The SOFA, TMS, and deltaSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay.

1,1'-Diethyl-2,2'-cyanine (decynium22) and 1,1'-diisopropyl-2,4'-cyanine (disprocynium24) are highly potent inhibitors of the extraneuronal monamine transporter. When given as i.v. bolus injections (4 mumol kg-1) to anaesthetized rabbits, both drugs elicited a transient fall in blood pressure without altering heart rate. The observed maximum fall in diastolic blood pressure was 59% after decynium22 and 43% after disprocynium24 administration. The pharmacokinetics of decynium22 and disprocynium24 were similar; they were characterized by short half-lives for elimination (8.2 and 4.5 min, respectively) and very high plasma clearances (173 and 180 ml kg-1 min-1, respectively). The mechanism underlying the blood pressure-lowering effect of decynium22 was explored in the isolated incubated rabbit aorta. Decynium22 antagonized the noradrenaline-induced contraction; the pA2 for this interaction was 7.6, and the slope of the corresponding Schild plot was unity. In a membrane preparation from rat myocardium, decynium22 as well as disprocynium24 inhibited the specific binding of [125I]-2-[beta-(4-hydroxy-3-iodophenyl)-ethylaminomethyl]- tetralone (125I-HEAT), a selective ligand to alpha 1-adrenoceptors. The Ki's were 5.3 and 240 mumol l-1 for decynium22 and disprocynium24, respectively. The type of binding inhibition by decynium22 was competitive. It is concluded that the two inhibitors of extraneuronal monoamine transport decynium22 and disprocynium24 lower blood pressure by blocking alpha 1-adrenoceptors. A comparison of their potencies in blocking extraneuronal monoamine transport and alpha 1-adrenoceptors clearly indicates that disprocynium24 is more suitable for studies designed to determine the role of extraneuronal monoamine transport in vivo. Considering its very fast elimination kinetics, disprocynium24 must be administered by constant rate-infusions in order to avoid large fluctuations of plasma levels.

Monitoring splanchnic perfusion by means of gastric intramucosal tonometry is carried out using saline, or more recently, air tonometry using the Tonocap. The objective of this study was the validation of the Tonocap in saline and perfluorocarbon FC 43. The two methods underestimated the predefined PCO2 value by an average of 10%, with clinically acceptable precision. Accuracy of the Tonocap improved at high PCO2 values (9.33 and 9.94 kPa), whereas saline tonometry was superior at low PCO2 values (3.99 and 3.75 kPa). The Tonocap provides a fast and reliable estimation of the PCO2, and with the revised software requiring only 10 min of equilibration, will increase the comparability of future studies.

The ryanodine-sensitive Ca2+ release channel (RyaCRC) of the sarcoplasmic reticulum plays a key role in the intracellular Ca2+ handling in cardiomyocytes. Altered expression of the RyaCRC has been supposed to contribute to abnormal cellular Ca2+ handling and to myocardial dysfunction in dilated and ischemic cardiomyopathy. In the present study the 3H-ryanodine binding site in human myocardial homogenates was characterized and the density of the RyaCRC (which corresponds to the cardiac ryanodine receptor) was determined in nonfailing and in failing human myocardium. Homogenates were prepared from nonfailing left ventricular myocardium from the hearts of 5 organ donors (NF) and from failing myocardium from 14 explanted hearts of transplant recipients with end-stage heart failure resulting from dilated (DCM, n = 5) or ischemic (ICM, n = 9) cardiomyopathy. Radioligand saturation binding experiments revealed a specific, high-affinity 3H-ryanodine binding site (Kd-values: NF: 0.65 +/- 0.11 nmol/l, DCM: 0.66 +/- 0.09 nmol/l, ICM: 0.88 +/- 0.18 nmol/l; n.s.) in all preparations. Specific 3H-ryanodine binding depended on the free Ca2+ concentration in the assay. It was maximal at 3-100 micro mol/l Ca2+. The binding was inhibited by the RyaCRC antagonists ruthenium red (Ki-value: 0.32 [0.18-0.56] micromol/l, n = 5) and Mg2+ (Ki-value: 2.95 [1.23-7.11] mmol/l, n = 5). The RyaCRC density was 103.5 +/- 11.9 fmol/mg protein in nonfailing myocardium. There was no significant change in the RyaCRC density in dilated or ischemic cardiomyopathy (112.4 +/- 17.1 and 122.7 +/- 13.9 fmol/mg protein) compared to nonfailing control myocardium. In summary, 3H-ryanodine binds specifically and with high-affinity to the RyaCRC in human myocardium. There is no change in the RyaCRC density in failing myocardium of patients with DCM or ICM in comparison to non-failing controls.

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