Left Ventricular Stroke Work Index Research Articles

Comparison of the hemodynamic effects of milrinone with dobutamine in patients after cardiac surgery

Objective: To compare the hemodynamic effects, efficacy, and safety of intravenous milrinone (M), 50 μg/kg during 10 minutes followed by 0.5 μg/kg/min, with intravenous dobutamine (D), 10 to 20 μg/kg/min, in patients with low cardiac output after cardiac surgery. Design: Randomized, open-label, multicenter study. Setting: Cardiothoracic surgery departments, operating rooms, and intensive care units in 6 university hospitals. Participants: Patients (n = 120; 60 per group) after elective cardiac surgery. Interventions: None. Measurements and Main Results: Analysis compared the hemodynamics at baseline and the percentage change from baseline during 4 hours of the drug infusion. The incidence of adverse events was recorded. Both groups had low mean (± SEM) cardiac indices (M, 1.6 ([0.03] L/min/m2; D, 1.7 [0.03] L/min/m2) in association with adequate mean pulmonary capillary wedge pressures (M, 13.7 [1.3] mmHg; D, 12.7 [1.9] mmHg) at baseline. Group M had significantly higher systemic arterial pressures and systemic vascular resistances compared with group D; otherwise, the hemodynamics in both groups were comparable. During the study, hemodynamic responses included the following: group D had greater increases in cardiac index (at 1 hour, D = 55%, M = 36%; p < 0.01), heart rate (at 1 hour, D = 35%, M = 10%; p < 0.001), arterial pressures (mean arterial pressure at 1 hour, D = 31%, M = 7%; p < 0.001), and left ventricular stroke work index (at 1 hour, D = 75%, M = 45%; p < 0.05). Group M had greater decreases in mean pulmonary capillary wedge pressure (at 1 hour, D = −3%, M = −14%; p < 0.05). Comparisons of adverse events showed that dobutamine was associated with a higher incidence of hypertension (D = 40%, M = 13%; p < 0.02) and change of rhythm from sinus to atrial fibrillation (D = 18%, M = 5%; p < 0.04). Milrinone was associated with a higher incidence of sinus bradycardia (D = 2%, M = 13%; p < 0.03). Conclusions: Milrinone and dobutamine are appropriate and comparable for the pharmacologic treatment of the low- output syndrome after cardiopulmonary bypass. Copyright © 2001 by W.B. Saunders Company

Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen extraction capabilities, and TNF release during acute endotoxic shock.

We explored the effects of the nucleoside transport inhibitor draflazine on regional blood flow, O2 extraction capabilities, and tumor necrosis factor (TNF) release in acute endotoxic shock. Fourteen anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin and were divided into two groups. Seven dogs received 0.1 mg/kg of draflazine 30 min before endotoxin, and 7 dogs served as a control group. Draflazine decreased arterial pressure without influencing cardiac index. Mesenteric and portal blood flow and ileum mucosal perfusion increased, but renal blood flow dramatically decreased. After endotoxemia, the draflazine-treated dogs had a lesser fall in cardiac index, filling pressures, and left ventricular stroke work index, and a lesser increase in pulmonary vascular resistance. After fluid resuscitation, they had a consistently lower renal blood flow and ileum mucosal perfusion, but a higher mixed venous and hepatic oxygen saturation and arterial pH than the control group. When cardiac index was reduced by tamponade to study the O2 extraction capabilities, renal blood flow and ileum mucosal perfusion remained lower in the draflazine group. Draflazine did not influence whole-body O2 extraction capabilities, but it delayed the occurrence of liver O2 supply dependency as indicated by a significantly lower liver DO2crit (27.7 +/- 3.9 vs. 43.3 +/- 10.8 mL/min) and a higher O2ERcrit (62.7 +/- 9.5 vs. 42.5 +/- 7.1%) than controls (both P< 0.05). On the other hand, draflazine increased intestinal DO2crit (42.4 +/- 15.4 vs. 27.7 +/- 6.5 mL/min, P < 0.05) compared to the control group. TNF levels remained higher in the draflazine group than in the control group, particularly 3 and 4 h after endotoxin administration. We conclude that nucleoside transport inhibition with draflazine does not alter global and hepatosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal blood flow. However, this intervention can improve liver O2 extraction capabilities in acute endotoxic shock.

Microperfusion enhancement after TMLR in chronically ischemic porcine hearts

Objective. The purpose of this study was to determine the effect of transmyocardial laser revascularization (TMLR) on myocardial perfusion and function in chronically ischemic myocardium.Methods. In the first operation a stenosis of the left anterior descending artery was created in 20 open-chest anesthetized pigs to implement this ischemic model. In contrast, four pigs served as controls (thoracotomy only). Seven days later (2nd operation), all animals were studied at baseline by analyzing different parameters of perfusion (radioactive microspheres), function, and intramyocardial pressure. Afterwards, pigs who received a left anterior descending artery stenosis were randomized into one of three groups: animals in laser group 1 (n=7) received one and in laser group 2 (n=7) two laser channels per cm2 in the left anterior descending artery territory. Animals of the ischemic group (n=6) underwent the same procedures without transmyocardial laser revascularization. Three months later, the animals were re-studied (3rd operation) and additional analysis of histochemistry and myocardial water content was performed.Results. Regional myocardial blood flow (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the ischemic group (0.39±0.13 versus 0.14±0.12 ml/min/g; P=0.043), after 3 months, whereas the absolute RMBF had not increased compared to the 1-week baseline values. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared to the initial values in all study groups (P=ns). Nevertheless, laser group 1 demonstrated relatively higher LVSWImax values compared to the ischemic (1.33±0.19 versus 0.93±0.16 mJ/kg; P=0.03) and laser group 2 (1.33±0.19 versus 1.02±0.15; P=0.024). Regional contractility of laser groups 1 and 2 recovered after 3 months (which had deteriorated shortly after transmyocardial laser revascularization) and increased under stress (100% versus 144.33±46.42, P=0.029 and 100% versus 116.26±21.06, P=0.034; respectively). In contrast, the corresponding ischemic group values were not different from intial values (P=ns).Conclusions. This model of chronic regional ischemia demonstrates that CO2-laser revascularization significantly improves microperfusion and regional function, whereas the overall perfusion and global LV function is unchanged.

Effect of Ischemic Preconditioning on Myocardial Protection in Coronary Artery Bypass Graft Patients: Can the Free Radicals Act as a Trigger for Ischemic Preconditioning?

To investigate the interrelationship of free radicals (FRs), ischemic preconditioning (IP), and hemodynamic function in coronary artery bypass graft (CABG) patients. Prospective, randomized, and controlled clinical study. Forty CABG patients were randomized into an IP group (n = 20) and a control group (n = 20). The IP group was preconditioned with two cycles of two-min ischemia followed by 3-min reperfusion before cross-clamping. FR content in coronary sinus blood was measured directly using alpha-phenyl-N-tert-butylnitrone-electron spin-trapped spectroscopy. A small amount of FRs was generated after the IP protocol (5.6% above the baseline) but not in control subjects. A larger amount was generated 10 min after declamping in both groups (8.4% in IP protocol and 7.7% in control subjects). Hemodynamic function recovered better in the IP group at 1 h and 6 h after declamping. There was a significant negative correlation between FR generation after declamping and left ventricular stroke work index (LVSWI) at 1 h and 6 h after declamping (r = -0.71 and - 0.59, respectively) in the control subjects but not in the IP group. There was a significant positive correlation between FR generation after the IP protocol and cardiac index at 1 h and 6 h (r = 0.50 and 0.61, respectively) and LVSWI at 1 h and 6 h (r = 0.56 and 0.54, respectively) after declamping in the IP group but not in the control subjects. FR generation after the operation correlates with ventricular functional depression in CABG patients. IP protects the stunning heart but does not alter FR generation. The association of better hemodynamic recovery after CABG with FR generation during the IP period suggests that FRs might act as one of the triggers for IP.

Cardiovascular effects of romifidine in dogs.

To characterize the cardiovascular effects of romifidine at doses ranging from 5 to 100 microg/kg of body weight, IV. 25 clinically normal male Beagles. Romifidine was administered IV at a dose of 5, 10, 25, 50, or 100 microg/kg (n = 5/group). Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and PCV were measured immediately prior to and at selected times after romifidine administration. Cardiac index, stroke index, rate-pressure product, systemic and pulmonary vascular resistance indices, and left and right ventricular stroke work indices were calculated. Degree of sedation was assessed by an observer who was blinded to the dose administered. Romifidine induced a decrease in heart rate, pulmonary arterial pressure, rate-pressure product, cardiac index, and right ventricular stroke work index and an increase in central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance index. In dogs given romifidine at a dose of 25, 50, or 100 microg/kg, an initial increase followed by a prolonged decrease in arterial pressure was observed. Arterial pressure immediately decreased in dogs given romifidine at a dose of 5 or 10 microg/kg. Results suggest that IV administration of romifidine induces dose-dependent cardiovascular changes in dogs. However, the 2 lowest doses (5 and 10 microg/kg) induced less cardiovascular depression, and doses > or = 25 microg/kg induced similar cardiovascular changes, suggesting that there may be a ceiling on the cardiovascular effects of romifidine.

Alpha-atrial natriuretic peptide, cyclic guanosine monophosphate, and endothelin in plasma as markers of myocardial depression in human septic shock.

To assess the value of alpha-atrial natriuretic peptide (alpha-ANP), second messenger cyclic guanosine monophosphate (cGMP,) and endothelin as markers of myocardial depression in septic shock. Prospective observational study. Medical intensive care unit (ICU) of a university hospital. Fourteen consecutive patients with septic shock and arterial and pulmonary artery catheters in place. Hemodynamic variables and plasma levels of alpha-ANP, cGMP, and endothelin were measured every 6 hrs for 3 days after admission. Eight patients died from shock in the ICU. The nadir left ventricular stroke work index (LVSWI) was below 35 g/m2 in all patients, and the median peak circulating alpha-ANP (n < 68 pg/mL) was 276 pg/mL (range, 79-1056), the median peak cGMP (n < 2.1 ng/mL) was 8.1 ng/mL (range, 3.2-29.7), and the median peak endothelin (n < 5.3 pg/mL) was 15.5 pg/mL (range, 8.5-33.9), supranormal in all patients. Outcome groups differed in the course of cardiac index and LVSWI, which were lower in nonsurvivors despite similar filling pressures and more intensive inotropic treatment (p < .01). The course of alpha-ANP, cGMP, and endothelin plasma levels also differed between groups, with higher levels in nonsurvivors (p < .05). As for pooled data, the mean daily or nadir LVSWI inversely related to mean daily or peak alpha-ANP, cGMP, and endothelin levels, respectively (p < .05). The area under the receiver operating characteristic curve for myocardial depression (LVSWI < 35 g/m2) was for alpha-ANP and endothelin 0.77, and for cGMP 0.85 (p < .01). The optimum cutoff values for alpha-ANP, cGMP, and endothelin were 172 pg/mL, 4.5 ng/mL, and 10.0 pg/mL, respectively. The sensitivity for myocardial depression of alpha-ANP, cGMP, and endothelin was 68%, 77%, and 72%, and the specificity was 82%, 93%, and 69%, respectively. Circulating alpha-ANP, endothelin, and, particularly, cGMP may be markers of the myocardial depression of human septic shock, which is associated with mortality.

Revascularization of severe hibernating myocardium in the beating heart: early hemodynamic and metabolic features

Background. We investigated the effects of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) in selected patients with severe hibernating myocardium. Methods. Twelve patients (EF = 25% ± 0.7%) with reversible ventricular dysfunction (from 2.0 ± 0.06 to 1.6 ± 0.05 left ventricular score index by echo-dobutamine, p < 0.01) in the territory of the left anterior descending artery (LAD) have been studied. Revascularization was achieved by anastomosing the left internal mammary artery to the LAD. The ischemic time of LAD was 9.0 ± 0.4 minutes. Results. Left ventricular function increased 6 hours and 48 hours after revascularization (left ventricular stroke work index from 32 ± 1.8 to 42 ± 1.5 and 40 ± 0.6 gxm/m 2, respectively: p = 0.0001). During the surgical procedure, the heart did not release lactate or creatine phosphokinase. There were no perioperative deaths or severe complications. Conclusions. Early hemodynamic and metabolic features of CABG without CPB in patients with hibernating myocardium suggest that this procedure is safe and results in a significant improvement of cardiac function without affecting myocardial metabolism.

Myocarditis and long-term survival in peripartum cardiomyopathy

Background The reported mortality rate of peripartum cardiomyopathy (PPCM) is high, although the potential for spontaneous recovery of ventricular function is well established. The prevalence of myocarditis in PPCM has varied widely between studies. The purposes of this study were to define the long-term prognosis in a referral population of patients with PPCM, to determine the prevalence of myocarditis on endomyocardial biopsy in this population, and to identify clinical variables associated with poor outcome. Methods We analyzed clinical, echocardiographic, hemodynamic, and histologic features of 42 women with PPCM evaluated at our institution over a 15-year period. Each patient underwent an extensive evaluation, including echocardiography, endomyocardial biopsy, and right heart catheterization. Data were analyzed to identify features at initial examination associated with the combined end point of death or cardiac transplantation by the use of Kaplan-Meier survival curves and a Cox proportional hazards model. Results Three (7%) patients died and 3 (7%) patients underwent heart transplantation during a median follow-up of 8.6 years. Endomyocardial biopsy demonstrated a high prevalence of myocarditis (62%), but the presence or absence of myocarditis was not associated with survival. Of the prespecified variables assessed, only decreased left ventricular stroke work index was associated with worsened outcome. Conclusions In patients with PPCM, (1) long-term survival is better than has been historically reported, (2) the prevalence of myocarditis is high, and (3) decreased left ventricular stroke work index is associated with worse clinical outcomes. (Am Heart J 2000;140:785-91.)

Hemodynamic effects of intermittent manual lung hyperinflation in patients with septic shock

Objective: The purposes of this study were to investigate the hemodynamic changes induced by intermittent manual lung hyperinflation (MHI) and to assess if these changes are adverse enough to warrant prohibition of MHI as a routine procedure in the care of patients with septic shock. Design: The study’s design was experimental prospective. Setting: The settings were university hospital intensive care units. Patients: Subjects included 13 consecutive mechanically ventilated patients with septic shock who met the inclusion criteria. Measurements And Results: Phasic MHI-related increments in mean inspiratory airway pressure were concordant to changes in mean pulmonary artery pressure (MPAP) (r2 = 0.67) with a 0.6 mm Hg rise in MPAP per cm H2O airway pressure. The magnitude of MPAP changes was not reflected in magnitude of stroke volume index (SVI) (r2 = 0.06). On average, MHI did not induce statistically significant hemodynamic changes and mean values returned to baseline level within 15 minutes. SVI during MHI increased slightly in 9 patients, from 37 ± 15 (mean ± SD) to 41 ± 17 mL/m2 (P <.05), and decreased in 4, from 60 ± 10 to 50 ± 14 mL/m2 (not significant). Patients with an increase in SVI had lower baseline values for SVI, cardiac index, and left ventricular stroke work index (P <.05) and higher values for systemic vascular resistance index compared with patients with a decrease in SVI (P <.05). Left ventricular stroke work index was higher in patients with a decrease in SVI than in patients with an increase in SVI (52 ± 9 vs 34 ± 8; P <.05). Tidal volume increased from 499 ± 176 mL before MHI to 587 ± 82 mL, 5 minutes after MHI (P <.05) with a return to baseline values within 15 minutes after the procedure. Conclusion: The hemodynamic effects of intermittent MHI in patients with septic shock are relatively small and insignificant and seem to be related to the cardiovascular state before the procedure. The risk of inducing hemodynamic changes with MHI should not be considered as a contraindication in patients with septic shock who are mechanically ventilated. (Heart Lung® 2000;29:356-66.)

Evaluation of the indirect revascularization method after 3 months chronic myocardial ischemia.

The long-term effectiveness of transmyocardial laser revascularization (TMLR) was evaluated in the setting of a severe left anterior descending artery (LAD) stenosis. To employ the chronic ischemic model, pigs underwent three operative procedures over a 13-week period. In the first operation, an operative stenosis of the LAD was created. One week later, the animals were studied at baseline by analyzing different parameters of perfusion (microspheres), function and ECG changes. Afterwards, pigs were randomized into one of three different experimental groups: animals in laser group 1 received one laser channel (n=9) and laser group 2 two channels per cm(2) (n=6) in the LAD territory (using a CO(2)-laser). Animals of the ischemic group (n=12) underwent the same procedures without TMLR-treatment. Twelve weeks later, the animals were re-studied (third operation) and killed. Additional analysis of myocardial water content and histochemistry was performed. Chronic myocardial ischemia and regional myocardial blood flow (RMBF) in laser group 2 revealed relatively higher RMBF values compared with the ischemic group (P=0.015), after 3 months, but no absolute improvement of perfusion at rest compared with baseline was observed in all experimental groups. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared with initial values in all study groups (P not significant). However, laser group 1 demonstrated relatively higher LVSWI(max) values in comparison with the ischemic group (P=0.013) as did laser group 2 (P=0.017). Regional contractility of the laser groups recovered after 3 months (which was deteriorated shortly after TMLR, P<0.001) and increased under stress compared with baseline (laser 1: P=0.015, laser 2: P=0.017). In contrast, the ischemic group did not show any difference from initial values (P not significant). The lased pigs of group 2 were less prone to intractable ventricular fibrillation (P=0.036 vs. ischemic group), and showed a significant smaller area of necrosis in the area at risk (P=0.012 vs. ischemic group). This model of chronic regional ischemia demonstrates that CO(2)-laser revascularization significantly ameliorates microperfusion and regional contractility, and diminishes the incidence of ventricular fibrillation and necrosis in the area at risk. However, it does not change the overall perfusion and global LV function.

Plasma substitutes for volume replacement in hemorrhagic shock: comparison of low and medium molecular weight hydroxyethyl starch

ObjectiveThe aim of this study was to assess the relative efficacy of 2 volume replacement therapies in a canine model of induced hemorrhagic shock. MethodsAnesthetized dogs were bled to maintain mean arterial pressure (mAP) at 50 mm Hg for 30 minutes and then administered a single bolus injection of 6% hydroxyethyl starch (HES) with a molecular weight of 70 kd (HES70 group) or 200 kd (HES200 group) at a volume equivalent to the blood withdrawn. We examined the efficacy of both therapies in maintaining hemodynamic variables and splanchnic organ blood flow (ie, blood flow through the renal cortex, renal medulla, liver, and pancreas). ResultsAfter resuscitation, hemodynamic variables were better maintained in the HES200 group than in the HES70 group. In particular, HES200 better preserved mAP, cardiac index, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, left ventricular stroke work index, and maximum rate of left ventricular pressure change. In both groups splanchnic organ blood flows decreased significantly after hemorrhagic shock but increased after volume replacement resuscitation. After resuscitation splanchnic organ blood flow was significantly greater in the HES200 group than in the HES70 group (P< 0.05). ConclusionsThe results of this study suggest that HES200 is more effective than HES70 as volume replacement therapy in a canine model of hemorrhagic shock, as measured by improvements in hemodynamic variables and splanchnic organ blood flow.

Correlating the severity of paraquat poisoning with specific hemodynamic and oxygen metabolism variables.

To investigate the hemodynamics and oxygen metabolism of patients with varying degrees of severity of paraquat poisoning. Prospective, observational, clinical study. Intensive care unit in a university hospital. Forty-three consecutive patients with paraquat and/or diquat poisoning were classified into three groups by the severity index of paraquat poisoning (SIPP; hr/mg/L). Standard treatments included specific respiratory management, fluid resuscitation, and aggressive circulatory support. Serum paraquat and diquat levels were measured at arrival, and SIPP was calculated. The cardiac index (CI), left ventricular stroke work index (LVSWI), systemic vascular resistance index (SVRI), oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER) were measured at 6, 12, 24, 36, 48, 72, and 96 hrs postadmission. A significant inverse correlation between SIPP and survival time was found in 31 fatal cases (r = .85; p < .001). In the SIPP 10-50 group, CI, DO2I, VO2I, and O2ER were maintained at higher levels than in the SIPP group of <10 (p < .05), whereas SVRI decreased significantly (p < .05). In the SIPP group of >50, CI, LVSWI, SVRI, DO2I, and VO2I decreased, whereas O2ER had a tendency to increase progressively. There was a significant correlation between SVRI and SIPP, O2ER and SIPP, and O2ER and SVRI 24 hrs after admission, respectively (p < .001). Paraquat poisoning is characterized by high oxygen consumption with high oxygen extraction, with the degree of derangement based on the severity index. The development of a marked imbalance between increased oxygen demand and decreased oxygen supply because of myocardial depression might be a possible cause of death in circulatory failure.

Systemic hemodynamics, gastric intramucosal PCO2 changes, and outcome in critically ill burn patients.

To define the hemodynamic and gastric intramucosal PCO2 (PiCO2) changes during the first 48 hrs after burn trauma and to analyze their relationship with outcome. Prospective, observational study in a cohort of consecutively admitted critically ill burn patients. Intensive care burn unit in a university hospital. Forty-two patients with burns covering >20% of body surface area or inhalation injury. None. Patients were monitored with an oximetric pulmonary arterial catheter and a gastric tonometer to measure PiCO2. The difference between arterial and gastric mucosal PCO2 (P[i-a]CO2) was considered indicative of gastric mucosal hypoxia. Hemodynamic and PiCO2 measurements were performed during the first 48 hrs after admission. Patients suffered burns covering 36.1% +/- 14.3% (mean +/- SD) and 45.3% +/- 21.9% of body surface area (survivors and nonsurvivors, respectively). All patients were successfully resuscitated by conventional standards. Nonsurvivors (n = 16) died a median of 17 days after admission. In univariate analysis, the presence of shock during the resuscitation phase, age, mixed venous pH, P[i-a]CO2, right atrial pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac index, systemic and pulmonary vascular resistance, left ventricular stroke work index, mixed venous oxygen saturation, and systemic oxygen delivery, consumption, and extraction ratio, measured over the first 12 hrs after admission, were significantly (p < .05) different between survivors and nonsurvivors. These differences disappeared after 12 hrs after admission. Multivariate analysis identified age, percentage body surface area burned, and oxygen delivery index (6 hrs after admission) as factors independently associated with a poor outcome. P[i-a]CO2 (12 hrs after admission) was significantly greater in patients with than in those without inhalation injury (17 +/- 13 torr [2.26 +/- 1.73 kPa] vs. 6 +/- 10 torr [0.79 +/- 1.33 kPa]; p = .005). Patients with a P[i-a]CO2 difference (6 hrs after admission) > or =10 torr (1.33 kPa) had a mortality rate of 56% vs. 25% of those patients with <10 torr (p = .044). Our data indicate that there are hemodynamic and biochemical changes that occur early after burn trauma that are associated with prognosis after an apparently successful resuscitation. Particularly, a hemodynamic profile characterized by systemic acidosis, low systemic blood flow, and systemic and pulmonary vasoconstriction early after trauma is associated with a poor outcome. Additionally, intestinal mucosal acidosis occurs after burn trauma, is influenced by inhalation injury, and is a variable related to outcome.

Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock

Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin’s cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

Reduction of the infarcted area with the use of simplified coronary sinus retroperfusion during experimental coronary artery occlusion

This study examined if the use of simplified coronary sinus retroperfusion would lead to any reduction in the infarcted area associated with improved right and left ventricular function. Twelve mongrel dogs were entered in this study. Following anesthesia, a fast response thermistor was placed on the pulmonary artery via the jugular vein and aorta via the left ventricular apex. The left anterior descending artery (LAD) was separated from the vein. A retrograde cardioplegia catheter was inserted into the coronary sinus. Following these procedures, LAD was occluded for a period of 3.5 h. After 30 min ischemia, the aorta-coronary sinus connection was established. The animals were divided into two equal groups. One group was not treated and was considered the control group (six animals). In the remaining group (six animals), retroperfusion was used and was considered the retroperfusion group. At the end of the study, the left ventricular ejection fraction was 65±15% in the retroperfusion group and 48±5% in the control group ( P<0.05). The left ventricular stroke work index was 0.44±0.04 (g m/kg) in the retroperfusion group and 0.31±0.05 (g m/kg) in the control group ( P<0.05). Cardiac output was 1650±75 ml/min in the retroperfusion group and 1250±125 ml/min in the control group. The ratio of the infarct size to the area at risk was 49±5% in the control group and 7±3% in the retroperfusion group. In light of these studies, we conclude that simplified coronary sinus retroperfusion appears to be an effective method that must be taken into consideration.

Plasma and urinary levels of heart fatty acid-binding protein in patients undergoing cardiac surgery.

To evaluate the clinical significance of the plasma and urinary levels of heart fatty acid-binding protein (H-FABP) in patients undergoing cardiac surgery, a prospective study was conducted. Ten patients undergoing coronary artery bypass grafting were enrolled. Blood samples for determination of plasma H-FABP (pH-FABP), the MB isoenzyme of creatine kinase (CK-MB) and troponin-T (TnT), and urine samples for determination of urinary H-FABP (uH-FABP) were collected serially. None of the patients had perioperative myocardial infarction. The time to reach the peak level after aortic declamping was significantly (p<0.05) shorter for pH-FABP (1.4+/-0.5 h) than for CK-MB (2.5+/-0.5 h), TnT (6.6+/-1.3 h) or uH-FABP (3.0+/-0.6 h). Peak levels of pH-FABP correlated with those of CK-MB (r = 0.51, p = 0.04), TnT (r = 0.60, p = 0.03) and uH-FABP (r = 0.61, p = 0.03), and peak levels of uH-FABP correlated with CK-MB (r = 0.57, p = 0.04). Postoperative uH-FABP levels correlated inversely with the left ventricular stroke work index (r = -0.63, p = 0.04). This study demonstrated that H-FABP appears rapidly in plasma after reperfusion and reaches its peak earlier than other available biochemical markers; it appears also in urine and the levels correlated with cardiac function. Plasma and urinary H-FABP may be an early and sensitive biochemical marker for the diagnosis of myocardial injury in patients undergoing cardiac surgery.

Amniotic Fluid Embolism: Early Findings of Transesophageal Echocardiography

Amniotic Fluid Embolism: Early Findings of Transesophageal Echocardiography

Myocardial cell injury in septic shock.

To determine the presence of otherwise undetected myocardial cell injury in patients with septic shock using daily measurements of cardiac troponin I (cTN I). Prospective observational study. Intensive care unit of a tertiary institution. Fifteen consecutive patients with septic shock and six mechanically ventilated patients without septic shock. Daily collection of blood for the measurement of cTN I serum levels. Regular biochemical and hemodynamic assessment. Illness severity assessment and collection of demographic data. Fifteen patients were studied for a median period of 3 days (range, 1 to 9 days). Serum cTN I concentrations were elevated to values otherwise considered diagnostic of acute myocardial infarction in 12 patients and were significantly higher than in critically ill controls (p = .01). All three patients who died in the intensive care unit and all four patients who did not survive beyond 28 days had elevated levels of cTN I. Survivors tended to lower levels of cTN I while in septic shock than nonsurvivors, and all three patients without increased cTN I survived. There was a significant positive correlation between vasoactive drug requirements and cTN I level (p = .04) and a significant negative correlation between cTN I concentration and left ventricular stroke work index (p = .01). Myocardial cell injury appears to be common in patients with septic shock and correlates with cardiac dysfunction.

Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-alpha attenuation during endotoxic shock.

To assess the effects of continuous venovenous hemofiltration (CWH) on global and regional hemodynamics, plasma lactate, and tumor necrosis factor-oa (TNF-a) levels during endotoxic shock in dogs. Thirty pentobarbital-anesthetized and mechanically ventilated dogs were divided into six groups of five dogs each. Group 1 served as a control, undergoing CWH at 3 Uhr without endotoxin. Group 2 served as the endotoxin-alone time-matching group. Group 3 received CWH 1 hr after endotoxin at 3 Uhr for 270 mins. Group 4 received CWH 1 hr after endotoxin at 3 Uhr for 150 mins and at 6 Uhr for an additional 120 mins. Group 5 and group 6 received the ultrafiltrate from group 1 and group 3, respectively. Three hours after endotoxin challenge, dogs treated with CWH at 3 Uhr had a higher cardiac output (4.9 + 0.6 vs. 2.9 + 0.6 Umin; p < .05) and stroke volume (35 + 7 vs. 20 + 4 mL; p < .05) and a lower pulmonary vascular resistance (116 26 vs. 331 + 126 dyne-sec/cm5; p < .05) than the endotoxin-alone group. Five hours after endotoxin, dogs treated with CWH at 6 Uhr also had higher hepatic (464 + 164 vs. 126 + 75 mUmin; p < .05) and femoral (95 + 46 vs. 30 + 34 mL/min; p < .05) blood flow. Moreover, dogs treated with CWH at 6 Uhr had higher mean arterial blood pressure (84 + 24 vs. 40 + 15 mm Hg; p < .05) and left ventricular stroke work index (1.1 + 0.6 vs. 0.2 + 0.2 g/kg; p < .05) than the endotoxin-alone group. Plasma lactate levels were lower in the CWH group at 6 Uhr (2.7 + 1.1 mmol/L) than in the endotoxin-alone group (4.4 + 0.6 mmol/L; p < .05). Plasma TNF-ao levels were unaffected, and only minor amounts of TNF-o were found in the ultrafiltrate. In this acute endotoxic shock model, CWH at 3 Uhr improved cardiac performance and decreased pulmonary vasoconstriction. Moreover, CWH at 6 LUhr also increased arterial blood pressure and left ventricular stroke work, increased hepatic and femoral arterial blood flow, and decreased blood lactate levels. These effects were not attributable to TNF-alpha removal.

Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds.

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.