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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concept of small-volume resuscitation, the rapid infusion of a small volume (4 ml/kg BW) of hyperosmolar 7.2-7.5% saline solution for the initial therapy of severe hypovolemia and shock was advocated more than a decade ago. Numerous publications have established that hyperosmolar saline solution can restore arterial blood pressure, cardiac index and oxygen delivery as well as organ perfusion to pre-shock values. Most prehospital studies failed to yield conclusive results with respect to a reduction in overall mortality. A meta-analysis of preclinical studies from North and South America, however, has indicated an increase in survival rate by 5.1% following small-volume resuscitation when compared to standard of care. Moreover, small-volume resuscitation appears to be of specific impact in patients suffering from head injuries with increased ICP and in severest trauma requiring immediate surgical intervention. Results from clinical trials in Austria, Germany and France have demonstrated positive effects of hyperosmolar saline solutions when used for fluid loading or fluid substitution in cardiac bypass and in aortic aneurysm surgery, respectively. A less positive perioperative fluid balance, a better hemodynamic stability and improved pulmonary function were reported. In septic patients oxygen consumption could significantly be augmented. The most important mechanism of action of small-volume resuscitation is the mobilisation of endogenous fluid primarily from oedematous endothelial cells, by which the rectification of shock-narrowed capillaries and the restoration of nutritional blood, flow is efficiently promoted. Moreover, after ischemia reperfusion a reduction in sticking and rolling leukocytes have been found following hyperosmolar saline infusion. Both may be of paramount importance in the long-term preservation of organ function following hypovolemic shock. An increased myocardial contractility in addition to the fluid loading effects of hyperosmolar saline solutions has been suggested as a mechanism of action. This, however, could not be confirmed by pre-load independent measures of myocardial contractility. Some concerns have been raised regarding the use of hyperosmolar saline solutions in patients with a reduced cardiac reserve. A slower speed of infusion and adequate monitoring is recommended for high risk patients. Recently, hyperosmolar saline solutions in combination with artificial oxygen carriers have been proposed to increase tissue oxygen delivery through enhanced O2 content. This interesting perspective, however, requires further studies to confirm the potential indications for such solutions. Many hyperosmolar saline colloid solutions have been investigated in the past years, from which 7.2-7.5% sodium chloride in combination with either 6-10% dextran 60/70 or 6-10% hydroxyethyl starch 200,000 appear to yield the best benefit-risk ratio. This has led to the registration of the solutions in South America, Austria, The Czech Republic, and is soon awaited for North America.
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PMID:[Small-volume resuscitation for hypovolemic shock. Concept, experimental and clinical results]. 922 85

Extreme arterial and venous constructions are common problems in microvascular surgery, often leading to tissue injury and flap failure. The ideal pharmacologic tool to counteract ischemia should exert its action both locally and distally in the microcirculation of the flap. In this study, the vascular properties of sodium nitroprusside, hydralazine, and cromakalin were evaluated and compared in in vitro and in vivo models in the rabbit carotid artery. In the in vitro study, 20 rings from the rabbit carotid artery were bathed in Krebs-Ringers solution, stretched progressively to an optimal tension of 3.7 to 4.2 gm, and their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 microM) and a dose-response curve was established by adding cumulatively either sodium nitroprusside (n = 7), cromokalin (n = 7), or hydralazine (n = 7) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 19 animals using 9-0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride, and served as control. The other side was treated blindly with the topical application of 1 ml of either sodium nitroprusside (10 mg/ml, n = 5), hydralazine (20 mg/ml, n = 5), or cromakalin (25 mg/ml, n = 4), during and after the anastomoses. Blood-flow changes in the vessels were continuously monitored with the transonic Doppler applied to both carotid arteries for 60 min after the procedure. Sodium nitroprusside and cromakalin elicited a concentration-dependent relaxation of norepinephrine-precontracted carotid artery rings in vitro. Sodium nitroprusside was significantly more effective than cromakalin in inducing relaxation. Hydralazine elicited a biphasic response, with low concentrations (1.5 x 10(-5) to 1.5 x 10(-3) M) potentiating the norepinephrine-induced contraction, and high concentrations relieving this contraction. Microsurgical anastomosis in the rabbit carotid artery-produced a significant decrease of blood flow through the vessel as measured by the transonic Doppler for 30 min. Topical application of heparinized saline did not significantly change the blood flow after the microvascular anastomosis. Topical application of sodium nitroprusside and cromakalin significantly increased the blood flow in the vessel after the anastomosis; however, the topical hydralazine did not significantly alter blood flow, but demonstrated a trend toward increased flow values. The data support the conclusion that sodium nitroprusside and cromakalin could be used to relieve vascular constriction. It is suggested that further studies on the clinical use of these drugs in microsurgery is warranted.
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PMID:Drug-induced vasodilation: the effects of sodium nitroprusside, hydralazine, and cromakalin on the rabbit carotid artery: in vitro and in vivo study. 927 4

The authors examined the effect of delayed high-concentration albumin therapy on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Male Sprague-Dawley rats weighing 270 to 320 g were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion induced by means of a poly-L-lysine-coated intraluminal nylon suture inserted retrograde via the external carotid artery into the internal carotid artery and MCA. The agent (20% human serum albumin [HSA]) or control solution (sodium chloride 0.9%) was administered intravenously at a dosage of 1% of body weight immediately after suture removal following a 2-hour period of MCA occlusion. The animals' neurological status was evaluated during MCA occlusion (at 60 minutes) and daily for 3 days thereafter. The brains were perfusion-fixed, and infarct volumes and brain edema were determined. The HSA significantly improved the neurological score compared with saline at 24 hours after MCA occlusion. The rats treated with HSA also had significantly reduced total infarct volume (by 34%) and brain edema (by 81%) compared with saline-treated rats. There was a strong correlation between hematocrit level and brain edema (p < 0.01), and between total infarct volume or brain edema and neurological score at 24, 48, and 72 hours postinjury (p < 0.0002). These results strongly support the beneficial effect of delayed albumin therapy in transient focal ischemia and indicate its possible usefulness in treating patients with acute ischemic stroke.
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PMID:Effect of delayed albumin hemodilution on infarction volume and brain edema after transient middle cerebral artery occlusion in rats. 932 48

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.
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PMID:Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery. 938 59

Ischemia/reperfusion events alter the cellular ion homeostasis by intracellular acidosis and a subsequent rise of sodium and calcium concentrations. Since disturbance of intracellular Ca2+ signaling pathways impairs cellular function, we investigated the effect of sodium bicarbonate infusion on hepatocellular Ca2+ dysregulation induced by resuscitation from hemorrhagic shock. Anesthetized Sprague-Dawley rats were bled to a mean arterial blood pressure of 40 mmHg for 60 min. Rats were resuscitated by retransfusion of shed blood (60%) in 20 min and three-fold the bleed out volume as lactated Ringers' during 60 min and received either a bolus infusion of sodium bicarbonate (2 mval/kg body weight) or an equal volume of sodium chloride (0.9%). After hepatocyte isolation by portal collagenase perfusion, the rate of Ca2+ influx (Ca2+in) in the absence and presence of epinephrine (100 nM), cellular Ca2+ uptake (Ca2+up) and membrane Ca2+ flux (Ca2+flux) were determined using 45Ca2+ incubation techniques. Hemorrhage/resuscitation substantially increased hepatocyte Ca2+up (3.44 +/- 0.2 nmol/mg protein) and Ca2+flux (32.8 +/- 5 pmol/mg protein x min) compared to sham-operated controls (2.57 +/- 0.1 and 15.2 +/- 3.5; P < 0.05). Resuscitation with sodium bicarbonate significantly prevented altered hepatocyte Ca2+ regulation (2.31 +/- 0.1 and 14.4 +/- 4.6; P < 0.05). These findings suggested that postischemic hepatocyte Ca2+ overload could partly be due to enhanced membrane Ca2+ movements to correct for altered intracellular pH homeostasis.
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PMID:Effect of sodium bicarbonate infusion on hepatocyte Ca2+ overload during resuscitation from hemorrhagic shock. 966 35

Flap ischemia is often encountered during pedicled and free tissue transfer. In this study, the vascular effects of varying doses of lidocaine, papaverine, and a combination of the two agents were evaluated and compared in an in vitro and in vivo model in the rabbit carotid artery. In the in vitro study, 14 rings from the rabbit carotid artery were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7-4.2 grams. Their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 microM), and a dose response curve was established by adding cumulatively either lidocaine (to 7 arterial rings) or papaverine (to 7 arterial rings) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 30 animals using 9-0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride and served as the control. The other side was treated blindly, during and after the anastomoses, with a topical application of 1 ml of either lidocaine 2% (n = 5), lidocaine 20% (n = 5), papaverine (30 mg/ml, n = 5), lidocaine 2% combined with papaverine (30 mg/ml, n = 5), or lidocaine 20% combined with papaverine (30 mg/ml, n = 5). For 30-60 minutes after the procedure, blood flow changes in the vessels were continuously monitored with a transonic doppler applied to both carotid arteries. The 20% lidocaine group was flushed with saline at the end of the first hour and monitored for an additional 60 minutes. Papaverine elicited a concentration-dependent relaxation of norepinephrine precontracted carotid artery rings in vitro. Lidocaine elicited a biphasic response, with low concentrations (10(-6)-10(-4) M) increasing the norepinephrine-induced contraction and high concentrations (10(-4)-10(-2) M) relieving this contraction. Microsurgical anastomosis produced a significant decrease of blood flow through the rabbit carotid artery as measured by the transonic doppler. Drug application did not alter the systemic blood pressure of the animals. Topical application of lidocaine 2% did not significantly change the blood flow after microvascular anastomosis. Topical application of lidocaine 20%, papaverine (30 mg/ml), or lidocaine (2% or 20%) combined with papaverine significantly increased the blood flow in the rabbit carotid artery. In the lidocaine 20% group, the blood flow remained significantly increased after the drug was flushed with heparinized saline solution. These results demonstrate that topical lidocaine 20%, papaverine, and lidocaine 2% or 20% combined with papaverine significantly increase blood flow in the rabbit carotid artery after microvascular anastomosis. The data confirm the use of papaverine and lidocaine 20%, alone or in combination, as spasmolytics during clinical microsurgery. This suggests that lidocaine 2% alone is not the ideal drug to relieve vascular constriction, and further studies on the clinical use of low concentrations of topical lidocaine in microsurgery is warranted.
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PMID:Drug-induced vasodilation: in vitro and in vivo study on the effects of lidocaine and papaverine on rabbit carotid artery. 967 23

We have shown that high-concentration albumin therapy is markedly neuroprotective in focal cerebral ischemia. The present study was conducted to ascertain the degree to which hemodynamic alterations are responsible for this therapeutic effect. Normothermic, physiologically regulated male Sprague-Dawley rats received a 2-h period of middle cerebral artery occlusion (MCAo) by insertion of an intraluminal suture coated with poly-L-lysine. Albumin (25% human serum albumin solution) or vehicle (0.9% sodium chloride) was administered intravenously at a dose of 1% of body weight immediately after suture withdrawal following 2-h MCAo. Local cerebral blood flow (LCBF) was measured autoradiographically with 14C-iodoantipyrine after 1 h of recirculation. Novel image-processing methods were used to compare average LCBF data sets against previously obtained infarction-frequency data on a pixel-by-pixel basis. Albumin therapy reduced mean hematocrit by 42% but produced no other systemic alterations. Pixel-based histopathological analysis revealed large, consistent cortical and subcortical infarcts in saline-treated rats with MCAo; albumin therapy reduced mean cortical infarct volume by 85%. Within regions showing albumin-associated neuroprotection, numbers of pixels having LCBF in the upper ischemic-core flow range (0.12-0.24 ml g-1 min-1) were reduced by 8.6-fold by albumin therapy when compared to saline-treated rats; and numbers of pixels with LCBF in the lower penumbral flow range (0.24-0.36 ml g-1 min-1) were reduced by 3. 1-fold in albumin-treated rats (p=0.04 by repeated-measures analysis of variance). Analysis of the [albumin-saline] 3-dimensional difference-image data set revealed a circumferential zone of statistically significant albumin-associated LCBF increase within the posterior portion of the ischemic hemisphere, surrounding the core-region of prior ischemia. Thus, high-concentration albumin therapy improves local perfusion to regions of critical LCBF reduction. The spatial extent of this LCBF effect, however, appears too small to account fully for the marked neuroprotective efficacy of this therapy. We suggest that other, non-hemodynamic mechanisms may also be contributory.
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PMID:The effect of high-dose albumin therapy on local cerebral perfusion after transient focal cerebral ischemia in rats. 972 10

BACKGROUND: We determined if a single administration of heparin or nonanticoagulant N-acetylheparin could reduce myocardial injury resulting from a 90-minute occlusion of the left circumflex coronary artery (LCX) and 6 hours of reperfusion in the anesthetized canine. METHODS AND RESULTS: Heparin (2 mg/kg), N-acetylheparin (2 mg/kg), or vehicle, 0.9% sodium chloride (control), was administered intravenously to separate groups of animals 2 hours before LCX occlusion. To ensure parity of LCX ischemia, only animals with ischemic zone regional blood flow < 0.16 mL/min/g tissue were included in the final analysis. Hemodynamics did not differ among the three study groups. Infarct size as a percentage of the left ventricular area at risk was obtained for each group. Myocardial infarct size was 43.0 +/- 3.9% in the vehicle, 28.8 +/- 5.8% in the heparin (P <.05 vs vehicle) and 24.7 +/- 4.6% (P <.05 vs vehicle) in the N-acetylheparin-treated animals. CONCLUSIONS: Pretreatment with heparin or its nonanticoagulant derivative, N-acetylheparin, provides significant protection to the regionally ischemic and reperfused canine myocardium independent of either plasma glycosaminoglycan concentration or alterations in the coagulation system.
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PMID:Reduction of Myocardial Necrosis After Glycosaminoglycan Administration: Effects of a Single Intravenous Administration of Heparin or N-Acetylheparin 2 Hours Before Regional Ischemia and Reperfusion. 1068 20

Experience of application of alprostan (PGE1, alprostadil) in 19 patients with atherosclerotic affection of vessels, chronic and acute ischemia of lower extremities in III-IV stage in combination with affection of other vascular basins was summarized. In 10 patients, to whom operative vascular reconstruction was contraindicated and/or technically unrealizable, the conservative treatment was conducted using alprostan during 12-25 days up to the clinical effect achievement (total dose up to 1.6 mg). In 9 patients after performance of conservative treatment using alprostan the vascular bed reconstruction was done. Daily infusion of alprostan in 0.1 mg dose diluted in 250-400 ml of isotonic solution of sodium chloride during 2.5-3 h with duration of course not less than 15 days and 1.2-2.2 mg total dose of preparation constitutes an optimal scheme of treatment. Good result was noted in treatment of patients in stage II of ischemia, application of alprostan in stage IV of ischemia had permitted to reduce the extremity amputation volume or to escape it on the whole, and to restore more rapidly the cutaneous integrity in the trophic disorders regions. The alprostan usage is trustworthy in patients with multifocal atherosclerosis with the cardiac coronary vessels affection in an ischemic heart disease.
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PMID:[Clinical efficacy of alprostan in treatment of obliterating multifocal atherosclerotic affection of arteries in patients with critical ischemia of lower extremities]. 1150 31

Dialysis hypotension occurs because a large volume of blood water and solutes are removed over a short period of time, overwhelming normal compensatory mechanisms, including plasma refilling and reduction of venous capacity, due to reduction of pressure transmission to veins. In some patients, seemingly paradoxical and inappropriate reduction of sympathetic tone may occur, causing reduction of arteriolar resistance, increased transmission of pressure to veins, and corresponding increase in venous capacity. Increased sequestration of blood in veins under conditions of hypovolemia reduces cardiac filling, cardiac output, and, ultimately, blood pressure. Adenosine release due to tissue ischemia may participate in reducing norepinephrine release locally, and activation of the Bezold-Jarisch reflex, perhaps in patients with certain but as yet undefined cardiac pathology, may be responsible for sudden dialysis hypotension. Patients with diastolic dysfunction may be more sensitive to the effects of reduced cardiac filling. The ultimate solution is reducing the ultrafiltration rate by use of longer dialysis sessions, more frequent dialysis, or reduction in salt intake. Increasing dialysis solution sodium chloride levels helps maintain blood volume and refilling but ultimately increases thirst and interdialytic weight gain, with a possible adverse effect on hypertension. Blood volume monitoring with ultrafiltration or dialysis solution sodium feedback loops are promising new strategies. Maintaining tissue oxygenation via an adequate blood hemoglobin level seems to be important. Use of adenosine antagonists remains experimental. Given the importance of sympathetic withdrawal, the use of pharmacologic sympathetic agonists is theoretically an attractive therapeutic strategy.
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PMID:Pathophysiology of dialysis hypotension: an update. 1160 56


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