A Circulating Myocardial Depressant Substance is Associated with Cardiac Dysfunction and Peripheral Hypoperfusion: Correlation of Ejection Fraction with Extent of Myocardial Cell Shortening

In: Septic Shock

7 Nov 2014

A Circulating Myocardial Depressant Substance is Associated with Cardiac Dysfunction and Peripheral Hypoperfusion: Correlation of Ejection Fraction with Extent of Myocardial Cell ShorteningCorrelation of Ejection Fraction with Extent of Myocardial Cell Shortening
Figure 3 illustrates the relationship between the radionuclide determined in vivo EF (days 2 to 4) and the in vitro percentage of change in extent of myocardial cell shortening in the 14 septic shock patients with MDS. As mentioned above, a positive assay for MDS was defined as at least a 20 percent in vitro depression of the extent of myocardial cell shortening. The degree of in vitro depression ranged from 20 percent to 62 percent, with a mean of 35 percent. The EFs ranged from 7 percent to 52 percent, with a mean of 28 percent. Using Spearman rank coefficients, there was a significant correlation between these two variables (r= -0.60, p<0.05).

Ultrafiltration Experiments
The results of ultrafiltration experiments on sera from critically ill nonseptic patients, septic patients with and without MDS activity, and normal human volunteers are summarized in Table 3. MDS activity did not pass through 10,000 or 30,000 dalton Amicon filters. No MDS activity was found in either the filtrate or the supernatant in critically ill nonseptic patients or in normal human volunteers. In patients positive for MDS, MDS activity was found only in supernatants containing molecules above 10,000 and 30,000 daltons. Serum with MDS activity maintained its activity despite multiple freezings at — 70°C and repetitive rapid thawings. there

Discussion
This study extends our understanding of cardiovascular dysfunction and the role of a circulating MDS in the pathogenesis of human septic shock. In this study, the presence of circulating myocardial depressant activity was temporally associated with cardiovascular abnormalities—specifically, reversible myocardial depression and ventricular dilatation, changes that characterize human septic shock. When compared with MDS negative patients, septic shock patients achieving strict criteria for the presence of a circulating MDS had a statistically greater decrease in LVEF and a lower minimum EF.

Figure 3. The relationship between the radionuclide determined in vivo EF (days 2 to 4) and the maximum in vitro percent change in extent of myocardial cell shortening with serum from 14 septic shock patients with MDS.

Figure 3. The relationship between the radionuclide determined in vivo EF (days 2 to 4) and the maximum in vitro percent change in extent of myocardial cell shortening with serum from 14 septic shock patients with MDS.

Table 3—Results of ImrajUtration Experiments in Septic Shock Patients with and without MDS, Critically IU ‘Nonseptic Patients, and Normal Human Volunteers

SubjectGroup 10,000 Daltons 30,000 Daltons
Filtrate Supernatant Filtrate Supernatant
MDS positive 0/6 6/6 0/8 7/8
MDS negative 0/3 0/3 0/3 0/3
Critically ill, nonseptic 0/5 0/5 0/5 0/5
Normal humans 0/4 0/4 0/4 0/4

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