Biomedical subjects

Z F Ba

Publications and source records attributed to Z F Ba.

61 records · Page 4Linked to original sources

PubMed1991

ATP-MgCl2 restores the depressed hepatocellular function and hepatic blood flow following hemorrhage and resuscitation.

Although ATP-MgCl2 produces a myriad of beneficial effects following organ ischemia and simple hemorrhagic shock in animal models which involved heparinization and/or blood resuscitation, it is not known whether ATP-MgCl2 has any salutary effect on the depressed active hepatocellular function (AHF) and hepatic microvascular blood flow (HMBF) in a nonheparinized model of trauma and severe hemorrhage in the absence of blood resuscitation. To determine this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with four times the volume of shed blood with RL. ATP-MgCl2, 50 mumoles/kg body weight (BW) each or an equivalent volume of normal saline, was infused intravenously for 95 min during and following crystalloid resuscitation. At 1.5 and 4 hr after resuscitation, AHF (Vmax, maximal velocity of indocyanine green clearance; Km, efficiency of the active transport process) was determined without blood sampling by using an in vivo indocyanine green clearance technique. HMBF was measured with laser Doppler flowmetry. Results indicate that Vmax, Km, and HMBF decreased significantly at 1.5-4 hr after hemorrhage and resuscitation. ATP-MgCl2 infusion restored the depressed Vmax, Km, and HMBF and prevented the occurrence of hepatic edema. The restoration of AHF with ATP-MgCl2 treatment may be due to its direct salutary effect on the active indocyanine green transport process and/or due to improvement in hepatic microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1991

The complex pattern of cytokines in sepsis. Association between prostaglandins, cachectin, and interleukins.

Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL). Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours). Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.

Animals↗

PubMed1991

Adequate crystalloid resuscitation restores but fails to maintain the active hepatocellular function following hemorrhagic shock.

Studies have shown that active hepatocellular function is depressed early after trauma-hemorrhage and persists despite resuscitation with two or three times (x) the volume of maximum bleedout (MB) with lactated Ringer's solution (LR). However, it is not known if a larger volume of fluid resuscitation corrects this dysfunction. To study this, rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the MB volume was returned in the form of LR, and then resuscitated with 4x or 5x the volume of MB with LR. Three doses of indocyanine green (ICG) were given intravenously and [ICG] measured in vivo using an in-vivo hemoreflectometer. The initial velocity of the clearance of ICG was calculated. Maximal velocity of the clearance (Vmax: the number of functional ICG receptors) and kinetic constant (Km: the efficiency of the active transport) were determined from the Lineweaver-Burk plot. Vmax decreased during hemorrhage, was restored to control levels at 0-4 hours after resuscitation, but decreased at 4-8 hours after resuscitation despite restoration of cardiac output following resuscitation with 5x LR. This could be the result of increased TNF release. The Km also decreased during hemorrhage, but increased at 0-1.5 hours and remained at control levels even 4-8 hours after resuscitation. Thus the failure of Vmax to remain at control levels following adequate fluid resuscitation may form the basis of cellular dysfunction and multiple organ failure after severe hemorrhagic shock.

Adenine Nucleotides↗

PubMed1991

Differential alterations in plasma IL-6 and TNF levels after trauma and hemorrhage.

Tumor necrosis factor (TNF) and interleukin 6 (IL-6) are purported to be important mediators of inflammatory responses. It is not known whether the plasma levels of these cytokines are altered after trauma and hemorrhage. Our objectives were to determine whether there is any elevation of plasma TNF or IL-6 after trauma and hemorrhage and to what extent these changes are due to tissue trauma vs. simple hemorrhage. Trauma was induced in Sprague-Dawley rats under light ether anesthesia by performing a 5-cm midline laparotomy. On closure, animals were catheterized, awakened, hemorrhaged to a mean blood pressure of 40 mmHg, and maintained at that pressure until 40% of maximum shed blood volume was returned in the form of Ringer lactate (RL). Animals were then resuscitated with RL equivalent to four times shed blood volume. Blood samples (0.5 ml) were taken before inducing hemorrhage, at maximal bleed out (45 min), and at 4 and 6 h posthemorrhage to obtain plasma. IL-6 and TNF levels were measured using cytokine-dependent cellular assays. TNF levels were significantly elevated at 45 min into hemorrhage and remained so up to 4 h after hemorrhage. IL-6 levels were also elevated 45 min into hemorrhage and remained so up to 6 h posthemorrhage. IL-6, unlike TNF, was already significantly increased after midline laparotomy and before initiation of hemorrhage compared with unmanipulated animals. Thus induction of IL-6 by trauma may be partially independent of those mechanisms in hemorrhage that are involved in the release of TNF.

Animals↗

PubMed1991

Increase in hepatic blood flow during early sepsis is due to increased portal blood flow.

Although hepatic blood flow increases significantly during early sepsis [as produced by cecal ligation and puncture (CLP)], it is not known whether this is due to the increase in portal or hepatic arterial blood flows. To study this, rats were subjected to CLP, after which they and sham-operated rats received either 3 or 6 ml normal saline/100 g body wt subcutaneously (i.e., all rats received crystalloid therapy). Blood flow in various organs was determined by using a radioactive microsphere technique at 5 and 20 h after CLP or sham operation. Portal blood flow was calculated as the sum of blood flows to the spleen, pancreas, gastrointestinal tract, and mesentery. Total hepatic blood flow was the sum of portal blood flow and hepatic arterial blood flow. A significant increase in portal blood flow and in total hepatic blood flow was observed at 5 h after CLP (i.e., early sepsis), and this was not altered by doubling the volume of crystalloid resuscitation after the induction of sepsis. In contrast, hepatic arterial blood flow during early sepsis was found to be similar to control; however, it was significantly reduced in late sepsis (i.e., 20 h after CLP). Cardiac output was significantly higher than the control in early sepsis. However, even in late sepsis, cardiac output and total hepatic blood flow were not significantly different from controls. These results indicate that the increased total hepatic blood flow during early hyperdynamic sepsis is solely due to the increased portal blood flow.

Animals↗

PubMed1991

Diltiazem administration after crystalloid resuscitation restores active hepatocellular function and hepatic blood flow after severe hemorrhagic shock.

Studies have shown that active hepatocellular function is depressed after hemorrhagic shock, despite crystalloid resuscitation. It is also known that calcium antagonists produce various beneficial effects on cell and organ function after ischemia and shock. However, it remains unknown whether such agents have any salutary effects on the depressed active hepatocellular function and hepatic blood flow in a nonheparinized model of trauma and hemorrhage. To study this, rats underwent a midline laparotomy (trauma-induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum bleedout was returned in the form of Ringer's lactate. They were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 minutes, during and after which diltiazem (400 micrograms/kg body weight) was infused intravenously over 95 minutes. Active hepatocellular function (Vmax and Km) was determined with an in vivo indocyanine green clearance technique. Effective hepatic blood flow (EHBF) was determined by Fick principle and corrected by the indocyanine green extraction ratio. Hepatic microvascular blood flow (HMBF) was measured by laser Doppler flowmetry. Results indicate that Vmax, Km, EHBF, and HMBF decreased significantly at 1.5 and 4 hours after resuscitation. Diltiazem infusion restored the depressed Vmax, Km, EHBF, and HMBF and prevented the occurrence of hepatic edema. Thus, diltiazem may be a useful adjunct in the treatment of trauma and severe hemorrhage even in the absence of blood resuscitation.

Analysis of Variance↗

PubMed1990

Preheparinization improves organ function after hemorrhage and resuscitation.

Recent studies indicate that heparinization before hemorrhage maintains microvascular patency in the liver and kidney during and after severe hemorrhagic shock. However, it is not known whether preheparinization has any protective effects on organ function after hemorrhage and resuscitation. To study this, unanesthetized rats (with or without preheparinization) were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum shed blood volume was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of the shed blood with RL. Cardiac output (CO), [3H]inulin clearance (CIn; renal function), hepatic microvascular blood flow (HMBF), and hepatocellular function (HF), i.e., maximal velocity of indocyanine green clearance (Vmax), were determined 1.5 h after resuscitation. Although CO decreased in both groups, the values in preheparinized rats were significantly higher than in the nonheparinized rats. The improvement in CIn as well as HMBF followed the same trends. HF (Vmax) was significantly depressed in the nonheparinized rats but was maintained in preheparinized rats. Thus administration of heparin before the onset of hemorrhage improves CO and renal function and restores HF to control after hemorrhage and resuscitation. These protective effects of preheparinization could be due to the maintenance of microvascular patency and prevention of blood sludging during and after hemorrhage.

Animals↗