IN VINO VERITAS?

Abstract

1991 Albert Einstein once said: “Truth is what stands the test of experience.” Earlier, cardiac derangements associated to sepsis have been ascribed to the inflammatory mediators known as myocardial depressant factors (1), coronary ischemia (2), nitric oxide excessive production (3), interstitial myocarditis (4), increased apoptosis (5), and even subcellular mechanisms involving sodium and calcium homeostasis (6). Discussions on the true involvement of the heart in sepsis and septic shock, regardless of hemodynamic conditions, date back to the early 1960s (7) when some studies already used endotoxic shock models in animals. In the 1980’s, using nuclear medicine techniques, Parker et al (8, 9) demonstrated the decreased biventricular ejection fraction in these septic patients. The connection between clinical myocardial depression and the effects of myocardial depressor substances was described by Parrillo et al (10) in the late 1980s by measuring the serum levels of the substances in these patients during the septic phase. This study established a strong tie between in vivo and in vitro observations of cardiac function and the activity of myocardial depressor substances in septic shock. In 1994, we and others (4) published the histopathological findings of the myocardium in 71 autopsies of patients who met morphological criteria of sepsis, comparing them to a control group and observing the presence of interstitial myocarditis in 27% of the sample, bacterial colonization in 11%, necrosis of cardiac fibers in 7%, and interstitial edema in 28%. Furthermore, the identification of troponin in 1999 as a reliable marker of myocardial injury in sepsis added some new insights to this complex disease (11). In this issue of Critical Care Medicine, Dr. Smeding and coworkers (12) added one more brick to this poorly understood wall. By studying the myocardial effects of resveratrol, a constituent of red wine, they could in fact document its salutary effects on myocardial energy production and mitigation of inflammation associated with sepsis by reversing sepsis-dependent downregulation of peroxisome proliferator–activated receptor  coactivator-1a. They succeeded in proving that resveratrol may in fact improve myocardial dysfunction in an experimental animal model, although we do have some major concerns. Maybe the major pitfall related to the study was their inability to document the status of the nonsurvivors group. Furthermore, mortality rate did not improve, groups did not receive classic treatment for sepsis as antibiotics and fluid resuscitation, and so this adjunctive therapeutic could not be evaluated. Ventricular function was improved in the resveratrol group, but what were the differences between the surviving and nonsurviving animals? Acting in many points, resveratrol can increase gene expression of peroxisome proliferator–activated receptor  coactivator-1a, and therefore explain myocardial protection on developing dysfunction. One could figure out that resveratrol is a weapon against sepsis because myocardial depression occurs in almost 40% of septic patients, and in general, it can be responsible for approximately 15% of the deaths related to septic shock (13). The question that remains is why couldn’t they observe any impact on mortality. We think there are in fact two different diseases under the same umbrella of myocardial dysfunction in sepsis: the one related to survivors and the most severe one related to nonsurvivors. But how can it be useful in clinical practice? It is too early, but there is some light at the end of the tunnel or some wine to drink. Could a cup of wine be a protective factor against developing myocardial depression in sepsis? In vino veritas? We are afraid that the whole truth may be too far... Constantino José Fernandes Jr, MD Hospital Israelita Albert Einstein Avenida Albert Einstein Sao Paulo, Brazil Murillo Santucci Assunção, MD Intensive Care Unit, Hospital Israelita Albert Einstein Avenida Albert Einstein Sao Paulo, Brazil