Biomedical subjects

D Petsikas

Publications and source records attributed to D Petsikas.

17 recordsLinked to original sources

PubMed2003

What keeps postpulmonary resection patients in hospital?

BACKGROUND: Prolonged air leak (longer than three days) was hypothesized to be the primary cause of extended hospital stays following pulmonary resection. Its effect on length of stay (LOS) was compared with that of suboptimal pain control, nausea and vomiting, and other causes. Predictors of prolonged LOS and of prolonged air leaks were investigated. DESIGN: Retrospective review of 91 patients. Primary reasons for prolonged hospitalization were determined. Patient characteristics (demographic information, pulmonary function test results, body habitus measurements, smoking history), operative factors (procedure performed, duration of operation, complications) and postoperative factors (time of chest tube removal) were considered. Student's t test and chi2 analysis were used to compare continuous and ratio data, respectively, and linear regression analysis was used to define the equation relating two variables. RESULTS: The mean postoperative LOS was 6.4 days. Only prolonged air leak was predictive of increased LOS (9.4 days versus 5.4 days, P<0.001). Forced expiratory volume in 1 s less than 1.5 L/min, carbon monoxide diffusing capacity less than 80% predicted and the detection of a pneumothorax were all predictive of prolonged air leak. A strong correlation between the time of chest tube removal and LOS was found (r=0.937, P<0.001). Linear regression analysis showed postoperative LOS and duration of thoracostomy tube insertion to be related by the equation y = 0.88x + 2.49 days. CONCLUSION: These results suggest that increased LOS following pulmonary resection is due primarily to prolonged air leaks. Furthermore, patients who have their chest tubes removed sooner are discharged sooner.

Adolescent↗

PubMed2001

Human lung microsomal cytochrome P4501A1 (CYP1A1) activities: impact of smoking status and CYP1A1, aryl hydrocarbon receptor, and glutathione S-transferase M1 genetic polymorphisms.

There are numerous conflicting epidemiological studies addressing correlations between cytochrome P450 1A1 (CYP1A1) genetic polymorphisms and lung cancer susceptibility, with associations plausibly linked to alterations in carcinogen bioactivation. Similarly, correlations between aryl hydrocarbon receptor gene (AHR) codon 554 genotype and CYP1A1 inducibility are controversial. The objective of this study was to determine whether smoking status, and CYP1A1, AHR, and glutathione S-transferase M1 gene (GSTM1) polymorphisms correlate with altered CYP1A1 activities. Lung microsomal CYP1A1-catalyzed 7-ethoxyresorufin O-dealkylation (EROD) activities were much higher in tissues from current smokers (n = 46) than in those from non-/former smokers (n = 24; 12.11 +/- 13.46 and 0.77 +/- 1.74 pmol/min/mg protein, respectively, mean +/- SD; P < 0.05). However, EROD activities in lung microsomes from current smokers CYP1A1*1/1 (n = 33) and heterozygous MspI variant CYP1A1*1/2A (n = 10) were not significantly different (12.23 +/- 13.48 and 8.23 +/- 9.76 pmol/min/mg protein, respectively, P > 0.05). Three current smokers were heterozygous variant CYP1A1*1/2B (possessing both *2A and *2C alleles), and exhibited activities similar to individuals CYP1A*1/1. One current smoker was heterozygous variant CYP1A1*4 and exhibited activities comparable with individuals CYP1A1*1/1 at that locus. EROD activities in microsomes from current smokers AHR(554)Arg/Arg (n = 41) and heterozygous variant AHR(554)Arg/Lys (n = 5) were not significantly different (12.13 +/- 13.56 and 12.01 +/- 14.23 pmol/min/mg protein, respectively; P > 0.05). Furthermore, microsomal EROD activities from current smokers with the GSTM1-null genotype (n = 28) were not significantly different from those (n = 18) carrying at least one copy of GSTM1 (12.61 +/- 14.24 and 11.34 +/- 12.53 pmol/min/mg protein, respectively; P > 0.05). Additionally, when genotypic combinations of CYP1A1, AHR, and GSTM1 were assessed, there were no significant effects on EROD activity. On the basis of microsomal enzyme activities from heterozygotes, CYP1A1*1/2A, CYP1A1*1/2B, CYP1A1*1/4, and AHR(554) Arg/Lys variants do not appear to significantly affect CYP1A1 activities in human lung, and we observed no association between CYP1A1 activity and the GSTM1-null polymorphism.

Adult↗

PubMed2000

Who should follow up lung cancer patients after operation?

BACKGROUND: It is unclear whether follow-up by a thoracic surgeon after lung cancer resection alters survival. METHODS: The charts of 245 early stage (< or = IIB) non-small cell lung cancer patients, diagnosed between 1988 and 1995, were reviewed. Follow-up data were complete to January 1, 1997, in 96.3% (236 of 245) of cases. RESULTS: Ninety of the 111 recurrences were detected before discharge from the thoracic clinic. Despite clinic follow-up, 66.7% (60 of 90) were identified by the family physician, and only 28.9% (26 of 90) by the surgeon. The remaining 4.4% (4 of 90) were detected by other physicians. Ninety-six percent (25 of 26) surgeon-detected recurrences had suspicious clinical or chest radiographic findings, compared with 92% for family physician-detected recurrences (55 of 60; not significant). The cost per recurrence detected by surgeons was Can $4,367. A 75% cost savings could ensure if patients were followed up by their family physician. There was no 5-year survival benefit for patients whose recurrence was detected by the surgeon. CONCLUSIONS: Long-term follow-up after limited-stage non-small cell lung cancer resection could possibly be performed by a family physician alone without compromising overall survival, and with significant cost savings.

Adult↗

PubMed1999

Glutathione S-transferase-catalyzed conjugation of bioactivated aflatoxin B(1) in human lung: differential cellular distribution and lack of significance of the GSTM1 genetic polymorphism.

Epidemiological studies suggest that aflatoxin B(1) (AFB(1)), a mycotoxin produced by certain Aspergillus species, may play a role in human respiratory cancers in occupationally-exposed individuals. AFB(1) requires bioactivation to the corresponding exo-8,9-epoxide for carcinogenicity, and glutathione S-transferase (GST)-catalyzed conjugation of the epoxide with glutathione (GSH) is a critical determinant of susceptibility to AFB(1). Of the purified human GST enzymes studied, the polymorphic hGSTM1-1 has the highest activity towards AFB(1) exo-epoxide. The influence of the GSTM1 polymorphism on AFB(1)-GSH formation, as well as the abilities of cytosols from preparations enriched in different isolated lung cell types to conjugate AFB(1)-epoxides, were examined. In whole-lung cytosols from patients undergoing clinically indicated lobectomy, GSTM1 genotype correlated with GSTM1 phenotype as determined by [(3)H]trans-stilbene oxide conjugation: GSTM1-positive = 295 +/- 31 pmol/mg/h (n = 6); GSTM1-negative = 92.8 +/- 23.3 pmol/mg/h (n = 4) (P < 0.05). In contrast, conjugation of microsome-generated [(3)H]AFB(1)-epoxides with GSH was low and variable between patients, and did not correlate with GSTM1 genotype: GSTM1-positive = 11.9 +/- 8.1, 111 +/- 66 and 510 +/- 248 fmol/mg/h (n = 6); GSTM1-negative = 15.3 +/- 16.7, 167 +/- 225 and 540 +/- 618 fmol/mg/h (n = 4) (for 1, 10 and 100 microM [(3)H]AFB(1), respectively). GSH conjugates of AFB(1) exo-epoxide and the much less mutagenic stereoisomer AFB(1) endo-epoxide were produced in a ratio of approximately 1:1 in cytosols from both whole lung and isolated cells. Total cytosolic AFB(1)-epoxide conjugation was significantly higher in fractions enriched in alveolar type II cells (3.07 +/- 1.61 pmol/mg/h) than in unseparated lung cells (0.143 +/- 0.055 pmol/mg/h) or fractions enriched in alveolar macrophages (0. 904 +/- 0.319 pmol/mg/h; n = 4) (P < 0.05). Furthermore, AFB(1)-GSH formation and percentage of alveolar type II cells in different cell fractions were correlated (r = 0.78, P < 0.05). These results demonstrate that human lung GSTs exhibit very low conjugation activity for both AFB(1)-8,9-epoxide stereoisomers, and that this activity is heterogeneously distributed among cell types, with alveolar type II cells exhibiting relatively high activity. Of the GSTs present in human peripheral lung which contribute to AFB(1) exo- and endo-epoxide detoxification, hGSTM1-1 appears to play at most only a minor role.

Aflatoxin B1↗

PubMed1999

Biotransformation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in freshly isolated human lung cells.

Metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was characterized in human lung cells isolated from peripheral lung specimens obtained from 12 subjects during clinically indicated lobectomy. NNK biotransformation was assessed in preparations of isolated unseparated cells (cell digest), as well as in preparations enriched in alveolar type II cells, and alveolar macrophages. Metabolite formation was expressed as a percentage of the total recovered radioactivity from [5-(3)H]NNK and its metabolites per 10(6) cells per 24 h. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was the major metabolite formed in all lung cell preparations examined, and its formation ranged from 0.50 to 13%/10(6) cells/24 h. Formation of alpha-carbon hydroxylation end-point metabolites (bioactivation) and pyridine N-oxidation metabolites (detoxification), ranged from non-detectable to 0.60% and from non-detectable to 1.5%/10(6) cells/24 h, respectively, reflecting a large degree of intercellular and inter-individual variability in NNK metabolism. Formation of the alpha-hydroxylation end-point metabolite 4-hydroxy-1-(3-pyridyl)-1-butanol (diol) was consistently higher in alveolar type II cells than in cell digest or alveolar macrophages (0.0146 +/- 0.0152, 0.0027 +/- 0.0037 and 0.0047 +/- 0.0063%/10(6) cells/24 h, respectively; n = 12; P < 0.05). SKF-525A was used to examine cytochrome P450 contributions to the biotransformation of NNK. SKF-525A inhibited keto reduction of NNK to NNAL by 85, 86 and 74% in cell digest, type II cells, and macrophages, respectively (means of 11 subjects, P < 0.05). Type II cell incubates treated with SKF-525A formed significantly lower amounts of total alpha-hydroxylation metabolites compared with type II cells without SKF-525A (0.0776 +/- 0.0841 versus 0.1694 +/- 0. 2148%/10(6) cells/24 h, respectively; n = 11; P < 0.05). The results of this first study examining NNK biotransformation in freshly isolated human lung cells indicate that NNK metabolism is subject to a large degree of inter-individual and intercellular variability, and suggest a role for P450s in human lung cell NNK metabolism. Both alveolar type II cells and alveolar macrophages may be potential target cells for NNK toxicity based on their alpha-carbon hydroxylation capabilities. In addition, carbonyl reduction of NNK to NNAL is SKF-525A sensitive in human lung cells.

Aged↗

PubMed1999

Cytochrome P-450-dependent bioactivation of 1,1-dichloroethylene to a reactive epoxide in human lung and liver microsomes.

We investigated the cytochrome P-450-dependent metabolism of 1, 1-dichloroethylene (DCE) by human lung and liver microsomes and compared the results from analogous experiments in mice. Metabolites were identified by HPLC analysis of their glutathione conjugates and/or hydrolyzed products and were detected by using [14C]DCE. The role of human CYP2E1 in the metabolic reactions was examined by comparing p-nitrophenol hydroxylase activities with levels of metabolites formed and by using the CYP2E1-selective inhibitor diallyl sulfone. The major products formed in microsomal incubations containing NADPH were the DCE-epoxide-derived glutathione conjugates 2-(S-glutathionyl)acetyl glutathione and 2-S-glutathionyl acetate. Lower levels of the acetal of 2,2-dichloroacetaldehyde were also detected. In lung samples from eight patients, the amounts of epoxide-derived conjugates formed ranged from 15.6 +/- 4.23 to 34.9 +/- 12.75 pmol/mg protein/min. The levels in murine lung were higher at 40.0 +/- 3.8 pmol/mg protein/min. In liver samples from five patients, conjugate levels ranged from 46.5 +/- 8.3 to 240.0 +/- 10. 5 pmol/mg protein/min, whereas levels in murine liver were 83.0 +/- 6.2 pmol/mg protein/min. Conjugate levels formed in human liver correlated with the relative levels of p-nitrophenol hydroxylase activity present, but this relationship was equivocal in human lung. Diallyl sulfone inhibited the formation of the glutathione conjugates (20-65%) in liver samples from all four patients, whereas only one of five human lung samples exhibited this inhibition (27%). These results demonstrated that the DCE-epoxide is a major metabolite formed by human microsomes and is mediated by CYP2E1 in liver and in some individuals in lung.

Adolescent↗

PubMed1997

Effects of albumin coating of knitted Dacron grafts on transinterstitial blood loss and tissue ingrowth and incorporation.

Transinterstitial blood loss at implantation and the degree of graft incorporation and inner capsule thickening was compared in serial explants of albumin-coated Dacron versus blood preclotted Dacron grafts in the canine thoracoabdominal aortic position (8 mm internal diameter x 30 cm length). The coated grafts were Bard DeBakey Vasculour II knitted Dacron prostheses impregnated with carbodiimide-cross-linked human albumin. Control grafts were otherwise identical and preclotted with the recipients' whole blood before heparinization during surgery. Transinterstitial blood loss after establishing flow was measured by weighing sponges wrapped around the grafts. Albumin pretreatment resulted in significantly less median blood loss (5.1 g versus 11 g, P=0.04; Mann-Whitney rank sum test). Grafts were explanted at 1 week, 4 weeks, 10 weeks, and 20 weeks. Patency was 100% in both groups. Graft incorporation at explantation was graded by the surgeon as: 1 = none, 2 = minimal, 3 = moderate, or 4 = extensive. No significant differences were noted at any time period. Inner capsule thickness measurements were made every 2.5 mm along the length of all explants. Grafts explanted at 1 week displayed no inner capsules. By 20 weeks, median inner capsule thickness was significantly less in albumin-coated grafts (190 microm versus 235 microm; P<0.0001). These inner capsules in both groups formed as islands, containing abundant myofibroblasts and collagen, covered by endothelial cells and surrounded by residual fibrin coagula. In conclusion, albumin-coated knitted Dacron grafts displayed less transinterstitial blood loss at implantation, and qualitatively similar incorporation, but significantly thinner inner capsules at 20 weeks.

Animals↗

PubMed1996

Dacron stimulation of macrophage transforming growth factor-beta release.

This study evaluated the effect of Dacron on the release of macrophage transforming growth factor-beta (TGF-beta),an endothelial cell growth inhibitor. Rabbit peritoneal macrophages were grown in minimum essential medium (MEM) with 10% fetal bovine serum (FBS) in the presence or absence of Dacron (0.5 mm x 3 mm particles). Media were collected three times each week for 7 weeks. For the TGF-beta bioassay, mink lung epithelial cells (CCL64) were grown in MEM with 10% FBS. Test-conditioned media, 100 mu 1, were added (n = 4), and incubated 48 h. 3(H)-Thymidine (3(H)-TdR) uptake was determined and compared with 3(H)-TdR uptake using known pure TGF-beta standards. Media samples were additionally pre-incubated with a neutralizing anti-TGF-beta(1) antibody and the 3(H)-TdR uptake again quantitated. TGF-beta activity in the conditioned media of macrophages exposed to Dacron exceeded the control media groups in all weeks, reaching significance (P<0.05) in weeks 3, 4,5, 6 and 7. Pre-incubation of media samples with the anti-TGF-beta antibody inhibited this TGF-beta activity in all weeks with statistical significance in weeks 1, 2, 3, 5 and 7. The inhibitory effects of Dacron on endothelialization may be explained by the Dacron-induced release of TGF-beta from macrophages.

Animals↗

PubMed1996

Biotransformation of aflatoxin B1 in human lung.

In addition to being a potent hepatocarcinogen, aflatoxin B1 (AFB1) is a pulmonary carcinogen in experimental animals, and epidemiological studies have shown an association between AFB1 exposure and lung cancer in humans. This study investigated AFB1 bioactivation and detoxification in human lung tissue obtained from patients undergoing clinically indicated lobectomy. [3H]AFB1 was bioactivated to a DNA binding metabolite by human whole lung cytosols in a time-, protein concentration-, and AFB1 concentration-dependent manner. Cytosolic activation of [3H]AFB1 correlated with lipoxygenase (LOX) activity and was inhibited by the LOX inhibitor nordihydroguaiaretic acid (NDGA; 100 microM), indicating that LOXs were largely responsible for the observed cytosolic activation of AFB1. In whole lung microsomes, low levels of indomethacin inhibitable prostaglandin H synthase (PHS)-mediated [3H]AFB1-DNA binding and cytochrome P-450 (P450)-mediated [3H]AFB1-DNA binding were observed. Cytosolic glutathione S-transferase (GST)-catalyzed detoxification of AFB1-8,9-epoxide, produced by rabbit liver microsomes, was minimal at 1 and 10 microM [3H]AFB1. With 100 microM [3H]AFB1, [3H]AFB1-8,9-epoxide conjugation with reduced glutathione was 0.34 +/- 0.26 pmol/mg/h (n = 10). In intact, isolated human lung cells, [3H]AFB1 binding to cellular DNA was higher in cell fractions enriched in macrophages than in either type II cell-enriched fractions or fractions containing unseparated cell types. Indomethacin produced a 63-100% decrease in [3H]AFB1-DNA binding in macrophages from five of seven patients, while NDGA inhibited [3H]AFB1-DNA adduct formation by 19, 40 and 56% in macrophages from three of seven patients. In alveolar type II cells, NDGA decreased [3H]AFB1-DNA binding by 30-100% in cells from three patients and indomethacin had little effect. SKF525A, an isozyme non-selective P450 inhibitor, enhanced [3H]AFB1 binding to cellular DNA in unseparated cells, macrophages, and type II cells, suggesting that P450-mediated bioactivation of AFB1 is not a major pathway by which AFB1-8,9-epoxide is formed in human lung cells. Overall, these studies suggest that P450 has a minor role in the bioactivation of AFB1 in human lung. Rather, LOXs and PHS appear to be important bioactivation enzymes. Co-oxidative bioactivation of AFB1, in combination with the low conjugating activity displayed by human lung cytosolic GSTs, likely contributes to human pulmonary susceptibility to AFB1.

Aflatoxin B1↗

PubMed1996

Revascularization of the ischemic gastric tube using the left internal thoracic artery.

Ischemia of the gastric tube during use as an esophageal substitute may have serious consequences. We describe a method to correct substernal gastric tube ischemia using the left internal thoracic artery as a source of arterial inflow to a short gastric artery. This permitted successful reconstruction of the upper alimentary tract in this patient.

Aged↗

PubMed1993

Kinetics of cell proliferation as a function of vascular graft material.

Bioresorbable vascular grafts constructed for polyglactin 910 (PG910) and polydioxanone (PDS) and nonresorbable Dacron were interposed into the infrarenal abdominal aortas of New Zealand White rabbits. The prosthesis/tissue complexes were harvested after 2, 3, 4, 12, and 52 weeks. Seventeen, 9, and 1 h prior to sacrifice, animals received tritiated thymidine (0.5 mCi/kg/dose). All specimens were studied grossly and by light and transmission electron microscopy. Mitotic indices (MI's) were determined by autoradiography for inner capsule myofibroblasts at the proximal, mid, and distal segments of each prosthesis. There were no aortic-related deaths. All grafts were patent with no aneurysmal dilatation. At 4 weeks, PG910 resorption was evidenced by macrophage phagocytosis, less so in PDS while Dacron remained intact. At 12 weeks, the PG910 was completely resorbed while PDS resorption continued. The latter was completely resorbed by 52 weeks. There was no significant difference in MI's between proximal, mid, and distal regions for each graft type. The mitotic index paralleled the rate of prosthetic resorption in both PG910 and PDS groups, as high as 28.34 +/- 23.21 in the former 3 weeks after implantation and significantly higher at 4 weeks (7.58 +/- 2.02 and 7.50 +/- 2.66, respectively) than at 52 weeks (0.72 +/- 0.98 and 1.00 +/- 0.22, respectively) in both groups. The mitotic index in the Dacron group never surpassed 1.22 +/- 0.90. We conclude that higher levels of early cell proliferation in bioresorbable grafts closely parallel the kinetics of prosthetic resorption.

Animals↗

PubMed1992

Enhanced endothelialization of expanded polytetrafluoroethylene grafts by fibroblast growth factor type 1 pretreatment.

BACKGROUND: Biomaterial pretreatment with endothelial cell mitogens may enhance endothelialization. METHODS: Modified fibrin glue (FG) containing 1 ng/cm2 recombinant 125I-labeled fibroblast growth factor type 1 (125I-FGF-1), 20 micrograms/cm2 heparin, 2.86 mg/cm2 fibrinogen, and 2.86 x 10(-2) units/cm2 thrombin was pressure perfused into expanded polytetrafluoroethylene (ePTFE) grafts. Grafts were interposed into infrarenal aortas of 24 New Zealand white rabbits and explanted after 0, 5, 30, and 60 minutes and 1, 7, 14, and 30 days. Residual radioactivity was determined by gamma-counting. Remaining 125I-FGF-1 is expressed as percent of value at time 0. To determine the effect of the FG/FGF-1 on graft healing, three groups of 50 x 4 mm 60 microns internodal-distance nonreinforced ePTFE grafts were implanted in the aortoiliac position of 12 dogs. Group I (n = 12) contained the complete modified FG, group II (n = 6) contained FG with heparin but no FGF-1, and group III (n = 6) contained untreated identical ePTFE. Tritiated thymidine (0.5 microCi/kg) was injected intramuscularly 10 hours before explantation after 7 and 28 days for light and electron microscopy and en face autoradiography. RESULTS: Retention of 125I-FGF-1 showed rapid initial loss (delta %/delta min = -24.1) followed by slow loss after 1 hour (delta %/delta min = -0.03), with 13.4% +/- 6.9% remaining at 1 week and 3.8% +/- 1.1% at 30 days. Every FG/FGF-1 graft at 28 days showed extensive capillary ingrowth and confluent endothelialized luminal surfaces, not seen in any specimen of the other two groups. Autoradiography revealed a significant increase (p less than 0.05) in 3H-thymidine incorporation in the FG/FGF-1 grafts at 28 days versus all groups as a function of time and graft treatment. CONCLUSIONS: Pressure perfusion of an FGF-1/FG suspension into 60 microns internodal-distance ePTFE grafts promotes endothelialization through capillary ingrowth and increased endothelial cell proliferation.

Animals↗

PubMed1991

Species differences in the infectability of vascular grafts.

The susceptibility of different species to bacteremia may influence the results of studies on vascular graft infection. The present study compares prosthetic graft infection in canine and porcine models. Thirty-four mongrel dogs and 38 Yorkshire pigs underwent replacement of the infrarenal aorta with a 3-cm segment of a woven Dacron prosthesis. At the time of closure, each animal received an intravenous inoculum of 10(2) to 10(8) Staphylococcus aureus (S. aureus). Graft cultures at 1 week produced a predictable infection rate in dogs, while pigs developed only random infections (dogs: 23/34; pigs: 7/38; p = .0001). The median infective dose (ID50) in dogs was 10(2.9) but pigs did not develop enough infections to determine this value. Electron microscopy revealed a smooth fibrin surface in grafts explanted from pigs, while grafts from dogs demonstrated bacteria enmeshed in an irregular fibrinous lining. Prosthetic vascular grafts in dogs are more susceptible to hematogenous infection than those in pigs. Because hematogenous infection in humans is a rare event, the swine model may be a more appropriate representation of the clinical situation.

Animals↗

PubMed1990

Segmental vascular resistance in postobstructive pulmonary vasculopathy.

Chronic unilateral pulmonary arterial ligation has been touted as a model of arteriopathy resulting in a tremendous increase in anastomotic bronchial flow (Qbr) via collaterals. To investigate its effects on the pulmonary vasculature, we ligated the left main pulmonary artery of seven dogs and 120 days later pump perfused their left lower lobes (LLL) via a cannula in the pulmonary artery at pulmonary arterial flow (Qpa) of 250 ml/min. We measured Qbr (330 ml/min) and compared LLL with control contralateral right lower lobes (RLL) and three LLL from normal dogs. Pressure-flow (P-Q) curves were obtained by varying Qpa. With arterial and venous occlusion we measured total, arterial, venous, and middle segment resistances under baseline conditions, after serotonin and histamine, either with or without Qpa and with antegrade and retrograde Qbr. Light microscopy was done postmortem. The slope of the P-Q curve was 33.4 mmHg.l-1.min in the ligated lobes compared with 15.9 in the controls, attributable by the occlusion technique mainly to a rise in arterial resistance (22.4 mmHg.l-1.min compared with 7.4 in the controls) with a small rise in venous resistance. This was explained by significant arterial medial muscle thickening and some loss of LLL volume. The arterial segment was markedly hypersensitive to serotonin, and the venous segment was mildly hypersensitive to histamine compared with controls. The occlusion data also enabled us to model the point of entry of the bronchial circulation into the pulmonary circuit at the precapillary level and to calculate bronchial vascular resistance. We conclude that postobstructive vasculopathy substantially raises pulmonary vascular resistance, mainly upstream from the site of entry of the bronchial circulation. The role of the latter may be to keep it from rising excessively in the segments it perfuses, i.e., the middle and venous ones.

Air Pressure↗

PubMed1990

General surgical procedures after heart transplantation.

Seventy-eight cardiac transplantations were performed between July 1982 and March 1989. The perioperative death rate was 10%. Overall survival was 86%. Among the long-term survivors, 14 patients underwent 16 noncardiac surgical procedures. Seven of them required emergency laparotomy, four for biliary tract disease, one for ruptured abdominal aortic aneurysm, one for suspected abdominal sepsis and one for enterocolitis. Elective surgical interventions included repair of symptomatic abdominal wall hernia, treatment of hemorrhoids or perianal condylomas, total hip arthroplasty, maxillary sinus drainage and resection of a duodenal villous adenoma. Preoperatively, all patients received cyclosporine orally. Ten of the 14 patients were on triple-drug immunosuppression (cyclosporine, azathioprine and low-dose prednisone [less than 0.20 mg/kg daily]). The remaining four patients took cyclosporine with either azathioprine or prednisone. There were no deaths. Complications were limited to residual choledocholithiasis treated by percutaneous removal, two cases of wound infection and an incisional hernia. The authors' experience indicates that noncardiac surgical procedures may be safely performed in patients who have received a heart transplant.

Adult↗

PubMedDate not supplied

Adenosine enhances left ventricular flow during 24-hour hypothermic perfusion of isolated cardiac allografts.

Left ventricular flow progressively decreases during preservation of ex vivo hearts by continuous hypothermic perfusion, according to previous studies. This study was done to determine whether left ventricular flow could be maintained during 24-hour hypothermic perfusion by the addition of adenosine to the perfusate. Isolated canine hearts were perfused with either a modified Krebs-Henseleit solution or with the control solution containing adenosine (20 mumol/L) for either 4 or 24 hours. On completion of the perfusion period, radioactive microspheres were injected into the arterial inflow of the hearts. Myocardial samples were then taken from the endocardial, midcardial, and epicardial portions of the free wall and papillary muscles of the right and left ventricles, as well as the interventricular septum. Concentrations of radioactivity were determined for each sample, summed, and averaged for each ventricle. The ratio of average concentrations (L/R ratio) was significantly increased in the 24-hour adenosine hearts compared with 24-hour controls (1.10 +/- 0.15 vs 0.64 +/- 0.21, p less than 0.005). The L/R ratio of 4-hour controls (1.30 +/- 0.48) was also greater than that of 24-hour controls (p less than 0.005). These results suggest that left ventricular flow decreases during continuous hypothermic perfusion. The tendency toward diminished left ventricular perfusion after 24 hours is reduced when adenosine is added to the perfusate. Adenosine may be beneficial in ex vivo heart preservation with hypothermic perfusion by improving left ventricular flow.

Adenosine↗

PubMedDate not supplied

Enhanced 24-hour in vitro heart preservation with adenosine and adenosine monophosphate.

Continuous hypothermic perfusion is an effective means of preserving ex vivo cardiac allografts. Using canine hearts, we assessed the ability of the high-energy phosphate precursors adenosine and adenosine monophosphate to enhance the protective effect of continuous hypothermic perfusion. Group 1 hearts (controls) were perfused for 24 hours with a modified Krebs-Henseleit solution. Group 2 hearts were perfused with control perfusate to which adenosine was added (20 mumol/L). Group 3 hearts were perfused with control perfusate with adenosine monophosphate (0.1 mmol/L). After perfusion heart weights increased similarly in all groups. Coronary vascular resistance increased during the preservation period in group 1 hearts, but decreased in groups 2 and 3 hearts. Developed pressures were 103 +/- 22 mm Hg in group 1, 163 +/- 27 mm Hg in group 2 (p less than 0.01), and 141 +/- 34 mm Hg (p less than 0.05) in group 3. The rate of pressure development in group 2 (2143 +/- 249 mm Hg) and group 3 (2059 +/- 395 mm Hg) hearts was significantly greater than in group 1 hearts (1434 +/- 363 mm Hg, p less than 0.01). Only group 3 myocardial adenosine triphosphate levels were significantly greater than controls (3.18 +/- 0.52 mumol/gm vs 2.12 +/- 0.74 mumol/gm, p less than 0.05) on completion of perfusion. Myocardial lactate levels at this time were significantly higher in group 1 hearts (7.48 +/- 3.96 mumol/gm) compared with groups 2 and 3 (0.34 +/- 0.58 mumol/gm and 1.50 +/- 0.91 mumol/gm, respectively, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗