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1.
Am J Physiol ; 264(5 Pt 2): R977-83, 1993 May.
Article in English | MEDLINE | ID: mdl-8498607

ABSTRACT

The aim of this study was to determine whether ATP-MgCl2 as an adjunct to resuscitation has any beneficial effect on the depressed gut absorptive capacity (GAC) after hemorrhage and, if so, whether alterations in whole blood viscosity (WBV) are, in part, responsible for those effects. Rats were anesthetized, a laparotomy was performed (i.e., trauma induced), and blood vessels were cannulated. The animals then underwent fixed pressure (40 mmHg) hemorrhage, followed by resuscitation with lactated Ringer solution. One group received 50 mumol/kg ATP-MgCl2 and another received saline during resuscitation. At 2 and 4 h after the end of hemorrhage, a 1-h D-xylose absorption test was performed. Viscosity determinations were made at corresponding time points in another set of rats subjected to sham hemorrhage, acute hemodilution, or hemorrhage and resuscitation. Results show that xylose absorption is depressed after hemorrhage and resuscitation and that ATP-MgCl2 restored it to normal. D-Xylose absorption was inhibited by glucose, indicating a facilitated transport process. Furthermore, WBV was reduced by the administration of ATP-MgCl2. Thus ATP-MgCl2 improves GAC early after hemorrhage and resuscitation, possibly by reducing WBV, and may be a useful adjunct to resuscitation, allowing for early enteral nutrition.


Subject(s)
Adenosine Triphosphate/pharmacology , Intestinal Absorption/drug effects , Shock, Hemorrhagic/metabolism , Wounds and Injuries/complications , Animals , Blood Pressure , Blood Viscosity , Central Venous Pressure , Hematocrit , Male , Portal Vein/physiopathology , Rats , Rats, Sprague-Dawley , Resuscitation , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/physiopathology , Venous Pressure , Xylose/pharmacokinetics
2.
J Trauma ; 34(5): 645-51; discussion 651-2, 1993 May.
Article in English | MEDLINE | ID: mdl-8496998

ABSTRACT

The aim of this study was to investigate whether heparan sulfate, as an adjunct to resuscitation following hemorrhagic shock: (1) improves gut absorptive capacity and if so, (2) whether the mechanism involved is alteration of whole blood viscosity (WBV). Rats were anesthetized, a laparotomy performed, and blood vessels cannulated. The conscious animals then underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with lactated Ringer's solution. One group received 7 mg/kg heparan sulfate, and another received saline, during resuscitation. At 2 hours and 4 hours after the end of hemorrhage, the oral D-xylose absorption test was performed. Viscosity determinations were made in another set of rats since lactated Ringer's solution replacement during the D-xylose test may affect hematocrit and hence WBV. These rats were subjected to hemorrhage and resuscitation as above, along with additional sham hemorrhage and acute hemodilution control groups. The WBV was determined at corresponding times to the D-xylose test. Results show that xylose absorption is depressed after hemorrhage and resuscitation, and heparan sulfate restored it to normal. The WBV was reduced by heparan sulfate. Thus heparan sulfate, as an adjunct to resuscitation of hemorrhagic shock, restores gut absorptive capacity to normal, possibly by reducing WBV.


Subject(s)
Blood Viscosity/drug effects , Heparitin Sulfate/administration & dosage , Intestinal Absorption/drug effects , Shock, Hemorrhagic/physiopathology , Wounds and Injuries/physiopathology , Animals , Blood Pressure/physiology , Hematocrit , Male , Rats , Rats, Sprague-Dawley , Resuscitation , Shock, Hemorrhagic/blood , Xylose/metabolism
3.
Circ Shock ; 39(4): 279-84, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8485819

ABSTRACT

Although recent studies have shown that gut absorptive function is significantly depressed even in the early hyperdynamic phase of sepsis, the mechanism responsible for this is unknown. Tumor necrosis factor (TNF-alpha) is a potent mediator of shock resulting in a marked inflammatory response leading to mucosal erosions of the gut and multiple organ failure. Although TNF is elevated in early sepsis, it remains unknown whether TNF plays any role in the depression of gut absorptive function under these conditions. To study this, we used the 1 hr D-xylose absorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery from anesthesia, 125 micrograms recombinant murine TNF-alpha (rMuTNF-alpha)/kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hour later, D-xylose was given orally. The systemic blood pressure was recorded 1 hr thereafter and D-xylose concentration in a sample of portal blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-alpha, D-xylose absorption was severely depressed. Thus the depressed gut absorptive function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-alpha.


Subject(s)
Intestinal Absorption/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Animals , Bacterial Infections/etiology , Bacterial Infections/physiopathology , Blood Pressure/drug effects , Intestinal Absorption/physiology , Mice , Mice, Inbred C3H , Recombinant Proteins/pharmacology , Tumor Necrosis Factor-alpha/physiology , Venous Pressure/drug effects , Xylose/pharmacokinetics
4.
Circ Shock ; 39(3): 231-6, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8453748

ABSTRACT

Although diltiazem improves function in several organs following trauma-hemorrhagic shock, the mechanism remains unknown. It is hypothesized that diltiazem maintains red blood cell calcium-to-magnesium ratio, resulting in better deformability of red blood cells. This should reduce blood viscosity, allowing red blood cells to traverse the microcirculation more efficiently and improve tissue oxygenation. To study this, rats (n = 23) underwent cannulation of various blood vessels and were divided into five groups: Group 1, control rats which had surgery only; Group 2, sham-operated rats which were not hemorrhaged but were infused with a volume of lactated Ringer's solution (LRS) equivalent to that given to the hemorrhaged animals (Groups 4 and 5); Group 3, hemodilution animals which were maintained at normal blood pressure but with the hematocrit lowered to values equivalent to hemorrhaged rats (Groups 4 and 5); Groups 4 and 5, animals which underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with LRS, 5x the shed blood volume, and were given IV saline (Group 4) or 400 micrograms diltiazem/kg (Group 5) with the resuscitation. Blood viscosity was measured at the end of resuscitation with a Brookfield DV-III viscometer. Results showed that blood viscosity was markedly reduced in the diltiazem treatment group, but was unchanged in any of the other groups versus the control. Thus, the beneficial effects of diltiazem after trauma-hemorrhage and resuscitation may be due in part to the marked decrease in blood viscosity allowing for improved oxygen delivery and removal of metabolites.


Subject(s)
Blood Viscosity/drug effects , Diltiazem/pharmacology , Resuscitation , Shock, Hemorrhagic/blood , Wounds and Injuries/blood , Animals , Blood Pressure/drug effects , Central Venous Pressure/drug effects , Hematocrit , Hemorrhage/physiopathology , Infusions, Intravenous , Male , Portal System/drug effects , Rats , Rats, Sprague-Dawley , Shock, Hemorrhagic/therapy , Venous Pressure/drug effects
5.
Am J Physiol ; 263(1 Pt 2): R19-23, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1636786

ABSTRACT

Although gut permeability increases and bacterial translocation occurs under certain pathological conditions, it remains unknown whether gut absorptive capacity (GAC) is altered early after the onset of sepsis. The aim of the present study was to investigate this and also to determine whether diltiazem has any effect on GAC in early sepsis. Rats were lightly anesthetized and cecal ligation and puncture (CLP) was performed. A nasogastric tube was inserted, cannulation of various blood vessels was carried out, and the animals were allowed to recover from anesthesia. One hour after CLP, one group of animals received a 1-ml bolus of normal saline intravenously, and another group received diltiazem, 400 micrograms/kg body wt. Sham animals had no CLP performed. GAC was determined by the D-xylose absorption test at 2 and 4 h after CLP. One hour after the administration of D-xylose via the nasogastric tube, its concentration in portal blood was determined colorimetrically. Results show that GAC is significantly depressed at 2 and 4 h after CLP despite the maintenance of normal blood pressure, central venous pressure, and portal pressure. Administration of diltiazem restored GAC to normal levels at 4 h after CLP. Thus diltiazem is a useful adjuvant in the treatment of sepsis because it restores gut absorptive capacity to normal and allows for early enteral nutrition.


Subject(s)
Diltiazem/pharmacology , Intestinal Mucosa/metabolism , Absorption , Animals , Blood Pressure , Central Venous Pressure , Intestines/drug effects , Intestines/physiopathology , Male , Portal Vein/physiopathology , Rats , Rats, Inbred Strains , Xylose/pharmacokinetics
6.
Ann Surg ; 215(4): 377-82, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1558419

ABSTRACT

Recently there has been increasing concern over transfusion-related diseases, especially acquired immune deficiency syndrome (AIDS). The authors therefore investigated the efficacy of lactated Ringer's solution (LRS) alone as compared with blood plus LRS resuscitation on body weight change and mortality rate after severe trauma-hemorrhagic shock. Rats, 250 to 310 g (n = 85), had a midline laparotomy performed (i.e., trauma induced), the incision was closed, and a carotid artery, jugular vein, and femoral artery were cannulated. The unrestrained, nonheparinized rats were allowed to recover from anesthesia and were bled within 10 minutes to a mean arterial pressure (MAP) of 40 mmHg. This MAP was maintained by removing more blood until the animal was unable to compensate (maximal bleedout; MB). The MAP was further maintained at 40 mmHg by returning fluid (LRS) until 50% of the MB volume (MBV) was returned. The rats were then resuscitated: group 1 with LRS 4 times the MBV; group 2 with 5 x LRS; group 3 with the shed blood returned + 2 x LRS. There was no difference between the groups in the initial weights, MAP, or hematocrit (Hct), percentage of blood volume removed, time to MB, or time to end of hemorrhage. The final Hct and MAP were higher in group 3 (p less than 10(-6)) than in either of the other groups. Body weight gain was greater in group 2 compared with either of the other groups (p less than 0.05) on day 1 after hemorrhage because of edema, but no differences were seen on subsequent days. There were no differences in the survival of animals in the different groups. These results suggest that there should perhaps be a higher threshold for blood transfusion in the management of severe trauma-hemorrhagic shock than is currently practiced.


Subject(s)
Blood Transfusion , Isotonic Solutions/therapeutic use , Plasma Substitutes/therapeutic use , Resuscitation , Shock, Hemorrhagic/therapy , Animals , Blood Pressure , Blood Volume , Body Weight , Crystalloid Solutions , Hematocrit , Male , Rats , Rats, Inbred Strains , Ringer's Lactate , Shock, Hemorrhagic/physiopathology , Survival Rate
7.
Ann Surg ; 214(6): 712-8, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1741651

ABSTRACT

Although bacterial translocation occurs after trauma-hemorrhage, it is unknown whether gut absorptive capacity (GAC) is altered under those conditions. The aim of this study, therefore, was to determine this and also whether diltiazem (DZ) has any effect on GAC after hemorrhage. Rats (n = 12; 270 to 300 g) were lightly anesthetized with ether and a 6-cm midline laparotomy performed (i.e., trauma induced). A nasogastric tube was inserted, cannulation of a carotid and femoral artery and a jugular and the portal veins performed, and the animals allowed to recover from anesthesia. They were then bled to a mean blood pressure of 40 mm Hg within 10 minutes and maintained at this pressure by further bleeding or return of fluid (lactated Ringer's solution [LRS] ) until 40% of the shed blood volume (SBV) had been returned in the form of LRS (end of hemorrhage, EH; time from onset of hemorrhage to EH = 93.4 +/- 4.4 minutes). The rats then were resuscitated with LRS, 3 times the SBV over 45 minutes, followed by 2x over 60 minutes. One group received 400 micrograms/kg DZ, and another group received saline, with the 2x LRS. Sham animals were not hemorrhaged. Gut absorptive capacity was determined by the 1-hour D-xylose absorption test at 2 and 4 hours after EH. Results demonstrate that GAC is significantly depressed after hemorrhage and resuscitation. Administration of diltiazem restored GAC to normal levels. Thus DZ is a useful adjuvant to treatment after trauma-hemorrhagic shock, because it restores GAC to normal and allows for early enteral nutrition.


Subject(s)
Diltiazem/therapeutic use , Intestinal Absorption , Shock, Hemorrhagic/physiopathology , Shock, Traumatic/physiopathology , Animals , Blood Pressure , Diltiazem/pharmacology , Intestinal Absorption/drug effects , Male , Rats , Rats, Inbred Strains , Shock, Hemorrhagic/drug therapy , Shock, Traumatic/drug therapy , Venous Pressure , Xylose/pharmacokinetics
8.
Am J Physiol ; 261(5 Pt 2): R1313-20, 1991 Nov.
Article in English | MEDLINE | ID: mdl-1951781

ABSTRACT

Recently, it has become evident that the gut plays a central role in the development of multiple organ failure in the critically ill patient after trauma-hemorrhage and sepsis. However, it remains unknown whether gut absorptive capacity (GAC) is altered under those conditions. The aim of this study, therefore, was to use a rat model for GAC measurements independent of the function of other organs and to determine whether GAC is altered after trauma. Rats (n = 79; 250-325 g) were lightly anesthetized with ether, and a 6-cm midline laparotomy was performed (i.e., trauma induced). A nasogastric tube was inserted and after cannulation of various blood vessels, the animals were allowed to recover from anesthesia. They were then divided into various groups for determinations of GAC over a period of 5 days. Control animals had GAC measurements without any surgery being performed on them. GAC was determined using the 1-h D-xylose absorption test and measuring D-xylose concentration in the portal blood. Results demonstrate that GAC 1) is significantly depressed for the first 48 h after trauma, 2) returns to normal 72 h after trauma, and 3) is further depressed by hemorrhage and resuscitation and by sepsis after trauma. Thus the model described here can be used to investigate the effects of trauma, trauma plus hemorrhage, trauma plus sepsis, hemorrhage alone, and sepsis alone on GAC, independent of the function of other organs.


Subject(s)
Intestinal Absorption , Xylose/metabolism , Analysis of Variance , Animals , Blood Pressure , Body Weight , Cecum/physiology , Hematocrit , Hemorrhage/physiopathology , Male , Rats , Rats, Inbred Strains , Reference Values , Sepsis/physiopathology , Xylose/blood
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