The Fundamental mechanisms of shock

A concerned group of approximately forty investigators from the United States and Canada met in Oklahoma City in 1964 to carry out experiments on animals in endotoxin shock. Nearly all of the proposed and then-current forms of therapy to prevent irreversible shock and death were attempted (J. Okla. State Med. Assoc. 59:407-484, 1966). Unfortunately, no clearly demonstrable therapeutic benefits accrued from this massive effort. However, this meeting was without historic precedence, marking the first time in which reportedly successful therapies had been attempted on a large scale. The results left most investigators puzzled and disappointed, and a pall descended over many laboratories of shock research. It seemed clear that we had failed to penetrate the hidden barriers to our understanding of the mechanisms of endotoxin shock. Even as this postmortem is laid bare eight years later, we still have no unequivocal proof of the precise chain of events leading to irreversible shock and death. Since the Shock Tour of 1964, the Oklahoma research group has regularly examined its position relative to an understanding of endotoxin shock. The critical need to clarify its mechanisms became apparent at that time, and we set to work conceiving experimental designs which might solve the problem. A great deal of research has been accomplished. Yet it appears that we are still skirting the core of the shock problem, endlessly wrestling with peripheral components, but never quite reaching the basic mechanisms. We have not advanced far enough in sequentially dissecting out those critical pathophysiological events early in shock which most assuredly lead to the irreversible state. The Oklahoma-based U.S. Navy Project THEMIS research group, activated in 1968 and composed of surgeons, internists, physiologists, pathologists, pharmacologists, and biochemists, represents the faculties and staff of the University of Oklahoma Medical School, the Veterans Administration Hospital, and the Oklahoma Medical Research Foundation. This group has attacked experimental septic shock with a wide spectrum of approaches, ranging from molecular to clinical studies. At times, we have become discouraged. The obstacles which block our understanding of the intimate mechanisms in shock have often seemed insurmountable. Nevertheless, these interdisciplinary efforts have stimulated an underlying conviction that the shock problem will be most effectively solved by vigorous team research. Well-trained, highly motivated investigators from the basic and clinical sciences must join together in a concerted effort to sort out and define the fundamental mechanisms in shock. The results of such studies are most likely to yield clinically applicable therapeutic procedures. In the spirit of this approach, we met with investigators from the United States, Canada, and Europe in Oklahoma City in October, 1971, to encourage an exchange of data and ideas, and hopefully to begin to unravel the fundamental mysteries of shock. These meetings were unique. A single, topically oriented conference provided a forum for an interdisciplinary group of research workers who might otherwise never have met in a single conference room for cross-pollination and challenge of one another's ideas. We hope that this symposium has proven its worth and that it establishes a pattern for future meetings.