived serine proteases. The findings from this study have future implications in how we treat cardiac dysfunction and failure in critically ill patients.

Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

The effects of high-frequency jet ventilation (HFJV) on pneumoperitoneum-induced cardiovascular changes during laparoscopic surgery

Standard mechanical ventilation may cause adverse cardiovascular effects in addition to those already related to positive-pressure pneumoperitoneum (PP) during laparoscopic surgery. High-frequency jet ventilation (HFJV) is associated with much less airway pressure, with potentially less influence on venous return, thus potentially it may reduce those effects. The aim of this study was to evaluate the benefits of HFJV to reduce the adverse cardiovascular effects during laparoscopic cholecystectomy. We conducted a randomized prospective trial, comparing 12 patients undergoing elective laparoscopic cholecystectomy under conventional mechanical ventilation (control) with 13 similar subjects under HFJV (study). Both groups were categorized as ASA I-II and underwent total intravenous anesthesia. Cardiac functionality was continuously evaluated by analysis of arterial pressure wave changes (Edwards Flo-Trac sensor and Vigileo monitor). There was no significant difference between both groups regarding age, gender, BMI, and general medical condition, as well as hemodynamic stability and blood gases throughout surgery. A significant reduction in cardiac output was noted in the control group under PP during the initiation of anti-Trendelenburg position (from 5.6 to 5.0 l/min, P = 0.049). A reciprocal change was observed regarding stroke volume. Such changes were not noticed under HFJV. Total peripheral resistance was significantly increased during PP, and heart rate was not significantly affected throughout surgery in both groups. Unexpectedly, we did not observe marked adverse hemodynamic changes in the control group during PP without position adjustment. The use of HFJV in upper laparoscopic surgery can impede the adverse cardiovascular changes that usually occur during induction of PP. We also suggest that the use of total intravenous anesthesia (as used in our study) may also lessen the cardiovascular impairment during PP.

Prevention and management of air in an IV infusion system

When air enters the circulatory system of the human body it can cause an air embolism. Air in the venous circulation will enter the right side of the heart where it may cause right ventricular outflow tract obstruction and acute pulmonary hypertension from pulmonary vasoconstriction. This compromises the pulmonary venous return to the left side of the heart, resulting in significant reduction in cardiac output and cardiovascular collapse. Air can pass into the left side of the heart via a patent foramen ovale or a septal defect. From the left side of the heart air will then enter the arterial circulation where it may embolize cerebral or coronary arteries with fatal consequences. Prevention of air embolism is therefore of utmost importance.

Alteration in hemodynamic effects of interleukin 2 after treatment with indomethacin in anesthetized rats

The cardiovascular effects of interleukin 2 (IL2), were investigated in animals pretreated with indomethacin. Bolus intravenous administration of IL2 alone caused a significant reduction in cardiac output over time. Pretreatment with indomethacin significantly accentuated the reduction in cardiac output produced by IL2. The administration of IL2 or indomethacin alone or combined had no significant effects on dP/dt, heart rate or plasma troponin levels. As well, administration of either compound alone or combined had limited effects on mean circulatory filling pressure and arterial blood pressure. Injection of IL2 alone significantly increased resistance to venous return and arterial resistance at 3h post injections. Pretreatment with indomethacin caused IL2 to produce a significantly greater increase in arterial resistance and resistance to venous return. Administration of IL2 and indomethacin combined also produced significant reduction in stroke volume than IL2 or indomethacin alone. The injection of IL2 or indomethacin alone or combined had no significant impact on blood volume. Acute administration of IL2 appears to have no negative inotropic or chronotropic effects and its impact in reducing cardiac output is the result of an increase in vascular resistance. It seems that activation of prostanoids, possibly prostacyclin, has an acute beneficial effect in attenuating the initial negative effects of IL2 on cardiac output.

Percutaneous caval stent valve implantation: investigation of an interventional approach for treatment of tricuspid regurgitation

Severe tricuspid regurgitation (TR) reduces cardiac output (CO) and increases central venous pressure leading to secondary organ dysfunction. To date, the open surgical approach is the only option to treat TR. Herein, we report our experience of treatment by percutaneous implantation of valved stents in the inferior vena cava (IVC) and superior vena cava (SVC) to substitute tricuspid valve function in a model of acute insufficiency. Acute TR grades III-IV was created in 13 sheep (54-75 kg) via papillary muscle and chordae avulsion using a 0.07 inch wire blade. Successful creation of TR was confirmed using angiography and by a prominent ventricular wave in central venous pressure recording. Two self-expanding nitinol stents containing a porcine pulmonary valve were then implanted in the IVC and SVC in a transcatheter approach. Implantation was performed through the right jugular vein by means of a 21 F catheter and guided by fluoroscopy. Haemodynamics were continuously monitored and valve function was verified by angiography and epicardial echocardiography. After successful implantation and proof of concept in the acute study (acute group, n = 9), chronic studies were (n = 4, 4 weeks follow-up) performed. Tricuspid regurgitation grades III-IV was successfully created in all animals and resulted in a significant reduction of CO. A ventricular wave in the IVC of 16.2 +/- 2.33 mmHg (acute group) and 14.9 +/- 1.71 mmHg (chronic group) confirmed the presence of severe TR. After deployment of the IVC and the SVC valve, the ventricular wave in the IVC significantly decreased to 13.9 +/- 2.97 mmHg (acute group) and 12.7 +/- 1.15 (chronic group), whereas CO significantly increased to 4.20 +/- 0.84 L/min (acute group) and 5.4 +/- 0.67 L/min (chronic group). At autopsy, correct device position was verified in all successfully implanted animals, no macroscopic damage resulting from the implantation procedure was observed. In high-grade tricuspid insufficiency, percutaneous implantation of valved stents in the central venous position reduces venous regurgitation and improves haemodynamics in the animal experiment. Implantation of one or two valves in central venous position is technically feasible. Functional replacement of the insufficient tricuspid valve leads to an increase in CO. This technique expands the potential therapeutic options for patients with relevant tricuspid valve regurgitation having a high risk for open heart surgery.