Regional changes in cerebral blood flow oxygenation can indicate global changes in cerebral blood flow during coronary artery occlusion in juvenile pigs.

Near infrared spectroscopy (NIRS) is a widely employed method for assessment of regional cerebral oxygenation (RcStO2). RcStO2 values are expected to vary with changes in the relative amount of oxyhaemoglobin. The present experimental study aimed to assess the response of RcStO2 to controlled alterations of carotid blood flow (CQ). Landrace pigs were anesthetized followed by surgical preparation. Cyclic variations in cardiac output were accomplished by intermittently occluding the main stem of the left coronary artery. A flow measurement probe for assessing CQ was placed around the left carotid artery. One NIRS probe was placed on the left ipsilateral forehead to assess regional cerebral oximetry. Simultaneous registration of CQ and RcStO2 was conducted. There was a strong correlation for variation in CQ and RcStO2 signal values. Based on coherence analysis the fraction of power of the RcStO2 that was coherent with the CQ signal reached 0.84 ± 0.12 (P < 0.05) for frequencies lower than 0.1 Hz. The agreement of the sample-to-sample co-variation, as assessed by the Pearson correlation coefficient, was 0.83 ± 0.08 (P < 0.05). One explanatory component for variations in cerebral oxygenation verified by NIRS should be attributed to variations in the cerebral blood flow.

Contributions of myocardial ischemia and heart rate to ST segment changes in patients with or without coronary artery disease.

BACKGROUND: ST changes related to ischemia at different heart rates (HRs) have not been well described. We aimed to analyze ST dynamic changes by vectorcardiography (VCG) during pacing-induced HR changes for subjects with proven coronary artery disease (CAD) and without (non-CAD). METHODS: Symptomatic CAD patients scheduled for elective surgery were enrolled along with a non-CAD group. During anesthesia, both groups were placed at multiple ascending levels. VCG ST data, and in particular in ST change vector magnitude (STC-VM) from baseline, along with arterial and great coronary artery vein (GCV) blood samples were collected to determine regional myocardial lactate production. RESULTS: A total of 35 CAD and 10 non-CAD patients were studied over six incremental 10 beat/min HR increases. STC-VM mean levels increased in the CAD group from 9+/-5 to 131+/-37 microV (standard deviation) compared with non-CAD subjects with 8+/-3-76+/-34 microV. Myocardial ischemia (lactate production) was noted at higher HRs and the positive predictive value for STC-VM to detect ischemia was 58% with the negative predictive value being 88%. STC-VM at 54 microV showed a sensitivity of 88% and a specificity of 75% for identification of ischemia. CONCLUSIONS: Both HR and ischemia at higher HRs contribute to VCG ST elevation. Established ST ischemia detection concerning HR levels is suboptimal, and further attention to the effects of HR on ST segments is needed to improve electrocardiographic ischemia criteria.

Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.

The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.

Measurement of the activated clotting time during cardiopulmonary bypass: differences between Hemotec ACT and Hemochron Jr apparatus.

BACKGROUND: Measurement of the activated clotting time (ACT) represents a standard method for coagulatory assessments. The test employs specific agents to trigger the coagulation process. The present study aimed to compare kaolin (Hemotec) versus a combination of silica, kaolin and phospholipid (Hemochron Jr) ACTs. METHODS: Hemotec and Hemochron Jr ACT monitors were compared by simultaneous measurement of paired arterial blood samples (n = 114) with respect to precision and bias during clinical conditions of cardiopulmonary bypass (CPB). The influence of haemodilution on the ACT was tested in an ex-vivo model. RESULTS: The precision of Hemotec and Hemochron Jr ACT measurements attained 21 +/- 2.6 s versus 27.0 +/- 2.6 s (p = 0.126) during CPB and 2.5 +/- 2.2 s versus 9.4 +/- 6.9 s (p = 0.000) after protamine administration, respectively. The Hemochron Jr monitor was associated with a bias of -102 +/- 13.7 s compared to the Hemotec ACT monitor (p = 0.000) during CPB and -6.9 +/- 2.9 s after protamine (p = 0.025). Linear regression analysis of ACT readings between monitors reached r = 0.526 (p = 0.000). Hemochron Jr ACT values correlated with the erythrocyte volume fraction r = 0.379 (p = 0.000). Ex-vivo data indicated that the Hemotec ACT monitor was associated with relatively higher ACT readings after haemodilution. CONCLUSION: The ACT is not a standardized measure. Test results are strongly associated with the specific compounds used to initiate the coagulation process.

Pressure-independent cardiac effects of angiotensin II in pigs.

BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in the development of cardiovascular disease. Earlier results have shown a positive acute inotropic effect of Ang II in anaesthetized pigs together with significant vasoconstriction. This investigation was designed to study cardiac effects of Ang II, when blood pressure was maintained constant by experimental means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n = 10) at two different arterial blood pressures, the first determined by the effects of Ang II alone, and the second maintained at baseline blood pressure with nitroprusside. Cardiac systolic and diastolic function was evaluated by analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate, end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2)) increased at both blood pressure levels, although less when blood pressure was kept constant with nitroprusside. The time constant for isovolumetric relaxation (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic and chronotropic properties independent of arterial blood pressure levels, although the effects seem to be blunted by pharmacological actions of the nitric oxide donor nitroprusside.

Preload changes by positive pressure ventilation can be used for assessment of left ventricular systolic function.

BACKGROUND: Assessment of preload independent left ventricular function with conductance volumetry is traditionally accomplished by inflating a balloon in the inferior caval vein. Our aim was to investigate if a similar change in preload could be achieved by positive pressure ventilation with large tidal volume. METHODS: Conductance volumetry generating left ventricular pressure-volume loops was used in seven pentobarbital-anesthetized pigs. Changes in preload recruitable stroke work were studied, comparing the effects of inferior vena cava occlusion (IVCO) or large tidal volume (LTV). Cardiodepression was induced by halothane anesthesia and halothane + phenylephrine, and stimulation by epinephrine infusion. RESULTS: Although the decreasis in left ventricular end diastolic volume was slightly less with LTV (16.5 +/- 1.7 ml, mean +/- SEM) than with IVCO (22.4 +/- 1.7 ml) (P < 0.0001) the PRSW-slopes showed a high degree of correlation (r=0.80, P < 0.0001). Although peak tracheal pressures increased significantly to 27.8 +/- 0.9 mmHg during LTV, esophageal pressures (used as an indicator of pericardial pressure) were unchanged. CONCLUSIONS: Positive pressure ventilation with LTV is similar to IVCO in creating transient changes in preload, necessary for assessment of left ventricular systolic function. This observation was valid also during drug-induced cardiac depression and stimulation. The preload recruitable stroke work used for this validation was shown to be a reliable and stable method.

Use of heparin-bonded circuits in cardiopulmonary bypass improves clinical outcome.

OBJECTIVE: The use of heparin-coated surfaces in cardiopulmonary bypass has been shown to decrease the inflammatory response imposed by the contact between blood and artificial surfaces. One would expect this reaction to improve clinical outcome. However, this has been difficult to verify. This investigation is based on an aggregation of two randomized studies from our institution and highlights possible effects of heparin coating on a number of clinically oriented parameters. DESIGN: Departmental analysis of patients subjected to coronary artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was employed using either the Carmeda or Duraflo heparin coatings compared with a control. The systemic heparin dose was reduced in the heparin-coated groups (ACT > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating related to clinical outcome were studied. RESULTS: The use of heparin-coated circuits reduced the mean length of stay in hospital from 7.8 +/- 2.5 to 7.3 +/- 1.8 days (p = 0.040) and postoperative ventilation time from 9.7 +/- 9.2 to 8.2 +/- 8.5 h (p = 0.018), blood loss 8 h post surgery from 676 +/- 385 to 540 +/- 245 ml (p = 0.001), individual perioperative change of haemoglobin loss (p = 0.001), leukocyte count (p = 0.000) and creatinine elevation (p = 0.000), proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% (p = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% (p = 0.006), postoperative deviations from the normal postoperative course 47.2 vs 36.7% (p = 0.035), neurological deviations 9.4 vs 3.9% (p = 0.021) and atrial fibrillation 26.4 vs 18.0% (p = 0.041). No effects were found with respect to perioperative platelet count, postoperative fever reaction and 5-year survival. CONCLUSION: Based on several indicators, the use of heparin coating in cardiopulmonary bypass is associated with improved clinical results.

Myocardial ischemia induces coronary t-PA release in the pig.

BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.

The cardiac effects of intracoronary angiotensin II infusion.

UNLABELLED: Angiotensin II (Ang II) is a potent vasoconstrictor, which recently has been shown to also have significant inotropic effects. Previous results regarding the mechanisms of the acute inotropic effects of Ang II are not conclusive. We designed this study to investigate the local cardiac effects of intracoronary Ang II infusion in doses not affecting systemic circulation. Ang II (2.5-40 microg/h) was infused in the left coronary artery of Yorkshire pigs (n = 9) reaching calculated intracoronary Ang II concentrations of 842 +/- 310, 3342 +/- 1238, and 12448 +/- 4393 pg/mL, respectively. Cardiac systolic and diastolic function was evaluated by analysis of the left ventricular pressure-volume relationship. Coronary flow was measured by using a coronary sinus catheter and the retrograde thermodilution technique. No significant changes were seen in the systolic and diastolic function variables of heart rate, end-systolic elastance, preload recruitable stroke work, the time constant for isovolumetric relaxation, or in coronary vascular resistance and flow. The positive inotropic and chronotropic effects of Ang II seen in previous studies seem thus to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs. IMPLICATIONS: The positive inotropic and chronotropic effects of angiotension II (Ang II) seen in previous studies seem to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs.

Acute effects of angiotensin II on myocardial performance.

BACKGROUND: Specific angiotensin II (Ang II) receptors exist in many organs including peripheral blood vessels, cardiac myocytes and the central nervous system. This suggests multiple sites of actions for Ang II throughout the cardiovascular system. Cardiac effects of Ang II are not completely understood, though its prominent vasoconstrictor actions are well described. This study was designed to assess left ventricular function during administration of Ang II using relatively load-independent methods in a whole-animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h(-1)) in anaesthetised instrumented pigs (n=10). Cardiac systolic and diastolic function were evaluated by analysis of the left ventricular pressure-volume relationship. RESULTS: Heart rate (HR), mean arterial pressure (MAP) and systemic vascular resistance (SVR) increased dose-dependently with Ang II, while cardiac output (CO) remained unchanged. Systolic function indices, end-systolic elastance (Ees) and preload recruitable stroke work (PRSW), demonstrated dose-dependent increases. The diastolic function parameter tau (tau) did not change with increasing Ang II dose. CONCLUSION: Ang II infusion caused increases in contractility indices in anaesthetised pigs in the doses used in this study. The mechanisms for these systolic function effects may be a direct myocardial effect or modulated through changes in autonomic nervous system activity.

Analysis of left ventricular systolic function during elevated external cardiac pressures: an examination of measured transmural left ventricular pressure during pressure-volume analysis.

BACKGROUND: Variations or disturbances in intrathoracic and extracardiac pressures (ECP) occur in critically ill and anaesthetised patients. There are uncertainties concerning the analysis of left ventricular pressure-volume relationship (LVPVR) and the calculation of systolic function parameters when conducted without reference to transmural left ventricular pressure (LVPtm) in the setting of elevated ECP. METHODS: In 7 anaesthetised adult pigs, we measured LVPVR using conductance volumetry and tip manometry along with measurement of pericardial and other intrathoracic pressures. Experimental pericardial infusion and pleural insufflation were performed. Transient controlled preload reductions were accomplished using balloon occlusion of the inferior vena cava. Preload recruitable stroke work (PRSW) was calculated using both intracavitary left ventricular pressure (LVPic) and LVPtm, and differences were tested for using a paired t-test. RESULTS: The pericardial and pleural interventions produced significant elevations in ECP. No difference in PRSW calculated using LVPic and LVPtm was detected. CONCLUSION: These results suggest that LVPtm need not be measured and included in LVPVR analysis of systolic function when there is significant external cardiac pressure. To be able to employ LVPVR analysis of systolic function without reference to LVPtm is important for simplified application in the clinical setting, particularly when elevated extracardiac pressures are suspected, or have been therapeutically induced, as with continuous positive pressure ventilation.

Heart-lung interactions during positive pressure ventilation: left ventricular pressure-volume momentary response to airway pressure elevation.

BACKGROUND: Left ventricular (LV) pressure and volume changes are known to occur in response to positive airway pressure (PAP). We aimed to further describe the immediate LV response to increased PAP as demonstrated in successive heart cycles with LV pressure and volume alterations. We postulated that these acute systematic LV events during institution of PAP can follow a distinct pattern that would allow calculation of parameters of systolic function, including end-systolic elastance (Ees) and preload recruitable stroke work (PRSW). We also aimed to examine the relationship of PAP-derived Ees and PRSW to the same parameters derived from vascular occlusion. METHODS: Eight anesthetized adult pigs were studied with invasive circulatory measurements including LV pressure and volume (conductance). The PAP intervention was an airway pressure plateau of 15 cm H2O for 6 s (APP). Venous occlusion was performed by transient balloon inflation in the inferior vena cava (IVCO). Ees and PRSW were derived for each APP and IVCO intervention. RESULTS: Central circulatory variables during APP and IVCO are reported. LV systolic function parameters could be derived from each of the heart-lung interactions during APP sequences. Ees and PRSW derived from APP showed a significant positive bias in relation to those derived from the IVCO sequence. CONCLUSIONS: We conclude that the heart-lung interactions during APP of the magnitude and duration shown here can allow derivation of Ees and PRSW. These parameters are not interchangeable with Ees and PRSW derived from IVCO.

Neurological and general outcome in low-risk coronary artery bypass patients using heparin coated circuits.

OBJECTIVE: The clinical significance of heparin coating in cardiopulmonary bypass has previously been investigated. However, few studies have addressed the possible influence on brain function and memory disturbances. METHODS: Three hundred low-risk patients exposed to coronary bypass surgery were randomised into three groups according to type of heparin coating: Carmeda Bioactive Surface, Baxter Duraflo II and a control group. Outcome was determined from a number of clinically oriented parameters, including a detailed registry of postoperative deviations from the normal postoperative course. Brain damage was assessed through S100 release and memory tests, including a questionnaire follow-up. RESULTS: Clinical outcome was similar for all groups. Blood loss (Duraflo only), transfusion requirements and postoperative creatinine elevation were reduced in the heparin-coated groups. A lower incidence of atrial fibrillation was noted in the Duraflo group. Heparin coating did not uniformly attenuate the release of S100 or the degree of memory impairment. CONCLUSIONS: Cardiopulmonary bypass (CPB) with heparin coating and a reduced dose of heparin seems to be safe. Clinical outcome and neurological injury seem not to be associated with type of heparin coating used for CPB. However, blood loss and transfusion requirements may be reduced.

Surgical stress induces acute coronary release of tissue-type plasminogen activator in the pig.

BACKGROUND: Tissue-type plasminogen activator (t-PA) is an endothelium derived key enzyme in the initiation of endogenous fibrinolysis. Acute regulated release of active t-PA occurs within minutes in response to threatening thrombotic vessel occlusion. The aim of this study was to investigate the impact of surgical stimulation on the kinetics of t-PA release in the coronary vascular bed in the pig. METHODS: In anaesthetised pigs (n=16), arterio-venous concentration gradients of t-PA, and plasma flows (retrograde thermodilution) were obtained across the coronary vascular bed before (control) and at 1, 3, 5 and 10 min after sternotomy. RESULTS: At control, no significant coronary net flux (release or uptake) of t-PA was observed, while sternotomy induced a rapid net release of total t-PA (132.6 ng x min(-1)), with an associated increase in active t-PA (93.6 ng x min(-1)). This response, evident already after 1 min, showed a peak at 5 min and returned towards baseline levels within 10 min. No concurrent alterations in aortic levels of active t-PA were found and haemodynamic variables were unaltered. CONCLUSION: The rapidly increasing and transient net coronary release of t-PA after sternotomy suggests that the endothelium actively promotes local endogenous fibrinolysis during surgery. Such events could reflect a dynamic responsiveness to protect the coronary circulation during stress.

Angiotensin II mesenteric and renal vasoregulation: dissimilar modulatory effects with nitroprusside.

BACKGROUND: The role of systemic arterial pressure for the vascular effects of angiotensin II (Ang II) and the interactions between Ang II and perfusion pressure-dependent local vascular control mechanisms are not well understood. This study addresses these aspects of exogenous Ang II in the mesenteric and renal regional circulations. METHODS: Ang II was infused in incremental doses (0-200 microg/h) in anesthetized instrumented pigs (n=10). Renal and portal blood flows were measured by perivascular ultrasound. In the second part of the study, sodium nitroprusside (SNP) was infused at doses titrated to keep mean arterial pressure constant, in spite of concurrent Ang II administration. RESULTS: Powerful dose-dependent vasoconstrictions by Ang II were found in renal and mesenteric vascular beds (at highest Ang II doses vascular resistances increased by 109% and 88% respectively). Ang II-induced vasoconstriction was fully inhibited in the mesenteric, but not in the renal circulation, during conditions of constant mean arterial pressures achieved by SNP infusion. CONCLUSIONS: Mesenteric, but not renal, vasoconstriction by Ang II was inhibited by pharmacological maintenance of perfusion pressure. This could reflect differences between these vascular beds as regards the importance of co-acting myogenic pressure-dependent vasoconstriction. Alternatively, as the drug chosen for pressure control, sodium nitroprusside, serves as a nitric oxide donor, the relative balance between nitric oxide-mediated vasodilation and Ang II-induced vasoconstriction could have regional differences.

Assessment of myocardium at risk in pigs with single photon emission computed tomography and computerized vectorcardiography during transient coronary occlusion.

Since myocardium at risk (MAR) is the major prognosticator of final infarct size and outcome in patients with acute myocardial infarction, it is highly desirable to estimate the size of the acutely ischemic myocardium, that is the MAR, in these patients. We assessed MAR size by Tc-99m-sestamibi-SPECT and computerized vectorcardiography using autoradiography as reference method. Transient myocardial ischemia was achieved in 12 pigs by coronary artery occlusion with PTCA catheters. During the procedure, computerized vectorcardiography was continuously recorded. After injection of Tc-99m-sestamibi and gadolinium-153-labelled microspheres, MAR size was estimated by SPECT and post-mortem autoradiography. Different cut-off levels (50-70%) were compared with respect to MAR-SPECT. Tc-99m-sestamibi-SPECT showed a good correlation with autoradiography (r = 0.94). Computerized vectorcardiography showed a good correlation with autoradiography as well as with Tc-99m-sestamibi-SPECT (STC-VM: r = 0.75 and 0.80, respectively, ST-VM: 0.75 and 0.87, respectively). It was found that 1) MAR assessed by Tc-99m-sestamibi-SPECT correlates closely with the autoradiographic reference; 2) a lower cut-off point of 60% of maximum uptake for MAR by Tc-99m-sestamibi-SPECT gives the closest correlation with the autoradiographic reference; and 3) ST-VM and STC-VM correlate well with MAR assessed by Tc-99m-sestamibi-SPECT and autoradiography.

Effects of desflurane on the pig intestinal circulation during hypotension.

BACKGROUND: The aim of the present study was to analyze the perfusion pressure dependency for the splanchnic vascular effects of desflurane (DES). METHODS: We measured portal blood flow (QPORT, perivascular ultrasound) and jejunal mucosal perfusion (JMP; laser Doppler) in pentobarbital-anesthetized pigs (n=10). Experimentally, decreases in mean arterial pressure (MAP) were produced by pericardial infusions of dextran. The protocol included sets of measurements at incremental doses of DES (1, 2, 4 and 6%) prior to and during pericardial infusions. RESULTS: Although QPORT and JMP decreased significantly during pericardial infusions, DES, irrespective of dose, did not reduce QPORT until MAP had decreased below 65-70 mm Hg. In higher MAP ranges, vasodilation in pre-portal tissues was powerful enough to maintain QPORT in spite of concurrent decreases in driving arterial pressure, as produced by either DES or pericardial infusion, or by a combination of both. We found no effects of DES on JMP even at very low MAP (about 40 mm Hg during pericardial infusion), indicating that the normal physiological response of the small intestine to redistribute blood flow from deeper to more superficial layers during hypotension was unimpaired by DES. CONCLUSIONS: Our data suggest a wide dose-tolerability of DES as regards the splanchnic circulation during hypotensive states.

Systemic levels and preportal organ release of tissue-type plasminogen activator are enhanced by PEEP in the pig.

BACKGROUND: Endothelium-derived tissue-type plasminogen activator, t-PA, is the key enzyme in the initiation of endogenous thrombolysis. Plasma levels of t-PA increase in response to sympatho-adrenergic activation. In the mesenteric vascular bed an increased norepinephrine spillover has been observed during positive end-expiratory pressure ventilation, PEEP. This experimental study examines the effects of PEEP-induced alterations on regional release rates and systemic levels of t-PA in vivo. METHODS: The protocol included measurements of arterio-venous concentration gradients of t-PA and the respective plasma flow across the pulmonary, coronary, hepatic and preportal vascular beds, in pigs, during zero-PEEP and at 2, 4 and 10 min after the application of a PEEP of 10 cm H2O. Both total plasma t-PA antigen (ELISA with a porcine t-PA standard) and active t-PA (spectrophotometric functional assay) were determined. RESULTS: During zero-PEEP, a high preportal basal net release and hepatic net uptake of total t-PA was observed. With PEEP, the magnitude of the preportal net release of t-PA was markedly enhanced (+24+/-5%), as was hepatic net uptake (+21+/-8%), simultaneously to a significant decrease in liver plasma flow (-30+/-2%). PEEP-induced alterations in active t-PA mirrored those observed in total t-PA. No significant net fluxes of total or active t-PA were observed across the coronary or the pulmonary vascular beds. CONCLUSIONS: Clinically used levels of PEEP induce increases in net release of endothelially derived t-PA within preportal organs. The application of PEEP is associated with increased systemic levels of total and active t-PA, in spite of a simultaneous increase in hepatic net uptake, indicating that the preportal vascular bed can not account for the systemic t-PA response.

Quality assurance in clinical perfusion.

OBJECTIVE: To investigate the properties and usefulness of prospective routine registration of incidents related to cardiopulmonary bypass and its clinical significance as a quality assurance instrument. METHODS: Incidents or deviations from the normal course observed during cardiopulmonary bypass procedures were registered in a computer database. Each incident was classified according to 14 pre-defined categories. The cause of each incident was evaluated, as well as patient outcome. Incidents leading to permanent or temporary injury were denoted accidents. The general- and category-related incidence rate was calculated for the observation period 1989-1997 encompassing 6918 cardiopulmonary bypass procedures. RESULTS: The general incidence rate varied between 4.5-7.6% per year during the registration period. Most incidents (57%) occurred during established, or start of, cardiopulmonary bypass, whereas the remaining proportion of incidents were detected either before (27%) or when terminating (16%). The most common category of incidents was oxygenator failure (1.6%), followed by mechanical (1.4%) and surgical (1.2%) incidents. Accidents and fatal outcomes occurred in 0.03% of the cases. CONCLUSIONS: Routine registration of incidents yields a clinically attractive instrument of controlling safety aspects and quality measures in cardiopulmonary bypass. The observed incidence rates are somewhat higher than previously reported, probably primarily related to the methodology implemented in this study.

The effects of desflurane on cardiac function as measured by conductance volumetry in swine.

UNLABELLED: The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. IMPLICATIONS: Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.