Biomedical subjects

S Rahman

Publications and source records attributed to S Rahman.

At least 109 records · Page 6Linked to original sources

PubMed1999

Comparison of C1q-receptors on rat microglia and peritoneal macrophages.

A comparison of the expression and ligand specificity of the C1q (first complement component) receptor on rat microglia and peritoneal macrophages was made. This revealed that radiolabelled C1q was competed from the peritoneal macrophages with intact C1q, and additively displaced by calf-skin collagen and purified C1q globular heads, suggesting the presence of at least two receptors. This was in contrast to microglia, where radiolabelled C1q was displaced with intact C1q and to a modest degree with collagen, but not with globular heads. Taken together, this implies that under these conditions, peritoneal macrophages and microglia both express a C1q receptor which binds to the collagen-like region, and that peritoneal macrophages additionally express a molecule which binds to the globular head of C1q. Analysis of the ligand bound by these cells reflected the differences observed in the competitive binding experiments, with the novel identification of naturally-occurring peptides from the globular head of C1q bound to the peritoneal macrophages, but not the microglia.

Amino Acid Sequence↗

PubMed1999

Superiority of magnesium cardioplegia in neonatal myocardial protection.

BACKGROUND: We have shown that magnesium can offset the detrimental effects of normocalcemic cardioplegia in hypoxic neonatal hearts. It is not known, however, whether magnesium offers any additional benefit when used in conjunction with hypocalcemic cardioplegia. METHODS: Twenty neonatal piglets underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) followed by 20 minutes of normothermic ischemia on cardiopulmonary bypass (hypoxic-ischemic stress). They then underwent 70 minutes of multidose blood cardioplegic arrest. Five (Group 1), received a hypocalcemic (Ca+2 0.2 to 0.4 mM/L) cardiologic solution without magnesium, whereas in 10, magnesium was added at either a low dose (5 to 6 mEq/L, Group 2) or high dose (10 to 12 mEq/L, Group 3). In the last 5 (Group 4), magnesium (10 to 12 mEq/L) was added to a normocalcemic cardioplegic solution. Function was assessed using pressure volume loops and expressed as percentage of control. RESULTS: Compared to hypocalcemia cardioplegic solution without magnesium (Group 1), both high- and low-dose magnesium enrichment (Groups 2 and 3) improved myocardial protection resulting in complete return of systolic (40% vs 101% vs 102%) (p < 0.001 vs Groups 2 and 3) and global myocardial function (39% vs 102% vs 101%) (p < 0.001 vs Groups 2 and 3), and reduced diastolic stiffness (267% vs 158% vs 154%) (p < 0.001 vs Groups 2 and 3). Conversely, even high-dose magnesium supplementation could not offset the detrimental effects of normocalcemic cardioplegia resulting in depressed systolic (End Systolic Elastance [EES] 41%+/-1%) (p < 0.001 vs Groups 2 and 3) and global myocardial function (40%+/-1%) (p < 0.001 vs Groups 2 and 3), and a marked rise in diastolic stiffness (258%+/-5%) (p < 0.001 vs Groups 2 and 3). Hypocalcemic magnesium cardioplegia has now been used successfully in 247 adult and pediatric patients. CONCLUSIONS: Magnesium enrichment of hypocalcemic cardioplegic solutions improves myocardial protection resulting in complete functional preservation. However, magnesium cannot prevent the detrimental effects of normocalcemic cardioplegia when the heart is severely stressed. This study, therefore, strongly supports using both a hypocalcemic cardioplegic solution and magnesium supplementation as their benefits are additive.

Adenosine Diphosphate↗

PubMed1999

Dose dependency of L-arginine in neonatal myocardial protection: the nitric oxide paradox.

OBJECTIVES: Recent experimental studies have suggested that enriching cardioplegic solution with L-arginine improves myocardial protection by increasing nitric oxide production. Nitric oxide, however, also generates the toxic oxygen-derived free radical peroxynitrite; thus these beneficial effects may be dose dependent, especially in vulnerable (stressed) hearts. METHODS: Fifteen neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of normothermic ischemia on cardiopulmonary bypass (stress). They were then protected for 70 minutes with multiple doses of blood cardioplegic solution. In 5 (group 1), the cardioplegic solution contained no L-arginine, in 5 (group 2), it was enriched with a 4 mmol/L concentration of L-arginine, and in 5 (group 3), a 10 mmol/L concentration of L-arginine. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control, and coronary vascular resistance and conjugated diene production were measured during infusions of cardioplegic solution. RESULTS: Compared with the protection afforded by blood cardioplegic solution without L-arginine (group 1), the addition of a 4 mmol/L concentration of L-arginine (group 2) significantly improved myocardial protection, resulting in complete return of systolic function (end-systolic elastance 38% vs 100%; P <.001 vs 4 mmol/L L-arginine) and preload recruitable stroke work (40% vs 100%; P <. 001 vs 4 mmol/L L-arginine); minimal increase in diastolic stiffness (239% vs 158%; P <.001 vs 4 mmol/L L-arginine); and lower coronary vascular resistance, conjugated diene production, and myeloperoxidase activity (P <.001 vs 4 mmol/L L-arginine in each case). Conversely, supplementing the cardioplegic solution with a 10 mmol/L dose of L-arginine (group 3) negated these beneficial effects, resulting in depressed systolic function (end-systolic elastance 41% +/- 2%; P <.001 vs 4 mmol/L L-arginine) and preload recruitable stroke work (40% +/- 2%; P <.001 vs 4 mmol/L L-arginine); increased diastolic stiffness (246% +/- 7%; P <.001 vs 4 mmol/L L-arginine); and higher conjugated diene production, myeloperoxidase activity, and coronary vascular resistance (P <.001 vs 4 mmol/L L-arginine in each case). CONCLUSIONS: Enriching cardioplegic solution with a 4 mmol/L concentration of L-arginine significantly improves myocardial protection by reducing oxygen-derived free radical formation by white blood cells, thus preserving vascular and myocardial function. However, these beneficial effects are dose dependent because 10 mmol/L concentrations of L-arginine increase oxygen-derived free radical production, resulting in vascular and myocardial dysfunction.

Animals↗

PubMed1999

L-arginine, prostaglandin, and white cell filtration equally improve myocardial protection in stressed neonatal hearts.

OBJECTIVES: L-Arginine may improve cardioplegic protection by increasing nitric oxide production. However, L-arginine may also be detrimental because it generates the free radical peroxynitrite. It would, therefore, be advantageous if the benefits of L-arginine could be achieved by another means. METHODS: Twenty neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass (stress) and were then protected for 70 minutes with multiple doses of blood cardioplegic solution. In 5 piglets (group 1), the cardioplegic solution was not modified; in 5 (group 2), low-dose L-arginine (4 mmol/L) was added; in 5 (group 3), prostaglandin E(1) (alprostadil, 4 microgram/L) was added; and in 5 (group 4), the cardioplegic solution was passed through a leukodepleting filter. Myocardial function was assessed by pressure volume loops and expressed as percentage of control, and coronary vascular resistance was measured with each cardioplegic infusion. RESULTS: Unmodified blood cardioplegic solution (group 1) was unable to protect the severely stressed myocardium, resulting in depressed systolic function (39% +/- 1%) and preload recruitable stroke work (40% +/- 1%), increased diastolic stiffness (239% +/- 3%), and high conjugated diene production, myeloperoxidase activity, and coronary vascular resistance. In contrast, cardioplegic solutions modified with L-arginine, prostaglandin E(1), or leukodepletion, resuscitated the stressed myocardium, resulting in complete return of systolic function (100% vs 101% vs 101%; P <.001 vs group 1) and preload recruitable stroke work (100% vs 101% vs 101%; P <.001 vs group 1), minimal increase in diastolic stiffness (160% vs 162% vs 160%; P <. 001 vs group 1), and lowered conjugated diene production, myeloperoxidase activity, and coronary vascular resistance (P <.001 vs group 1 for each). CONCLUSIONS: (1) Unmodified blood cardioplegic solution is unable to protect the severely stressed myocardium. (2) L-Arginine, prostaglandin E(1), and leukocyte filtration all improve myocardial protection equally and appear to work by limiting a white blood cell-mediated injury. This reduces oxygen-derived free radical formation, maintains vascular function, and restores functional recovery. Since L-arginine may be detrimental, surgeons should consider using prostaglandin E(1) and/or a leukocyte filter instead.

Alprostadil↗

PubMed1999

Adjusted and unadjusted energy usage rates both determine body fat and plasma leptin in male Fischer 344 rats.

Previous studies of the relationship between plasma leptin and energy usage have yielded contradictory findings. The present study was therefore conducted to clearly distinguish and measure the energy usage rate and the energy usage rate adjusted for a surrogate of metabolically active tissue mass. We investigated the simultaneous relationships between these two measures of energy usage, leptin, and body fat in 21-month-old adult male Fischer 344 rats on three different long-term dietary regimens: (1) continuous ad libitum feeding (Ad-lib); (2) ad libitum feeding until early adulthood, and then continuous 60% caloric restriction (CR); and (3) ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, and then ad libitum feeding for 5 months (CR/Ad-lib). Two versions of the daily usage rate were measured: daily dietary caloric intake (DCI), and daily energy expenditure (EE) based on indirect calorimetry. Two versions of the metabolically active tissue mass were also measured: fat-free mass (FFM), and the sum of the weight of the heart, brain, liver, and kidneys. Energy usage rates were adjusted for these measures of metabolically active tissue mass to yield measures of the energy metabolic rate. Correlation, regression, and path analyses showed that both the energy usage rate and adjusted energy usage rate played important independent roles in determining body fat and plasma leptin, but only after multivariate techniques were used to account for the simultaneous interactions between variables. Increases in the energy usage rate were associated with increases in body fat and the adjusted energy usage rate. Increases in the adjusted energy usage rate were associated with decreases in body fat and plasma leptin. These findings suggest that differences in subjects adjusted energy usage rate could explain some of the apparently contradictory findings concerning the relationship between energy usage and plasma leptin in previously published studies. In conclusion, this appears to be the first study to clearly separate and quantify the effects of the energy usage rate and adjusted energy usage rate on body fat and plasma leptin. The findings suggest that under conditions of long-term stable body weight, both of these measures of energy usage play independent simultaneous roles in determining body fat and plasma leptin.

Adipose Tissue↗

PubMed1999

Long-term neurological complication following traumatic damage to the spinal cord with a 25 gauge whitacre spinal needle.

Neurological complications following regional anaesthesia may arise due to compression of the spinal cord or nerve roots secondary to haematoma or abscess, trauma, neurotoxicity or ischaemia. We report a patient who developed prolonged left lower limb paresis following combined spinal epidural (CSE) anaesthesia for emergency caesarean section. Magnetic resonance imaging (MRI) showed marked swelling of the lower end of the spinal cord suggesting traumatic damage of the cord by the spinal needle.

Journal Article↗

PubMed1999

Identification of a novel mutation in a non-Jewish factor XI deficient kindred.

The role of factor XI (FXI) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68-year-old woman, presented with a cerebral thromboembolic event but had no history of bleeding (FXI activity 1.6 U/dl). A sensitive ELISA failed to detect FXI antigen in the propositus. Sequence analysis of the entire FXI gene revealed a TGG to TGC transversion in codon 228 of exon 7 (FXI-W228C). This missense mutation results in a Trp to Cys substitution within the third apple domain of FXI. We conclude that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of FXI and was responsible for the inherited abnormality seen in this kindred. It is unclear why this kindred does not exhibit a bleeding tendency but it may correlate with a FXI-like antigen and factor IX binding activity expressed on platelets.

Aged↗

PubMed1999

A missense mutation of cytochrome oxidase subunit II causes defective assembly and myopathy.

We report the first missense mutation in the mtDNA gene for subunit II of cytochrome c oxidase (COX). The mutation was identified in a 14-year-old boy with a proximal myopathy and lactic acidosis. Muscle histochemistry and mitochondrial respiratory-chain enzymology demonstrated a marked reduction in COX activity. Immunohistochemistry and immunoblot analyses with COX subunit-specific monoclonal antibodies showed a pattern suggestive of a primary mtDNA defect, most likely involving CO II, for COX subunit II (COX II). mtDNA-sequence analysis demonstrated a novel heteroplasmic T-->A transversion at nucleotide position 7,671 in CO II. This mutation changes a methionine to a lysine residue in the middle of the first N-terminal membrane-spanning region of COX II. The immunoblot studies demonstrated a severe reduction in cross-reactivity, not only for COX II but also for the mtDNA-encoded subunit COX III and for nuclear-encoded subunits Vb, VIa, VIb, and VIc. Steady-state levels of the mtDNA-encoded subunit COX I showed a mild reduction, but spectrophotometric analysis revealed a dramatic decrease in COX I-associated heme a3 levels. These observations suggest that, in the COX protein, a structural association of COX II with COX I is necessary to stabilize the binding of heme a3 to COX I.

Acidosis, Lactic↗

PubMed1999

Specific cognitive deficits in mild frontal variant frontotemporal dementia.

Eight patients with relatively mild frontal variant frontotemporal dementia (fvFTD) were compared with age- and IQ-matched control volunteers on tests of executive and mnemonic function. Tests of pattern and spatial recognition memory, spatial span, spatial working memory, planning, visual discrimination learning/attentional set-shifting and decision-making were employed. Patients with fvFTD were found to have deficits in the visual discrimination learning paradigm specific to the reversal stages. Furthermore, in the decision-making paradigm, patients were found to show genuine risk-taking behaviour with increased deliberation times rather than merely impulsive behaviour. It was especially notable that these patients demonstrated virtually no deficits in other tests that have also been shown to be sensitive to frontal lobe dysfunction, such as the spatial working memory and planning tasks. These results are discussed in relation to the possible underlying neuropathology, the anatomical connectivity and the hypothesized heterogeneous functions of areas of the prefrontal cortex. In particular, given the nature of the cognitive deficits demonstrated by these patients, we postulate that, relatively early in the course of the disease, the ventromedial (or orbitofrontal) cortex is a major locus of dysfunction and that this may relate to the behavioural presentation of these patients clinically described in the individual case histories.

Adult↗

PubMed1999

The localization and expression of the class II starch synthases of wheat.

The starch granules of hexaploid wheat (Triticum aestivum) contain a group of three proteins known as SGP-1 (starch granule protein-1) proteins, which have apparent molecular masses of 100, 108, and 115 kD. The nature and role of these proteins has not been defined previously. We demonstrate that these polypeptides are starch synthases that are present in both the starch granule and the soluble fraction at the early stages of wheat endosperm development, but that are exclusively granule bound at mid and late endosperm development. A partial cDNA clone encoding a fragment of the 100-kD protein was obtained by screening a wheat endosperm cDNA expression library using monoclonal antibodies. Three classes of cDNA were subsequently isolated from a wheat endosperm cDNA library by nucleic acid hybridization and were shown to encode the 100-, 108-, and 115-kD proteins. The cDNA sequences are highly homologous to class II starch synthases and have the highest homology with the maize SSIIa (starch synthase IIa) gene. mRNA for the SGP-1 proteins was detected in the leaf, pre-anthesis florets, and endosperm of wheat and is highly expressed in the leaf and in the grain during the early to mid stages of development. We discuss the roles of the SGP-1 proteins in starch biosynthesis in wheat.

Amino Acid Sequence↗

PubMed1999

Comparative cognitive neuropsychological studies of frontal lobe function: implications for therapeutic strategies in frontal variant frontotemporal dementia.

Patients with mild frontal variant frontotemporal dementia (fvFTD) who attend the clinic are usually unaware of the pervasive changes in their personality and behaviour, despite the fact it is these changes which have prompted the referral from the patient's spouse or carer. Comparative studies across various species offer unique insights into the heterogeneous structure and functions of the prefrontal cortex, and can allow a novel approach to the precise identification of the neuropsychological deficits present in these patients. We have found that they may show marked deficits on tests sensitive to ventromedial prefrontal or orbitofrontal function, in the relative absence of impairments on tests sensitive to dorsolateral prefrontal function. We highlight important differences in the neurocognitive profile of these patients with that of patients with other neurodegenerative conditions, including basal ganglia diseases and dementia of the Alzheimer type. The specific nature of these neuropsychological deficits, together with converging evidence from clinical and neuropathological studies, may provide useful clues about the predominant locus of dysfunction in the early stages of fvFTD and possible underlying neurotransmitter abnormalities. This is important for the successful development of therapeutic intervention strategies for both cognitive and behavioural symptoms in fvFTD. Finally, we evaluate critically the rationales for therapeutic modulation of noradrenergic, serotonergic and dopaminergic neurotransmitter systems at various stages of disease.

Cognition↗

PubMed1999

A nutritional profile of non-pregnant women from the slums of Dinajpur, Bangladesh.

The health and nutritional status of many urban slum dwellers in the developing world is said to be deteriorating. The nutritional profile of 328 adult, non-pregnant women from the slums of Dinajpur, Bangladesh, confirms this. Results of a cross-sectional survey showed that approximately half the women were acutely malnourished and all but six were anaemic. This, despite the fact that the slums of Dinajpur are considered relatively 'better-off' than many in the developing world; most families having permanent land tenureship, and access to basic education and health services.

Adolescent↗

PubMed1999

Inside-outside technique for posterior occipitocervical spine instrumentation and stabilization: preliminary results.

OBJECT: The authors present a series of 16 patients who underwent inside-outside occipital and posterior cervical spine stabilization. METHODS: In this technique, the screw was placed from the inside of the occiput to the outside. An articular (lateral) mass plate was contoured to the shape of the occipital bone and the cervical spine and affixed to the occiput with a flat-headed screw or stud placed through a burr hole in the calvaria with the flat head of the screw in the epidural space and the threads facing outward. The bone plate was then secured with a nut to the occipital screw and the cervical plate was attached to the spine with a bone screw that coursed through the plate and into the articular pillar. Our series included six children and 10 adults. In five patients, previous fusion had failed; in two patients spinal instability was secondary to Down's syndrome; two patients' instability was related to developmental anomalies; and in five patients spinal instability was due to the presence of tumor. One patient with rheumatoid arthritis had undergone a transoral procedure. Two patients had suffered traumatic fracture. Three patients died of causes unrelated to the procedure, one patient died of metastatic cancer, and one patient died in a long term care facility of cardiopulmonary complications. One patient with renal failure suffered a hemorrhage from an arteriovenous fistula after being treated with dialysis. In one child, a nut backed off after 3 months. The nut was reseated, and a maturing arthrodesis was present. CONCLUSIONS: The authors conclude that the inside-outside occipitocervical fixation is an effective technique for stabilizing the cervical spine.

Adolescent↗

PubMed1999

The Ha locus of wheat: identification of a polymorphic region for tracing grain hardness in crosses.

The grain softness proteins or friabilins are known to be composed of three main components: puroindoline a, puroindoline b, and GSP-1. cDNAs for GSP-1 have previously been mapped to group-5 chromosomes and their location on chromosome 5D is closely linked to the grain hardness (Ha) locus of hexaploid wheat. A genomic DNA clone containing the GSP-1 gene (wGSP1-A1) from hexaploid wheat has been identified by fluorescent in situ hybridization as having originated from the distal end of the short arm of chromosome 5A. A genomic clone containing the gene (wGSP1-D1) was also isolated from Aegilops tauschii, the donor of the D genome to bread wheat. There are no introns in the GSP-1 genes, and there is high sequence identity between wGSP1-A1 and wGSP1-D1 up to 1 kb 5' and 300 bp 3' to wGSP1-D1. However, regions further upstream and downstream of wGSP1-D1 share no significant sequence identity to corresponding sequences in wGSP1-A1. These regions therefore identified potentially valuable sequences for tracing the Ha locus through assaying polymorphic DNA sequences. The sequence from 300 to 500 bp 3' to wGSP1-D1 (wGSP1-D13) was mapped to the Ha locus in a mapping population. wGSP1-D13 was also tightly linked to genes for puroindoline a and puroindoline b which have been previously mapped to be at the Ha locus. In addition wGSP1-D13 was used to detect RFLPs between near isogenic soft and hard Falcon lines and in a random selection of soft and hard wheats.

Base Sequence↗

PubMed1998

Modulation of RGD sequence motifs regulates disintegrin recognition of alphaIIb beta3 and alpha5 beta1 integrin complexes. Replacement of elegantin alanine-50 with proline, N-terminal to the RGD sequence, diminishes recognition of the alpha5 beta1 complex with restoration induced by Mn2+ cation.

Several recent studies have demonstrated that the amino acid residues flanking the RGD sequence of high-affinity ligands modulate their specificity of interaction with integrin complexes. The present study has addressed the role of the residues flanking the RGD sequence in regulating the recognition by disintegrin of the alphaIIb beta3 and alpha5beta1 complexes by construction of a panel of recombinant molecules of Elegantin (the platelet aggregation inhibitor from the venom of Trimerasurus elegans) expressing specific RGD sequence motifs. Wild-type Elegantin (ARGDNP) and several variants including Eleg. AM (ARGDMP), Eleg. PM (PRGDMP) and Eleg. PN (PRGDNP) were expressed as glutathione S-transferase (GST) fusion proteins in Escherichia coli. The inhibitory efficacies of the panel of Elegantin variants were analysed in platelet adhesion assays with substrates immobilized with fibrinogen and fibronectin. Elegantin molecules containing an Ala residue N-terminal to the RGD sequence (wild-type Elegantin and Eleg. AM) showed strong inhibitory activity towards alphaIIbbeta3-dependent platelet adhesion on fibronectin, whereas a Pro residue in this position (Eleg. PM and Kistrin, the inhibitor from the venom of Calloselasma rhodostoma) engendered lower activity. The decreased activity could not be attributed to a decrease in the affinity of the disintegrin for the alphaIIb beta3 complex because both Eleg. AM and Eleg. PM had similar Kd (app) values. In contrast, Elegantin molecules into which a Met residue was introduced in place of the Asn residue C-terminal to the RGD sequence showed 10-13-fold elevated inhibitory activity towards platelet adhesion on fibrinogen and this was maintained with either a Pro or Ala residue N-terminal to the RGD sequence. In experiments with the alpha5 beta1 complex on K562 cells, the inhibitory efficacies of the panel of Elegantin molecules were analysed under two different cation conditions. First, in the presence of Ca2+/Mg2+, K562 cell adhesion on fibronectin was inhibited equally well by Elegantin and Eleg. AM but inhibited poorly by Eleg. PM and Kistrin. In contrast with platelets, the decreased inhibitory efficacy of the PRGDMP disintegrins was due to poor recognition of the alpha5 beta1 complex. In the presence of Mn2+ cation, K562 cell adhesion on fibrinogen was observed in an alpha5 beta1-dependent manner. Under these conditions both PRGD and ARGD containing disintegrins were strong inhibitors of K562 cell adhesion on fibrinogen and this was due to a markedly improved recognition of the alpha5 beta1 complex by the PRGD molecules. These observations demonstrate the pivotal role of the amino acids flanking the RGD sequence for disintegrin recognition of integrin complexes and highlight the subtle nature by which integrin-ligand binding specificity can be modulated by both cation and adhesive motif.

Amino Acid Sequence↗

PubMed1998

Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.

BACKGROUND: Posttransplantation lung reperfusion injury continues to be a major problem. We have shown that controlling the initial period of reperfusion limits this injury after 2 hours of warm lung ischemia. The effectiveness of this modality, however, is unknown after longer periods of cold ischemia, which more closely mimics the clinical situation. METHODS: After baseline measurements, 10 pigs had the left lung flushed with a modified Euro-Collins solution, explanted, stored at 4 degrees C for 24 hours, and transplanted into 10 other pigs. Five (group 1) underwent uncontrolled reperfusion created by removal of the vascular clamps after implantation of the new left lung, mimicking the clinical situation. The other five (group 2) underwent controlled reperfusion, which we performed by taking blood from the femoral artery, mixing it with a crystalloid solution (using a mixer heater) to make the blood hyperosmolar, alkalotic, and substrate-enriched, and pumping it through a leukocyte-depleting filter into the transplanted lung for 10 minutes at a pressure of 20 to 30 mm Hg before removing the pulmonary artery clamp. The right pulmonary artery and bronchus were then ligated, and left lung function was assessed each hour for 4 hours and compared with baseline. RESULTS: Controlled reperfusion (group 2) minimized the reperfusion injury, preserving posttransplant pulmonary compliance (92% +/- 1% versus 68% +/- 1%; p < 0.001), reducing the rise in pulmonary vascular resistance (27% +/- 2% versus 166% +/- 3%; p < 0.001), improving oxygenation (PO2, 425 +/- 14 versus 82 +/- 11 mm Hg; p < 0.001), and lowering myeloperoxidase activity (0.22 +/- 0.02 versus 0.45 +/- 0.02 deltaOD/mg protein per minute; p < 0.001) and tissue edema (83.0% +/- 0.3% versus 84.9% +/- 0.3%; p < 0.001) compared with uncontrolled reperfusion, which resulted in an injury so severe that 3 of 5 pigs died before the 4-hour measurements. CONCLUSIONS: After 24 hours of cold ischemia uncontrolled reperfusion results in a severe pulmonary reperfusion injury. This injury is almost completely avoided by controlling the composition (modified solution and white blood cell filter) and conditions (pressure) of the reperfusion. Because this experiment mimics the clinical situation, it suggests surgeons should begin to use this modality to limit reperfusion injury after lung transplantation.

Animals↗

PubMed1998

The importance of cardioplegic infusion pressure in neonatal myocardial protection.

BACKGROUND: Cardioplegia infusion pressure is usually not directly monitored during neonatal heart operations. We hypothesize that the immature newborn heart may be damaged by even moderate elevation of cardioplegic infusion pressure, which in the absence of direct aortic monitoring may occur without the surgeon's knowledge. METHODS: Twenty neonatal piglets received cardiopulmonary bypass and the heart was protected for 70 minutes with multidose blood cardioplegia infused at an aortic root pressure of 30 to 50 mm Hg (low pressure) or 80 to 100 mm Hg (high pressure). Group 1 (n = 5, low pressure), and group 2 (n = 5, high pressure) were uninjured (nonhypoxic) hearts. Group 3 (n = 5, low pressure) and group 4 (n = 5, high pressure) first underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) before initiating cardiopulmonary bypass to produce a clinically relevant hypoxic stress before cardiac arrest. Function was assessed using pressure volume loops (expressed as a percentage of control), and coronary vascular resistance was measured with each cardioplegic infusion. RESULTS: In nonhypoxic (uninjured) hearts (groups 1 and 2) cardioplegic infusion pressure did not significantly affect systolic function (end systolic elastance, 104% versus 96%), preload recruitable stroke work (102% versus 96%) diastolic compliance (152% versus 156%), or coronary vascular resistance but did raise myocardial water (78.9% versus 80.1%; p < 0.01). Conversely, if the cardioplegic solution was infused at even a slightly higher pressure in hypoxic hearts (group 4), there was deterioration of systolic function (end systolic elastance, 28% versus 106%) (p < 0.001) and preload recruitable stroke work (31% versus 103%; p < 0.001), rise in diastolic stiffness (274% versus 153%; p < 0.001), greater myocardial edema (80.5% versus 79.6%), and marked increase in coronary vascular resistance (p < 0.001) compared to hypoxic hearts given cardioplegia at low infusion pressures (group 3), which preserved function. CONCLUSIONS: Hypoxic neonatal hearts are very sensitive to cardioplegic infusion pressures, such that even moderate elevations cause significant damage resulting in myocardial depression and vascular dysfunction. This damage is avoided by using low infusion pressures. Because small differences in infusion pressure may be difficult to determine without a direct aortic measurement, we believe it is imperative that surgeons directly monitor cardioplegia infusion pressure, especially in cyanotic patients.

Animals↗

PubMed1998

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation.

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.

Animals↗