Biomedical subjects

El Rasheid Zakaria

Publications and source records attributed to El Rasheid Zakaria.

15 recordsLinked to original sources

PubMed2006

Hypertonic saline resuscitation improves intestinal microcirculation in a rat model of hemorrhagic shock.

BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock (HS) often restores and maintains hemodynamics but fails to restore intestinal perfusion. Post-CR intestinal ischemia has been implicated in the initiation of a gut-derived exaggerated systemic inflammatory response and in the progressive organ failure following HS. We propose that intestinal ischemia can be prevented with hypertonic saline resuscitation (HTSR). METHODS: Anesthetized male Sprague-Dawley rats (200 to 215 g) were hemorrhaged to 50% of mean arterial pressure (MAP) for 60 minutes and randomly assigned to 1 of the resuscitation groups (n = 7 each): Group I: sham operation and no HS; Group II: HS + CR with the return of the shed blood + 2 volumes of normal saline (NS); Group III: HS + return of the shed blood + hypertonic saline (HTS); (7.5 % NaCl, 4 ml/kg); Group IV: HS + HTS, then return of the shed blood after 60 minutes; Group V: HS + HTS, then 1 volume of NS after 60 minutes. Microvascular diameters of inflow (A1) and proximal and distal premucosal arterioles (A3) in terminal ileum and flow in A1 were measured using in vivo videomicroscopy and optical Doppler velocimetry. Hematocrit, plasma osmolarity, and electrolytes were measured in Groups II and III. RESULTS: HS caused a selective vasoconstriction in A1 arterioles that was not seen in the premucosal arterioles. CR restored and maintained MAP and caused generalized, progressive vasoconstriction at all intestinal arteriolar levels that is associated with hypoperfusion. HTSR failed to restore or maintain MAP or intestinal A1 arteriolar blood flow until the shed blood was returned. However, HTSR prevented the post-resuscitation, premucosal vasoconstriction and produced an insidious selective vasodilation in the A3 arterioles, which was most significant with early blood return (Group III). This selective arteriolar vasoactivity was associated with a significant improvement of endothelial cell function. Plasma hyperosmolality and hypernatremia persisted during the entire 2 hours post-resuscitation with HTS. CONCLUSIONS: Small-volume HTSR can be used as a resuscitation regimen at the trauma scene and for selective clinical conditions where hypotensive resuscitation is indicated. HTSR improves intestinal perfusion by selective vasodilation of the precapillary arterioles even at MAP close to shock levels.

Animals↗

PubMed2006

Clinical peritoneal dialysis solutions modulate white blood cell-intestinal vascular endothelium interaction.

BACKGROUND: Hemorrhagic shock (HS) with conventional resuscitation (CR) (HSCR) primes neutrophils and modulates leukocyte (WBC)-endothelium interaction as part of an exaggerated systemic inflammatory response. We hypothesize that topical application of clinical peritoneal dialysis solutions (PD) modulates such interaction. METHODS: Intestinal intravital microscopy was used to measure WBC rolling in terminal ileum post capillary venules (V2 and V3) in sham-operated animals, and in animals that underwent fixed pressure hemorrhage (50% mean arterial pressure for 60 minutes), followed by conventional resuscitation with the return of the shed blood and 2 vol of saline. Number of rolling WBCs per thirty seconds in selected V2 and V3, bathed in either Kreb's solution or a 2.5% clinical peritoneal dialysis solution (PD) was quantified. Diameters were measured for the in-flow arterioles (A1), and out-flow venules (V1), for calculation of local blood flow with optical Doppler velocimetry. RESULTS: The PD solution significantly (P < .05, n = 11) attenuated WBC-endothelium interaction in sham-operated animals while no significant difference was elicited in HSCR (P > .05, n = 9 Kreb's, n = 7 PD). In addition, the PD solution produced an instantaneous dilation at all levels of the intestinal arterioles in both sham and HSCR. While intestinal venular blood outflow was increased by the PD solution, venular diameters changed very little. CONCLUSION: Superfusion of the gut with glucose-based peritoneal dialysis solutions decreases the concentration of rolling leukocytes along the venular vascular endothelium by a vasodilation-mediated increase in arteriolar inflow and venous outflow mechanism. Hemorrhagic shock and conventional resuscitation enhance the concentration of rolling leukocytes presumably by mechanisms related to upregulation of the adhesion molecules and the low-flow state. Hemorrhage and resuscitation-enhanced leukocytes rolling was not reversed by adjunctive DPR despite the associated marked increase in arterial inflow and venous outflow. The status of the endothelium and the level of leukocyte priming in low-flow states are stronger predictors of leukocyte-endothelium interaction than rheology factors.

Animals↗

PubMed2005

Disparity in osmolarity-induced vascular reactivity.

Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat endothelium-intact and -denuded aortic rings (2 mm) was studied ex vivo in a standard tissue bath. In both studies, suffusion of the vessels was performed with filter-sterilized isotonic and hypertonic solutions that contained glucose or mannitol as osmotic agents. PDS served as a control (Delflex 2.25%). Hypertonic glucose and mannitol solutions produced a significant vascular reactivity in aortic rings and instantaneous and sustained vascular relaxation at all levels of the intestinal microvasculature. Similarly, lactate that was dissolved in a low-pH isotonic physiologic salt solution produced significant force generation in aortic rings. Whereas isotonic glucose and mannitol solutions had no vasoactivity in aortic rings, isotonic glucose produced a selective, insidious, and time-dependent vasodilation in the intestinal premucosal arterioles (18 +/- 0.2% of baseline), which was not observed in the larger inflow arterioles (100 mum). This isotonic glucose-mediated vascular relaxation can be attenuated by approximately 50% with combined adenosine A(2a) and A(2b) receptor antagonists and completely abolished by adenosine A(1) receptor inhibition. By using two different experimental techniques, this study demonstrates that hyperosmolality and lactate are the major vasoactive components of clinical peritoneal dialysis solutions. The pattern and the magnitude of such reactivity are dependent on vessel size and on the solutes' metabolic activity. Low pH of conventional PDS is not a vasoactive component by itself but renders lactate vasoactive. Energy-dependent transport of glucose into cells mediates vasodilation of small visceral arterioles by an adenosine receptor-mediated mechanism and constitutes a significant fraction of PDS-mediated vascular reactivity in the visceral microvasculature.

Animals↗

PubMed2005

Peritoneal resuscitation.

BACKGROUND: After resuscitation from hemorrhagic shock, intestinal microvessels constrict leading to impaired mucosal blood flow. This occurs despite restoration of central hemodynamics. We review studies on the use of peritoneal dialysis fluid as an adjunct treatment in amelioration of this gut hypoperfusion. METHODS: Using in vivo microscopy of the intestinal microcirculation, the effects of topically applied dextrose-based peritoneal dialysis fluid was measured. In other words, animal experiments, the survival benefits, the morbidity, blood flow distribution, and the postresuscitation inflammatory response to direct peritoneal resuscitation (DPR) were determined. RESULTS: Simulated DPR caused a dramatic vasodilation compared with a progressive vasoconstriction when used during conventional resuscitation (CR) from hemorrhagic shock. It also reversed established vasoconstriction 2 and 4 hours after CR. In CR animals, there was a 40% mortality compared with 100% survival in DPR animals. DPR resulted in a downregulation of the gut-associated proinflammatory response noted after CR and similarly prevented edema formation. CONCLUSION: DPR enhances organ blood flow to organs incited in the pathogenesis of multiple organ failure and improves survival after severe hemorrhage and CR.

Analysis of Variance↗

PubMed2005

Direct energy delivery improves tissue perfusion after resuscitated shock.

BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock (HS) does not restore intestinal blood flow. Indicators of anaerobic metabolism suggest that cellular energy production also is compromised. We hypothesize that the direct intravenous delivery of lipid-encapsulated high-energy phosphates to cells improves intestinal perfusion during HS and resuscitation (RES). METHODS: MAP (MAP) was monitored in male rats (200 g), terminal ileum microvessel diameters were measured by in vivo videomicroscopy, and blood flow (Doppler velocimetry) was calculated. Cellular energy delivery was accomplished by intravenous infusion during RES of fusogenic unilamellar lipid vesicles that contain adenosine triphosphate (ATP; VitaSol). Our protocol was HS to 50% baseline MAP for 60 minutes, 30 minutes of RES, and continued microscopy observation for 120 minutes. Experimental groups (n=8 each) were HS+CR (group I); HS+CR+ VitaSol (group II); HS+CR+Vehicle, Vehicle is the phospholipid vesicles without magnesium ATP, (group III); HS+ VitaSol (group IV); sham-operated control+VitaSol (group V); and a time-matched sham-operated control (group VI). The survival outcome and total tissue water from wet weight/dry weight ratio as a function of adjunct VitaSol resuscitation were evaluated in separate intact animal experiments. RESULTS: HS caused a selective vasoconstriction of the intestinal inflow arterioles (100 microm), which was not seen in the smaller intestinal premucosal arterioles (7-15 microm). CR, which restored baseline hemodynamics, resulted in an initial restoration of intestinal microvascular diameters at all arteriolar levels. However, this was followed by a progressive vasoconstriction and hypoperfusion in premucosal vessels at 120 minutes after RES (-20.48% +/- 2.95% from baseline diameters). In contrast, VitaSol with CR caused enhanced premucosal dilation (+34.27% +/- 4.62%) and augmented flow (+20.50% +/- 10.70%) above prehemorrhage baseline. Vesicles alone had no effect, and VitaSol alone caused only a modest dilation. CR of moderate HS (40% of baseline MAP for 60 minutes, n=10) caused 20% mortality, whereas adjunct VitaSol resuscitation had a 100% survival and less tissue water content. CONCLUSIONS: Our data confirms that CR causes progressive intestinal hypoperfusion. Cellular resuscitation with direct intravenous energy delivery improves intestinal perfusion after CR and results in improved survival and less tissue edema.

Adenosine Triphosphate↗

PubMed2005

Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation.

BACKGROUND: After conventional resuscitation from hemorrhagic shock, splanchnic microvessels progressively constrict, leading to impairment of blood flow. This occurs despite restoration and maintenance of central hemodynamics. The authors' recent studies have demonstrated that topical and continuous ex vivo exposure of the gut microvasculature to a glucose-based clinical peritoneal dialysis solution (Delflex), as a technique of direct peritoneal resuscitation (DPR), can prevent these postresuscitation events when initiated simultaneously with conventional resuscitation. This study aimed to determine whether DPR applied after conventional resuscitation reverses the established postresuscitation intestinal vasoconstriction and hypoperfusion. METHODS: Male Sprague-Dawley rats were bled to 50% of baseline mean arterial pressure and resuscitated intravenously over 30 minutes with the shed blood returned plus two times the shed blood volume of saline. Initiation of ex vivo, topical DPR was delayed to 2 hours (group 1, n = 8), or to 4 hours (group 2, n = 8), respectively, after conventional resuscitation. Intravital microscopy and Doppler velocimetry were used to measure terminal ileal microvascular diameters of inflow A1 and premucosal A3 (proximal pA3, distal dA3) arterioles and blood flow in the A1 arteriole, respectively. Maximum arteriolar dilation capacity was obtained from the topical application, in the tissue bath, of the endothelium-independent nitric oxide-donor sodium nitroprusside (10M). RESULTS: Hemorrhagic shock caused a selective vasoconstriction of A1 (-24.1% +/- 2.15%) arterioles from baseline, which was not seen in A3 vessels. This caused A1 blood flow to drop by -68.6% of the prehemorrhage value. Conventional resuscitation restored and maintained hemodynamics in all the animals without additional fluid therapy. In contrast, there was a generalized and progressive postresuscitation vasoconstriction of A1 (-21.7%), pA3 (-18.5%), and dA3 (-18.7%) vessels. The average postresuscitation A1 blood flow was -49.5% of the prehemorrhage value, indicating a persistent postresuscitation hypoperfusion. Direct peritoneal resuscitation reversed the postresuscitation vasoconstriction by 40.9% and enhanced A1 blood flow by 112.9% of the respective postresuscitation values. CONCLUSIONS: Delayed DPR reverses the gut postresuscitation vasoconstriction and hypoperfusion regardless of the initiation time. This occurs without adverse effects on hemodynamics. Direct peritoneal resuscitation-mediated enhancement of tissue perfusion results from the local effects from the vasoactive components of the Delflex solution, which are hyperosmolality, lactate buffer anion, and, to a lesser extent, low pH. The molecular mechanism of this vasodilation effect needs further investigation.

Analysis of Variance↗

PubMed2004

Microvascular responses to adenosine help explain functional and pathologic differences between intestinal segments.

BACKGROUND: Many physiologic (post-prandial hyperemia), pathologic (inflammatory bowel disease), and clinical (enteral feeding) phenomena involve changes in microvascular blood flow to the intestine. Adenosine (Ado) derived from energy metabolism causes vasodilation and appears to be involved in some of these events. The Ado-mediated control mechanisms appear to vary with the diameter of the microvessels and the function of the tissue. This suggests the possibility that Ado-based microvascular control varies between anatomic intestinal segments and microvascular levels in those intestinal segments. METHODS: In vivo digital intravital microscopy was used to measure the responses of larger distributing (A1) and smaller premucosal (A3) vessels to Ado in intact neurovascular loops of jejunum and terminal ileum of the rat. Dose-response curves to Ado were determined. RESULTS: Microvascular dilation and augmented blood flow to Ado were significantly greater in the jejunum than in the terminal ileum. Ado-induced dilation was greater in the smaller A3 than in the larger A1 microvessels. DISCUSSION: These data indicate (1) different vasodilator mechanisms for the jejunum and the terminal ileum, (2) a greater role for Ado-related microvascular control in the jejunum compared with the ileum, and (3) a greater Ado-related control in the premucosal (A3) vessels. These findings suggest that Ado-mediated microvascular effects could explain why some clinical phenomena vary in intensity in selective intestinal segments, and are likely to involve different microvascular control mechanisms in the different segments. Knowledge of these Ado mechanisms could be beneficial in certain clinical scenarios to control blood flow during pathologic conditions.

Adenosine↗

PubMed2004

Direct peritoneal resuscitation as adjunct to conventional resuscitation from hemorrhagic shock: a better outcome.

BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock often culminates in multisystem organ failure and death, commonly attributed to a progressive splanchnic vasoconstriction and hypoperfusion, a gut-derived systemic inflammatory response (SIR), and fluid sequestration. Direct peritoneal resuscitation (DPR) produces a sustained state of tissue hyperperfusion in splanchnic and distant organs. In this study we evaluated the therapeutic potential of DPR on the SIR and fluid sequestration as parameters of treatment outcome. METHODS: Anesthetized nonheparinized rats continuously monitored for hemodynamics were bled to 40% of mean arterial pressure for 60 minutes. Animals were randomized for CR or CR plus DPR under aseptic conditions. Sham nonhemorrhaged rats served as control. Qualitatively, animals were blindly observed for body weight, illness score, or death for 72 hours. Tissues were harvested from survivors, and SIR was measured by interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and enzyme-linked immunosorbent assay, and fluid sequestration was measured by dry weight/wet weight ratio (DW/WW). RESULTS: Adjunct DPR caused a marked increase (P >.01 by analysis of variance) in the immunoregulator IL-10 in the liver (10,990 +/- 1,470 pg/g) and gut (1815 +/- 640 pg/g), compared to CR rats (6450 +/- 1000 pg/g and 1555 +/- 590, respectively), which is associated with down-regulation of IL-6 and tumor necrosis factor-alpha in liver and gut, from 57 +/- 4 and 20 +/- 3 pg/g, respectively, to 42 +/- 4 and 9 +/- 2 pg/g in DPR-treated animals. CR animals had a lower DW/WW ratio in liver (-36%), spleen (-22%), and lung (-24%) compared to DPR (P <.05), where the DW/WW ratio did not differ from control animals. This fluid sequestration is consistent with a 12% and 5% gain in prehemorrhage body weight at 24 and 72 hours after treatment in the CR animals. Thirty percent of CR animals died within 24 hours, and survivors were squeaking, cold, and pale in eyes and ears and oliguric despite features of fluid overload. In comparison, DPR animals exhibited normal appearance by 24 hours and demonstrated a 100% survival at 72 hours. CONCLUSIONS: This study demonstrates that DPR as adjunct to CR has beneficial effects on the pathophysiology of resuscitated hemorrhagic shock. In addition to restoration of tissue perfusion, DPR has immunomodulation and anti-fluid sequestration effects. These modulations result in improved outcome.

Animals↗

PubMed2004

Impairment of endothelium-dependent dilation response after resuscitation from hemorrhagic shock involved postreceptor mechanisms.

Resuscitation from hemorrhagic shock is associated with impairment of the endothelium-dependent dilation response, whereas the dilation response induced by the endothelium-independent pathway, which is mediated by nitroprusside, a nitric oxide (NO) donor and a direct activator of guanylate cyclase, remains unaltered. Whether the impairment of the endothelium-dependent dilation response is caused by a specific receptor alteration or generally a defect in signal transduction pathway remains undetermined. Anesthetized rats were monitored for hemodynamics, and the terminal ileum was prepared for intravital videomicroscopy. Hemorrhage was 50% of mean arterial pressure for 60 min followed by resuscitation with the shed blood returned plus 2 volumes of normal saline. Intestinal microvascular reactivity to the endothelium-dependent receptor-dependent agonists acetylcholine or substance P (10(-8) or 10(-6) M), as well as the endothelium-dependent receptor-independent calcium ionophore, was determined at baseline and at 2 h postresuscitation from hemorrhagic shock. Measured vascular diameters for premucosal A3 arterioles (pA3 and dA3) were normalized and expressed as percentage of the maximal dilation capacity, as obtained from the response to the endothelium-independent NO donor sodium nitroprusside (10(-4) M). At 2 h postresuscitation, there was a marked constriction of pA3 (-70.1 +/- 20) and dA3 (-61.5 +/- 11.6) from maximal dilation capacity. Baseline premucosal arteriolar response to substance P (10(-8) M) was 30.68 +/- 4.19% and 34.66 +/- 5.82% for pA3 and dA3 arterioles, respectively. This was significantly reduced to 20.97 +/- 2.41% and 17.94 +/- 3.60% at 2 h postresuscitation. However, no significant difference between baseline and postresuscitation arteriolar responses was observed at the higher dose of substance P (10(-6) M). Postresuscitation premucosal arteriolar response to the endothelium-dependent receptor-independent calcium ionophore (10(-9) to 10(-5) M) is characterized by a marked decrease in sensitivity and an enhanced threshold for calcium ionophore-mediated dilation. The logEC50 was -7.62 +/- 0.39 and -7.75 +/- 0.32 for the pA3 and dA3 at baseline, respectively. This was significantly (P < 0.01) reduced to -5.15 +/- 0.14 and -4.39 +/- 0.71 at 2 h postresuscitation. These data suggest that impairment of the endothelium-dependent dilation response after resuscitation from hemorrhagic shock is not mediated by specific receptor alteration. Cellular mechanisms that participate in or are part of oxygen free radical formation after resuscitation from hemorrhagic shock such as Ca2+ and leukocytes, appear to have a pivotal role in the mechanism of cellular dysfunction.

Animals↗

PubMed2004

Role of neutrophils on shock/resuscitation-mediated intestinal arteriolar derangements.

Adequate resuscitation from hemorrhagic shock that preserves hemodynamics is associated with a generalized and progressive intestinal arteriolar vasoconstriction and hypoperfusion coupled with impairment of the endothelium-dependent dilation response. This study was performed to investigate the role of neutrophils on the postresuscitation intestinal arteriolar derangements. Experiments were performed in anesthetized rats 24 h after neutrophil depletion. Neutropenia was induced with antineutrophil serum by tail vein injection. Rats injected with rabbit serum lacking anti-rat neutrophil antibody served as controls. Hemorrhagic shock was 50% of mean arterial pressure for 60 min. Resuscitation was with the shed blood returned plus 2 volumes of saline. A nonhemorrhage group served as control. Intravital videomicroscopy of the terminal ileum was used to measure microvascular diameter and centerline red cell velocity. Endothelial function was assessed from the response to the endothelium-dependent dilator acetylcholine (10(-9) to 10(-4) M). Regardless of neutrophil count, hemorrhagic shock caused selective vasoconstriction of inflow A1 arterioles (-21.49 +/- 0.67%) from baseline, which was not seen in the premucosal A3 vessels (pA3, dA3). At 2 h postresuscitation, there was a generalized vasoconstriction from baseline diameter in A1 (-21.26 +/- 2.29%), pA3 (-22.66 +/- 5.02%), and dA3 (-17.62 +/- 4.84%). Neutrophil depletion caused a significant reset of baseline A1 blood flow from 701 +/- 90 nL/s to 978 +/- 90 nL/s and attenuated the postresuscitation hypoperfusion. This occurred independently of the A1 diameter change. Hemorrhagic shock/resuscitation caused impairment of the endothelium-dependent dilation response irrespective of neutrophil count. This study demonstrates that neutrophils do not contribute to the hemorrhagic/resuscitation-mediated intestinal arteriolar derangements, but appear to possess a role in the intestinal arteriolar blood flow regulation under normal and low flow states possibly via a rheologic effect.

Acetylcholine↗

PubMed2003

A novel method of peritoneal resuscitation improves organ perfusion after hemorrhagic shock.

BACKGROUND: After resuscitation from hemorrhagic shock, intestinal microvessels constrict leading to impairment of blood flow. This occurs despite restoration and maintenance of central hemodynamics. Our recent studies have demonstrated that topical and continuous exposure of the gut microvasculature to a clinical solution (Delflex; Fresenius Medical Care), as a technique of direct peritoneal resuscitation (DPR), reverses the postresuscitation vasoconstriction and hypoperfusion to a sustained dilation and hyperperfusion. We hypothesize that initiation of DPR simultaneously with resuscitation from hemorrhagic shock enhance organ blood flow to all tissues surrounding the peritoneal cavity as well as distant organs. METHODS: Male Sprague-Dawley rats were anesthetized, intubated and cannulated for monitoring of hemodynamics and for withdrawal of blood. Rats were hemorrhaged to 50% of mean blood pressure for 60 minutes prior to resuscitation with shed blood plus 2 volumes of saline. Animals were randomized for intraperitoneal therapy with 30 mL saline (group 1, n = 9), or Delflex (group 2, n = 9). Whole organ blood flow was measured by colorimetric microsphere technique with phantom organ at baseline, after completion of resuscitation, and at 120 minutes postresuscitation. Replenishment of the dwelling intraperitoneal saline or Delflex was performed in (group 3, n = 8), and (group 4, n = 8), respectively at 90 minutes postresuscitation, and a single whole organ blood flow was performed at 120 minutes postresuscitation. RESULTS: Direct peritoneal resuscitation caused a significant increase in blood flow to the jejunum (35%), ileum (33%), spleen (48%), and pancreas (57%), whereas a marked increase in blood flow was detected in the lung (111%), psoas major muscle (115%), and diaphragm (132%), as compared with the saline treated animals in group 1. At 120 minutes postresuscitation, organ blood flow returned to the prehemorrhagic shock baseline level in all organs irrespective of peritoneal therapy. Replenishment of the intraperitoneal solution in group 3 and 4, enhanced blood flow to the liver, kidneys, and diaphragm. CONCLUSIONS: Direct peritoneal resuscitation enhanced blood flow to organs incited in the pathogenesis of multiple organ failure that follows hemorrhagic shock.

Animals↗

PubMed2003

Intraperitoneal resuscitation improves intestinal blood flow following hemorrhagic shock.

OBJECTIVE: To study the effects of peritoneal resuscitation from hemorrhagic shock. SUMMARY BACKGROUND DATA: Methods for conventional resuscitation (CR) from hemorrhagic shock (HS) often fail to restore adequate intestinal blood flow, and intestinal ischemia has been implicated in the activation of the inflammatory response. There is clinical evidence that intestinal hypoperfusion is a major factor in progressive organ failure following HS. This study presents a novel technique of peritoneal resuscitation (PR) that improves visceral perfusion. METHODS: Male Sprague-Dawley rats were bled to 50% of baseline mean arterial pressure (MAP) and resuscitated with shed blood plus 2 equal volumes of saline (CR). Groups were 1) sham, 2) HS + CR, and 3) HS + CR + PR with a hyperosmolar dextrose-based solution (Delflex 2.5%). Groups 1 and 2 had normal saline PR. In vivo videomicroscopy and Doppler velocimetry were used to assess terminal ileal microvascular blood flow. Endothelial cell function was assessed by the endothelium-dependent vasodilator acetylcholine. RESULTS: Despite restored heart rate and MAP to baseline values, CR animals developed a progressive intestinal vasoconstriction and tissue hypoperfusion compared to baseline flow. PR induced an immediate and sustained vasodilation compared to baseline and a marked increase in average intestinal blood flow during the entire 2-hour post-resuscitation period. Endothelial-dependent dilator function was preserved with PR. CONCLUSIONS: Despite the restoration of MAP with blood and saline infusions, progressive vasoconstriction and compromised intestinal blood flow occurs following HS/CR. Hyperosmolar PR during CR maintains intestinal blood flow and endothelial function. This is thought to be a direct effect of hyperosmolar solutions on the visceral microvessels. The addition of PR to a CR protocol prevents the splanchnic ischemia that initiates systemic inflammation.

Animals↗

PubMed2002

Resuscitation regimens for hemorrhagic shock must contain blood.

Endothelial cell dysfunction occurs during hemorrhagic shock (HS) and persists despite adequate resuscitation (RES) that restores and maintains hemodynamics. We hypothesize that RES from HS with crystalloid solutions alone aggravate the endothelial cell dysfunction. To test this hypothesis, anesthetized nonheparinized rats were monitored for hemodynamics, and the terminal ileum was studied with intravital video microscopy. HS was 50% of mean arterial pressure (MAP) for 60 min. Four hemorrhaged groups (10 animals in each group) were randomized for RES: group I with shed blood returned + equal volume of normal saline (NS); group II with shed blood returned + 2x NS; group III with 2x NS only; and group IV with 4x NS only. Two hours post-RES, endothelial cell function was assessed with the endothelial-dependent agonist acetylcholine (ACh, 10(-9)-10(-4) M). Maximum arteriolar diameter was elicited by the endothelial-independent agonist sodium nitroprusside (NTP, 10(-4) M). HS caused a selective vasoconstriction associated with low blood flow in inflow A1 arterioles in all hemorrhaged groups. Post-RES vasoconstriction developed in A1 and premucosal arterioles (pA3 and dA3) In all hemorrhaged groups regardless of the RES regimen. However, A1 vasoconstriction and flow were significantly worst in the animals RES with NS alone (-43% and -75%, respectively) compared with those resuscitated with blood and NS (-27% and -57%). Impaired dilation response to ACh was noted in all hemorrhaged animals. However, a significant shift to the right of the dose-response curve (decreased sensitivity) was observed in the animals resuscitated with NS alone irrespective of the RES volume. These animals required at least two orders of magnitude greater ACh concentration to produce a 20% dilation response. For all vessel types, Group II had the best preservation of endothelial cell function. In conclusion, HS causes a selective vasoconstriction of A1 arterioles, which was not observed in A3 vessels. RES from HS results in progressive vasoconstriction in all intestinal arterioles irrespective of the RES regimen. Crystalloid RES after HS does not restore hemodynamics to baseline and is associated with a marked endothelial cell dysfunction. Blood-containing RES regimens preserve and maintain hemodynamics and are associated with the least microvascular dysfunction. Therefore, regimens for RES from HS must contain blood. Endothelial cell dysfunction is not the sole etiologic factor of post-RES microvascular impairment.

Animals↗

PubMed2001

Improving contact area between the peritoneum and intraperitoneal therapeutic solutions.

A general assumption in peritoneal dialysis or intraperitoneal chemotherapy has been that a volume of 2 to 3 L in the human is sufficient to make contact with the entire anatomic peritoneum. On the basis of our previous experimental work and that of others, it was hypothesized that only a fraction of the anatomic peritoneum was in contact with the therapeutic solution in the cavity over a short period of time. It was also hypothesized that use of agitation of the experimental animal or a surfactant in the dialysis fluid would increase the contact area of the intraperitoneal solution. These hypotheses were tested by developing a method to measure the peritoneal contact area simultaneously with the anatomic peritoneal area. Anesthetized mice (25 to 35 g) received an injection of a relatively large volume (10 ml) of isotonic solution containing a radiolabeled protein that adhered to the peritoneum with which it came in contact. After a dwell of 1 to 24 h, the animal was killed and frozen. Cross sections of the abdominal and pelvic cavities were cut and placed against film to develop into autoradiograms, which represent the linear dimension of fluid contact in each sampling plane. The tissue sections that corresponded to the autoradiograms were stained to display the linear dimension of the anatomic peritoneum in the sampling plane. By imaging both the autoradiogram and the corresponding histologic slide, an estimate of the ratio of the contact area to anatomic area in each plane can be calculated (R(mean) = average of all ratios). Applying this method to mice that were dialyzed with an isotonic salt solution under quiescent conditions for 1 h produced R(mean) = 0.43 +/- 0.03. With rapid shaking of the animal, R(mean) = 0.54 +/- 0.03 (P: < 0.05). Addition of the surfactant dioctyl sodium sulfosuccinate (DSS) 0.5% to the solution under quiescent conditions increased R(mean) to 1.07 +/- 0.03 (P: < 0.001). Lengthening the dwell of the isotonic solution to 24 h increased R(mean) to >0.90. In further study of the effect of the concentration of DSS on contact area, there was a direct correlation of R(mean) with concentrations ranging from 0.0005 to 0.05% DSS. It is concluded that less than half of the mouse peritoneum is in contact with a large volume of solution in the peritoneal cavity. Maneuvers such as agitation and use of surfactant in the intraperitoneal solution increase the fraction of contact area. Also demonstrated was a direct dose-response of contact area versus intraperitoneal concentration of DSS, which may be useful in intraperitoneal therapies of peritoneal dialysis or intraperitoneal chemotherapy.

Animals↗

PubMedDate not supplied

Generalized dilation of the visceral microvasculature by peritoneal dialysis solutions.

OBJECTIVES: Conventional peritoneal dialysis solutions are vasoactive. This vasoactivity is attributed to hyperosmolality and lactate buffer system. This study was conducted to determine if the vasodilator property of commercial peritoneal dialysis solutions is a global phenomenon across microvascular levels, or if this vasodilation property is localized to certain vessel types in the small intestine. DESIGN: Experimental study in a standard laboratory facility. INTERVENTIONS: Hemodynamics of anesthetized rats were monitored while the terminal ileum was prepared for in vivo intravital microscopy. Vascular reactivity of inflow arterioles (A1), branching (A2), and arcade, as well as pre-mucosal (A3) arterioles was assessed after suffusion of the terminal ileum with a non-vasoactive solution or a commercial 4.25% glucose-based solution (Delflex; Fresenius USA, Ogden, Utah, USA). Vascular reactivity of three different level venules was also assessed. Maximum dilation response was obtained from sequential applications of the endothelial-dependent dilator, acetylcholine (10(-5) mol/L), and the endothelial-independent nitric oxide donor, sodium nitroprusside (NTP; 10(-4) mol/L). RESULTS: Delflex induced an instant and sustained vasodilation that averaged 28.2% +/- 2.4% of baseline diameter in five different-level arterioles, ranging in size between 7 mu and 100 mu. No significant vascular reactivity was observed in three different-level venules. Delflex increased intestinal A1 blood flow from baseline 568 +/- 31 nL/ second to 1,049 +/- 46 nL/sec (F= 24.7, p< 0.001). Similarly, intestinal venous outflow increased to 435 +/- 17 nL/sec from a baseline outflow of 253 +/- 59 nL/sec (F= 4.7, p < 0.05). Adjustment of the initial pH of Delflex from 5.5 to 7.4 resulted in similar microvascular responses before pH adjustment. CONCLUSIONS: Ex vivo exposure of intestinal arterioles to conventional peritoneal dialysis solutions produces a sustained and generalized vasodilation. This vasoactivity is independent of arteriolar level and the pH of the solution. Dialysis solution-mediated vasodilation is associated with doubling of A1 intestinal arteriolar blood flow. Addition of NTP at an apparent clinical dose does not appear to produce any further significant arteriolar dilation than that induced by dialysis solution alone. Experimental data that estimate the exchange vessel surface area per unit volume of tissue will be required to make a correlation with permeability in order to extrapolate our findings to clinical in vivo conditions.

Animals↗