ABSTRACT
Objective: This study aimed to discover the HIV infection and associated factors among male sex workers (MSW) who provide sexual services for men. Data from this study thus can be used to provide evidence for designing related intervention programs. Methods: In this observational study, MSW were recruited from May to July, 2019 in KTV venues in Wuxi, China. A questionnaire was used to collect information with blood sample collected and tested for HIV and syphilis. EpiData 3.0 and SPSS 17.0 software were used to clean up data and statistical analysis. Results: A number of 500 MSW were involved including 243 (48.6%) heterosexual and 257 (51.4%) homosexual MSW. The overall HIV prevalence was 5.4%(27/500) among all the MSW. there were significant differences between the HIV prevalence rates, the heterosexual MSW (3.3%, 8/243) and the homosexual MSW (7.4%, 19/257)(χ(2)=4.112, P=0.043). In the past 3 months, 28.0% (72/257) of the homosexual MSW mainly engaged in receptive anal sex which was higher than 11.5%(28/243) of the heterosexual MSW. Compared to 15.6% (40/257) of the homosexual MSW who engaged in heterosexual behavior, a higher proportion of 98.4% (239/243) was noticed among the heterosexual MSW. Higher percentage (44.9%, 109/243) appeared among the heterosexual MSW who had not been tested for HIV than the homosexual MSW (20.6%, 53/257). Results from logistic regression multivariate analysis showed that age ≥30 (aOR=7.54, 95%CI: 2.53-37.11), having unprotected anal sexual practice (aOR=3.76, 95%CI:1.15-12.23), having anal sex after drinking alcohol (aOR=10.91, 95%CI: 2.29-51.87) and syphilis tested positive (aOR=8.23, 95%CI:1.29-52.51) were risk factors associated with HIV infection among the heterosexual MSW. Having unprotected anal sexual behavior (aOR=2.94, 95%CI: 1.17-7.37), having group anal sex (aOR=4.08, 95%CI:1.05-15.81), without record on HIV testing (aOR=6.58, 95%CI: 2.01-18.06) and syphilis tested positive (aOR=4.55, 95%CI: 1.15-18.06) were risk factors associated with HIV among the homosexual MSW. Conclusions: High HIV prevalence was discovered among both heterosexual and homosexual MSW in Wuxi, China. Differences in sexual behaviors between these two groups should be considered when designing targeted HIV intervention programs for these populations.
Subject(s)
HIV Infections , Homosexuality, Male , Sex Workers , China/epidemiology , HIV Infections/epidemiology , Homosexuality, Male/statistics & numerical data , Humans , Male , Prevalence , Risk Factors , Sex Workers/statistics & numerical dataABSTRACT
BACKGROUND: Blood flow patterns are important modifiers of platelet interactions with plasma coagulation factors. However, it is not feasible to evaluate rheological effects of haemodilution on coagulation using conventional coagulation testing. METHODS: We evaluated thrombus formation with a microchip-based flow-chamber system using whole blood from 12 healthy volunteers (with/without 40% dilution with saline), and 15 cardiac patients [before/after cardiopulmonary bypass (CPB)] in parallel with thromboelastometry. The in vitro additions of von Willebrand factor (vWF, 1.5 U ml(-1)), prothrombin complex concentrate (PCC, 0.3 U ml(-1)), fibrinogen (2 g litre(-1)), or combined PCC (0.3 U ml(-1)) and fibrinogen (1 g litre(-1)) were examined. Recalcified whole-blood samples were perfused over the microchip coated with collagen and tissue thromboplastin at flow rates of 10 and 3 µl min(-1). RESULTS: Dilution of whole blood led to delayed onset of thrombus formation (Ton), and thrombus growth (T80). Changes relative to baseline values were more extensive at 10 µl min(-1) (≥85% prolongation for Ton and T80) than at 3 µl min(-1) (≥40% prolongation for Ton and T80). Adding vWF accelerated thrombus formation only at 10 µl min(-1), while PCC increased thrombin generation in the thrombus at both flow rates. Fibrinogen increased mural thrombus formation at 3 µl min(-1). Decreased clot strength after dilution was restored by fibrinogen, but not by vWF or PCC on thromboelastometry. Additive effects of fibrinogen and PCC in post-CPB blood were demonstrated by both flow chamber and thromboelastometry. CONCLUSIONS: Blood flow affects thrombus formation after haemodilution and subsequent haemostatic component interventions, with differential effects at low and high flow.
Subject(s)
Blood Coagulation/drug effects , Hemodilution/methods , Hemostatics/pharmacology , Adult , Aged , Blood Flow Velocity/physiology , Blood Specimen Collection/methods , Cardiac Surgical Procedures , Coronary Artery Bypass , Diffusion Chambers, Culture , Female , Fibrinogen/pharmacology , Hemorheology/drug effects , Hemorheology/physiology , Humans , Lab-On-A-Chip Devices , Male , Microscopy, Confocal/methods , Microscopy, Video/methods , Middle Aged , Thrombelastography/methods , Thrombosis/blood , Thrombosis/pathology , Thrombosis/physiopathology , Young AdultABSTRACT
BACKGROUND: Pazopanib has shown clinical activity against multiple tumour types and is generally well tolerated. However, isolated elevations in transaminases and bilirubin have been observed. This study examined polymorphisms in molecules involved in pharmacokinetic and pharmacodynamic pathways of pazopanib and their association with hepatic dysfunction. METHODS: Twenty-eight polymorphisms in 11 genes were evaluated in pazopanib-treated renal cell carcinoma patients. An exploratory analysis was conducted in 116 patients from a phase II study; a replication study was conducted in 130 patients from a phase III study. RESULTS: No polymorphisms were associated with alanine aminotransferase elevation. The Gilbert's uridine-diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) TA-repeat polymorphism was significantly associated with pazopanib-induced hyperbilirubinemia in the phase II study. This association was replicated in the phase III study (P<0.01). Patients with TA6/TA6, TA6/TA7, and TA7/TA7 genotypes experienced median bilirubin increases of 0.31, 0.37, and 0.71 x upper limit of the normal range (ULN), respectively. Of the 38 patients with hyperbilirubinemia (> or = 1.5 x ULN), 32 (84%) were either TA7 homozygotes (n=18) or TA7 heterozygotes (n=14). For TA7 homozygotes, the odds ratio (95% CI) for developing hyperbilirubinemia was 13.1 (5.3-32.2) compared with other genotypes. CONCLUSIONS: The UGT1A1 polymorphism is frequently associated with pazopanib-induced hyperbilirubinemia. These data suggest that some instances of isolated hyperbilirubinemia in pazopanib-treated patients are benign manifestations of Gilbert's syndrome, thus supporting continuation of pazopanib monotherapy in this setting.
Subject(s)
Antineoplastic Agents/adverse effects , Gilbert Disease/genetics , Glucuronosyltransferase/genetics , Hyperbilirubinemia/chemically induced , Kidney Neoplasms/drug therapy , Polymorphism, Genetic , Pyrimidines/adverse effects , Sulfonamides/adverse effects , Aged , Alanine Transaminase/metabolism , Antineoplastic Agents/therapeutic use , Bilirubin/metabolism , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/surgery , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Female , Genotype , Glucuronosyltransferase/antagonists & inhibitors , Humans , Hyperbilirubinemia/epidemiology , Hyperbilirubinemia/etiology , Indazoles , Kidney Neoplasms/surgery , Liver/enzymology , Male , Middle Aged , Nephrectomy , Pyrimidines/therapeutic use , Sulfonamides/therapeutic useABSTRACT
The nematode Caenorhabditis elegans is a well-known model organism for research on aging and life span, but very little is known about its ecology and natural history. The strain N2 is the standard wild-type C. elegans and arose from the progeny of a single hermaphrodite. Since N2 has passed through laboratory culture, the influence of inadvertent selection and genetic drift on C. elegans strains kept in culture is unclear. Because it seems that other wild-type strains have also been subject to lengthy laboratory culture, the life span and biodemography of wild-caught C. elegans is of interest. We recovered C. elegans from snails (Helix aspersa) in ca. 50% of the California locations where we made collections. In experiments with one of the wild-caught isolates, it differed in important demographic properties, mortality, fertility, fitness, and activity patterns, from the standard N2 strain, when both strains were evaluated in a common laboratory environment. The differences were not only statistically significant; they were also large enough to be biologically important. The differences are consistent with the hypothesis that N2 has adapted to laboratory conditions.
Subject(s)
Caenorhabditis elegans/physiology , Ecosystem , Adaptation, Physiological/physiology , Aging/physiology , Animals , Behavior, Animal/physiology , California , Fertility/physiology , Life Expectancy , Longevity/physiology , Population GrowthABSTRACT
Chitinolytic microflora may contribute to biological control of plant-parasitic nematodes by causing decreased egg viability through degradation of egg shells. Here, the influence of Lysobacter enzymogenes strain C3 on Caenorhabditis elegans, Heterodera schachtii, Meloidogyne javanica, Pratylenchus penetrans, and Aphelenchoides fragariae is described. Exposure of C. elegans to L. enzymogenes strain C3 on agar resulted in almost complete elimination of egg production and death of 94% of hatched juveniles after 2 d. Hatch of H. schachtii eggs was about 50% on a lawn of L. enzymogenes strain C3 on agar as compared to 80% on a lawn of E. coli. Juveniles that hatched on a lawn of L. enzymogenes strain C3 on agar died due to disintegration of the cuticle and body contents. Meloidogyne javanica juveniles died after 4 d exposure to a 7-d-old chitin broth culture of L. enzymogenes strain C3. Immersion of A. fragariae, M. javanica, and P. penetrans juveniles and adults in a nutrient broth culture of L. enzymogenes strain C3 led to rapid death and disintegration of the nematodes. Upon exposure to L. enzymogenes strain C3 cultures in nutrient broth, H. schachtii juveniles were rapidly immobilized and then lysed after three days. The death and disintegration of the tested nematodes suggests that toxins and enzymes produced by this strain are active against a range of nematode species.
ABSTRACT
Here, we consider that most of the research concerning Caenorhabditis elegans has been laboratory focused and that only limited research has directly considered the worm's biology relative to its natural history in the wild. We describe that, although the worm has traditionally been considered a soil nematode, we could not find it in soil but frequently recovered it from snails. Finally, we discuss how a better understanding of the natural history of C. elegans may enhance its usefulness as a model organism for studying aging and other phenomena.
Subject(s)
Caenorhabditis elegans/growth & development , Longevity/physiology , Animals , Caenorhabditis elegans/genetics , Ecosystem , Helix, Snails/growth & development , Models, BiologicalABSTRACT
BACKGROUND: Chronic heart failure is associated with impairment of the myocardial beta-adrenergic receptor (beta-AR) system. In this study, the effects of G protein-coupled receptor kinase 5 (GRK5) overexpression on myocardial performance were directly assessed in the hearts of transgenic mice using an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS: A controlled experimental study was performed to evaluate cardiac function in both transgenic mice with a 30-fold overexpression of GRK5 (n = 9, 23 to 29 g) and littermate controls (n = 10, 22 to 29 g). Preload-dependent cardiac output, contractility, stroke work, stroke volume, and heart rate were compared between the two groups. RESULTS: Significant decreases in preload-dependent cardiac output and contractility were observed in the mice with GRK5 overexpression when compared with control group mice and occurred in association with significant decreases in stroke work and stroke volume. There was no significant difference in the average heart rate between the two groups. CONCLUSIONS: These data suggest that GRK5 upregulation may be partially responsible for alterations in myocardial function in chronic heart failure.
Subject(s)
Cardiac Output/physiology , Myocardial Contraction/physiology , Myocardium/enzymology , Protein Serine-Threonine Kinases/metabolism , Animals , G-Protein-Coupled Receptor Kinase 5 , Heart Rate/physiology , Hemodynamics , Mice , Mice, Transgenic , Models, Animal , Reference Values , Sensitivity and Specificity , Stroke Volume/physiologyABSTRACT
OBJECTIVE: Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model. METHODS: Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons. RESULTS: All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons. CONCLUSIONS: The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental.
Subject(s)
Antibodies/immunology , Graft Rejection/immunology , Lung Transplantation/immunology , Transplantation Immunology , Transplantation, Heterologous/immunology , Animals , Papio , SwineABSTRACT
BACKGROUND: It is unclear whether right ventricular dysfunction after transplantation is due to donor brain death-related myocardial injury or recipient pulmonary hypertension. METHODS: A canine donor model of brain death and a monocrotaline pyrrole-induced chronic pulmonary hypertension recipient model were established, and used for 30 orthotopic bicaval cardiac transplantations divided into three groups: Controls (group A, normal donor/recipient), group B (brain-dead donors/normal recipient), and group C (normal donor/recipients with pulmonary hypertension). Right ventricular function was measured before transplant and brain death, 4 hours after brain death, and after transplant (1 hour off bypass) by load-independent means plotting stroke work versus end-diastolic volume during caval occlusion. Right ventricular total power and pulmonary vascular impedance were determined by Fourier analysis. RESULTS: In comparison to the control group right ventricular preload-recruitable stroke work and total power decreased significantly after brain death and transplant in group B (from 22.7 x 10(3) erg (+/-1.2) at baseline to 15.6 x 10(3) (+/-0.9) after brain death and to 11.3 x 10(3) (+/-0.9) after transplant). In group C there was a significant increase in pulmonary artery pressure, impedance, right ventricular preload-recruitable stroke work, total power after transplant. CONCLUSIONS: Normal donor hearts adapt acutely to the recipient's elevated pulmonary vascular resistance by increasing right ventricular power output and contractility. Brain death caused significant right ventricular dysfunction and power loss, which further deteriorated after graft preservation and transplantation. The effects of donor brain death on myocardial function contribute to right ventricular dysfunction after cardiac transplantation.
Subject(s)
Heart Transplantation/physiology , Postoperative Complications/physiopathology , Tissue Donors , Ventricular Dysfunction, Right/physiopathology , Animals , Brain Death/physiopathology , Dogs , Fourier Analysis , Hemodynamics/physiology , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/physiopathology , Postoperative Complications/diagnosis , Risk Factors , Treatment Outcome , Ventricular Dysfunction, Right/diagnosis , Ventricular Function, Right/physiologyABSTRACT
BACKGROUND: Chronic pulmonary hypertension can lead to compensatory changes in the right ventricle. In this study, the adaptive mechanisms of the right ventricle in the setting of pulmonary hypertension were assessed at the molecular and functional level using a canine model of monocrotaline pyrrole-induced pulmonary hypertension. METHODS: Animals underwent pulmonary artery catheterization to measure pulmonary hemodynamics before and 8 weeks after an injection of monocrotaline pyrrole, 3 mg/kg (n = 8) or placebo (n = 8) (controls). Systolic function was assessed with load-insensitive means (preload-recruitable stroke work). Myocardial biopsy specimens were collected to analyze membrane alpha1- and beta-adrenergic receptor density and adenylate cyclase activity. RESULTS: Eight weeks after injection, significant increases in pulmonary hemodynamic indices were noted in monocrotaline-injected dogs. Significant increases in right ventricular preload-recruitable stroke work were also observed in these animals compared with controls and occurred in association with significant increases in right ventricular alpha1- and beta-adrenergic receptor density and isoproterenol hydrochloride-stimulated adenylate cyclase activity. No significant differences in basal adenylate cyclase activity in the right ventricle were noted between the two groups. CONCLUSIONS: These data suggest that alterations in right ventricular function in the setting of chronic pulmonary hypertension may partially be due to changes in myocardial adrenergic receptor signaling.
Subject(s)
Adaptation, Physiological , Adenylyl Cyclases/metabolism , Hypertension, Pulmonary/physiopathology , Myocardium/metabolism , Receptors, Adrenergic, alpha/analysis , Receptors, Adrenergic, beta/analysis , Ventricular Function, Right/physiology , Animals , Chronic Disease , Dogs , Hemodynamics/physiology , Hypertension, Pulmonary/chemically induced , Monocrotaline/analogs & derivatives , Pulmonary Circulation/physiology , Stroke Volume/physiologyABSTRACT
ABSTRACT The hypothesis that host plants exert selection pressure on Heterodera schachtii populations was tested. Host selection of genotypes from three genetically distinct isolates of H. schachtii was assessed using cabbage, sugar beet, oilseed radish (Raphanus sativus), and white mustard (Sinapis alba). The plants represent a range of susceptibility to H. schachtii and included R. sativus and S. alba, because cultivars of those species have been used as trap crops for H. schachtii in Europe. Genotypic differences in amplified fragment length polymorphism (AFLP) and random amplified polymorphic DNA (RAPD) markers were detected among the isolates after they reproduced on the different hosts. The poorest host plant, R. sativus, resulted in the greatest number of changes in both AFLP and RAPD markers. Oilseed radish selected nematode genotypes in less than four nematode generations. The nematode population genotypes detected by RAPD analyses after selection on oilseed radish were observed even after nematode populations were transferred back to the other three hosts. The genetic markers that were detected after selection were influenced by the genotypes of the original nematode isolates. The results indicate the utility of RAPDs and AFLPs for identifying and monitoring intraspecific genetic variability in nematodes and for understanding nematode population responses to host plants. Nematode management practices such as using resistant cultivars may alter gene frequencies, thereby reducing the efficacy of the tactic and exacerbating the nematode's potential to damage subsequent crops.
ABSTRACT
BACKGROUND: beta-Adrenergic receptor kinase 1 (beta ARK1) mediates beta-adrenergic receptor signaling via receptor phosphorylation, which results in functional uncoupling. The physiological importance of beta ARK1 on cardiac performance in the setting of ischemia and reperfusion injury, however, has not been clearly established. In this study, the effects of beta ARK1 overexpression on myocardial recovery after ischemia and reperfusion injury were evaluated in transgenic mice with the use of an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS AND RESULTS: A controlled, experimental study was performed to compare cardiac function in the hearts of both transgenic mice with a 3-fold overexpression of beta ARK1 (n = 6; weight, 25 to 29 g) and littermate controls (n = 9; weight, 25 to 28 g). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the 2 groups before and after a 6-minute period of normothermic ischemia. Before ischemia, significant decreases were observed in all parameters of myocardial performance in beta ARK1 mice compared with control mice. After ischemia and reperfusion, significant decreases in cardiac function were observed in both experimental groups; however, significantly lower percentages of myocardial recovery occurred in beta ARK1 hearts compared with control hearts. CONCLUSIONS: After global normothermic ischemia, significant decreases in cardiac function were observed in both beta ARK1 and control mice; however, significantly lower percentages of myocardial recovery occurred in beta ARK1 mice. These data suggest that myocardial beta ARK1 overexpression significantly impairs cardiac function in the setting of ischemia and reperfusion injury.
Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Heart/physiopathology , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/physiopathology , Myocardium/metabolism , Animals , Cyclic AMP-Dependent Protein Kinases/genetics , Mice , Mice, Transgenic/genetics , Reference Values , beta-Adrenergic Receptor KinasesABSTRACT
BACKGROUND: Total orthotopic heart transplantation was recently introduced into clinical practice as an alternative technique of orthotopic heart transplantation, adding bicaval and left and right pulmonary vein anastomoses to pulmonary artery and ascending aorta connection (total technique). The conventional technique (ventricular transplantation with atrioplasty) is compared with the total technique with particular emphasis on right ventricular performance. METHODS: Forty-eight mongrel dogs (23 to 31 kg) were used for 12 total and 12 standard orthotopic heart transplantations. Right ventricular (RV) function and atrial systole were analyzed with the use of micromanometry, sonomicrometry, and ultrasonic flow probes (preload-independent RV recruitable stroke work, RVPRSW). Fourier analysis was used to calculate RV power and pulmonary vascular impedance. RESULTS: There was no significant difference in cardiac ischemic and bypass times between the two groups. After transplantation, sinus rhythm was preserved after all total transplantations and after only one standard transplantation; no significant hemodynamic differences were observed. RVPRSW in the total group was conserved after transplantation; however, RVPRSW decreased by 39% (+/-8, p < .05) in the standard group. There was also a significant decrease in the rate of RV filling in the standard group after transplantation, suggesting decreased right atrial function. Pulmonary vascular impedance and RV power output were not significantly different after transplantation between the two groups. CONCLUSIONS: Total atrioventricular transplantation is a feasible alternative and conserves normal sinus rhythm. Ischemic and bypass times were not significantly different when the superior vena cava anastomosis is performed last after the release of the aortic cross-clamp. The insignificant decrease in the rate of RV filling with the use of the total technique suggests conserved RV diastolic function after transplantation with less decreased RV function in the total group.
Subject(s)
Heart Transplantation/methods , Heart/physiology , Animals , Dogs , Heart Function Tests , Heart Transplantation/adverse effects , Heart Ventricles , Myocardial Ischemia/etiologyABSTRACT
BACKGROUND: Right ventricular failure remains an important cause of early morbidity and death after heart transplantation and is commonly related to preexistent recipient chronic pulmonary hypertension, which occurs as a result of long-standing congestive heart failure. In this study, the hemodynamic and inotropic effects of milrinone were assessed after bicaval heart transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs were used for 10 successfully completed transplantation experiments. Recipient animals underwent right atrial injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Hemodynamic and functional data were taken 1 hour after termination of cardiopulmonary bypass and after milrinone infusion. Myocardial function was assessed with load-insensitive means (preload-recruitable stroke work) and pulmonary vascular impedance was calculated with Fourier analysis. RESULTS: At the time of transplantation, before cardiopulmonary bypass, pulmonary hemodynamic indexes in recipient animals were significantly increased when compared with donors and were further significantly increased after cardiopulmonary bypass. Two animals died after transplantation as a result of acute right ventricular failure. In surviving animals milrinone infusion led to significant increases in right ventricular function, which occurred in association with significant improvements in pulmonary vascular impedance and transpulmonary efficiency. CONCLUSIONS: In the setting of monocrotaline pyrrole-induced recipient pulmonary hypertension, milrinone was associated with significant improvements in pulmonary vascular impedance, right ventricular function, and transpulmonary efficiency. These data suggest that milrinone is an effective means to improve right ventricular dysfunction and pulmonary vascular efficiency after bicaval heart transplantation in the setting of recipient chronic pulmonary hypertension.
Subject(s)
Heart Transplantation , Hemodynamics/drug effects , Hypertension, Pulmonary/physiopathology , Myocardial Contraction/drug effects , Phosphodiesterase Inhibitors/pharmacology , Pyridones/pharmacology , Animals , Dogs , Heart Transplantation/physiology , Hypertension, Pulmonary/chemically induced , Milrinone , Monocrotaline/analogs & derivatives , Pulmonary Circulation/drug effects , Ventricular Dysfunction, Right/drug therapy , Ventricular Function, Right/drug effectsABSTRACT
BACKGROUND: Right ventricular (RV) hypertrophy is an adaptive process that occurs in the setting of chronic pulmonary hypertension (CPH) and can lead to alterations in normal RV diastolic properties. This study was designed to investigate the effects of NO and milrinone on RV diastolic dysfunction in the setting of CPH and RV hypertrophy by use of a canine model of monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Sixteen mongrel dogs (22 to 24 kg) were used. Animals underwent percutaneous pulmonary artery (PA) catheterization to measure pulmonary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after injection, all hearts were instrumented with a PA flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after both NO and milrinone administration. Diastolic properties were quantified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks after injection, significant increases in the PA pressure and pulmonary vascular resistance were observed in MCTP dogs. Significant worsening of RV diastolic function occurred in association with significant increases in the ratio of RV dry weight to LV+septal dry weight. NO and milrinone administration both led to significant improvements in RV diastolic properties. CONCLUSIONS: In the setting of MCTP-induced CPH, significant worsening of RV diastolic function was observed in association with significant increases in the ratio of RV dry weight to LV+septal dry weight, suggesting that these changes are partially due to RV hypertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may be effective forms of pharmacological therapy for improving RV diastolic dysfunction in the setting of CPH.
Subject(s)
Cardiotonic Agents/administration & dosage , Heart Ventricles/physiopathology , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/physiopathology , Nitric Oxide/administration & dosage , Pyridones/administration & dosage , Administration, Inhalation , Animals , Chronic Disease , Diastole/drug effects , Dogs , MilrinoneABSTRACT
UNLABELLED: The use of nonhuman lung donors, such as swine, has the potential to provide an unlimited supply of organs. However, hyperacute rejection has prevented pulmonary xenotransplantation. OBJECTIVE: Our aim was to test the hypothesis that immunodepletion by pretransplantation swine lung perfusion will prevent hyperacute swine-to-primate pulmonary xenograft rejection and allow for a functional swine pulmonary xenograft. METHODS: Seven baboons underwent left pneumonectomy followed by orthotopic transplantation of the swine left lung. Four baboons received immunodepletion by perfusion with swine lungs before transplantation, and three received no treatment before transplantation. RESULTS: After transplantation, pulmonary xenografts from immunodepleted baboons had a low pulmonary vascular resistance and a high pulmonary blood flow compared with control animals, which had a high pulmonary vascular resistance and a low pulmonary blood flow. After 60 minutes of reperfusion, three of four immunodepleted animals also tolerated complete occlusion of the right pulmonary artery, with the baboon relying completely on the swine pulmonary xenograft for respiratory function for 11 hours. Pathologic analysis of peripheral lung biopsy specimens taken from control lungs displayed alveolar disruption and hemorrhage within small vessels, whereas swine lungs transplanted into immunodepleted baboons displayed little histologic evidence of injury. Furthermore, pulmonary xenografts transplanted into immunodepleted baboons demonstrated excellent respiratory function and adequate hemodynamics during occlusion of the right pulmonary artery. CONCLUSION: Hyperacute pulmonary xenograft rejection can be prevented by pretransplantation swine lung perfusion. Swine pulmonary xenografts can provide complete respiratory support in primates when rejection is prevented.
Subject(s)
Graft Rejection/immunology , Lung Transplantation/physiology , Transplantation, Heterologous/physiology , Animals , Drug Therapy, Combination , Graft Rejection/prevention & control , Immunosuppression Therapy/methods , Immunosuppressive Agents/administration & dosage , Lung/pathology , Lung Transplantation/immunology , Papio , Perfusion , Premedication , Pulmonary Circulation/physiology , Swine , Transplantation, Heterologous/immunologyABSTRACT
OBJECTIVE: Myocardial injury after ischemia and reperfusion may be mediated, in part, by oxygen-derived free radicals. In this study the protective effects of extracellular superoxide dismutase overexpression were directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS: A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the two groups before and after a 6-minute period of normothermic ischemia. RESULTS: No differences were found between extracellular superoxide dismutase hearts and control hearts in any parameter of myocardial function before ischemia. After ischemia, decreases in cardiac output occurred in both groups; however, this decrease was larger in control mice compared with extracellular superoxide dismutase mice. A higher percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dismutase hearts compared with control hearts. CONCLUSION: After global normothermic ischemia and subsequent reperfusion, decreases in cardiac function occurred in both extracellular superoxide dismutase and control mice; however, a higher percentage of recovery was observed in the extracellular superoxide dismutase overexpressed hearts. These data suggest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial function after ischemia and reperfusion injury.
Subject(s)
Myocardial Contraction , Myocardial Reperfusion Injury/physiopathology , Superoxide Dismutase/genetics , Animals , Body Temperature , Extracellular Space , Mice , Mice, Transgenic , Myocardial Reperfusion Injury/genetics , Single-Blind Method , Up-RegulationABSTRACT
BACKGROUND: Right ventricular (RV) failure remains an important risk factor for early morbidity and mortality after orthotopic cardiac transplantation and is most commonly related to preexistent chronic pulmonary hypertension (CPH) in the recipient, which occurs secondary to long-standing congestive heart failure. This study was designed to assess the compensatory mechanisms of the acutely transplanted RV in the setting of recipient CPH using a canine model of bicaval cardiac transplantation (TX) and monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Twenty adult mongrel dogs were used for 10 successfully completed TX experiments. Recipients received an injection of 3 mg/kg MCTP 4 months before TX. RV function was assessed with load-insensitive means (preload recruitable stroke work), and Fourier analysis was used to calculate RV hydraulic power and transpulmonary efficiency. At the time of TX, significant increases in the mean pulmonary artery pressure, mean right ventricular pressure, and pulmonary vascular resistance were observed in recipients compared with donors and were further significantly increased after cardiopulmonary bypass. Significant increases in RV preload recruitable stroke work and RV hydraulic power were observed after TX compared with before TX and occurred in association with significant decreases in transpulmonary efficiency. CONCLUSIONS: Significant increases in pulmonary hemodynamic indexes occurred after MCTP injection and were further significantly increased after cardiopulmonary bypass. In the setting of recipient CPH, RV performance adapts acutely after bicaval TX with significant increases in power and contractility. However, a significant decrease in transpulmonary efficiency was also observed, which may improve over time as the RV adapts to the increased afterload.
Subject(s)
Heart Transplantation , Hypertension, Pulmonary/physiopathology , Ventricular Function, Right , Adaptation, Physiological , Animals , Cardiopulmonary Bypass , Chronic Disease , Dogs , Hemodynamics , Lung/physiopathology , Myocardium/pathologyABSTRACT
STUDY OBJECTIVES: Recipient chronic pulmonary hypertension (CPH), secondary to long-standing congestive heart failure, represents a significant risk factor for right ventricular (RV) dysfunction following orthotopic cardiac transplantation (TX). This study was designed to characterize the changes occurring in pulmonary hemodynamics, pre-TX and post-TX, using Fourier analysis, a canine model of bicaval TX, and monocrotaline pyrrole (MCTP)-induced recipient CPH. DESIGN: Prospective, controlled study. SETTING: Experimental laboratory. PARTICIPANTS: Twenty adult male mongrel dogs (23 to 26 kg). INTERVENTIONS: Recipients underwent pulmonary artery injection of 3 mg/kg MCTP 4 months pre-TX. On the day of TX, donor hearts were instrumented with an ultrasonic flow probe and micromanometers. Harmonic derivation of functional data was achieved with Fourier analysis. MEASUREMENTS AND RESULTS: At the time of TX, significant increases were observed in the mean pulmonary artery pressure and pulmonary vascular resistance of recipient animals in comparison to donors, which were further significantly increased following the termination of cardiopulmonary bypass. Significant increases were also observed in the input resistance, characteristic impedance, and RV hydraulic power post-TX compared to pre-TX, and occurred in association with a significant decrease in the transpulmonary efficiency. CONCLUSIONS: In the setting of MCTP-induced recipient CPH donor hearts were exposed to significant alterations in cardiopulmonary hemodynamics following bicaval TX. Pulmonary blood flow is maintained by a significantly higher energy expenditure by the RV, but at a lower level of efficiency. This experimental model may provide a useful means by which to evaluate therapeutic options to better manage cardiopulmonary hemodynamics in order to prevent RV failure following TX in the setting of recipient CPH.
Subject(s)
Heart Transplantation/physiology , Hypertension, Pulmonary/physiopathology , Pulmonary Artery/physiopathology , Animals , Chronic Disease , Disease Models, Animal , Dogs , Electric Impedance , Fourier Analysis , Heart Transplantation/methods , Hemodynamics , Hypertension, Pulmonary/chemically induced , Male , Monocrotaline/analogs & derivatives , Poisons , Prospective StudiesABSTRACT
BACKGROUND: Recipient pulmonary hypertension secondary to chronic congestive heart failure is a significant risk factor for right ventricular failure after cardiac transplantation. In this study, the hemodynamic and inotropic effects of nitric oxide (NO) were examined after bicaval cardiac transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs underwent 10 successfully completed transplantation experiments. Recipients underwent pulmonary artery injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Measurements were taken 1 hour after cessation of cardiopulmonary bypass and after NO inhalation. Pulmonary vascular impedance was calculated using Fourier analysis, and cardiac function was assessed with load-insensitive means (preload recruitable stroke work). RESULTS: At the time of transplantation, the precardiopulmonary bypass levels of pulmonary vascular resistance in recipient animals were significantly greater when compared with donor levels, and were further significantly increased after cardiopulmonary bypass. Three recipients died after transplantation secondary to acute right ventricular failure. In the surviving animals, NO led to significant improvements in pulmonary vascular resistance and vascular impedance, which occurred in association with significant increases in transpulmonary efficiency. No significant changes were observed in right and left ventricular preload recruitable stroke work after NO inhalation. CONCLUSIONS: These data suggest that NO may be an effective means to improve vascular impedance and pulmonary vascular efficiency after cardiac transplantation in the setting of recipient chronic pulmonary hypertension.