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Three cases are presented showing retrograde alternate Wenckebach periods. Retrograde alternate Wenckebach periods were defined as 2:1 ventriculoatrial (VA) block in which the conducted beats showed progressive prolongation of conduction (VA) time. The sequence terminates with two or three successively blocked ventricular beats. In one of the three cases the level of block was identified as being in the atrioventricular (AV) node. In the other two the level of block could not be clearly identified. This report provides further evidence for the concept of multilevel block within the AV node. Retrograde alternate Wenckebach periods may explain some instances of variation of atrial depolarization intervals during episodes of ventricular tachycardia and may be clinically significant.

Left ventricular performance was evaluated in 133 patients with myocardial disease: 49 with hypertrophic obstructive, 30 with hypertrophic nonobstructive, and 54 with hypokinetic cardiomyopathies. Left ventricular volumes were evaluated by single plane cineangiography and left ventricular pressures by a Miller tip manometer catheter. Compliance was measured by the coefficient K of diastolic pressure volume curve p = b • eK • V, DV/DP, and DV/DP • V according to Gaasch et al. Left ventricular performance was evaluated by mean rate of circumferential fiber shortening (VCF c/s) and by Vmax (using instantaneous pressure and k = 28), or VPm, using an on-line computer. The results were correlated with clinical parameters, and prognosis according to the N.Y.H.A. During isometric exercise, contractility reserve was measured, taking into account changes of left ventricular end-diastolic pressure (LVEDP) and VPm.

In contrast to thymine and 5-fluorouracil (FUra) which were cleared from the bloodstream within 2-4 h after their i.p. administration (200 mumol/kg) to rat, (E)-5-(2-bromovinyl)uracil (BVUra) maintained a concentration of 50-70 microM for at least 6 h and was still present in the plasma 24 h after its administration. In vitro experiments with rat liver extracts indicated that BVUra was not a substrate but an inhibitor for the reductive step in pyrimidine degradation catalyzed by dihydrothymine dehydrogenase. Kinetic and dialysis experiments suggested that BVUra was an irreversible inhibitor of this enzyme. The binding of BVUra to the enzyme depended on the presence of reduced nicotinamide adenine dinucleotide phosphate in the reaction mixture. Dihydrothymine dehydrogenase activity was also inhibited in the dialysed 105,000 X g supernatant fraction of livers from rats that had previously been treated with BVUra. Such inhibitory effects also occurred in vivo; previous administration of BVUra increased the plasma half-lives of thymine and FUra by 10- and 5-fold and their area under the curve by 9- and 8-fold, respectively. The effect of BVUra on the antitumor activity of FUra was evaluated in DBA/2 mice inoculated with 10(6) P388 leukemia cells. The mean survival times for the control and FUra-treated mice (5 mg/kg at 1, 3, 5, and 7 days after tumor cell inoculation) were 9.7 and 12.4 days, respectively. When BVUra (200 mumol/kg) was administered 1 h before each injection of FUra, the mean survival time was extended to 17.1 days. BVUra alone did not affect the mean survival time. When the dose of FUra was increased to 20 mg/kg, the mean survival time was 15.3 days; upon a preceding injection of BVUra the mean survival time decreased to 9.2 days. The latter effect probably resulted from an increased toxicity of FUra. Similar results were obtained if FUra was replaced by 5-fluoro-2'-deoxyuridine and BVUra by (E)-5-(2-bromovinyl)-2'-deoxyuridine. The enhancement of both the antitumor and toxic effects of FUra by BVUra were most probably due to an inhibition of FUra degradation, since, like in rats, BVUra increased the plasma half-life of FUra in DBA/2 mice. Hence BVUra appears to be an interesting compound, increasing the potency of FUra by decreasing its degradation.