[Cancer pain therapy in palliative care patients: knowledge of prehospital emergency physicians in training. Prospective questionnaire-based investigation]. / Kenntnisse angehender Notfallmediziner über die Tumorschmerztherapie bei Palliativpatienten. Prospektive fragebogenbasierte Untersuchung.

BACKGROUND: Cancer diseases are often associated with acute and chronic pain. Therefore, cancer pain is a symptom frequently reported by palliative care patients with cancer diseases. Prehospital emergency physicians may be confronted with exacerbation of pain in cancer patients. The aim of this study was to evaluate the knowledge of prehospital emergency physicians in training concerning cancer pain therapy. METHODS: A total of 471 prehospital emergency physicians received a questionnaire (period of time: 2007-2009). The questionnaire was prepared for the study ("mixed methods design"). Twenty-four questions concerning cancer pain therapy (response options: scaling, open) were designed. The evaluation was done descriptively according to professional experience, field name and experience in treating patients with cancer as well. RESULTS: A total of 469 participants completed the questionnaire (response rate 99%). On average, 10.8 (SD +5.7, range 2-24) questions were answered correctly. Resident physicians answered statistically significantly more questions correctly than consultants (p=0.02). Only physicians working in internal medicine achieved statistically significantly better results than other disciplines (e.g., surgery; p=0.01). Physicians with professional experience of less than 5 years answered statistically significantly more questions correctly (p=0.004). CONCLUSIONS: The results of this study verify that emergency physicians in training have insufficient knowledge of pain therapy and end-of-life decisions. The data of this investigation suggest that more attention should be paid to education on pain therapy and end-of-life care in medical curricula. Prehospital emergency physicians may thus be better prepared to provide quality care for palliative patients.

Effect of ACE inhibition on the fibrinolytic system in patients requiring coronary artery bypass grafting.

BACKGROUND: Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system. Thus, alterations in the renin-angiotensin system by ACE inhibitors probably result in modification of the fibrinolytic system. We examined the effect of a short-term treatment with the ACE inhibitor enalapril in 47 patients with severe coronary artery disease requiring coronary artery bypass grafting (CABG). METHODS: Patients received either 20 mg/d enalapril or placebo for 6 days. Tissue-type plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), plasmin-a2-antiplasmin-complex (PAP) and D-dimers were measured initially and after treatment. RESULTS: In the enalapril group PAI-1 levels were significantly reduced after treatment (11.9 +/- 2.3 U/ml vs. 17.1 +/- 3.0 U/l; P < 0.05). In the placebo group PAP levels were significantly higher ( P < 0.05) after treatment compared to initial values. No differences could be detected between the study groups with regard to TPA and D-dimers. CONCLUSION: Although PAI-1 activity levels are reduced after short-term treatment with ACE inhibitors in patients with stable angina pectoris while TPA antigen is unaffected, treatment with ACE inhibitors does not lead to a marked change in plasmin activation.

Laryngoscopic versus intubating LMA guided tracheal intubation by novice users--a manikin study.

AIM OF THE STUDY: Airway control is a potentially lifesaving procedure but tracheal intubation by direct laryngoscopy is difficult. This pilot study was conducted to determine whether tracheal intubation was more rapid and the success rate higher using an intubating laryngeal mask airway. MATERIAL AND METHODS: The success rates of 119 medical students without prior airway management experience in ventilating and then intubating the trachea of a Laerdal Airway Management Trainer with two different methods were compared. The methods were bag-mask ventilation (BM-V) followed by laryngoscopic intubation (LG-TI), and intubating laryngeal mask ventilation (ILMA-V) followed by ILMA-guided tracheal intubation (ILMA-TI). After an introductory lecture and demonstration, each student was allowed three attempts to intubate using each method in random order. RESULTS: All participants were successful with BM-V and ILMA-V on the first attempt. Laryngoscopic tracheal intubation was achieved by 60 (50.4%), 31 (26.1%) and 12 (10.1%) participants on the first, second and third attempt, respectively, while 16 (13.4%) failed in all three attempts. In the ILMA-TI group, 107 (90.0%), 10 (8.4%) and 2 (1.6%) succeeded on the first, second and third attempt, respectively. None failed. The intergroup difference is highly significant (p<0.001). Male participants were more successful with LG-TI than female (p<0.01), but not with ILMA-TI. CONCLUSION: Laryngoscopic orotracheal intubation is difficult for the untrained, but all participants were successful with ILMA-TI. These data suggest that alternative devices such as the ILMA should be included in the medical school curriculum for airway management.

Instantaneous diastolic pressure-flow relationship in arterial coronary bypass grafts.

OBJECTIVE: The objective of this study was to describe the diastolic pressure-flow relationship and to assess critical occlusion pressure in arterial coronary bypass grafts in human beings. METHODS AND RESULTS: Fifteen patients were studied following elective surgical coronary artery bypass grafting. Flow in the left internal mammary artery bypass to the left anterior descending artery was measured and simultaneously, aortic pressure, coronary sinus pressure and left ventricular end-diastolic pressure were recorded. The zero-flow pressure intercept as a measure of critical occlusion pressure was extrapolated from the linear regression analysis of the instantaneous diastolic pressure-flow relationship. Mean diastolic flow was 46 +/- 17 mL min(-1), mean diastolic aortic pressure was 60.5 +/- 10.0 mmHg. Diastolic blood flow was linearly related to the respective aortic pressure in all patients (R-values 0.7-0.99). The regression lines had a mean slope of 2.1 +/- 1.2 mL min(-1) mmHg(-1). Mean critical occlusion pressure was 32.3 +/- 9.9 mmHg and exceeded mean coronary sinus pressure and mean left ventricular end-diastolic pressure by factors of 3.1 and 2.6, respectively. CONCLUSIONS: Our data demonstrate the presence of a vascular waterfall phenomenon in the coronary circulation after internal mammary artery bypass grafting. Critical occlusion pressure in arterial grafts considerably exceeds coronary sinus pressure as well as left ventricular end-diastolic pressure and should thus be used as the effective downstream pressure when calculating coronary perfusion pressure. Our data further suggest that the slope of diastolic pressure-flow relationships provides a more rational approach to assess regional coronary vascular resistance than conventional calculations of coronary vascular resistance.

Increased fibrin specificity and reduced paradoxical thrombin activation of the combined thrombolytic regimen with reteplase and abciximab versus standard reteplase thrombolysis.

In patients with acute myocardial infarction treated with thrombolytics, platelet activation as well as alterations of the hemostatic and fibrinolytic systems have been described favoring early infarct-related artery reocclusion. We investigated the effects of a newer thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full-dose reteplase (2 x 10 IU, 18 patients) on the fibrinolytic and the hemostatic system in patients with acute ST-segment elevation (in the electrocardiogram) myocardial infarction. The thrombolytic regimen with half-dose reteplase in combination with abciximab caused in vivo a lower systemic plasminemia and a lower paradoxical activation of the contact phase of the coagulation system (measured as activated factor XII); a lower paradoxical thrombin activation/generation; and a lesser extent of fibrinogen breakdown compared with the reteplase regimen. These results could be, at least in part, a possible explanation for the observed significantly lower rates of reinfarction until 7 days after enrollment and of recurrent ischemia in the combination group in the Global Use of Strategies to Open Occluded Coronary Arteries V (GUSTO V) trial.

Benefical effects of reteplase in combination with abciximab: platelet/leukocyte interactions and coagulation system.

Pathophysiological aspects of acute myocardial infarction include altered hemostatic and fibrinolytic systems as well as platelet activation. Treatment with thrombolytics and GP IIb/IIIa antagonists has been described as having an additional influence on these systems. We investigated the effects of a new thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full dose reteplase (2 x 10 IU, 18 patients) on platelet-granulocyte complexes and on thrombin-antithrombin III complexes in patients with acute ST-segment elevation myocardial infarction. In vivo, the thrombolytic regimen with half-dose reteplase in combination with abciximab caused fewer platelet-granulocyte aggregates (measured as percentage of CD41-positive granulocytes) and a lower paradoxical activation of the coagulation system (measured as thrombin-antithrombin III complex) compared with the reteplase regimen. The combination regimen could therefore have benefical effects on platelet-induced leukocyte activation and leukocyte-mediated proinflammatory/cytotoxic effects as well as on granulocyte-induced effects on endothelium, tissue damage and coagulation. This could be, at least in part, a possible explanation for the significantly lower rates of reinfarction, recurrent ischaemia and percutaneous coronary interventions observed during the early phase after an acute myocardial infarction in the combination group in the GUSTO-V trial.

Single atriocaval cannulation is associated with increased incidence of hypercirculatory failure after cardiopulmonary bypass.

UNLABELLED: Cardiopulmonary bypass (CPB) can lead to hypercirculatory cardiac failure (HCF). Despite the activation of inflammatory mediators, the infusion of cardioplegic solution into the systemic circulation may result in decreased systemic vascular resistance and thus may cause HCF. The present prospective study was conducted to investigate in cardiac surgical patients the effects of single atrial versus bi-caval venous drainage and intraoperative hemofiltration on the incidence of HCF. METHODS AND RESULTS: 120 patients undergoing coronary artery bypass surgery (CABG) were randomized in 3 groups: A- single atrial cannulation; B- single atrial cannulation and intraoperative zero fluid balance hemofiltration; C- bi-caval cannulation. Myocardial protection was performed using cold crystalloid cardioplegia (Bretschneider's HTK) administrated into the aortic root and moderate hypothermia (32 degree C). Hemodynamics, fluid balance, vasoactive drugs, body temperature, and hemoglobin/hematocrit ratio were recorded during and up to 12 hours after surgery. We noted a significantly increased incidence of HCF in-group A (32%, n=13) and B (40%, n=16) when compared to group C (10%, n=4, p<0.05), with significantly increased requirements for vasoactive medication in patients developing HCF. CONCLUSION: The present study results demonstrate that single atrial cannulation is associated with a significantly higher incidence of HCF. This is presumably caused by infusion of cardioplegic solution into the systemic circulation.

Assessment of cardiac preload by indicator dilution and transoesophageal echocardiography.

BACKGROUND AND OBJECTIVE: Assessment of cardiac preload is of major importance in the management of critically ill patients. Echocardiographic determined left ventricular end-diastolic area and indicator dilution derived intrathoracic blood volume are used as surrogates for cardiac preload. However, no controlled comparison studies on the relationship between induced changes in end-diastolic area and intrathoracic blood volume and concomitant changes in stroke volume index are available. METHODS: The effects of a change in body position on these variables were investigated in 10 anaesthetized patients. RESULTS: Intrathoracic blood volume and end-diastolic area decreased by 18 +/- 11% and 27 +/- 13% respectively. Stroke volume index concomitantly decreased by 19 +/- 11%. Correlation analysis revealed a close relation between stroke volume index and intrathoracic blood volume (r=0.75) and end-diastolic area (r=0.76). CONCLUSIONS: Within the observed range of data, intrathoracic blood volume and end-diastolic area are equivalent indices of cardiac preload.

Changes in cardiac output and intrathoracic blood volume: a mathematical coupling of data?

BACKGROUND: Measurements of intrathoracic blood volume (ITBV) provide volumetric information about cardiac preload and are used to investigate the cause of alterations in cardiac output (CO). On the other hand, CO is required to calculate ITBV. Thus, concerns have been raised with respect to a mathematical coupling of data. The aim of this prospective, clinical study was to investigate whether a variation in CO induced by high-dose beta-blockade influences thermodilution measurements of ITBV in the absence of changes in intravascular volume in patients undergoing minimally invasive coronary artery bypass grafting. METHODS: Sixteen patients undergoing elective minimally invasive direct coronay artery bypass (MIDCAB) surgery were studied. Transpulmonary thermodilution measurements of ITBV and CO were simultaneously performed before bypass grafting, during beta-blockade induced by high-dose esmolol and at the end of surgery. RESULTS: During esmolol administration, CO significantly decreased by 33%, whereas ITBV remained unchanged compared to control values (876+/-46 ml m-2 during control versus 860+/-61 ml m-2 during esmolol administration). After the end of esmolol administration, CO significantly increased by 79%. Again, ITBV remained virtually unchanged (860+/-61 ml m-2 during esmolol administration versus 911+/-38 ml m-2 after esmolol administration). CONCLUSIONS: The results of the present study demonstrate that substantial alterations in CO as a consequence of high-dose esmolol infusion are not associated with changes in ITBV. Because haemodynamic changes were induced by factors other than variation of preload, these findings suggest that changes in cardiac output do not influence thermodilution measurements of ITBV in this setting.

Myocardial troponin T release is associated with enhanced fibrinolysis in patients with acute coronary syndromes.

Patients with acute coronary syndromes (ACS) frequently present with signs of disturbed fibrinolysis. The present study investigates the correlation of alterations in the fibrinolytic system and the amount of myocardial damage characterized by troponin release. In 85 patients with ACS markers of plasmin activation, plasminogen activator system and troponin T (TnT) were measured initially and after 48 h. Patients with TnT release (> or = 0.01 microg/l) at admission had higher TPA levels than those without release (10.2+/-0.7 ng/ml vs. 7.6+/-0.5 ng/ml; p <0.01). Additionally, patients with positive TnT had higher D-dimer levels initially (457+/-39 ng/ml vs. 316+/-22 ng/ml; p <0.01) and 48 h later (451+/-42 ng/ml vs. 275+/-37 ng/ml; p <0.01). The association of myocardial damage with a prothrombotic state and an enhanced fibrinolysis may explain the high prognostic value of troponin measurements in respect to future coronary events.

Comparison of ventilatory and haemodynamic effects of BIPAP and S-IMV/PSV for postoperative short-term ventilation in patients after coronary artery bypass grafting.

The aim of the present multiple cross-over study was to compare the effects of biphasic positive airway pressure (BIPAP) ventilation with synchronized intermittent mandatory ventilation combined with pressure support ventilation (S-IMV/PSV) in sedated and awake patients after coronary artery bypass grafting (CABG) surgery. Twenty-four patients with no evidence of preoperative respiratory dysfunction and an uncomplicated intraoperative course were investigated. The patients were randomly assigned to one of two groups starting with either BIPAP or S-IMV/PSV mode. Haemodynamic measurements and blood gas analyses were performed during sedation with 2.0 mg kg(-1) h(-1) propofol in the primary mode, after switching to the alternative ventilatory mode, and in the primary mode again. The same sequence of measurements was repeated in awake patients who had reached extubation criteria. In awake patients, PSV was performed instead of S-IMV. Statistical analysis of data was performed using non-parametric tests. Inspiratory peak pressure increased significantly during S-IMV/PSV in sedated patients in both groups. Other ventilatory parameters did not differ significantly between BIPAP and S-IMV/PSV in both groups. Similarly, haemodynamic parameters and blood-gas analyses did not vary with the ventilatory mode. Our results demonstrate that BIPAP ventilation has comparable effects on haemodynamics and pulmonary gas exchange compared with S-IMV/PSV and PSV when used for short-term ventilatory support in patients after cardiac surgery.

Fibrin specificity and procoagulant effect related to the kallikrein-contact phase system and to plasmin generation with double-bolus reteplase and front-loaded alteplase thrombolysis in acute myocardial infarction.

This study was undertaken to compare the effects of reteplase and alteplase regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI). Thrombolytic treatment in patients with AMI is hampered by paradoxical procoagulant effects that favor early reocclusion. In vivo data comparing this effect and the fibrin specificity of double-bolus reteplase and front-loaded alteplase regimens are not available. In a prospective, randomized study, 50 patients with AMI were either treated with double bolus (10 + 10 U) reteplase or with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset. Thirty apparently healthy persons served as controls. Molecular markers of coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical thrombin activation at 3 hours after initiation of therapy was comparable between reteplase and alteplase. Reteplase (65 +/- 5 U/L) and alteplase (72 +/- 8 U/L) caused significantly elevated kallikrein activity at 3 hours after adminstration (p <0.01 vs controls 30 +/- 1 U/L). Fibrin specificity was less for reteplase (p <0.05) with a decrease in fibrinogen at 3 hours to 122 +/- 27 mg/dl versus 224 +/- 28 mg/dl for alteplase (p <0.01 and p <0.05 vs controls). D-Dimer levels at 3 hours were higher (p <0.05) after reteplase (5,459 +/- 611 ng/ml) versus alteplase (3,445 +/- 679 ng/ml) (both p <0.01 vs controls 243 +/- 17 ng/ml). Plasmin generation (plasmin-antiplasmin complexes) was significantly (p <0.01) increased at 3 hours with both regimens to 27,079 +/- 3,964 microg/L (reteplase) and 19,522 +/- 2,381 microg/L (alteplase). The data from 3 hours after start of thrombolytic therapy proved less marked fibrin specificity of the reteplase regimen (in vivo) compared with front-loaded alteplase. Both regimens have a moderate procoagulant effect without differences in activation of the kallikrein system.

Cerebrovascular tone rather than intracranial pressure determines the effective downstream pressure of the cerebral circulation in the absence of intracranial hypertension.

Cerebral perfusion pressure is commonly calculated from the difference between mean arterial pressure and intracranial pressure because intracranial pressure is known to represent the effective downstream pressure of the cerebral circulation. Studies of other organs, however, have shown that effective downstream pressure is determined by a critical closing pressure located at the arteriolar level. This study was designed to investigate the effects of PCO2-induced variations in cerebrovascular tone on the effective downstream pressure of the cerebral circulation. Sixteen patients recovering from head injury were studied. Intracranial pressure was assessed by epidural pressure transducers. Blood flow velocity in the middle cerebral artery was monitored by transcranial Doppler sonography. Effective downstream pressure was derived from the zero flow pressure as extrapolated by regression analysis of instantaneous arterial pressure/middle cerebral artery flow velocity relationships. PaCO2 was varied between 30 and 47 mm Hg in randomized sequence. Intracranial pressure decreased from 18.5+/-5.2 mm Hg during hypercapnia to 9.9+/-3.1 mm Hg during hypocapnia. In contrast, effective downstream pressure increased from 13.7+/-9.6 mm Hg to 23.4+/-8.6 mm Hg and exceeded intracranial pressure at hypocapnic PaCO2 levels. Our results demonstrate that, in the absence of intracranial hypertension, intracranial pressure does not necessarily represent the effective downstream pressure of the cerebral circulation. Instead, the tone of cerebral resistance vessels seems to determine effective downstream pressure. This suggests a modified model of the cerebral circulation based on the existence of two Starling resistors in a series connection.

Myocardial consequences of remifentanil in patients with coronary artery disease.

Remifentanil may be an alternative to conventional opioids for minimally invasive direct coronary artery bypass surgery because of its extremely short duration of action. The aim of this study was to investigate the effects of remifentanil on myocardial blood flow, metabolism and systemic haemodynamic variables in patients with coronary artery disease. After approval by the local ethics committee, 12 male patients were investigated before elective coronary artery bypass grafting. Systemic haemodynamic variables, myocardial blood flow and metabolism were measured when patients were awake and when they were anaesthetized with high-dose remifentanil (2.0 micrograms kg-1 min-1), or with remifentanil 0.5 microgram kg-1 min-1 combined with propofol (target-controlled infusion aiming at a plasma concentration of 2.0 micrograms ml-1). Myocardial blood flow was measured using a modified Kety-Schmidt technique. High-dose remifentanil anaesthesia significantly reduced cardiac index (CI) (-25%) as a consequence of a decrease in stroke volume index (SVI) (-14%) and heart rate (-13%). Mean arterial pressure (MAP) was 30% lower than that in the awake patient. Myocardial blood flow and myocardial oxygen uptake (MVO2) decreased by 30% and 42%, respectively. In contrast to high-dose remifentanil anaesthesia, systemic vascular resistance index (-14%) during remifentanil/propofol anaesthesia was significantly lower than that in the awake patient. Other haemodynamic variables, and myocardial blood flow and MVO2, did not significantly differ from the high-dose remifentanil period. In conclusion, high-dose remifentanil reduces SVI, heart rate, MAP, myocardial blood flow and MVO2 and its effects do not differ from those of remifentanil/propofol anaesthesia.

Effects of the sitting position on the distribution of blood volume in patients undergoing neurosurgical procedures.

The use of the sitting position in neurosurgery is often associated with decreased arterial pressure (MAP) and stroke volume index (SVI). A shift in blood from the intra- to the extrathoracic compartment may be responsible for this cardiovascular response. However, little is known of the amount of shift in blood volume after transfer from the supine to the sitting position. Therefore, we measured simultaneously changes in intrathoracic blood volume (ITBV) caused by a change in body position in anaesthetized patients. Measurements of cardiac index (CI), ITBV, pulmonary (PBV) and total circulating (TBVcirc) blood volumes were performed in the supine and sitting position. CI, ITBV, PBV and TBVcirc were measured using a thermodye dilution technique. Fluid input was restricted to 14 ml kg-1 before induction of anaesthesia. Change in body position caused a significant decrease in ITBV and was accompanied by a significant decrease in CI, SVI and MAP. Changes in ITBV correlated (r = 0.78) with changes in SVI. Thus a change in blood volume distribution between the intra- and extrathoracic compartment occurred after a change from the supine to the sitting position. Indicator dilution enables quantification of this shift and may be helpful in guiding fluid therapy in selected patients.

[Does method of anesthesia modify postoperative ischemia incidence? A study of patients after aortocoronary bypass operations]. / Beeinflusst das Anästhesieverfahren die postoperative Ischämieinzidenz? Eine Untersuchung an Patienten nach aortokoronaren Bypassoperationen.

In the postoperative period after coronary artery bypass graft surgery, the physician's enhanced attention should be focused on the incidence of myocardial ischaemia. The increased stress in the awakening patient as well as the return of autonomous reflexes can be the cause of imbalances in myocardial oxygen supply and uptake. Therefore, a probable influence of the pharmacologic profile of the intraoperatively applied anaesthetics on the incidence of postoperative myocardial ischaemia is of importance for adapting therapy on ICU to minimize any ischaemic risk. After approval by the ethics committee, a prospective randomized study was performed in 40 male patients who underwent coronary artery bypass graft surgery. The aim of the study was to compare balanced anaesthetic techniques performed with fentanyl and halothane, isoflurane and enflurane, respectively, with total intravenous anaesthesia performed with fentanyl and midazolam. An index to classify detection of ischaemia into three categories (ischaemia, probable ischaemia, no ischaemia) was established, based on measurements of myocardial lactate extraction and ST-segment analysis. Simultaneously, measurements of haemodynamic parameters and serum concentrations of catecholamines and intraoperatively applied anaesthetics were taken. In 8% of all measurements (30% of all patients) ischaemia was detected in the observation period and in 37% of all measurements (72.5% of all patients) probable ischaemia was detected. No significant difference was found concerning the incidence of myocardial ischaemia between all groups. The results of this investigation indicate that the application of inhalational anaesthetics for maintaining anaesthesia in coronary artery bypass graft surgery does not increase the risk of postoperative myocardial ischaemia.

Comparison of cardiac output assessed by pulse-contour analysis and thermodilution in patients undergoing minimally invasive direct coronary artery bypass grafting.

OBJECTIVE: To investigate the precision and accuracy of continuous pulse contour cardiac output (PCCO) compared with intermittent transcardiopulmonary (TCPCO) and pulmonary artery thermodilution (TDCO) measurements in patients undergoing minimally invasive coronary bypass surgery (MIDCAB). DESIGN: Prospective, controlled, clinical study. SETTING: University hospital. PARTICIPANTS: Twelve patients undergoing MIDCAB. INTERVENTIONS: Thirty-six measurements of PCCO and thermodilution cardiac output (CO) were simultaneously performed after the start of surgery, during bypass grafting, and at the end of surgery. TCPCO and TDCO were simultaneously assessed by three injections of ice-cold saline randomly spread over the respiratory cycle. The pulse contour device was initially calibrated with an additional set of aortic thermodilution measurements. MEASUREMENTS AND MAIN RESULTS: Absolute values of CO ranged between 1.6 and 9.2 L/min. A close agreement among the three techniques was observed at all measurements. Mean bias between PCCO and TDCO and TCPCO was 0.003 L/min (2 SD of differences between methods = 1.26 L/min) and 0.27 L/min (2 SD of differences between methods = 1.16 L/min), respectively. The correlation coefficients were r2 = 0.90 for TCPCO versus PCCO and r2 = 0.88 for TDCO versus PCCO. CONCLUSION: The results of the present study show that compared with thermodilution CO, pulse contour analysis enables accurate measurement of continuous CO in patients undergoing MIDCAB.

Action of aprotinin in myocardial ischemia - an investigation using a plasma-free model.

BACKGROUND: The protease inhibitor aprotinin has been reported to have an anti-ischemic effect on left-ventricular myocardium in patients undergoing cardiopulmonary bypass operation. To examine the anti-ischemic properties beside its antifibrinolytic and inhibitory action on the kallikrein-bradykinin system, we investigated this substance in buffer-perfused rat hearts. METHODS: 24 isolated isovolumically contracting rat hearts received a 10-minute infusion of either 10000 units aprotinin or pure saline followed by 30 minutes of no-flow global ischemia and 45 minutes of reperfusion. Hemodynamics, high-energy phosphates, and troponin T as molecular marker of cardiac injury were studied. RESULTS: During 15 minutes of reperfusion steady state function was identical in both groups, with a recovery of the developed left-ventricular pressure to 81.9+/-1.5% after protease inhibition and 83.0+/-2.6% in the controls. Coronary flow, myocardial oxygen consumption, and contractile reserve after maximum Ca++ stimulation were also identical. High-energy phosphates were comparably reduced in both groups (adenine nucleotides: 3.1+/-0.3 micromol/g ww after aprotinin vs. controls 2.7+/-0.4 micromol/g ww and creatine phosphate: 6.5+/-0.9 micromol/g ww vs. controls 4.7+/-1.1 micromol/g ww). However, release of the cardiac specific marker troponin T was lower after ischemia at several measurements (p<0.05). The total release of troponin T was 44+/-10 ng in the aprotinin treated hearts vs. 90+/-17 ng in the postischemic control hearts (p<0.05). CONCLUSIONS: The findings demonstrate that aprotinin in a moderate dose is effective in reducing postischemic troponin release in a non-blood perfused system. Measurement of myocardial high-energy phosphates after aprotinin use was performed for the first time and indicates that not a reduction in severity of direct myocardial ischemic intensity but a beneficial action on processes causing release of troponin is the mode of action of this effect.