Sudden Death and Staged Therapy for Hemodynamic Stabilization in Patients Enrolled in a Heart Transplantation Program

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14%± 5%, New York Heart Association Class IIl/IIIIV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirtyseven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninetynine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE₁ for preand afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 ± 9 months; patients who underwent staged therapy for 9 ±5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure. Thus, patients who underwent staged therapy were at increased risk for sudden death (P = 0.01, relative risk 3.4, 95% confidence interval 1.2–9.7) but were at lower risk for death from pump failure (P = 0.009, relative risk 0.44, 95% confidence interval 0.22–0.84). In patients who underwent therapy with continuous outpatient PGE₁ (n = 7) or dobutamine (n= 21), risk for sudden death (P = NS by log rank test) did not increase. In conclusion, staged therapy significantly reduced death from pump failure; however, patients who could be stabilized and considered too well for heart transplantation were at increased risk for sudden death. Thus, overall survival did not improve. Of note, outpatient dobutamine did not increase the risk for sudden death.     

Effects of liver ischemia on degradation of different classes of hepatic proteins

The effects of liver ischemia on hepatic protein degradation were studied in rats. In one series of experiments degradation was measured in incubated liver slices as release of trichloroacetic acid soluble radioactivity from proteins prelabelled with L-(¹⁴C)-leucine during 4 h (short-lived proteins) or during 24 h (long-lived proteins). In another series of experiments protein degradation was determined in vivo by measuring decay of radioactivity in hepatic proteins prelabelled with (¹⁴C)-sodium bicarbonate administered intraperitoneally 4 h or 24 h before induction of liver ischemia. Degradation of short-lived proteins was reduced by 50% both in vitro and in vivo during liver ischemia while breakdown of long-lived proteins was unchanged. Thus, short-lived and long-lived proteins were differently affected by liver ischemia. These results are consistent with the concept of distinct proteolytic pathways for different classes of proteins.     

Comparing Cause-Specific Infant Mortality in a West German State and the United States of America

ABSTRACT. The infant mortality rate in North Rhine Westphalia (NRW), the most populous West German state, has continuously been around 10 % higher than the German national average in the post-war period. Using white singleton data from the US 1980 National Infant Mortality Surveillance project (NIMS) and similar 1980/1981 data from NRW we compared infant mortality by birthweight and cause to describe the distribution of excess mortality in NRW. The US infant mortality rate was 8.7 deaths per 1000 live births, compared with 13.1/1000 for NRW (rate difference: 4.3/1000). Of the 4.3/1000 overall rate difference, 1.9/1000 was attributable to neonatal deaths, 2.4/1000 to postneonatal deaths. A major proportion, 2.0/1000, of the overall rate difference of 4.3/1000 was attributable to normal birthweight deaths postneonatally. 0.85/1000 of this 2.0/1000 rate difference was attributable to SIDS, 0.44/1000 to external causes and 0.42/1000 to infections.     

The impact of performance uncertainty on the postimperative negative variation

In a delayed matching-to-sample task, the impact of clear or ambiguous go versus clear no-go signals on the post-imperative negative variation (PINV) was examined in 11 patients with a chronic schizophrenic disorder (DSM-III-R) and in a control group of 13 healthy subjects matched to the patient sample by age, sex, and education. Size and spatial position of a visual S2 had to be matched to one of two visual patterns in the S1 presented 4 s earlier. In 96 trials, the S2 was identical in size with one of the two patterns of S1 (clear matching). These trials varied pseudorandomly, with 60 trials in which the S2 was of intermediate size. On a randomly interspersed additional 48 trials, an S2 differing in color and shape signaled no-go. The electroencephalogram was recorded from Fz, Cz, Pz, F3, F4, C3, C4, P3, and P4. Although groups did not differ in contingent negative variation amplitude the PINV was generally more pronounced in patients than in controls. In both groups, ambiguity of the to-be-matched S2 produced larger PINV amplitudes; the no-go signal elicited only a small PINV. Differential effects of ambiguity and no-go on PINV amplitude and its scalp distribution suggest that “performance” and “action” uncertainty contribute to PINV generation and that thresholds for both effects are reduced in schizophrenics.     

Effects of liver ischemia on hepatic protein synthesis in vitro and in vivo

When an in vitro system is used to study the influence of ischemia on hepatic protein synthesis, an important question is whether alterations observed in vitro reflect changes in vivo. In the present study the effects of liver ischemia on protein synthesis were investigated in rats both in vitro and in vivo. Liver ischemia was induced by hepatic artery ligation. Protein synthesis in vitro was determined from leucine incorporation into proteins in liver slices incubated in a medium containing ¹⁴C-leucine (0.5 mmol/l) and in vivo from leucine incorporation into hepatic proteins after intraportal injection of a tracer dose of ¹⁴C-leucine. Leucine incorporation rate in non-ischemic liver was 0.16 pmol * g pror¹ h-¹ in vitro and 19.6 μmol g prot-¹. h^-1 in vivo. After hepatic artery ligation protein synthesis in vitro was reduced by about 60% and in vivo by about 80%. Thus, the relative changes were of the same magnitude in vitro and in vivo. This indicates that an in vitro system can be used to evaluate the effects of liver ischemia on hepatic protein synthesis.