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P Colson

Publications and source records attributed to P Colson.

At least 109 records · Page 6Linked to original sources
PubMed1993

A tandem repeat of the SPKK peptide motif induces psi-type DNA structures at alternating AT sequences.

The interaction between a tandem repeat of the SPKK peptide motif and calf thymus DNA or several polynucleotides has been investigated by circular dichroism. The octapeptide SPKKSPKK does not induce any important changes in the CD spectra of the polynucleotides poly(dG).poly(dC), poly(dG-dC).poly(dG-dC) and poly(dA).poly(dT) while the spectrum of calf thymus DNA is slightly modified. Binding of this basic peptide to the alternating copolymer poly(dA-dT).poly(dA-dT) results in a marked psi-type condensation in a manner similar to that induced by the entire C-terminal domain of histone H1.

Amino Acid Sequence↗
PubMed1993

Angiotensin-converting enzyme inhibitors in cardiovascular anesthesia.

Besides the long-term regulation of extracellular fluid volume, the RAS plays an important physiologic role in maintaining venous return and blood pressure during acute hemodynamic stresses. ACE inhibitors may therefore alter venous return and cardiac output regulation during anesthesia and surgery. This may be regarded as a drawback of ACE inhibition when other factors interfere with cardiovascular homeostasis; deleterious hemodynamic events may therefore occur when blood volume is decreased, which may be frequent during cardiovascular anesthesia and surgery. However, the alternative solution should not be to stop ACE inhibitors preoperatively. This would allow recovery of RAS control of blood pressure, but at the expense of some regional circulations. From this point of view, preliminary results from early studies during cardiovascular anesthesia and surgery showing redistribution of regional blood flow with inhibition of ACE are encouraging; whether postoperative outcome can be improved deserves further studies. At this time, the evidence is that ACE inhibition does not allow the anesthesiologist to be tolerant of hypovolemia.

Anesthesia, General↗
PubMed1993

Effect of organic effectors on chromatin solubility, DNA-histone H1 interactions, DNA and histone H1 structures.

We have extended our previous investigations on the effect of organic osmolytes (glycine, proline, taurine, mannitol, sorbitol and trimethylammonium oxide (TMAO)) on chromatin solubility, to the study of their influence on DNA stability and DNA-histone interactions. Our aim was to understand the molecular origin of the protection effects observed. To this end, we determined the amount of histone H1 required to precipitate DNA or H1-depleted chromatin, at various salt concentrations, in the presence of the above mentioned organic compounds. We found a shift of the H1/DNA ratio required to reach 50% precipitation, towards higher values. Taurine was the most efficient compound followed by mannitol and glycine, then sorbitol and proline. On the contrary, TMAO favoured the precipitation process. We attempted to interpret these results on the basis of Manning's counterion condensation theory. Changes in histone H1 structure folding and in DNA melting temperature Tm were also analyzed. Glycine, taurine, sorbitol and TMAO increased the degree of secondary structure folding of the protein while mannitol and sorbitol had no effect. Taurine, glycine and proline decreased the Tm of DNA, TMAO largely destabilized DNA, but mannitol and sorbitol had no effect. Measurements of NaCl activity in the presence of organic osmolytes did not reveal sufficiently large changes to account for their protection effect against chromatin precipitation. The osmotic coefficient j of the organic effectors solutions increased in the order: taurine < glycine < sorbitol < mannitol < proline << TMAO. For the two latter compounds, the j values increased above 1 at high concentration. We consider that the organic compounds investigated may be classified into three categories: (i) class I (zwitterionic compounds: glycine, proline, taurine) would produce sodium ions release from the DNA surface; (ii) class II (the very polar molecule TMAO) would increase sodium counterions condensation on DNA together with histone H1 folding; (iii) class III compounds (mannitol and sorbitol) would possibly produce a modification of NaCl activity but no definite explanation could be found for the complex behavior of these compounds.

Animals↗
PubMed1993

[The cardiologist as consultant to the anesthetist].

The combination of surgery and heart disease is common. The incidence of both heart disease and surgery increase with the age of patients. However, the surgical risk in the cardiac patient and particularly in the coronary or heart failure patient is considerably aggravated. Surgery is a major factor in cardiac decompensation, which can accelerate the progress of the disease. Pre-anesthetic cardiological consultation is therefore an important part of the evaluation and preparation of the patient before surgery. This is carried out at the request of the anesthetist and can provide a diagnosis or adapt a treatment and above all define the cardiovascular competence of the patient. Diagnostic and therapeutic means available to the cardiologist are essential in defining and if possible reducing the cardiac handicap of patients before the hemodynamic challenge represented by the combination of anesthesia and surgery.

Anesthesia↗
PubMed1993

Binding to DNA, cellular uptake and biological activity of a distamycin-ellipticine hybrid molecule.

A hybrid molecule which conjugates the minor groove binding agent distamycin and an ellipticine derivative was synthesized and evaluated for cytostatic and cytotoxic activities against L1210 leukaemia cells in vitro. The binding of the hybrid molecule, named 'Distel', to a range of natural DNAs and synthetic polynucleotides with different base pair arrangements was studied by electric linear dichroism. The interaction with DNA simultaneously implicates binding of the distamycin part in the minor groove and intercalation of the ellipticine chromophore. The drug binds to DNA without any apparent preference for AT or GC polynucleotides, and can accommodate both homopolymeric and co-polymeric sequences as a binding site. However, the geometry of the drug-DNA complex varies depending on the targeted sequence. The lower activity of the hybrid as compared to the ellipticine derivative cannot be explained in terms of DNA binding. Taking advantage of the fluorescence of the pyridocarbazole chromophore, fluorescence microscopy was used to map cellular uptake of the hybrid molecule compared to the ellipticine derivative. Both the conjugate and the ellipticine derivative preferentially accumulate in the nuclei of HeLa cells rather than in the cytoplasm. Nuclei of ellipticine derivative-treated cells appear markedly more fluorescent than those of cells treated with the hybrid, which seems to be preferentially located in the nucleoli. Therefore, we consider the possibility that the difference in cytotoxicity between the two ellipticine-containing drugs is due to different intranuclear concentrations of these two compounds.

Animals↗
PubMed1992

Binding of a distamycin-ellipticine hybrid molecule to DNA and chromatin: spectroscopic, biochemical, and molecular modeling investigations.

A bifunctional molecule in which an ellipticine chromophore is attached to a distamycin residue via a diaminopropyl tether has been designed and synthesized in the expectation of creating a hybrid molecule capable of bidentate binding to DNA by both intercalation and minor-groove interactions. The strength and mode of binding to DNA of this conjugate have been studied by means of circular and linear dichroism as well as by stopped-flow kinetics and measurements of reactivity toward a chemical probe. The results converge to reveal that the ellipticine moiety of the hybrid largely dominates the binding reaction with DNA. In the presence of chromatin, the hybrid molecule binds preferentially to the internucleosomal DNA, a preference dictated by its intercalating chromophore. Theoretical computations were performed on the comparative complexation energies of distamycin, the ellipticine derivative, and the hybrid ligand with a B-representative octanucleotide, d(GCATATGC)2. The best binding configuration of the ellipticine derivative locates its aminoalkyl side chain in the minor groove where distamycin is also present. The molecular modeling analysis fully supports the involvement of a bimodal binding process for the hybrid and reveals that the binding of the conjugate to DNA favors a pronounced bending toward the minor groove. This effect is attributed to intercalation of the ellipticine chromophore. An interesting link is established between the DEPC reactivity experiments and the theoretical computations, suggesting that DEPC can be used as a probe for drug-induced DNA bending. On the basis of these results, we propose the design of a new hybrid ligand bearing an additional positively-charged amidine side chain to confer higher DNA-binding affinity.

Autoradiography↗
PubMed1992

Binding properties and DNA sequence-specific recognition of two bithiazole-linked netropsin hybrid molecules.

We report the DNA binding properties of two hybrid molecules which result from the combination of the DNA sequence-specific minor groove ligand netropsin with the bithiazole moiety of the antitumor drug bleomycin. The drug-DNA interaction has been investigated by means of electric linear dichroism (ELD) spectroscopy and DNase I footprinting. In compound 1 the two moieties are linked by a flexible aliphatic tether while in compound 2 the two aromatic ring systems are directly coupled by a rigid peptide bond. The results are consistent with a model in which the netropsin moiety of compound 1 resides in the minor groove of DNA and where the appended bithiazole moiety is projected away from the DNA groove. This monocationic hybrid compound has a weak affinity for DNA and shows a strict preference for A and T stretches. ELD measurements indicate that in the presence of DNA compound 2 has an orientation typical of a minor groove binder. Similar orientation angles were measured for netropsin and compound 2. This ligand which has a biscationic nature tightly binds to DNA (Ka = 6.3 x 10(5) M-1) and is mainly an AT-specific groove binder. But, depending on the nature of the sequence flanking the AT site first targeted by its netropsin moiety, the bithiazole moiety of 2 can accommodate various types of nucleotide motifs with the exception of homooligomeric sequences. As evidenced by footprinting data, the bithiazole group of bleomycin acts as a DNA recognition element, offering opportunities to recognize GC bp-containing DNA sequences with apparently a preference (although not absolute) for a pyrimidine-G-pyrimidine motif. Thus, the bithiazole unit of bleomycin provides an additional anchor for DNA binding and is also capable of specifically recognizing particular DNA sequences when it is appended to a strongly sequence selective groove binding entity. Finally, a model which schematizes the binding of compound 2 to the sequence 5'-TATGC is proposed. This model readily explains the experimentally observed specificity of this netropsin-bithiazole conjugate.

Base Sequence↗
PubMed1992

Biological activity and molecular interaction of a netropsin-acridine hybrid ligand with chromatin and topoisomerase II.

A hybrid molecule, which combines an anilinoacridine chromophore related to the antitumour drug amsacrine (m-AMSA) and a bispyrrole moiety analogous to the antiviral agent netropsin, has been examined for its ability to bind chromatin and to modulate the activity of topoisomerase II. The results show that the presence of histones does not alter the bimodal DNA binding process. Intercalation of the acridine and groove binding of the netropsin part of the drug are both observed with chromatin preparations. Moreover, the hybrid has a clear topoisomerase II-DNA cleavable complex-inducing activity close to that of m-AMSA. The role of the two parts of the hybrid ligand is discussed in relation to ternary complex formation. Two cell lines (L1210 leukemia and MCF7 mammary carcinoma) were compared in their sensitivity to the tested ligand. The drug, which appears to be an efficient growth inhibitor of leukemic cells in vitro, reveals moderate activity against P388 leukemia in vivo. The biological activity of the hybrid may derive from a mechanism that involves DNA binding and topoisomerase II inhibition. This study demonstrates that agents which intercalate and bind to the minor groove of DNA simultaneously represent a new class of drugs interfering with topoisomerase II and provide opportunities for the development of new antitumour agents.

Amsacrine↗
PubMed1992

Drug-DNA sequence-dependent interactions analysed by electric linear dichroism.

The interactions between 20 drugs and a variety of synthetic DNA polymers and natural DNAs were studied by electric linear dichroism (ELD). All compounds tested, including several clinically used antitumour agents, are thought to exert their biological activities mainly by virtue of their abilities to bind to DNA. The selected drugs include intercalating agents with fused and unfused aromatic structures and several groove binders. To examine the role of base composition and base sequence in the binding of these drugs to DNA, ELD experiments were carried out with natural DNAs of widely differing base composition as well as with polynucleotides containing defined alternating and non-alternating repeating sequences, poly(dA).poly(dT), poly(dA-dT).poly(dA-dT),poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC). Among intercalating agents, actinomycin D was found to be by far the most GC-selective. GC selectivity was also observed with an amsacrine-4-carboxamide derivative and to a lesser extent with methylene blue. In contrast, the binding of amsacrine and 9-aminoacridine was practically unaffected by varying the GC content of the DNAs. Ethidium bromide, proflavine, mitoxantrone, daunomycin and an ellipticine derivative were found to bind best to alternating purine-pyrimidine sequences regardless of their nature. ELD measurements provided evidence for non-specific intercalation of amiloride. A significant AT selectivity was observed with hycanthone and lucanthone. The triphenyl methane dye methyl green was found to exhibit positive and negative dichroism signals at AT and GC sites, respectively, showing that the mode of binding of a drug can change markedly with the DNA base composition. Among minor groove binders, the N-methylpyrrole carboxamide-containing antibiotics netropsin and distamycin bound to DNA with very pronounced AT specificity, as expected. More interestingly the dye Hoechst 33258, berenil and a thiazole-containing lexitropsin elicited negative reduced dichroism in the presence of GC-rich DNA which is totally inconsistent with a groove binding process. We postulate that these three drugs share with the trypanocide 4',6-diamidino-2-phenylindole (DAPI) the property of intercalating at GC-rich sites and binding to the minor groove of DNA at other sites. Replacement of guanines by inosines (i.e., removal of the protruding exocyclic C-2 amino group of guanine) restored minor groove binding of DAPI, Hoechst 33258 and berenil. Thus there are several cases where the mode of binding to DNA is directly dependent on the base composition of the polymer. Consequently the ELD technique appears uniquely valuable as a means of investigating the possibility of sequence-dependent recognition of DNA by drugs.

Base Sequence↗
PubMed1992

Hemodynamic effect of calcium channel blockade during anesthesia for coronary artery surgery.

Because the choice of anesthetic technique does not influence the incidence of perioperative myocardial ischemia, reduction of ischemic risk may require specific antianginal therapy. Calcium entry blockers are effective drugs in antianginal therapy. Diltiazem reduces myocardial oxygen demand through decreases in heart rate, inotropy, and systolic function, while increasing myocardial oxygen delivery through coronary vasodilation. These potentially beneficial effects of diltiazem were evaluated in 15 of 29 patients (diltiazem v placebo, double-blind study) scheduled for coronary artery bypass graft surgery. Continuous infusion of diltiazem (0.15 mg/kg bolus followed by 2 micrograms/kg/min), during anesthesia and surgery before cardiopulmonary bypass, significantly reduced the major MVO2 determinants during anesthesia with moderate doses of fentanyl and a benzodiazepine (midazolam in 8 of 14 control patients and 9 of 15 treated patients, or flunitrazepam in the others). Heart rate, mean arterial pressure, and inotropy were decreased during the most stressful events of surgery when plasma diltiazem concentrations were in the therapeutic range (greater than 96 ng/mL). The number of patients with perioperative ischemia was 2 of 15 in the treated group and 4 of 14 in the control group. Provided that diltiazem plasma concentrations are sufficient, it can contribute to lowering the ischemic burden during anesthesia for coronary artery surgery.

Anesthesia, Intravenous↗
PubMed1992

Effects of halothane and isoflurane on transient renal dysfunction associated with infrarenal aortic cross-clamping.

Aortic cross-clamping for reconstructive aortic surgery is associated with impairment of renal function. Halothane or isoflurane was used to assess the influence of volatile anesthesia on renal hemodynamics during aortic surgery. Nineteen patients with normal preoperative creatinine clearances who were scheduled for reconstructive aortic surgery were randomly divided into two groups: halothane group (n = 9) and isoflurane group (n = 10). Induction of anesthesia consisted of midazolam, fentanyl, and pancuronium. Anesthesia was maintained with fentanyl and halothane or isoflurane in nitrous oxide and oxygen (50/50). Systemic hemodynamics were similar in both groups throughout surgery. Before aortic cross-clamping, effective renal plasma flow (ERPF) (131I-hippuran clearance) and glomerular filtration rate (GFR) (99Tc-DTPA clearance) were significantly lower in the halothane group (118.4 +/- 25.6 and 19.7 +/- 5.2 mL/min, respectively) than in the isoflurane group (253.4 +/- 51.5 and 44.9 +/- 8.4 mL/min) (P less than 0.05 for both). During cross-clamping, the renal variables were not markedly affected in either group and remained higher in the isoflurane-anesthetized patients (232.9 +/- 47.1 and 49.5 +/- 1.2 mL/min for ERPF and GFR, respectively) than in the halothane-anesthetized patients (132.4 +/- 31.6 and 14.8 +/- 3.7 mL/min, respectively) (P less than 0.05). After aortic unclamping, ERPF increased markedly in both groups (467.8 +/- 122 and 362.5 +/- 57.7 mL/min in the halothane and isoflurane groups, respectively), as did GFR (74.8 +/- 22 and 71.8 +/- 13.1 mL/min, respectively). These results suggest that anesthesia with halothane is associated with transient renal vasoconstriction during abdominal surgery. In contrast, aortic cross-clamping during isoflurane anesthesia was not associated with renal hemodynamic impairment.

Adult↗
PubMed1992

[Anesthetic consequences of hemodynamic effects of angiotensin converting enzyme inhibitors].

Angiotensin converting enzyme inhibitors (ACEI) are used increasingly to treat cardiovascular diseases, and so, therefore, the number of patients scheduled for surgery and treated preoperatively with these drugs. Haemodynamic instability has sometimes been observed during anaesthesia in these patients, leading some authors to discontinue ACEI administration before anaesthesia. However, recent physiological data concerning the renin angiotensin system (RAS) and ACEI pharmacological data may increase our understanding of the mechanisms of cardiovascular interaction between ACEI and anaesthesia. The RAS is involved in blood pressure regulation when extracellular fluid volume is decreased and in case of hypovolaemia, by inducing vasoconstriction and longterm volume regulation. Arterial vasoconstriction is the target for ACEI. However, venoconstriction may maintain venous return and cardiac output in spite of reduced blood volume. On the other hand, ACEI treatment impedes cardiac adaptation to acute changes in extracellular fluid volume. This effect may be increased by underlying pathology (especially in hypertension) as well as by anaesthesia. A combination of an increased sensitivity to acute changes in ventricular load due to treatment with ACEI and anaesthesia in hypertensive patients or in patients with cardiac failure may carry a high risk of hypotension. Specific studies on haemodynamic tolerance of anaesthesia in patients chronically treated with ACEI are required to assess the prevalence of this risk and how to manage it.

Anesthesia, General↗
PubMed1992

Myocardial depressant effect of nitrous oxide after coronary artery bypass graft surgery.

We have studied the cardiovascular effects of nitrous oxide after cardiac ischaemia-reperfusion injury caused by aortic cross-clamping and unclamping during coronary artery bypass grafting (CABG). At the time of chest closure, 20 patients were allocated randomly to receive oxygen and air (FIO2 = 0.5) or 50% nitrous oxide in oxygen in addition to anaesthesia with fentanyl. Nitrous oxide significantly decreased mean arterial pressure (P less than 0.01) and cardiac index (P less than 0.05), which suggests that nitrous oxide with fentanyl may significantly depress left ventricular performance after CABG. Although ischaemia-reperfusion cardiac injury did not appear to increase the myocardial depressant effect of nitrous oxide, the use of nitrous oxide is not recommended immediately after CABG.

Aged↗
PubMed1992

Upregulation of V1a vasopressin receptors by glucocorticoids.

WRK1 cells (a rat mammary tumor cell line) exhibit a vasopressinergic receptor of V1a subtype tightly coupled to phospholipase C. Addition of dexamethasone to the culture medium principally potentiated the vasopressin-sensitive accumulation of inositol phosphates and to a lesser extent the NaF-sensitive phospholipase C activity. On the opposite, such treatment was without effect on the basal level of intracellular inositol phosphates or on bradykinin- or serotonin-sensitive phosphoinositide metabolisms. Glucocorticoid receptors were probably involved in these actions since dexamethasone was found to be more potent than aldosterone or corticosterone. Dexamethasone treatment also increased the number of vasopressin binding sites without affecting its affinity for vasopressin or other specific vasopressin analogues. These results strongly suggest that dexamethasone principally acts at the vasopressin receptor level by affecting its synthesis and/or the translation of its mRNA and also affects the G protein that couples the V1a receptor to the phospholipase C. These results explain how glucocorticoids may regulate the transduction mechanisms involved in vasopressin actions on WRK1 cells. They provide explanations for understanding the cross talk between adrenal steroids and hormones, which mobilize intracellular calcium.

Animals↗
PubMed1992

Does choice of the anesthetic influence renal function during infrarenal aortic surgery?

Reconstructive infrarenal aortic surgery is associated with impairment of renal function owing to vasoconstriction during and after aortic cross-clamping. To assess the influence of anesthetic technique on renal hemodynamics during aortic surgery, 34 patients received one of four anesthetics: isoflurane (n = 10), halothane (n = 9), droperidol (n = 8), and flunitrazepam (n = 7). Supplemental anesthesia consisted of midazolam, fentanyl, nitrous oxide in oxygen (50%), and pancuronium. Before aortic cross-clamping, effective renal plasma flow (ERPF) (131iodohippuran clearance) and glomerular filtration rate (GFR) (99technetium-DTPA clearance) were low in the halothane and flunitrazepam groups (118.4 +/- 25.6 and 170 +/- 35 mL/min for ERPF; 19.7 +/- 5.2 and 26.9 +/- 5.8 mL/min for GFR, respectively) and better preserved in the isoflurane group (253.4 +/- 51.5 and 44.9 +/- 8.4 mL/min, respectively; P less than 0.05 between isoflurane and halothane groups) or in the droperidol group as regards GFR (75.4 +/- 9.4 mL/min, P less than 0.05). During clamping, both renal variables were not markedly affected in any group except in the droperidol group in whom GFR significantly decreased from preclamp value. The GFR was then significantly higher in the isoflurane group (49.5 +/- 9.2 mL/min) than in the halothane and flunitrazepam groups (14.8 +/- 3.7 and 26.5 +/- 10.1 mL/min, respectively; P less than 0.05). After aortic declamping, ERPF and GFR increased markedly in the halothane group, and there was no significant difference between the groups. These results suggest that renal hemodynamics are less altered with droperidol-fentanyl anesthesia during abdominal surgery but not during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hemodynamic effects of anesthesia in patients chronically treated with angiotensin-converting enzyme inhibitors.

Angiotensin-converting enzyme inhibitors (ACEIs) are increasingly used in the treatment of cardiovascular disease, but recent reports have warned of some hemodynamic risk (hypotension and bradycardia) when associated with anesthesia. To assess the hemodynamic effects of induction of anesthesia in patients chronically treated with ACEIs, 16 hypertensive patients scheduled for coronary artery bypass graft surgery (n = 12) or vascular surgery (n = 4) were studied. Eight of them were chronically treated (for at least 1 mo) with ACEIs (ACEI group), and the remaining eight (control group) were treated with other classes of antihypertensive drugs. Induction of anesthesia, which consisted of flunitrazepam (0.03 mg/kg), fentanyl (0.006 mg/kg), and pancuronium (0.1 mg/kg) IV, was followed by a significant decrease in mean arterial blood pressure from baseline in both groups (by 16.8% in controls [P = 0.001] and 33.5% in ACEI-treated patients [P = 0.001] [P = 0.041 between groups]). In control patients, mean arterial blood pressure decrease was only associated with a significant decrease in cardiac index (-18%, P = 0.014). In ACEI-treated patients, the arterial blood pressure decreases were associated with consistent reductions in pulmonary capillary wedge pressure (-26.4%; P = 0.035) and cardiac index (-23.9%; P = 0.001). Systemic vascular resistance index and heart rate were moderately changed (-14.2% and -4.5%, respectively). Rapid restoration of arterial blood pressure was obtained in all ACEI-treated patients, mainly with the intravenous administration of 0.4 to 0.7 L of lactated Ringer's solution. Phenylephrine (0.38 +/- 0.9 mg) was, however, required in four patients when mean arterial blood pressure was less than 60 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Mechanisms of renal hemodynamic impairment during infrarenal aortic cross-clamping.

Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction, the mechanism of which remains under debate. To assess the renal effect of two potent renal vasodilators (enalapril, a converting enzyme inhibitor, and nicardipine, a calcium antagonist), 24 patients scheduled for reconstructive aortic surgery were randomly allocated to one of three treatment groups (n = 8 each) and received either a placebo, nicardipine, or enalapril. Anesthesia consisted of flunitrazepam, fentanyl, pancuronium, and, occasionally, droperidol. Although aortic cross-clamping was associated with no change in mean arterial blood pressure, decreased cardiac output and increased systemic vascular resistance occurred in control patients (33% and 43%, respectively, both P less than 0.05 versus baseline) and nicardipine-treated patients (51.7% and 67.7%, respectively, both P less than 0.05 versus baseline); however, changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients. Glomerular filtration rate (technetium 99-diethylenetriaminepentacetic acid clearance) and effective renal plasma flow (iodo-Hippuran 131 clearance) decreased for the duration of aortic cross-clamping in control patients (42.9% and 18.5%, respectively, both P less than 0.05 versus baseline) and enalapril-treated patients (34.0% and 38.1%, respectively, both P less than 0.05 versus baseline), but no change was observed in nicardipine-treated patients. These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping. In contrast, renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine, which probably acts at the level of the preglomerular resistance vessels.

Adult↗