The additional use of methylene blue has a decatecholaminisation effect on cardiac vasoplegic syndrome after cardiac surgery.

BACKGROUND: Postoperative vasoplegia with minimal responsiveness to vasopressors is common after cardiac surgery. Called cardiac vasoplegic syndrome (CVS), it is caused by multiple factors. Treating CVS involves a high dose of fluids and catecholamines, however high doses of catecholamines and fluids are associated with serious side effects. There is evidence that new therapeutic strategies can lead to a reduction in norepinephrine doses and mortality in CVS. Specifically, the use of non-adrenergic vasopressors such as methylene blue (MB) can be beneficial. METHODS: We retrospectively analyzed the electronic records of 8716 adult cardiac surgery patients from November 2008 to December 2016. Medication, hemodynamic and outcome parameter data were analyzed for CVS until discharge. We determined CVS according to the following parameters: a postoperative onset of ≤24 h, a reduced mean arterial pressure (MAP) of < 70 mmHg, a dose of norepinephrine ≥0.8 mg*h- 1 and a continuously increasing need for catecholamine, without ventricular dysfunction. RESULTS: We identified 513 patients with CVS. Perioperative risk factors were higher in patients treated with methylene blue (MB). Before MB administration patients had a significantly higher dose of norepinephrine, and MAP increased after MB administration. Norepinephrine could be reduced after MB administration and MAP remained stable at the same level even after the reduction of norepinephrine. CONCLUSIONS: CVS patients have a severe systemic disease accompanied by significant operative stress and a high catecholamine requirement. The administration of MB in addition to standard treatment for CVS in the first 24 h was accompanied by an increase in MAP followed by a decrease in vasopressor requirement, indicating that early MB administration can be beneficial.

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: A retrospective analysis.

OBJECTIVES: Surgery for acute type A aortic dissection is associated with several perioperative complications, such as acute respiratory dysfunction (ARD). The aim of this study was to investigate perioperative risk factors involved in the development of ARD and whether antibiotic treatment has an impact. METHODS: 243 patients underwent surgery for acute type A aortic dissection between 2008 and 2017. The patients were retrospectively divided into the ARD and NON-ARD group. ARD was defined as PaO2/FiO2 ≤ 200 mmHg (PF ratio) within 48 hours after surgery. All patients received either narrow- or broad-spectrum antibiotics. RESULTS: After the exclusion of 42 patients, 201 patients were analyzed. The PF ratio of the ARD group was significantly lower than of the NON-ARD group within the first 7 days. ARD patients (n = 111) were significantly older (p = .031) and had a higher body mass index (BMI) (p = .017). ARD patients required longer postoperative ventilation (2493 vs. 4695 [min], p = .006) and spent more days in the intensive care unit (7.0 vs. 8.9 [days], p = .043) compared to NON-ARD. The mortality was significantly lower for ARD than for NON-ARD patients (p = .030). The incidence of pneumonia was independent of the antibiotic treatment regime (p = .391). Renal and neurological complication rate was higher in patients treated with broad-spectrum antibiotic. CONCLUSION: ARD is the main complication (55%) that occurs approximately 24 hours after surgery for acute type A aortic dissection. The preoperative risk factors for ARD were higher age and increased BMI. Patients on broad-spectrum antibiotics did not show an improved postoperative outcome compared to patients with narrow-spectrum antibiotics.

In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats.

INTRODUCTION: Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions. METHODS: Sham surgery or CLP was performed in male Wistar rats (n = 60). Animals were randomized into four groups: physostigmine, 100 µg/kg; neostigmine, 75 µg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at t = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined. RESULTS: CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at t > 6 h, AChE activity did not change in the sham group. BChE activity decreased at t > 20 h in the control animals. CONCLUSION: While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.

Complications after transcatheter aortic valve implantation using transfemoral and transapical approach in general anaesthesia.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure used to treat degenerative heart valve disease. The implantation requires a highly specific and interdisciplinary management approach. Currently, TAVI is performed with the patient under local or general anaesthesia. METHODS: This study was a retrospective analysis of all TAVI procedures performed at the University Hospital of Regensburg between January 2009 and July 2015. All pre-, intra and postoperative data focusing on perioperative complications were recorded. RESULTS: A total of 853 transfemoral- and transapical-TAVI patients were included in the study. All patients underwent general anaesthesia. The ASA classifications were primarily 3-4. The average logistic EuroScores for the transfemoral- and transapical-TAVI patients were 18 ± 12% and 21 ± 15% (p = 0.002), respectively. The anaesthesia coverage time was 170 ± 49 min., including 37 ± 12 minutes for anaesthetic management. Overall, 458 complications were recorded; with pneumonia, acute renal failure, indication for a permanent pacemaker and non-extubation in the operating theatre the most frequently recorded complications. CONCLUSION: In the present study, we showed that our patients' outcomes are comparable to those reported in the available literature. Compared to TF, TA patients show an overall worse physical condition as well as a higher perioperative morbidity and mortality. Consequently TA patients need additional care and should only be operated in appropriately experienced medical centres.

Adenosine A2A and A2B Receptor Substantially Attenuate Ischemia/Reperfusion Injury in Septic rat Hearts.

INTRODUCTION: Mechanical and morphological ischemia and reperfusion (I/R) injury is reduced in septic hearts. The mechanism behind this "cardioprotection" is less well understood. As adenosine receptors play a major role for cardioprotection in non-septic hearts, we investigated the influence of adenosine receptors in a model of I/R in septic hearts. METHODS: SHAM operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats (n = 60). After 24 h of incubation, hearts were isolated and randomly assigned to a group with or without adenosine receptor (Ador) antagonists (SCH 58261 and MRS 1706) administered before reperfusion. Ischemia and reperfusion lasted for 40 min each. Cardiac function of the heart was determined by measuring left ventricular pressure (LVP). RESULTS: Before I/R, CLP hearts showed a significant mechanical left ventricular impairment (CLP: 63 ± 5 mmHg vs. SHAM: 104 ± 6 mmHg. After I/R, left ventricular function was significantly reduced in SHAM (24 ± 32 mmHg), but not in CLP hearts (65 ± 13 mmHg). mRNA expression for the AdorA2a and AdorA2b was significantly increased in CLP, but not in SHAM hearts. LVP of CLP hearts deteriorated when AdorA2a and AdorA2b were blocked. CONCLUSIONS: The morphological and functional I/R injury in septic animals is less pronounced compared to non-septic animals. By a combined blockade of AdorA2a and AdorA2b this "cardioprotective" effect is nearly abolished in septic hearts. This is the first study showing, that AdorA2a and AdorA2b may play an important role for a reduced functional I/R injury in the septic heart.

Species- and concentration-dependent differences of acetyl- and butyrylcholinesterase sensitivity to physostigmine and neostigmine.

Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a common protocol regarding concentration- and species-dependent differences in inhibitory potency (IC 50) of clinical relevant ChE-Is is still not available. To evaluate the in vitro sensitivity of Acetyl- and Butyrylcholinesterase (AChE, BChE), we compared the concentration-response effects of physostigmine and neostigmine on cholinesterases in whole blood from rat and human. A spectrophotometrical test system based on in vitro Ellman's reagent has been used to determine the kinetic properties of clinical relevant ChE-Is. In vitro, the enzyme activity of human AChE and BChE was inhibited in a concentration-dependent manner until a residual activity of 4-6% for AChE and 20-30% for BChE (IC 50 human AChE: 0.117 ± 0.007 µM physostigmine, 0.062 ± 0.003 µM neostigmine; IC 50 human BChE: 0.373 ± 0.089 µM neostigmine; 0.059 ± 0.012 µM physostigmine). The inhibition curve of rat BChE in contrast showed no concentration-dependency for physostigmine and neostigmine (87% residual activity even at high inhibitor concentrations). Rat AChE was inhibited in a concentration-dependent manner until a residual activity of 53%. The results suggest that cholinesterases from human and rat show marked species- and inhibitor-dependent differences in sensitivity to physostigmine and neostigmine. Knowledge of such differences may be critical in assessing the possible therapeutic effects of ChE-Is in both species and may guide researchers in the optimal design of future experiments regarding the application of ChE-Is.

Anaesthetic management of cytoreductive surgery followed by hyperthermic intrathoracic chemotherapy perfusion.

BACKGROUND: Macroscopic cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion (HITHOC) is a new multimodal approach for selected patients with primary and secondary pleural tumors, which may provide the patient with better local tumor control and increased overall survival rate. METHODS: We present a single-center study including 20 patients undergoing cytoreductive surgery and HITHOC between September 2008 and April 2013 at the University Medical Center Regensburg, Germany. Objective of the study was to describe the perioperative, anaesthetic management with special respect to pain and complication management. RESULTS: Anaesthesia during this procedure is characterized by increased intrathoracic airway and central venous pressure, hemodynamic alterations and the risk of systemic hypo- and hyperthermia. Securing an adequate intravascular volume is one of the primary goals to prevent decreased cardiac output as well as pulmonary edema. Transfusion of packed red blood cells (PRBC) was necessary in seven of 20 (35%) patients. Only two patients (10%) showed an impairment of coagulation in postoperative laboratory analysis. Perioperative forced diuresis is recommended to prevent postoperative renal insufficiency. Supplementary thoracic epidural analgesia in 13 patients (65%) showed a significant reduction of post-operative pain compared with peroral administration of opioid and non-opioid analgesics. CONCLUSION: This article summarizes important experiences of the anaesthesiological and intensive care management in patients undergoing HITHOC.

Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle.

BACKGROUND: Cardiovascular resuscitation upon intoxication with lipophilic ion channel-blocking agents has proven most difficult. Recently, favorable results have been reported when lipid rescue therapy is performed, i.e., the infusion of a triglyceride-rich lipid emulsion during resuscitation. However, the mechanism of action is poorly understood. METHODS: The authors investigate the effects of a clinically used lipid emulsion (Lipovenös® MCT 20%; Fresenius Kabi AG, Bad Homburg, Germany) on the block of the fast Na current (INa) induced by the lipophilic local anesthetic bupivacaine in adult rat left ventricular myocytes by using the whole cell patch clamp technique. RESULTS: Bupivacaine at 10 µm decreased INa by 54% (-19.3 ± 1.9 pApF vs. -42.3 ± 4.3 pApF; n = 17; P < 0.001; VPip = -40 mV, 1 Hz). Addition of 10% lipid emulsion in the presence of bupivacaine produced a 37% increase in INa (-26.4 ± 2.8 pApF; n = 17; P < 0.001 vs. bupivacaine alone). To test whether these results could be explained by a reduction in the free bupivacaine concentration by the lipid (lipid-sink effect), the authors removed the lipid phase from the bupivacaine-lipid mixture by ultracentrifugation. Also, the resulting water phase led to an increase in INa (+19%; n = 17; P < 0.001 vs. bupivacaine), demonstrating that part of the bupivacaine had been removed during ultracentrifugation. The substantially less lipophilic mepivacaine (40 µm) reduced INa by 27% (n = 24; P < 0.001). The mepivacaine-lipid mixture caused a significant increase in INa (+17%; n = 24; P < 0.001). For mepivacaine, only a small lipid-sink effect could be demonstrated (+8%; n = 23; P < 0.01), reflecting its poor lipid solubility. CONCLUSION: The authors demonstrate lipid rescue on the single-cell level and provide evidence for a lipid-sink mechanism.

The impact of crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance in isolated hearts.

INTRODUCTION: Recent data suggested an interaction between plasma constituents and the endothelial glycocalyx to be relevant for vascular barrier function. This might be negatively influenced by infusion solutions, depending on ionic composition, pH and binding properties. The present study evaluated such an influence of current artificial preparations. METHODS: Isolated guinea pig hearts were prepared in a modified Langendorff mode and perfused with Krebs-Henseleit buffer augmented with 1g% human albumin. After equilibration the perfusion was switched to replacement of one half buffer by either isotonic saline (NaCl), ringer's acetate (Ri-Ac), 6% and 10% hydroxyethyl starch (6% and 10% HES, resp.), or 4% gelatine (Gel), the artificial colloids having been prepared in balanced solution. We analysed glycocalyx shedding, functional integrity of the vascular barrier and heart performance. RESULTS: While glycocalyx shedding was not observed, diluting albumin concentration towards 0.5g% by artificial solutions was associated with a marked functional breakdown of vascular barrier competence. This effect was biggest with isotonic saline and significantly attenuated with artificial colloids, the difference in the pressure dependent transvascular fluid filtration (basal vs. during infusion in groups NaCl, Ri-Ac, 6% HES, 10% HES and Gel, n = 6 each) being 0.31 ± 0.03 vs. 1.00 ± 0.04; 0.27 ± 0.03 vs. 0.81 ± 0.03; 0.29 ± 0.03 vs. 0.68 ± 0.02; 0.32 ± 0.03 vs. 0.59 ± 0.08 and 0.31 ± 0.04 vs. 0.61 ± 0.03 g/5min, respectively. Heart performance was directly related to pH value (7.38 ± 0.06, 7.33 ± 0.03, 7.14 ± 0.04, 7.08 ± 0.04, 7.25 ± 0.03), the change in the rate pressure product being 21,702 ± 1969 vs. 21,291 ± 2,552; 22,098 ± 2,115 vs. 14,114 ± 3,386; 20,897 ± 2,083 vs. 10,671 ± 1,948; 21,822 ± 2,470 vs. 10,047 ± 2,320 and 20,955 ± 2,296 vs. 15,951 ± 2,755 mmHg × bpm, respectively. CONCLUSIONS: It appears important to maintain the pH value within a physiological range to maintain optimal myocardial contractility. Using colloids prepared in calcium-containing, balanced solutions for volume replacement therapy may attenuate the breakdown of vascular barrier competence in the critically ill.

First experience with the deltastream(R) DP3 in venovenous extracorporeal membrane oxygenation and air-supported inter-hospital transport.

OBJECTIVES: Based on continuous technical innovations and recent research, extracorporeal membrane oxygenation (ECMO) has become a promising tool in the treatment of patients with acute (cardio)pulmonary failure. Nevertheless, any extracorporeal technique requires a high degree of experience and knowledge, so that a restriction to specialized centres seems to be reasonable. As a consequence of this demand, the need for inter-hospital transfer of patients with severely impaired (cardio)pulmonary function is rising. Unfortunately, most of the ECMO devices used in the clinical setting are not suitable for inter-hospital transport because of their size, weight or complexity. In this article, we describe our first experiences with the airborne transport of 6 patients on a new portable, miniaturized and lightweight extracorporeal circulation system, the Medos deltastream® DP3. METHODS: Six patients suffering acute respiratory failure were taken on venovenous ECMO (DP3) out-of-centre and transferred to the University Medical Center Regensburg by helicopter. All cardiorespiratory-relevant parameters of the patients and the technical functioning of the device were continuously monitored and documented. RESULTS: Implantation of the device and air-supported transport were performed without any technical complications. The patients were transported from a distance of 66-178 km, requiring a time of 40-120 min. With the help of the new deltastream® DP3 ECMO device, a prompt stabilization of the cardiopulmonary function could be achieved in all patients. One patient was under ongoing cardiopulmonary resuscitation by the time our ECMO team arrived at the peripheral hospital and died shortly after arrival in the central emergency ward. CONCLUSIONS: Our experience shows that the deltastream® DP3 is an absolutely reliable and safe ECMO device that could gain growing importance in the field of airborne transportation of patients on ECMO due to its unsophisticated, miniaturized and lightweight characteristics.

Modulation of immune functions in polymorphonuclear neutrophils induced by physostigmine, but not neostigmine, independent of cholinergic neurons.

BACKGROUND: Cholinesterase inhibitors (Ch-I) improve survival in experimental sepsis consistent with activation of the cholinergic-anti-inflammatory-pathway. So far, less is known about whether Ch-I have a direct immunomodulatory effect on immune cells (polymorphonuclear neutrophils, PMN) in the absence of cholinergic neurons. We investigated the concentration-response-effects of physostigmine and neostigmine on the oxidative burst activity (human and rat PMN) and the expression of adhesion molecules on the surface of human PMN under in vitro conditions. METHODS: PMN from 10 healthy humans or 10 rats were pretreated with 2, 10, 24, 97 µM physostigmine or 3, 15, 30, 150 µM neostigmine, primed with tumor-necrosis-factor-alpha (TNF-alpha) followed by stimulation with n-formyl-methionyl-leucylphenylalanine (fMLP) or stimulated with phorbol-12-myristate-13-acetate (PMA). Human and rat samples were assessed by flow cytometry for the generation of oxidative free radicals. Stimulated human PMN were additionally incubated with antibodies against Mac-1 (CD11b) or L-selectin (CD62l). RESULTS: Physostigmine and neostigmine did not alter oxidative burst activity or the expression of adhesion molecules of PMN induced by receptor-dependent activators like fMLP or TNF-alpha/fMLP (rat and human PMN, p=n.s.). Physostigmine, but not neostigmine, inhibited the protein-kinase-C-mediated oxidative burst activity by PMA in a dose-dependent manner (rat and human PMN, p<0.05). Physostigmine, in the concentration range tested, suppressed the expression of CD11b following stimulation with PMA not significantly (human PMN: control: 63.1±10.7 vs. 97 µM physostigmine: 49.9±12.8 MESF, p=n.s.). CONCLUSION: While neostigmine has no effect on functional and phenotypic changes of PMN, the lipid soluble Ch-I physostigmine causes a dose dependent reduction in PMA-induced oxidative burst, independent of neuronal released acetylcholine.

Clinical experience does not correlate with the perceived need for cardiopulmonary resuscitation training.

BACKGROUND: The efficiency of cardiopulmonary resuscitation (CPR) training is dependent upon different influencing factors, such as the presented concepts, the participants' willingness to learn, and the interval between training sessions. However, the optimal interval for refreshing CPR training is less clear. OBJECTIVE: We evaluated the perceived need of simulator-based CPR training for nurses and correlated it with their clinical experience. METHODS: The 60 invited nurses were trained in simulator-based CPR. Knowledge about adult advanced life support was evaluated using a questionnaire after training, and participants rated their desired individual frequency of simulator-based training as well as the value of the presented training using a six-point Likert scale. The same questions were asked again after 1 year. RESULTS: All participants agreed about the usefulness of this type of simulator-based training. The average number of correct answers about typical facts in adult advanced life support showed an almost bell-shaped distribution, with the highest point at 6-15 years of clinical experience and the lowest points at≤5 and≥21 years. The desired training-frequency need was inversely correlated with clinical experience. CONCLUSIONS: There is a high interest in CPR training among nursing staff. Self-assessment about the training-frequency need was inversely correlated with clinical experience. However, the average number of correct answers on resuscitation questions decreased with clinical experience. Therefore, the training effectiveness seems to be extremely dependent on clinical experience, and therefore, training experienced senior nurses might be more challenging than training novice nurses.

Successful use of hirudin during cardiac surgery using minimized extracorporeal circulation in patients with heparin-induced thrombocytopenia.

In this case series, we describe our successful use of a reduced hirudin dosage as an anticoagulant during cardiac surgery using minimized extracorporeal circulation in patients with heparin-induced thrombocytopenia.

Minimized extracorporeal circulation system in coronary artery bypass surgery: a 10-year single-center experience with 2243 patients.

OBJECTIVE: Coronary artery bypass grafting (CABG) is the gold standard for the surgical therapy of multivessel coronary artery disease. To reduce the side effects, associated with standard extracorporeal circulation (ECC), a concept of minimal extracorporeal circulation (MECC) was devised in our center. We report on our 10-year experience with the MECC for coronary revascularization. METHODS: From January 1998 to August 2009, 2243 patients underwent CABG with MECC in our center. In a retrospective observational study, we analyzed indication, preoperative patient co-morbidity, postoperative clinical course, and perioperative outcome of all patients operated on with MECC. Furthermore, the risk factors for mortality in the MECC group were assessed. RESULTS: Patients showed a mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 4.5±0.1%. The mean age of the patients was 66.8±9.1 years. The overall 30-day mortality after CABG with MECC was 2.3%, ranging from 1.1% for elective to 13.0% for emergent patients and was significantly better than standard ECC. Only 15.3% (n=344) of patients with MECC required intra-operative blood transfusion. Postoperative catecholamine support, red blood cell transfusion, need for hemodialysis, release of creatinine kinase, incidence of stroke, and postoperative delirium were low after MECC revascularization. Ejection fraction below 30% (odds ratio (OR): 5.1), emergent operation (OR: 9.4), and high-dose catecholamine therapy (OR: 2.6) were associated predictors for mortality. CONCLUSION: MECC until now is an established concept and has become an alternative for ECC in routine CABG in our center. The use of the MECC system is associated with low mortality and conversion rate. Excellent survival rates and low transfusion requirements in the perioperative course were achieved.

Prehospital emergency treatment of palliative care patients with cardiac arrest: a retrolective investigation.

BACKGROUND: Today, prehospital emergency medical teams (EMTs) are confronted with emergent situations of cardiac arrest in palliative care patients. However, little is known about the out-of-hospital approach in this situation and the long-term survival rate of this specific patient type. The aim of the present investigation was to provide information about the strategic and therapeutic approach employed by EMTs in outpatient palliative care patients in cardiac arrest. METHODS: During a period of 2 years, we retrolectively analysed emergency medical calls with regard to palliative care emergency situations dealing with cardiac arrest. We evaluated the numbers of patients who were resuscitated, the prevalence of an advance directive or other end-of-life protocol, the first responder on cardiac arrest, the return of spontaneous circulation (ROSC) and the survival rate. RESULTS: Eighty-eight palliative care patients in cardiac arrest were analysed. In 19 patients (22%), no resuscitation was started. Paramedics and prehospital emergency physicians began resuscitation in 61 cases (69%) and in 8 cases (9%), respectively. A total of 10 patients (11%) showed a ROSC; none survived after 48 h. Advance directives were available in 43% of cases. The start of resuscitation was independent of the presence of an advance directive or other end-of-life protocol. CONCLUSIONS: Strategic and therapeutic approaches in outpatient palliative care patients with cardiac arrest differ depending on medical qualification. Although many of these patients do not wish to be resuscitated, resuscitation was started independent of the presence of advance directive. To reduce legal insecurity and to avoid resuscitation and a possible lengthening of the dying process, advance directives and/or "Do not attempt resuscitation" orders should be more readily available and should be adhered to more closely.

Direct cardiac effects of dobutamine, dopamine, epinephrine, and levosimendan in isolated septic rat hearts.

In septic patients, myocardial depression-the so-called septic cardiomyopathy-needing inotropic support is common. The aim of this study was to compare the dose-responsive electrophysiological and mechanical properties concerning metabolic effects of clinically available inotropic agents in an isolated septic rat heart model. After 20 h of incubation, both sham-operated and septic (cecal ligation and single puncture) hearts from male Wistar rats (n = 64) were isolated and received dobutamine, dopamine, epinephrine, or levosimendan at concentrations of 10 to 10 M. Electrophysiological, mechanical, and metabolic properties were measured, and the myocardial oxygen supply-demand ratio and cardiac efficiency were calculated. With the exception of levosimendan, all of the drugs tested showed dose-dependent, significantly positive changes in chronotropy, inotropy, and lusitropy in all hearts. Maximum increases in septic hearts were dose-dependent and were ordered as follows: epinephrine > dopamine > dobutamine >>> levosimendan. These increases in cardiac performance were accompanied by a decrease in the myocardial oxygen supply-demand ratio. However, cardiac efficiency was significantly improved in the epinephrine-treated septic hearts. With the drug-induced increase in cardiac performance, the myocardial oxygen supply-demand ratio decreased proportionally in the epinephrine-, dobutamine-, and dopamine-treated septic hearts. However, epinephrine showed the most favorable results with regard to cardiac efficiency, and levosimendan showed no beneficial effect in septic hearts with regard to efficiency in this study.