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At least 415 records · Page 23Linked to original sources
PubMed2004

The clamp-loading complex for processive DNA replication.

DNA polymerase requires two processing factors, sliding clamps and clamp loaders, to direct rapid and accurate duplication of genomic DNA. In eukaryotes, proliferating cell nuclear antigen (PCNA), the ring-shaped sliding clamp, encircles double-stranded DNA within its central hole and tethers the DNA polymerases onto DNA. Replication factor C (RFC) acts as the clamp loader, which correctly installs the sliding clamp onto DNA strands in an ATP-dependent manner. Here we report the three-dimensional structure of an archaeal clamp-loading complex (RFC-PCNA-DNA) determined by single-particle EM. The three-dimensional structure of the complex, reconstituted in vitro using a nonhydrolyzable ATP analog, reveals two components, a closed ring and a horseshoe-shaped element, which correspond to PCNA and RFC, respectively. The atomic structure of PCNA fits well into the closed ring, suggesting that this ternary complex represents a state just after the PCNA ring has closed to encircle the DNA duplex.

Adenosine Triphosphate↗
PubMed2000

The effects of fenoldopam on renal blood flow and tubular function during aortic cross-clamping in anaesthetized dogs.

Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Fenoldopam, a selective dopamine agonist, may increase renal blood flow and decrease tubular oxygen consumption. The objective of this study was to quantify the effects of fenoldopam (0.1 microg kg-1 min-1) on renal blood flow and renal tubular function in anaesthetized dogs that have undergone aortic cross clamping. Eight labrador dogs were selected to receive either saline or fenoldopam (0.1 microg kg-1 min-1) intravenously. Arterial pressure, heart rate, renal blood flow, urinary output, fractional excretion of sodium, creatinine clearance and lithium clearance were measured (a) prior to infusions of saline or fenoldopam (b) 1 h after commencing the infusion (c) during a 90-min period of infrarenal aortic cross-clamping with concurrent infusion of fenoldopam or saline and (d) for 1 h after simultaneous aortic declamping and discontinuation of the infusions. There was no haemodynamic instability upon commencing the infusion of fenoldopam (0.1 microg kg-1 min-1). Creatinine clearance (2.03 +/- 0.5-2.45 +/- 0.3 mL min-1 kg-1 (mean +/- SD)), urine output (0.23 +/- 0.16-0.35 +/- 0.23 mL min-1 (mean +/- SD)), and fractional excretion of sodium (0.7 +/- 0.52-1.3 +/- 0.73% (mean +/- SD)) increased (P < 0.05), following commencement of the fenoldopam infusion. Fractional excretion of sodium (1.2 +/- 0.7% (mean +/- SD)) and urine output (0. 36 +/- 0.21 mL min-1 (mean +/- SD)) were maintained during the aortic cross-clamp period (P < 0.05). Renal blood flow increased when the fenoldopam infusion was commenced (145 +/- 43.3-161 +/- 39. 2 mL min-1 (mean +/- SD)) and remained greater than baseline during the aortic cross-clamping period (152 +/- 44 mL min-1 (mean +/- SD)), although these increases did not reach statistical significance. The most striking abnormalities observed by electron microscopy were marked disruption of the microvillus brush border in proximal tubules, vacuolation and separation of epithelial cells on basolateral infolds. The changes were similar in the two groups. In conclusion fenoldopam (0.1 microg kg-1 min-1) may have renoprotective effects which persist during infrarenal aortic cross clamping.

Anesthesia, General↗
PubMed2002

In vivo fracture of a new rubber-dam clamp.

AIM: This study was carried out to investigate the reasons for fracture of a new rubber-dam clamp used for the first time. SUMMARY: The fractured surfaces of the broken clamp were studied with optical microscopy. Characteristic surface patterns of tensile fracture were identified. Cracks originated from the groove of letter D mechanically engraved on the inner surface of the clamp bow, and developed with high velocity (unstable crack growth rate) leading to catastrophic fracture. This behaviour was attributed to the residual stresses introduced by the labelling technique due to local thermal alterations. KEY LEARNING POINTS: The labelling technique used to number clamps may be implicated with catastrophic failure. Dentists should be aware that even new clamps can fracture. It is important that clamps are secured to prevent inhalation of metal fragments, should catastrophic failure occur.

Dental Equipment↗
PubMed2004

Crystal structure of the chi:psi sub-assembly of the Escherichia coli DNA polymerase clamp-loader complex.

The chi (chi) and psi (psi) subunits of Escherichia coli DNA polymerase III form a heterodimer that is associated with the ATP-dependent clamp-loader machinery. In E. coli, the chi:psi heterodimer serves as a bridge between the clamp-loader complex and the single-stranded DNA-binding protein. We determined the crystal structure of the chi:psi heterodimer at 2.1 A resolution. Although neither chi (147 residues) nor psi (137 residues) bind to nucleotides, the fold of each protein is similar to the folds of mononucleotide-(chi) or dinucleotide-(psi) binding proteins, without marked similarity to the structures of the clamp-loader subunits. Genes encoding chi and psi proteins are found to be readily identifiable in several bacterial genomes and sequence alignments showed that residues at the chi:psi interface are highly conserved in both proteins, suggesting that the heterodimeric interaction is of functional significance. The conservation of surface-exposed residues is restricted to the interfacial region and to just two other regions in the chi:psi complex. One of the conserved regions was found to be located on chi, distal to the psi interaction region, and we identified this as the binding site for a C-terminal segment of the single-stranded DNA-binding protein. The other region of sequence conservation is localized to an N-terminal segment of psi (26 residues) that is disordered in the crystal structure. We speculate that psi is linked to the clamp-loader complex by this flexible, but conserved, N-terminal segment, and that the chi:psi unit is linked to the single-stranded DNA-binding protein via the distal surface of chi. The base of the clamp-loader complex has an open C-shaped structure, and the shape of the chi:psi complex is suggestive of a loose docking within the crevice formed by the open faces of the delta and delta' subunits of the clamp-loader.

Adenosine Triphosphate↗
PubMed2001

Comparison between 1-hour and 24-hour drain clamping using diluted epinephrine solution after total knee arthroplasty.

A prospective study was conducted to determine the optimal clamping time in the drain-clamping method after total knee arthroplasty. In a randomized trial, 44 primary total knee arthroplasties were studied after the drain-clamping method using diluted epinephrine solution was applied for 1 hour or 24 hours. The mean blood loss into the drains was less in the 24-hour group compared with the 1-hour group (35 mL in the 24-hour group and 247 mL in the 1-hour group). No statistically significant difference was found in hemoglobin or hematocrit levels between the 2 groups after surgery. Only 1 patient (4.5%) in the 1-hour group and 2 patients (9.1%) in the 24-hour group received blood transfusion. There were significantly more complications in the 24-hour group (P <.05). Two patients (9.1%) in this group required additional surgery. One-hour clamping is preferable to 24-hour clamping in the drain-clamping method for minimizing complications.

Aged↗
PubMed2002

Effect of sequence, timing of vascular anastomosis, and clamp removal on survival of microsurgical flaps.

The effects of the timing and order of clamp removal in microsurgical transplants were studied in rat groin skin flap and rat latissimus dorsi muscle flap models. Forty rats were divided into four groups. In Group 1, the arterial pedicle of the skin flap was anastomosed first, and the clamp was released after the anastomosis was completed. The venous pedicle was then repaired after inflow was restored. In Group 2, the venous pedicle of the skin flap was anastomosed first. The venous clamp was not released until completion of the arterial anastomosis. In Group 3, the arterial pedicle was anastomosed first in the muscle flap. The venous anastomosis was then performed after the arterial clamp was released. In Group 4, the venous pedicle was anastomosed first, and both clamps were released simultaneously. The blood perfusion of the skin flaps was examined after both clamps were released in Groups 1 and 2. The flap survival status was examined 5 days postoperatively for skin flaps and at 3 days for muscle flaps. Skin flaps in an additional six rats were harvested for histology. The results showed that the flap blood flow for Group 1 was statistically significantly higher than for Group 2 flaps in the first 20 min after reperfusion. There was no significant difference of flow between these two groups during the 30 to 90 min after reperfusion. The difference in survival rates for the four groups was not significant. Histology revealed extensive congestion in the flaps from Group 1 after completion anastomoses, but the congestion was significantly decreased at 3 hr following reperfusion. In conclusion, a brief venous stasis during anastomosis, after establishment of arterial inflow, is not detrimental to flap survival. The sequence of anastomosis will not affect outcome for either the cutaneous flap or the muscle flap models. Early flap perfusion was increased when the arterial anastomosis was performed first.

Analysis of Variance↗
PubMed1987

The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man.

6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C-peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Delayed cord clamping in cesarean section with general anesthesia.

Delay in cord clamping after vaginal delivery increases the blood volume of the newborn. Similar effects have also been observed in cesarean section births. Other effects of delayed cord clamping in cesarean section have not been investigated. In a group of nineteen healthy mothers having elective cesarean sections the cord clamping time was increased from 0 minutes to 1.5 and 3 minutes. Significantly lowered PO2 and pH and elevated plasma lactate levels were observed in infants with 3 minutes' delay when compared with the early clamping group. We conclude that, when healthy mature newborns are considered, early clamping of umbilical cord in cesarean section with general anesthesia is preferable to late clamping.

Adult↗
PubMed1992

Selective deep hypothermia of the spinal cord prevents paraplegia after aortic cross-clamping in the dog model.

We tested, in the dog, the hypothesis that selective deep hypothermia (19 degrees to 12 degrees C) of the spinal cord protects it from the ischemia that follows double aortic cross-clamping. The extracorporal perfusion system consisted of heat exchanger and a pump, infusing saline solution at 5 degrees C into the subarachnoid space (L-6) and draining it through the cisterna magna. After 30 minutes this system cools a normally perfused spinal cord to a stable temperature gradient of 13 degrees C (inflow) to 18 degrees C (outflow). Proximal and distal intrathecal, proximal and distal aortic, and central venous pressures were continuously recorded. Rectal temperature was maintained between 36.5 degrees C and 38.5 degrees C. Eight control dogs had cross-clamping of the aorta below the left subclavian artery and above the diaphragm without cord hypothermia. Nine experimental dogs had cord hypothermia initiated 50 minutes before systemic heparinization (100 U/kg) and double cross-clamping of the aorta. Cross-clamping was maintained for 45 minutes. The aorta was then unclamped, heparin was reversed, cord cooling was discontinued, and the dura was closed. Hindlimb function of animals was graded by use of Tarlov's scale at recovery and 24 hours later. The dogs were then killed, and the cords were removed and fixed for microscopy. All control animals were paraplegic and had histologic confirmation of spinal cord infarction. All experimental animals had intact hindlimb function and normal appearing cords on histologic examination. A two-tailed Fisher's exact test (chi square) shows this difference to be significant to p = 0.00004. In the dog selective deep hypothermia of the cord avoids the ischemic injury induced by aortic cross-clamping that results in paraplegia. The implications of these findings in thoracoabdominal aortic clamping in humans is discussed.

Animals↗
PubMed2004

Protein associations in DnaA-ATP hydrolysis mediated by the Hda-replicase clamp complex.

In Escherichia coli, the activity of ATP-bound DnaA protein in initiating chromosomal replication is negatively controlled in a replication-coordinated manner. The RIDA (regulatory inactivation of DnaA) system promotes DnaA-ATP hydrolysis to produce the inactivated form DnaA-ADP in a manner depending on the Hda protein and the DNA-loaded form of the beta-sliding clamp, a subunit of the replicase holoenzyme. A highly functional form of Hda was purified and shown to form a homodimer in solution, and two Hda dimers were found to associate with a single clamp molecule. Purified mutant Hda proteins were used in a staged in vitro RIDA system followed by a pull-down assay to show that Hda-clamp binding is a prerequisite for DnaA-ATP hydrolysis and that binding is mediated by an Hda N-terminal motif. Arg(168) in the AAA(+) Box VII motif of Hda plays a role in stable homodimer formation and in DnaA-ATP hydrolysis, but not in clamp binding. Furthermore, the DnaA N-terminal domain is required for the functional interaction of DnaA with the Hda-clamp complex. Single cells contain approximately 50 Hda dimers, consistent with the results of in vitro experiments. These findings and the features of AAA(+) proteins, including DnaA, suggest the following model. DnaA-ATP is hydrolyzed at a binding interface between the AAA(+) domains of DnaA and Hda; the DnaA N-terminal domain supports this interaction; and the interaction of DnaA-ATP with the Hda-clamp complex occurs in a catalytic mode.

Adenosine Triphosphatases↗
PubMed2005

Maturation of bacteriophage T4 lagging strand fragments depends on interaction of T4 RNase H with T4 32 protein rather than the T4 gene 45 clamp.

In the bacteriophage T4 DNA replication system, T4 RNase H removes the RNA primers and some adjacent DNA before the lagging strand fragments are ligated. This 5'-nuclease has strong structural and functional similarity to the FEN1 nuclease family. We have shown previously that T4 32 protein binds DNA behind the nuclease and increases its processivity. Here we show that T4 RNase H with a C-terminal deletion (residues 278-305) retains its exonuclease activity but is no longer affected by 32 protein. T4 gene 45 replication clamp stimulates T4 RNase H on nicked or gapped substrates, where it can be loaded behind the nuclease, but does not increase its processivity. An N-terminal deletion (residues 2-10) of a conserved clamp interaction motif eliminates stimulation by the clamp. In the crystal structure of T4 RNase H, the binding sites for the clamp at the N terminus and for 32 protein at the C terminus are located close together, away from the catalytic site of the enzyme. By using mutant T4 RNase H with deletions in the binding site for either the clamp or 32 protein, we show that it is the interaction of T4 RNase H with 32 protein, rather than the clamp, that most affects the maturation of lagging strand fragments in the T4 replication system in vitro and T4 phage production in vivo.

Amino Acid Sequence↗
PubMed1971

Membrane currents in mammalian ventricular heart muscle fibers using a voltage-clamp technique.

Bundles of sheep ventricular fibers were voltage-clamped utilizing a modified sucrose gap technique and intracellular voltage control. An action potential was fired off in the usual way, and the clamp circuit was switched on at preselected times during activity. Clamping the membrane back to its resting potential during the early part of an action potential resulted in a surge of inward current. The initial amplitude of this current surge decreased as the clamp was switched on progressively later during the action potential. Inward current decreasing as a function of time was also recorded if the membrane potential was clamped beyond the presumed K equilibrium potential (to -130 mv). Clamping the membrane to the inside positive range (+40 mv to +60 mv) at different times of an action potential resulted in a step of outward current which was not time-dependent. The results suggest that normal repolarization of sheep ventricle depends on a time-dependent decrease of inward current (Na, Ca) rather than on a time-dependent increase of outward current (K).

Action Potentials↗
PubMed1999

Division of labor--sequential ATP hydrolysis drives assembly of a DNA polymerase sliding clamp around DNA.

The beta sliding clamp encircles DNA and enables processive replication of the Escherichia coli genome by DNA polymerase III holoenzyme. The clamp loader, gamma complex, assembles beta around DNA in an ATP-fueled reaction. Previous studies have shown that gamma complex opens the beta ring and also interacts with DNA on binding ATP. Here, a rapid kinetic analysis demonstrates that gamma complex hydrolyzes two ATP molecules sequentially when placing beta around DNA. The first ATP is hydrolyzed fast, at 25-30 s(-1), while the second ATP hydrolysis is limited to the steady-state rate of 2 s(-1). This step-wise reaction depends on both primed DNA and beta. DNA alone promotes rapid hydrolysis of two ATP molecules, while beta alone permits hydrolysis of only one ATP. These results suggest that beta inserts a slow step between the two ATP hydrolysis events in clamp assembly, during which the clamp loader may perform work on the clamp. Moreover, one ATP hydrolysis is sufficient for release of beta from the gamma complex. This implies that DNA-dependent hydrolysis of the other ATP is coupled to a separate function, perhaps involving work on DNA. A model is presented in which sequential ATP hydrolysis drives distinct events in the clamp-assembly pathway. We also discuss underlying principles of this step-wise mechanism that may apply to the workings of other ATP-fueled biological machines.

Adenosine Triphosphate↗
PubMed2006

Hypothesis: bacterial clamp loader ATPase activation through DNA-dependent repositioning of the catalytic base and of a trans-acting catalytic threonine.

The prokaryotic DNA polymerase III clamp loader complex loads the beta clamp onto DNA to link the replication complex to DNA during processive synthesis and unloads it again once synthesis is complete. This minimal complex consists of one delta, one delta' and three gamma subunits, all of which possess an AAA+ module--though only the gamma subunit exhibits ATPase activity. Here clues to underlying clamp loader mechanisms are obtained through Bayesian inference of various categories of selective constraints imposed on the gamma and delta' subunits. It is proposed that a conserved histidine is ionized via electron transfer involving structurally adjacent residues within the sensor 1 region of gamma's AAA+ module. The resultant positive charge on this histidine inhibits ATPase activity by drawing the negatively charged catalytic base away from the active site. It is also proposed that this arrangement is disrupted upon interaction of DNA with basic residues in gamma implicated previously in DNA binding, regarding which a lysine that is near the sensor 1 region and that is highly conserved both in bacterial and in eukaryotic clamp loader ATPases appears to play a critical role. gamma ATPases also appear to utilize a trans-acting threonine that is donated by helix 6 of an adjacent gamma or delta' subunit and that assists in the activation of a water molecule for nucleophilic attack on the gamma phosphorous atom of ATP. As eukaryotic and archaeal clamp loaders lack most of these key residues, it appears that eubacteria utilize a fundamentally different mechanism for clamp loader activation than do these other organisms.

Adenosine Triphosphatases↗
PubMed1997

Response to clamping of the inferior vena cava as a factor for predicting postreperfusion syndrome during liver transplantation.

Postreperfusion syndrome (PRS) is an important cause of hemodynamic deterioration during orthotopic liver transplantation (OLT). We retrospectively studied 94 patients who had undergone OLT in an effort to establish whether the hemodynamic response to clamping of the inferior vena cava (IVC) could be used to predict hemodynamic behavior on reperfusion of the grafted liver. PRS was defined as a decrease in the mean arterial pressure of more than 30% below the baseline value for more than 1 min during the first 5 min after reperfusion of the graft. The patients were divided into two groups: those who developed PRS (PRS group) and those who did not (non-PRS group). We analyzed hemodynamic response before (dissection stage) and after (anhepatic stage) clamping of the IVC. Based on multivariate analysis methods (logistic regression), the percentage of change in the vascular resistance index from before clamping to after clamping of the IVC was an indicator of the risk of developing PRS, with an adjusted odds ratio of 1.04 for each unit of change (ENTER method, P = 0.01). In the non-PRS group, clamping of the IVC was followed by a 47.1% decrease in the cardiac index, compared with a 27.9% decrease in the PRS group (P < 0.05). The systemic vascular resistance index (SVRI) increased by 49% in the PRS group, as opposed to 85.7% in the non-PRS group (P < 0.05). PRS occurred in only 17.5% of patients in whom the SVRI increased by more than 50%. We conclude that the integrity of the vasoconstrictive response (increase in the peripheral vascular resistance greater than 50%) as measured immediately after clamping of the IVC correlates with occurrence of PRS.

Adult↗
PubMed1980

Hemodynamic response to infrarenal aortic cross-clamping in patients with and without coronary artery disease.

The effect of coronary artery disease (CAD) on hemodynamic response to infrarenal aortic cross-clamping was studied in 25 patients undergoing either aortofemoral bypass or abdominal aortic aneurysmectomy. Ten patients had evidence of CAD and 15 did not. Systemic, pulmonary artery (PAP), and pulmonary capillary wedge pressures (PCWP), thermodilution cardiac output, and heart rate were measured immediately before, and 2 and 5 min after infrarenal aortic cross-clamping. Heart rate decreased and arterial pressures and pulmonary and systemic vascular resistances increased in both CAD and non CAD groups after aortic clamping. Cardiac index decreased after clamping in both groups and was significantly lower in the patients with CAD. However, PCWP decreased after clamping in patients without CAD as compared to a significant increase in the patients with CAD. The significantly lower cardiac index (1.8-1.9 L/min x M2) and increased PCWP (13-15 torr) in patients with preexisting CAD scheduled for aortofemoral surgery may suggest that this subgroup is at greater risk for myocardial dysfunction immediately after aortic cross-clamping.

Aged↗
PubMedDate not supplied

Clamping short-term indwelling catheters: a systematic review of the evidence.

OBJECTIVE: The objective of this review is to determine the effects of clamping short-term indwelling urethral catheters before removal on the incidence of urinary tract infection, time to first void, voiding dysfunction, incidence of recatheterization, and the length of hospital stay. MATERIALS AND METHODS: Published and unpublished randomized and quasi-randomized controlled trials, completed between January 1966 and July 2004, in English and other languages that compared the effects of clamping short-term indwelling urethral catheters, were systematically reviewed using multiple electronic databases. Determination of eligibility of trials for inclusion in the review, assessment of methodological quality, and data extraction were undertaken independently by 2 reviewers. Relative risks for dichotomous data and a weighted mean difference for continuous data were calculated with 95% confidence intervals. Where synthesis was inappropriate, a narrative overview has been undertaken. RESULTS: Three trials that investigated the effect of clamping the indwelling urethral catheter compared to free drainage before removal were eligible for inclusion. Two trials reported no significant difference in the incidence of urinary tract infection (UTI), number of patients who developed urinary retention or required recatheterization, and the length of hospital stay between the 2 groups. Another reported that the postvoid residual urine volume for patients who did not receive reconditioning of the bladder increased from 4.25 mL at baseline to 42.25 mL after removal of the indwelling urethral catheter, whereas the residual urine volume for patients who received reconditioning increased from 17.25 mL at baseline to 22 mL at follow-up. CONCLUSIONS: The evidence for clamping indwelling urethral catheters before removal remains equivocal. Given the current state of evidence, procedures relating to clamping of indwelling urinary catheters should not be initiated. Until stronger evidence becomes available, however, practices relating to clamping indwelling urethral catheters will continue to be dictated by local preferences and cost factors.

Catheters, Indwelling↗
PubMed1996

Cardiovascular responses to experimental infra-renal aortic cross-clamping. Modulating effects of isoflurane, sodium nitroprusside and milrinone.

BACKGROUND: Pharmacological control of blood pressure is usually indicated during aortic cross-clamping (AXC). The aim of this study was to analyze the modulation by isoflurane (ISO), sodium nitroprusside (SNP) and milrinone (MIL) of the systemic circulatory responses to a standardized infra-renal AXC. METHODS: Chloralose-anaesthetized pigs were exposed to AXC at control (no vasoactive drugs) and during the administration of each of the drugs. RESULTS: During control, AXC increased mean arterial pressure (MAP, 17 +/- 4%) and systemic vascular resistance (SVR, 27 +/- 7%), but induced no significant changes in cardiac output (CO), heart rate (HR), pulmonary arterial pressures, pulmonary vascular resistance or central venous pressure. Low-dose ISO (0.7%) and investigated doses of SNP and MIL did not significantly alter this response. High-dose ISO (1.4%, attenuated the AXC-induced increase in SVR, but not in MAP. All drugs decreased non-clamp MAP levels. Therefore, with low-dose ISO and with SNP or MIL, peak MAP during AXC was not significantly different from control non-clamp levels (i.e. prior to pharmacological or surgical interventions). High-dose ISO was associated with a MAP during AXC that was below control non-clamp levels. CONCLUSIONS: The objective that during AXC MAP should not exceed control non-clamp levels was achieveable by ISO, SNP or MIL. The modulating actions of the drugs on MAP during AXC were exerted mainly through reductions in non-clamp levels. This systemic hypotension was associated with decreased CO and SVR during ISO, and with decreased SVR and increased HR during SNP and MIL. Attenuation of the AXC-induced increase in SVR was produced only by 1.4% ISO.

Anesthetics, Inhalation↗