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L C Casey

Publications and source records attributed to L C Casey.

28 records · Page 2Linked to original sources
PubMed1984

Dexamethasone causes less steroid-induced alkalemia than methylprednisolone or hydrocortisone.

Corticosteroid-induced metabolic alkalemia is an important ICU problem because many of these patients may compensate by alveolar hypoventilation. The effects of 3 commonly used steroids on arterial pH, PaCO2, and serum bicarbonate concentrations were studied in 24 healthy male baboons randomly divided into 3 groups. Each group of 8 animals received 7-day dose-equivalent courses of either hydrocortisone (300 mg daily), methylprednisolone (60 mg daily), or dexamethasone (15 mg daily). Treatment with either hydrocortisone or methylprednisolone increased arterial pH (p less than .05) and serum bicarbonate levels (p less than .01) and the animals receiving hydrocortisone showed significant (p less than .05) compensatory alveolar hypoventilation. Dexamethasone therapy did not cause any of these steroid-induced changes.

Acid-Base Imbalance↗
PubMed1984

Sympathetic nervous system sensitivity to hemorrhagic hypotension in the subhuman primate.

The endogenous catecholamine response to hemorrhagic hypotension is poorly defined since most data have been derived from experiments in lower animal species. To clarify this situation we studied the plasma norepinephrine (NE) and epinephrine (Epi) responses to hemorrhagic hypotension in ten healthy male baboons (Papio anubis). After an overnight fast, animals were tranquilized with 100 mg of ketamine hydrochloride after which femoral artery and vein catheters were inserted. The animals then underwent phlebotomy of 20 ml/kg over 60 minutes with retransfusion of the autologous blood over the next 30 minutes. Plasma specimens for catecholamines were collected at 5, 15, 30, and 60 minutes during phlebotomy and again at 15 and 30 minutes during retransfusion. Plasma NE and Epi concentrations were measured by a radioenzymatic technique. Mean arterial blood pressure (MAP) decreased (p less than 0.01) and heart rate (HR) increased (p less than 0.01) within 15 minutes of phlebotomy, and these variables returned to baseline with retransfusion. Plasma NE and Epi levels increased (p less than 0.025) within 5 minutes of the onset of 'hemorrhage' and within 15 minutes plasma NE concentrations were 56% above baseline, whereas plasma Epi levels were six times greater than baseline. With retransfusion, plasma NE and Epi levels returned to baseline concentrations. We conclude: 1) in a primate species, the sympathetic nervous system responds rapidly to hemorrhage; 2) contrary to prior studies in rats, plasma NE increases as rapidly as Epi but not to the same degree; 3) plasma NE and Epi concentrations rapidly return to baseline levels with fluid resuscitation; and 4) there is little justification for the use of exogenous synthetic catecholamines in hemorrhagic hypotension where fluid resuscitation remains the treatment of choice.

Animals↗
PubMed1984

Epinephrine absorption after intratracheal administration.

Tracheal intubation during cardiopulmonary resuscitation often precedes establishment of an intravenous route for the administration of drugs. To determine the efficacy of intratracheal administration of drugs during cardiopulmonary resuscitation we measured plasma catecholamine levels and hemodynamic responses to intratracheal epinephrine (EPI) administration using a double-blind, randomized crossover design in 7 male baboons (Papio anubis), each studied twice, who received 5 ml of 1:10000 EPI on one day and 5 ml of 0.9% NaCl on another day. Arterial blood samples for measurement of plasma EPI and norepinephrine (NE) concentrations were collected, and heart rate (HR) and mean arterial blood pressure (MAP) were measured before and 1, 2, 4, 8, 16, and 30 min after intratracheal drug administration. Intratracheal EPI significantly (P less than 0.05) elevated HR to 120 +/- 6 from 105 +/- 6 beats/min, MAP to 120 +/- 4 from 112 +/- 5 mm Hg, and plasma EPI to 8882 +/- 2143 from 928 +/- 209 pg/ml within 1 min of administration, and these effects persisted for 30 min. Plasma NE levels did not change after intratracheal EPI administration. None of the four variables changed after intratracheal saline was given. We conclude that in subhuman primates, intratracheal EPI is rapidly absorbed and is an effective pressor agent when given by this route; and that these data lend support to the clinical practice of intratracheal EPI administration during cardiac arrest or in the treatment of shock.

Absorption↗
PubMed1983

Development of a primate model of exposure hypothermia.

A nonhuman primate model of exposure-induced hypothermia was developed and the hemodynamic effects of hypothermia were evaluated in five animals. With decreasing core temperature from 37 degrees C to 33 degrees C there was a 47% increase in heart rate, a 23% increase in mean arterial pressure, a 48% increase in cardiac output, a 260% increase in oxygen consumption, and a 237% increase in minute ventilation. As the core temperature decreased from 33 degrees C to 29 degrees C there were decreases in the heart rate, blood pressure, and cardiac output such that at 29 degrees C these values were not significantly different from the values obtained at 37 degrees C. However, the oxygen consumption was still 180% increased and the minute ventilation 40% higher at 29 degrees C than at 37 degrees C. This model will allow the evaluation of the physiology of hypothermia and the effectiveness of different rewarming techniques.

Animals↗
PubMed1982

Association of prostacyclin production with resistance of C3H/HeJ mice to endotoxin shock.

Persistence of inflammatory cells in the microcirculation due to altered proportions of arachidonate metabolites could contribute to death from endotoxin (ET) shock. We tested this hypothesis by observing ET-induced cellular accumulations in capillaries of genetically resistant C3H/HeJ and sensitive C3HeB/FeJ mice after challenge with 1,000 micrograms of Salmonella typhi ET, a dose lethal only for the sensitive strain. These data were correlated with prostaglandin production by lung tissue. Six hours after challenge with ET, lung capillaries of sensitive animals were occluded with amorphous material and occasional polymorphonuclear leukocytes (PMNL). This inflammation, along with reduction in alveolar volume, was not observed in resistant mice. At this time only 10 PMNL/high-power field were seen with light microscopy in capillaries of resistant mice compared to 60 PMNL/high-power field in sensitive animals. Lung parenchymal tissue was excised from resistant and sensitive (C3H/HeN) mice six hours postchallenge with 800 micrograms of endotoxin and release in vitro of thromboxane A2 (TXA2) or prostacyclin (PGI2) over a 30-minute period was determined by radioimmunoassay. TXA2 and PGI2 released by lung fragments taken six hours after challenge with ET did not differ from normal levels of these substances in C3H/HeN mice. TXA2 release was normal at six hours in C3H/HeJ mice, but PGI2 was significantly increased (from 2.95 ng/mg to 5.73 ng/mg, P less than 0.005). The ratio of PGI2/TXA2 in resistant mice was 24.3 as compared to 10.3 in sensitive mice. Since PGI2 can reduce leukocyte adhesion, an increase in the ratio of this substance to TXA2 may be associated with resolution of PMNL from the pulmonary microcirculation of ET-resistant mice.

Animals↗
PubMed1982

Prevention of endotoxin-induced pulmonary hypertension in primates by the use of a selective thromboxane synthetase inhibitor, OKY 1581.

Endotoxin-induced pulmonary hypertension can be attenuated by nonsteroidal anti-inflammatory drugs and is associated with increased plasma levels of thromboxane (Tx) B2, prostaglandin (PG) F2, PGE and PGI2. Because nonsteroidal anti-inflammatory drugs block prostacyclin production and may also shift arachidonic acid into the lipoxygenase pathway, we have evaluated a selective Tx synthetase inhibitor (OKY 1581) as a means for preventing endotoxin-induced pulmonary hypertension. An LD70 dose of Escherichia coli endotoxin (6 mg/kg) was given i.v. to two groups of unanesthetized baboons. Group I received endotoxin alone and Group II was pretreated with i.v. OKY 1581 (2 mg/kg) 10 min before the endotoxin. OKY 1581 produced a significant decrease in the basal plasma TxB2 from 0.432 +/- 0.82 to 0.147 +/- 0.032 ng/ml (P less than .01), but no significant change in plasma 6-keto PGF1 alpha. After the administration of the endotoxin, Group I developed pulmonary hypertension (from 11 +/- 1 to 19 +/- 2 mm Hg. P less than .005) and an 8-fold increase in plasma TxB2 (P less than .02), whereas Group II did not develop pulmonary hypertension or an increase in plasma TxB2. However, Group II had a 26-fold increase in plasma 6-keto PGF1 alpha (P less than .05). From these studies, we conclude that: 1) OKY 1581 is an effective Tx synthetase inhibitor in vivo; 2) endotoxin-induced pulmonary hypertension is mediated largely by increased Tx; and 3) the inhibition of Tx synthetase results in shunting of endoperoxides into the prostacyclin pathway.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Lidocaine increases prostacyclin in the rat.

In the rat, the effect of intravenous lidocaine was evaluated on plasma prostacyclin concentration as well as the concentration of prostacyclin in aortic ring incubation chambers and in the effluent of isolated perfused lungs. Prostacyclin was assayed using a radioimmunoassay for its stable product 6-Keto PGF1 alpha. Lidocaine in therapeutic doses (2 mg/kg) will significantly increase 6-Keto PGF1 alpha in plasma as well as in aortic ring incubation chambers and in the effluent of isolated perfused lungs when compared to saline treated controls.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Treatment of sepsis and septic shock: a review.

Septic shock is one of the leading causes of death in intensive care units, and its incidence is increasing. Mortality rates as high as 95% are reported, with rates of 60% or more even when diagnosed and treated promptly. This review examines the definition of septic shock, its pathogenesis, and supportive therapy, with particular attention to intervention during the septic shock cascade.

Humans↗