Intercellular adhesion molecule-5 induces dendritic outgrowth by homophilic adhesion.

Intercellular adhesion molecule-5 (ICAM-5) is a dendritically polarized membrane glycoprotein in telencephalic neurons, which shows heterophilic binding to leukocyte beta(2)-integrins. Here, we show that the human ICAM-5 protein interacts in a homophilic manner through the binding of the immunoglobulin domain 1 to domains 4-5. Surface coated ICAM-5-Fc promoted dendritic outgrowth and arborization of ICAM- 5-expressing hippocampal neurons. During dendritogenesis in developing rat brain, ICAM-5 was in monomer form, whereas in mature neurons it migrated as a high molecular weight complex. The findings indicate that its homophilic binding activity was regulated by nonmonomer/monomer transition. Thus, ICAM-5 displays two types of adhesion activity, homophilic binding between neurons and heterophilic binding between neurons and leukocytes.

Hormonal stress response and hemodynamic stability in patients undergoing endovascular vs. conventional abdominal aortic aneurysm repair.

BACKGROUND AND AIMS: To investigate the effect of two different surgical techniques with different anesthetic modes on intraoperative and postoperative hormonal stress response, hemodynamic stability, fluid loading and renal function in patients scheduled for elective infrarenal abdominal aortic aneurysm (AAA) repair. MATERIALS AND METHODS: Forty consecutive patients scheduled for elective infrarenal AAA repair were allocated without randomizing into two groups: an endovascular (EVAR, n = 20) and a conventional (CAR, n = 20) aneurysm repair group according to aneurysm morphology as determined by preoperative computed tomography and angiography. The EVAR group were operated under spinal anesthesia and the CAR group using general anesthesia with epidural blockade. RESULTS: Patients undergoing CAR showed lower intraoperative mean arterial pressure and significantly higher plasma norepinephrine before aortic cross-clamping and significantly higher lactate after aortic declamping and postoperatively than patients in the EVAR group. Postoperatively, vasopressin and serum cortisol were also significantly higher in the CAR group. Fluid loading and estimated blood loss were more excessive in the CAR group. CONCLUSIONS: Stress response was lower and hemodynamic stability and lower body perfusion superior and renal function also better maintained in patients undergoing EVAR under spinal anesthesia as compared to those undergoing CAR using general anesthesia with epidural blockade.

Distinct expression of type XIII collagen in neuronal structures and other tissues during mouse development.

Type XIII collagen is a type II transmembrane protein found in adhesive structures of mature tissues. We describe here its expression and spatio-temporal localization during mouse fetal development. Type XIII collagen mRNAs were expressed at a constant rate during development, with an increase of expression towards birth. Strong type XIII collagen expression was detected in the central and peripheral nervous systems of the developing mouse fetus in mid-gestation. Cultured primary neurons also expressed this collagen, and it was found to enhance neurite outgrowth. The results suggest that type XIII collagen is a new member among the proteins involved in nervous system development. Strong expression during early development was also detected in the heart, with localization to cell-cell contacts and accentuation in the intercalated discs perinatally. During late fetal development, type XIII collagen was observed in many tissues, including cartilage, bone, skeletal muscle, lung, intestine and skin. Clear developmental shifts in expression suggest a role in endochondral ossification of bone and the branching morphogenesis in the lung. Notable structures lacking type XIII collagen were the endothelia of most blood vessels and the endocardium. Its initially unique staining pattern began to concentrate in the same adhesive structures where it exists in adult tissues, and started to resemble that of the beta1 integrin subunit and vinculin during late intrauterine development and in the perinatal period.

Hemodynamic effects of iloprost, a prostacyclin analog.

Iloprost is a chemically stable derivative of carbaprostacyclin. We studied its hemodynamic effects in 10 patients in an intensive care unit. Iloprost was infused intravenously for 3 days for the treatment of advanced obliterative arterial disease of the lower extremities. Clinically significant hemodynamic responses were obtained with an infusion rate of 0.5 ng/kg/min. All subjects tolerated the dose of 4 ng/kg/min, which increased heart rate an average of 11% and cardiac index an average of 26%. This infusion rate decreased mean arterial pressure by 15%, total peripheral resistance by 31%, and pulmonary vascular resistance by 34%. Mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left and right ventricular stroke work indices, and rate pressure product did not change. At higher doses of up to 8 ng/kg/min, responses were augmented only slightly, but side effects such as headache, nausea, and abdominal colics became more prominent. The data show iloprost to be a potent vasodilator that reduces both pre- and afterload and presumably induces a compensatory increase in cardiac output and heart rate, but does not increase the work load or oxygen demand of the heart.

Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting.

OBJECTIVE: There are several reports of the use of adenosine as a cardioprotective agent during cardiac surgery. Adenosine treatment might affect neutrophils and inflammatory mediators. The present prospective randomized study was designed to investigate the effect of adenosine pretreatment on myocardial recovery and inflammatory response in patients undergoing elective coronary artery bypass surgery. DESIGN: A prospective, randomized, controlled study. SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS: Thirty male patients undergoing primary, elective coronary revascularization. INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and hemodynamics were recorded. Perioperative leukocyte and cytokine release were measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an improved postbypass cardiac index. Similar leukocyte counts and cytokine responses were seen in both groups perioperatively. Neutrophil counts were similar between the groups before and after myocardial ischemia when measured simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present results support the hypothesis that adenosine pretreatment is cardioprotective in humans, but the present dose failed to regulate the inflammatory responses after coronary artery bypass grafting.

The protective effects of preconditioning decline in aged patients undergoing coronary artery bypass grafting.

OBJECTIVE: We sought to investigate the effects of myocardial ischemic preconditioning in adult and aged patients undergoing coronary artery bypass grafting. METHODS: Eighty patients with 3-vessel disease undergoing coronary artery bypass grafting were randomized into one of the following groups: adult ischemic preconditioning, adult control, aged ischemic preconditioning, and aged control. Hemodynamic data and cardiac troponin I values were compared between the groups. The ischemic preconditioning groups received 2 periods of 2 minutes of ischemia, followed by 3 minutes of reperfusion. The Student t test, chi(2) test, and analysis of variance for repeated measures were used for the statistical analysis. RESULTS: The baseline for right ventricular ejection fraction and cardiac index was similar. Right ventricular ejection fraction was depressed after the operation in all groups. Ischemic preconditioning significantly improved the recovery of right ventricular ejection fraction and cardiac index after the operation in adult patients (P =.013 and.001, respectively), but in the aged group there was no difference in the changes of ejection fraction and cardiac index (P =.232 and.889, respectively). The cardiac troponin I value in the adult patients subjected to ischemic preconditioning was lower than that in the adult control subjects (P =.046), but in aged patients undergoing ischemic preconditioning, the value was similar to that in aged control subjects (P =.897). Ischemic preconditioning also resulted in a shorter postoperative mechanical ventilation time and in less inotropic use in the adult group. CONCLUSION: Ischemic preconditioning protects the heart from ischemic reperfusion injury in adult patients undergoing coronary artery bypass grafting. The beneficial effects of ischemic preconditioning are manifested as a better recovery of right ventricular and global hemodynamic function, cellular viability, and surgical outcome. The protective effect of ischemic preconditioning is diminished in aged patients undergoing coronary bypass.

Effect of ischemic preconditioning on myocardial protection in coronary artery bypass graft patients : can the free radicals act as a trigger for ischemic preconditioning?

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

Non-invasive measurement of cardiac output: whole-body impedance cardiography in simultaneous comparison with thermodilution and direct oxygen Fick methods.

OBJECTIVE: To determine the reliability of whole-body impedance cardiography (ICGWB), with electrodes attached to wrists and ankles, in the measurement of cardiac output (CO) on the basis of simultaneous comparison with thermodilution (TD) and direct oxygen Fick (Fick) methods. DESIGN: Prospective clinical study. SETTING: A surgical intensive care unit at a university hospital. PATIENTS: Thirty consecutive subjects undergoing a coronary artery bypass surgery were investigated preoperatively. MEASUREMENTS: ICGWB derived CO was measured simultaneously with the TD and Fick methods to establish the biases and limits of agreement (LA) between the methods. RESULTS: The results obtained by ICGWB and the invasive methods showed good agreement. The bias and LA between COTD and COICG were 0.00 l/min: 1.37 and 1.37 l/min, respectively, and were close to those obtained between COTD and COFICK, 0.32 l/min; 1.74 and -1.10 l/min. The bias and LA between the COFICK and COICG were -0.32 l/min; -2.24 and 1.60 l/min respectively. The repeatability value of consecutive single measurements for ICGWB (RVICG = 0.57 l/min) was much better than for the TD method (RVTD = 1.10 l/min). CONCLUSION: There was close agreement between the results of the three methods in the measurement of CO. In sedated preoperative patients the accuracy of ICGWB is within clinically acceptable limits and its repeatability is excellent. ICGWB provides a useful alternative to the TD and Fick methods in cases where the pressures supplied by the pulmonary artery catheter are not essential.

Significance of electrical brain activity in brain-stem death.

A 46-year-old man was diagnosed clinically brain dead after sustaining head trauma. The patient was in deep coma, brain nerves were unresponsive and spontaneous breathing was absent. However, EEG showed well preserved activity, but no reactivity to external stimuli. EEG activity disappeared within 40 h. BAEP were highly abnormal, flash-VEP as recorded 3 h after the diagnosis of brain stem death was of high amplitude but of simplified form. The neurophysiological findings revealed that the main reason for deep coma was brain stem damage while cortical activity was still present. This condition raises ethical questions when brain death is diagnosed clinically prior to removal of organs for transplantation.

Plasma thromboxane B2 levels and thromboxane B2 production by platelets are increased in patients during spinal and epidural anesthesia.

Concentrations of thromboxane (Tx) B2 in plasma and its production by platelets were measured in 20 spinal and 10 epidural anesthesia patients scheduled for small operations in the lower extremities. The main metabolite of prostacyclin, 6-keto-PGF1 alpha and prostaglandin (PG) E2 in plasma were also determined. Plasma TxB2 and TxB2 production by platelets increased during both spinal and epidural anesthesia. Plasma TxB2 levels also remained elevated 1 h after anesthesia. The plasma concentrations of 6-keto-PGF1 alpha and PGE2 did not change during spinal or epidural anesthesia. In in vitro studies, only low concentrations of lidocaine (0.5-1.0 micrograms/ml) and bupivacaine (0.5-3.0 micrograms/ml) increased platelet TxB2 production. In platelet rich plasma, neither lidocaine nor bupivacaine in concentrations of 0.5-3.0 micrograms/ml caused constant changes in ADP-induced platelet aggregation, but they inhibited it in toxic concentrations (12 micrograms/ml). The results suggest that the increased TxB2 plasma levels and platelet TxB2 production during regional anesthesia are not caused by local anesthetics itself but by other factors, e.g. tissue trauma. In clinically found concentrations, local anesthetics do not cause any constant changes in platelet aggregation.

Theophylline infusion modulates prostaglandin and leukotriene production in man.

Although theophylline has been used in the treatment of asthma for decades, it is not a first line choice any more. It is a well-known bronchodilator, but was recently discovered also to be an anti-inflammatory, immunomodulatory and bronchoprotective agent. Therefore we wanted to establish the role of theophylline on prostaglandin and leukotriene production, which plays a part in the pathogenesis of asthma. Theophylline was infused (bolus 5 mg/kg in 15 min and infusion 0.4 mg/kg/h for 1 h 45 min) into healthy volunteers. Thromboxane B2, prostaglandin E2 and leukotriene E4 were measured from the A23187-stimulated whole blood samples and stable metabolites of thromboxane A2; prostacyclin and leukotriene E4 were measured from urine. Theophylline increased prostaglandin E2 production and decreased leukotriene E4 production ex vivo in whole blood, thus increasing the prostanoid/leukotriene ratio. It did not change thromboxane B2 production stimulated by either spontaneous clotting or A23187 in the whole blood. Theophylline had hardly any effect on in vivo thromboxane, prostacyclin and leukotriene E4 production measured as urinary metabolites, 11-dehydro-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1alpha and leukotriene E4, respectively. Serum theophylline concentrations were at the lower level of normal therapeutic range during the infusion. The increase in PGE2 and the decrease in LTE4 synthesis ex vivo may offer a new explanation for the mode of antiasthmatic action of theophylline. It is notable that this phenomenon occurs at low serum theophylline concentrations. These results confirm the idea that theophylline has an anti-inflammatory and bronchoprotective action and support the use of theophylline as a therapeutic agent in asthmatic patients.

Noradrenaline and dopamine infusions modulate arachidonic acid cyclooxygenase and 5-lipoxygenase pathways ex vivo in man.

We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (TX/LT) ratio in whole blood in healthy volunteers. The aim of the present study was to see whether other catecholamines--noradrenaline and dopamine--are also capable of modulating arachidonic acid (AA) metabolism in man. Low doses of noradrenaline (0.025 microgram/kg/min) and dopamine (3.0 micrograms/kg/min), which did not change hemodynamics, were infused for 60 min into healthy male volunteers. Both dopamine and noradrenaline decreased TX synthesis stimulated by spontaneous clotting, but no remarkable effect was seen when calcium ionophore A23187 was used as a stimulus. Dopamine but not noradrenaline increased prostaglandin E2 (PGE2) synthesis in A23187-stimulated whole blood. They both marginally decreased LTB4 formation in A23187-stimulated whole blood. The findings indicate that not only adrenaline but also noradrenaline and dopamine modulate AA metabolism in man.

Beneficial effects of ischemic preconditioning on right ventricular function after coronary artery bypass grafting.

BACKGROUND: Preservation of right ventricular myocardium is unsatisfactory in patients with critical stenosis or occlusion of the right coronary artery. The aim of this study was to investigate whether ischemic preconditioning (IP) improved the recovery of right ventricular function after coronary artery bypass grafting. METHODS: Forty patients with three-vessel disease who had coronary artery bypass grafting were randomly assigned to the IP group (n = 20) or control group (n = 20). In the IP group, two cycles of two minutes of ischemia after three minutes of reperfusion were given before cross-clamping. Hemodynamic data were collected. Right ventricular ejection fraction was measured by thermodilution. RESULTS: Right ventricular ejection fraction and right ventricular systolic volume index were decreased post-operatively (lowest value at 6 hours postoperatively). The changes in right ventricular ejection fraction were significantly milder in the IP group postoperatively (p = 0.012). The decrease in right ventricular systolic volume index postoperatively was also less in IP patients (p = 0.002). Fewer inotropic drugs were used in the IP group compared with controls. CONCLUSIONS: Ischemic preconditioning had a myocardial protective effect on recovery of right ventricular contractility in patients who had coronary artery bypass grafting.

Effects of noradrenaline and dopamine infusions on arachidonic acid metabolism in man.

We infused noradrenaline (0.025 micrograms/kg/min for 60 min, n=7) and dopamine (3.0 micrograms/kg/min for 60 min, n=6) into healthy male volunteers to study the effects of these catecholamines on in vivo thromboxane A2, prostacyclin and leukotriene E4 production measured as urinary excretions of 11-dehydro-thromboxane (TX) B2, 2,3-dinor-6-keto-prostaglandin (PG) F1alpha and leukotriene (LT) E4, respectively. Plasma noradrenaline and dopamine concentrations were 2.9+/-0.3 and 233+/-17 nmol/l at the endo fo the noradrenaline and dopamine infusions, respectively. Noradrenaline decreased thromboxane production and increased leukotriene production almost two fold. It had hardly any effect on prostacyclin production. Dopamine had no significant effects on any of the variables, however, it had a tendency to increase prostacyclin and leukotriene production. The results indicate that noradrenaline is a more important modulator of arachidonic acid metabolism than dopamine in vivo.

CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man.

Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.

Effect of surgical stress on the erythrocyte insulin receptor.

The aim of this study was to investigate whether surgical trauma causes changes in insulin receptors which may have significance on the causation of post-traumatic insulin resistance. Twenty-four patients scheduled for lumbar intervertebral disc operations or thoracotomy were investigated. In patients who did not receive glucose during operation blood glucose and plasma insulin concentrations did not change but lipolysis was induced as indicated by the increase of serum free fatty acids concentration. Glucose infusion (5% w/v) caused a hyperglycaemic and hyperinsulaenemic response without lipolysis. In patients not receiving a glucose load the number of insulin receptors on erythrocyte measured 4 h postoperatively increased from the preoperative values and the affinity of the receptors to insulin in physiological concentration range increased. In patients with glucose load the number of receptors decreased and receptor affinity to insulin at physiological concentration decreased. The results suggest that in patients receiving a glucose load the receptor changes indicate the perioperative development of insulin resistance at receptor level.

Amino acids and glucose in human cerebrospinal fluid after acute ischaemic brain damage.

In the search for potential biochemical markers of value for prognosis after acute hypoxic brain damage, amino acids and glucose were assessed in the cerebrospinal fluid (CSF) and glucose in blood. Samples were taken by lumbar puncture 4, 28, 76 and 172 h after resuscitation from 20 patients and once from 10 control patients. Eight of the resuscitated patients recovered neurologically but 12 remained comatose. The concentrations of alanine (P less than 0.001) and phenylalanine (P less than 0.035) differed most in 4-h samples between the groups. The concentration of alanine was higher in all patient groups with hypoxic brain damage as compared to the controls, the concentrations in patients dying within 76 h (disabled-s group) being higher than in the recovered patients. Phenylalanine in the disabled-s group was significantly higher than the control value. Furthermore, there were significant differences between various patient groups in the concentrations of glutamine, isoleucine, leucine, lysine, serine, tyrosine and valine. When taking into account the permeability of the BBB to these amino acids, alanine, valine and isoleucine most clearly represent brain amino acid metabolism. CSF glucose in the control group and in the recovered patients was lower than in patients dying within 76 h.

Fluid resuscitation of hypotensive emergency patients with and without an algorithm.

Seventy-seven consecutive hypotensive (mean arterial pressure (MAP) less than 80 mmHg) surgical emergency patients were resuscitated according to either physicians' individual orders (38 patients) or an algorithm (39 patients). The shock was mainly caused by accidental injuries or acute gastrointestinal bleeding. The patients of the algorithm group were given more plasma expanders than the patients of the control group, while the total amount of fluids administered was similar in both groups. The primary goal of the resuscitation (MAP greater than 80 mmHg) was reached within 30 min in three cases in the control group and in seven cases in the algorithm group. The treatment times at the emergency department and the intensive care unit were similar for the groups. The number of severe and moderate pulmonary disturbances was the same, but mild disturbances were significantly more common in the control group. Renal failure was somewhat more common in the control group and the renal function disturbances were significantly more severe among the control patients. The results suggest that the physicians in some extent altered their practices in fluid resuscitation when the algorithm was put to use, and that this change, perhaps, produced the somewhat better outcome of the patients. The authors recommend the algorithm to be used as a basis of shock treatment and particularly in those emergency departments where the resuscitation of hypotensive patients is performed by junior or inexperienced physicians.

Ischemic preconditioning protects right ventricular function in coronary artery bypass grafting patients experiencing angina within 48-72 hours.

BACKGROUND: To test whether ischemic preconditioning (IP) is able to protect the myocardium in recently unstable CABG patients. EXPERIMENTAL DESIGN: prospective, randomised, controlled clinical study. SETTING: University Hospital. PATIENTS: Forty CABG patients with recent unstable angina were randomised into an IP group (n=20) and a control group (n=20). Subgroup was divided based on the time of the most recent ischemia onset before the operation. INTERVENTION: The IP group was preconditioned with 2 cycles of 2-min ischemia followed by 3-min reperfusion before cross clamping. MEASURES: Hemodynamic data were monitored till the 1st POD. Biochemical markers were measured till the 2nd POD. RESULTS: There were no differences in cardiac index (Cl) and right ventricular ejection fraction (RVEF) in patients experiencing angina within 48 hours prior to operation. The percentage changes in CI and RVEF at 1 hour after declamping were significantly better in the IP group in patients experienced angina within 48-72 hours (106% vs 88% of baseline, p=0.027 and 103% vs 81% of baseline, p=0.023). No difference in postoperative cardiac troponin I (CTnI) and CK-MB was found between the IP and controls in either subgroup. CONCLUSIONS: IP has a beneficial effect on global and right ventricular hemodynamic functional recovery in unstable CABG patients experiencing angina within 48-72 hours prior to the operation. However, IP has no additional protective effects in unstable CABG patients who experience angina within 48 hours.

Application of computer modelling and lead field theory in developing multiple aimed impedance cardiography measurements.

Conventional impedance cardiography (ICG) methods estimate parameters related to the function of the heart from a single waveform that reflects an integrated combination of complex sources. We have previously developed methods and tools for calculating measurement sensitivity distributions of ICG electrode configurations. In this study, the methods were applied to investigate the prospects of recording multiple aimed ICG waveforms utilizing the 12-lead electrocardiography (ECG) electrode locations. Three anatomically realistic volume conductor models were used: one based on Visible Human Man cryosection data and two on magnetic resonance (MR) images representing end diastolic and end systolic phases of the cardiac cycle. Based on the sensitivity distributions obtained, 236 electrode configurations were selected for preliminary clinical examination on 12 healthy volunteers and 9 valvular patients. The model study suggested that a variety of configurations had clearly enhanced sensitivity to the cardiovascular structures as compared to conventional ICGs. Simulation data and clinical experiments showed logical correspondence supporting the theoretically predicted differences between the configurations. Recorded 12-lead ICG signals had characteristic waveforms and landmarks not coinciding with those of conventional ICG. Furthermore, configurations showing resemblance to invasive data and morphological variations in disease are of interest. The results indicate the applicability of the modelling approach in developing ICG measurement configurations. However, the level of clinical relevance and potential of the 12-lead method remains to be explored in studies employing dynamic modelling and acquisition of invasive reference data.