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The crucial point in the pathogenesis of isoproterenol-induced myocardial necrotization is an abundant intracellular Ca accumulation leading to high energy phosphate exhaustion. Accordingly, in the early stage of the isoproterenol-induced necrotization process, the onset of ATP and creatine phosphate breakdown strictly parallels the acute Ca gain. In this type of necrosis, the Mg losses from the myocardium appear as a concomitant phenomenon. The hearts can be protected against the deleterious Ca overload and necrotization by increasing the plasma concentration of Mg, K, or H ions in order to counterbalance Ca according to the ration (see article). On the other hand, if Mg, K, or H ion concentrations are too low, isoproterenol-induced Ca uptake and myocardial lesions are potentiated.

The self-association of nucleosides decreases within the series adenosine greater than guanosine greater than inosine greater than cytidine approximately uridine. The same trend is observed for the corresponding nucleotides, though less pronounced, as the charge effect governs series like adenosine much greater than AMP2- greater than ADP3- approximately greater than ATP4-. Protonation of adenosine considerably reduces its self-stacking tendency: this is different with ATP4-, where a maximum is reached for H2(ATP)2- caused by additional ionic interactions in the [H2(ATP)]2(4-) dimer. Metal ion coordination may promote self-association, e.g., of ATP4- via (mainly) charge neutralization (Mg2+) and the formation of intermolecular bridges in dimeric stacks (Zn2+, Cd2+). These results allow definition of conditions with negligible self-association and thus the determination of the stability and structure of monomeric nucleotide complexes in aqueous solution, e.g., quantification of macrochelate formation in M(ATP)2- complexes. Some biological implications of the results are indicated.

Using local time activity curves parameters are calculated which depend on the local wall motion of the heart cavities. These functional parameters allow the determination of the contours of the heart cavities and the assessment of segmental wall motion disorders. The left ventricular ejection fraction has been calculated by enddiastolic and endsystolic counts using a method which takes into account background inhomogeneity.

Ejection fraction and end-diastolic volume (EDV) are valuable parameters of left ventricular function. They can be measured by radionuclide ventriculography. This study examines EDV in comparison to two other methods. A comparison was made between EDV derived from radionuclide ventriculography (RNV), standard contrast ventriculography and a 'hybrid' method, which calculates EDV from ejection fraction, heart rate and thermodilution cardiac output. Two groups of patients were examined: 54 patients with various cardiac diseases by contrast and radionuclide ventriculography (RNV); and 18 patients with typical angina were examined by RNV at rest and during exercise three times: Control without medication, 20 minutes after 10 mg metoprolol i.v. and again 10 minutes after the second exercise and 10 mg isosorbide dinitrate sublingually. In comparison to contrast ventriculography RNV overestimated EDV by 27%, and in comparison to the hybrid method by 11% with satisfactory linearity. The extent of error increases with decrease of ventricular volume. The assumption that the two short axes of the left ventricle are equally long causes one quarter of total error. Errors caused by the algorithm delineating the borders of the left ventricle cannot be measured. For clinical purposes radionuclide ventricular EDV seems to yield satisfactory results.

The concentration dependence of the chemical shifts of the protons H-2, H-8 and H-1' of ATP4- and of Mg(ATP)2- , of all non-labile protons of adenosine, of H-5, H-6 and H-1' of TUP, and of H-5, H-6, H-1', and H-2' of uridine have been measured. The results for the purine derivatives are consistent with the isodesmic model of indefinite non-cooperative stacking; for adenosine K = 15 +/- 2M-1, for ATP K = 1.3 +/- 0.2 M-1 and for Mg(ATP)2-K = 3.6 +/- 0.3 M-1. For the pyrimidines, uridine and TUP, stacking is much weaker and the stability constant could only be estimated; for uridine k is less than or equal to 0.5 M-1, and for UTP K approximately 0.3 M-1.

The clinical diagnosis of mitral-valve prolapse was made in ten patients on the basis of a late systolic murmur with or without a click. In each case the echocardiogram confirmed the diagnosis. In five it was further confirmed by angiocardiography. The late systolic murmur, with or without click, accentuated after nitroglycerin, is characteristic for mitral-valve prolapse.

Fifteen consecutive patients (mean age 54 years) with proven coronary heart disease were studied with radionuclide ventriculography. After resting and exercise control studies, repeat studies were performed after administration of 4 mg of molsidomine sublingually and again after administration of 10 mg of metoprolol intravenously. Rest to exercise ejection fraction (EF) decreased significantly. This was significantly attenuated by molsidomine and by metoprolol. In a subset of nine patients with exercise ischemia, EF showed significant (p less than 0.05) improvement after molsidomine administration (46.7 +/- 13.7% to 57.1 +/- 16.7%), which was diminished to 54.4 +/- 10.5% after metoprolol administration. In the subgroup without exercise ischemia, molsidomine increased the EF to a lesser extent (47.3 +/- 12.7% to 52.6 +/- 13.4%, p less than 0.05). After administration of metoprolol the EF decreased below the control level (44.4 +/- 10.6%). Regional Fourier amplitudes accentuated the differences between the two groups. We conclude that molsidomine and metoprolol improve left ventricular function in patients with coronary heart disease and ischemia during exercise. In patients with reduced left ventricular function without signs of ischemia, molsidomine improves function as well and should be used additionally, if beta blockers are indicated for other reasons.