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A Bersten

Publications and source records attributed to A Bersten.

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Hematocrit modifies the circulatory control of systemic and myocardial oxygen utilization in septic sheep.

OBJECTIVE: To describe the relationship between hematocrit and oxygen utilization before and after the onset of a hyperdynamic septic state. DESIGN: Prospective, observational study. SETTING: Laboratory of a large university-affiliated medical school. SUBJECTS: Thirty mature sheep, each weighing 30 to 40 kg (0.9 to 1.1 m2 body surface area). INTERVENTIONS: After baseline measurements, cecal ligation and perforation were used to establish an intra-abdominal source of infection. The abdominal wound was closed and animals were studied on the second postoperative day. An increase in cardiac output of > or = 30% was used to arbitrarily define the onset of sepsis. Repeat measurements were performed and the animal was killed. RESULTS: The circulatory response to this septic insult included an increase in both cardiac index (change, baseline to sepsis, delta +2.24 +/- 0.75 L/min/m2; p < .01) and myocardial blood flows (delta +76.4 +/- 56 mL/100 g/min; p < .01). We found a negative correlation between the hematocrit and cardiac index (r2 = .21; p < .01) during the septic study, and noted that the amount (p < .01) of this correlation was significantly greater in the septic than the nonseptic study. Concurrently, the negative correlation observed between hematocrit and whole-body oxygen extraction (r2 = .21; p < .01) was significantly lower (p < .01) across the range of hematocrit values examined during the septic study vs. the similar relationship in the nonseptic study (r2 = .27; p < .01). The increase in myocardial oxygen consumption paralleled the relationship between cardiac work and hematocrit in the septic study, and was accompanied by increases in both myocardial blood flows (r2 = .25; p < .01) and myocardial oxygen extraction (r2 = .35; p < .01). CONCLUSIONS: The normal circulatory compensation to anemia in hyperdynamic sepsis includes increases in cardiac index and whole-body oxygen extraction, although greater reliance is likely placed on the use of systemic flow reserve to maintain tissue oxygen uptake in septic vs. healthy study conditions. Furthermore, increased reliance on myocardial oxygen extraction in sepsis suggests that the normal flow-reserve supporting myocardial oxygen availability may be limited in this syndrome.

Animals

PEEP increases non-pulmonary microvascular fluid flux in healthy and septic sheep.

The potential for significant interaction between PEEP and the peripheral microcirculations is not as well appreciated as are its central circulatory effects. Therefore, we studied the effects of PEEP, 15 mm Hg, on microvascular fluid flux in the hindlimb of ten mature sheep. Changes in prefemoral lymph flow (QL) and in lymph to plasma [L/P] total protein (TP) ratios were measured following the application of PEEP for 2 h, before and during hyperdynamic sepsis. Sepsis was induced by cecal ligation and perforation (CLP). Although the onset of sepsis was not associated with an increase in prefemoral QL, the [L/P] ratio of iodinated 125I human serum albumin (125I-HSA) was significantly greater 72 h after CLP than during the nonseptic baseline study. Histologic examination of gastrocnemius muscle also demonstrated an increase in protein-rich interstitial edema during the septic studies. During the 2 h of PEEP, prefemoral QL increased equally (p less than 0.05) in three study periods: (1) baseline nonseptic, delta QL = +1.2 +/- 1.4 ml/h; (2) septic period 1, 24 to 48 h after CLP, delta QL = +1.3 +/- 1.2 ml/h; and, (3) septic period 2, 72 h after CLP, delta QL = 1.0 +/- 0.6 ml/h. Calculated microvascular hydrostatic pressures also rose significantly during PEEP therapy in all three study periods. We conclude that PEEP, 15 mm Hg, increased hindlimb microvascular fluid flux and may thereby increase interstitial fluid content in tissues drained by the prefemoral lymph node. These effects of PEEP were not aggravated by hyperdynamic sepsis, despite a presumed increase in systemic microvascular permeability at this time.

Animals

Acute lung injury in septic shock.

Over the past 20 years, substantial information has been gained concerning sepsis-associated ALI. Although the mortality from ARDS remains unchanged, the spectrum of disease has altered. Patients rarely die acutely from the direct sequelae of ALI, including hypoxemia, but most commonly demonstrate a protracted clinical course that eventuates in MSOF. Further, with improved resuscitation of medical and surgical emergencies, the profile of patients who develop ARDS has changed and now reflects an older and more complex patient. While the pathophysiology and mediators of tissue injury in septic ARDS is now better understood, effective therapeutic interventions have not yet resulted from early multicenter trials. It is clear from the recent multicenter trials on the effects of methylprednisolone dose that apparently useful therapies in animal models must undergo this form of investigation before widespread clinical dissemination. Without an effective and singular "golden bullet" for the treatment of the varied presentation of ARDS, it remains our contention that basic management principles of ARDS must continue to emphasize an aggressive approach to the identification and treatment of the septic focus while all efforts are concurrently exploited to reduce the potentially aggravating effects of secondary injury on microvascular function. Currently research into the diagnosis, prevention, and treatment of nosocomial pneumonia is an example of how secondary injury may be minimized in ALI. Further, it is important to recognize the potentially detrimental effects of various therapies on the microvascular membrane in ARDS.

Animals

Circulatory disturbances in multiple systems organ failure.

Circulatory disturbances in MSOF disturb normal metabolic autoregulation, the ability to continuously couple tissue oxygen delivery with oxygen need. These may occur at three levels of the circulation: the heart; the regional circulations; and the microcirculation. This article will summarize evidence demonstrating that MSOF is associated with reduced tissue oxygen delivery by virtue of changes in all three circulatory components governing the inadequacy of metabolic autoregulation in sepsis.

Cardiovascular System