Abstract

Specific changes in hepatic gene expression following resuscitation from cardiogenic shock are identified. Aberrantly sustained or prematurely terminated programs of liver gene expression account for the dysregulated metabolism of multiple organ system failure. Having shown that cardiogenic shock induces several transcriptional programs which are mutually exclusive and which have an intrinsic hierarchy, he proposes to identify which hepatic transcriptional programs are regulated during the hypermetabolic state of late MOSF and to define the molecular mechanisms responsible for their persistence or termination. Comparing heart tamponade and E. coli IP swine shock models, he will: (1) Show whether the differences noted in the hepatic transcriptional programs 8 hours after cardiogenic shock versus late sepsis are due to the types of shock, """"""""ebb"""""""" versus """"""""flow"""""""" or both; (2) Find the mechanism for the transcriptional shutoff of the genes apparently specific for cardiogenic shock and (3) Identify those genes transcribed during hypermetabolic late sepsis which are not transcribed during early cardiogenic shock and then define their regulatory mechanisms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Modified Research Career Development Award (K04)
Project #
5K04GM000581-03
Application #
3072978
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1991-07-01
Project End
1994-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Abello, P A; Buchman, T G (1994) Heat shock-induced cell death in murine microvascular endothelial cells depends on priming with tumor necrosis factor-alpha or interferon-gamma. Shock 2:320-3
Buchman, T G; Kubos, K L; Seidler, A J et al. (1994) A comparison of statistical and connectionist models for the prediction of chronicity in a surgical intensive care unit. Crit Care Med 22:750-62
Schoeniger, L O; Curtis, W; Esnaola, N F et al. (1994) Myocardial heat shock gene expression in pigs is dependent on superoxide anion generated at reperfusion. Shock 1:31-5
Abello, P A; Fidler, S A; Buchman, T G (1994) Thiol reducing agents modulate induced apoptosis in porcine endothelial cells. Shock 2:79-83
Buchman, T G (1994) Manipulation of stress gene expression: a novel therapy for the treatment of sepsis? Crit Care Med 22:901-3
Abello, P A; Fidler, S A; Bulkley, G B et al. (1994) Antioxidants modulate induction of programmed endothelial cell death (apoptosis) by endotoxin. Arch Surg 129:134-40;discussion 140-1
De Maio, A; Beck, S C; Buchman, T G (1993) Induction of translational thermotolerance in liver of thermally stressed rats. Eur J Biochem 218:413-20
De Maio, A; Beck, S C; Buchman, T G (1993) Heat shock gene expression and development of translational thermotolerance in human hepatoblastoma cells. Circ Shock 40:177-86
Buchman, T G; Abello, P A; Smith, E H et al. (1993) Induction of heat shock response leads to apoptosis in endothelial cells previously exposed to endotoxin. Am J Physiol 265:H165-70
Phillips, J A; Buchman, T G (1993) Optimizing prehospital triage criteria for trauma team alerts. J Trauma 34:127-32

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