Cardiac dysfunction after acute endotoxin administration in conscious sheep.

We evaluated cardiac function in an unanesthetized ovine model of hyperdynamic endotoxemia. The animals were instrumented for crystallographic dimension analysis of the left ventricle (LV) and measurement of LV, aortic, atrial, central venous, and pulmonary arterial pressures, and cardiac output. Seven sheep received 1.5 micrograms/kg of Escherichia coli endotoxin [lipopolysaccharide (LPS) LPS-P group] and were compared to a sham group. The sham group demonstrated no significant change in any of the variables. In the LPS-P group, the cardiac index increased (5.7 +/- 0.4 to 7.9 +/- 0.6 l.min-1.m-2) between 8 and 12 h after LPS. Concomitantly, the maximum elastance of LV end-systolic pressure-volume relations significantly decreased (2.88 +/- 0.27 mmHg/ml) compared with baseline (3.89 +/- 0.50 mmHg/ml). Other indexes of the LV contractility (maximum pressure development and ejection fraction) were also reduced. There was a simultaneous increase in the LV end-systolic and diastolic volumes. These findings confirm the hypothesis that there is a myocardial depression during LPS in the ovine model.

Reassessment of primary resection of the perforated segment for severe colonic diverticulitis.

Primary resection with colostomy has been widely adopted during the past decade for the treatment of patients with severe complications of diverticulitis. Because of this, a retrospective review was performed of all patients undergoing surgery for colonic diverticular disease during the two time periods 1974 to 1978 (n = 196) and 1982 to 1986 (n = 230). Forty-three patients had abscess or peritonitis from 1974 to 1978, whereas 52 had these complications from 1982 to 1986. Colostomy and drainage alone were used for 31 of 43 patients (72%) from 1974 to 1978, while primary resection with colostomy was used for 39 of 52 patients (75%) from 1982 to 1986 (p less than or equal to 0.5). Despite this shift in treatment method, mortality increased from 14% in 1974 to 1978 to 19% in 1982 to 1986 (p = NS). Patients with peritonitis had identical mortalities (22%) during both intervals. Patients with abscess experienced an increase in mortality from 8% in 1974 to 1978 to 15% in 1982 to 1986 (p = NS). The widespread use of primary resection for patients with severe complications of diverticulitis appears not to have altered mortality for those with diffuse peritonitis and may have worsened the outcome for those with abscess.

Pulmonary microvascular changes following fluid resuscitation in an ovine model of endotoxemia.

Fluid resuscitation is complicated in hypotensive septic patients by their susceptibility to pulmonary edema. This problem was evaluated in the ovine model of endotoxemia with a chronic lung lymph fistula. Escherichia coli endotoxin (lipopolysaccharide, 1.5 micrograms/kg) was given intravenously over 30 minutes. Group M (n = 9) continued to receive baseline fluids (2 mL/kg/h), while group R (n = 6) received 7 mL/kg/h of Ringer's lactate. After an initial drop in cardiac index, animals in both groups developed a hyperdynamic state. The fall in mean arterial pressure seen in group M was absent from group R. The higher fluid volume resulted in a rise in left atrial pressure and pulmonary microvascular pressure. The lung lymph flow and permeability index were elevated in both groups but were higher in group R. The calculated filtration coefficient showed a threefold increase in both groups. Augmented fluid resuscitation during endotoxemia resulted in an elevated interstitial fluid flux and permeability index secondary to an increase in pulmonary microvascular pressure and greater surface area of the injured microvascular beds being perfused.

Zolantidine (SK&F 95282) is a potent selective brain-penetrating histamine H2-receptor antagonist.

1. The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H2-receptors in guinea-pig atrium and rat uterus. Only apparent pA2 values of 7.46 and 7.26 respectively could be calculated since the slopes of the Schild plots were significantly less than unity. 2. Zolantidine is equally potent as an antagonist at histamine H2-receptors in guinea-pig brain. The compound inhibited histamine stimulated adenylate cyclase (pKi 7.3) and dimaprit stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation (approx pA2 7.63), and competed with [3H]-tiotidine binding (pKi 7.17). 3. Zolantidine is at least 30 fold more potent at H2-receptors than at other peripheral and central receptors investigated. 4. Infusion of zolantidine into rats produces a brain concentration greater than the plateau blood concentration (brain/blood ratio 1.45). 5. Zolantidine is thus characterized as a potent selective brain-penetrating H2-receptor antagonist, and will be a valuable pharmacological tool for investigating possible physiological and pathological roles for histamine in the central nervous system.