Cold Denaturation of Proteins in the Absence of Solvent: Implications for Protein Storage.

The effect of temperature on the stability of proteins is well explored above 298 K, but harder to track experimentally below 273 K. Variable-temperature ion mobility mass spectrometry (VT IM-MS) allows us to measure the structure of molecules at sub-ambient temperatures. Here we monitor conformational changes that occur to two isotypes of monoclonal antibodies (mAbs) on cooling by measuring their collision cross sections (CCS) at discrete drift gas temperatures from 295 to 160 K. The CCS at 250 K is larger than predicted from collisional theory and experimental data at 295 K. This restructure is attributed to change in the strength of stabilizing intermolecular interactions. Below 250 K the CCS of the mAbs increases in line with prediction implying no rearrangement. Comparing data from isotypes suggest disulfide bridging influences thermal structural rearrangement. These findings indicate that in vacuo deep-freezing minimizes denaturation and maintains the native fold and VT IM-MS measurements at sub ambient temperatures provide new insights to the phenomenon of cold denaturation.

Methanol oxidation on Fe2O3 catalysts and the effects of surface Mo.

The adsorption of methanol on haematite has been investigated using temperature programmed methods, combined with in situ DRIFTS. Model catalysts based on this material have then been made with a shell-core configuration of molybdenum oxide monolayers on top of the haematite core. These are used as models of industrial iron molybdate catalysts, used to selectively oxidise methanol to formaldehyde, one of the major chemical outlets for methanol. Haematite itself is completely ineffective in this respect since it oxidises it to CO2 and the DRIFTS shows that this occurs by oxidation of methoxy to formate at around 200 °C. The decomposition behaviour is affected by the absence or presence of oxygen in the gas phase; oxygen destabilises the methoxy and enhances formate production. In contrast, when a monolayer of molybdena is placed onto the surface by incipient wetness, and it remains there after calcination, the pathway to formate production is blocked and formaldehyde is the main gas phase product in TPD after methanol dosing.

Time dependence of biomarkers: non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer.

BACKGROUND: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial. METHODS: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years. RESULTS: We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R(2) between 5 and 6% and increases in D-statistic between 0.16 and 0.21. CONCLUSIONS: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.

Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively planned analysis of the TEAM trial.

BACKGROUND: Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers. METHODS: Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years. RESULTS: Among 4541 eligible samples, 4225 (93%) had complete HER1-3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1-3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52-0.87), in the HER1-3-positive subgroup, the HR was 1.15 (95% CI, 0.85-1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1-3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39-0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36-0.85; P=0.005). This effect was time dependent. CONCLUSION: In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses.

Evolution of active catalysts for the selective oxidative dehydrogenation of methanol on Fe2O3 surface doped with Mo oxide.

Iron molybdate catalysts are used for the selective oxidation of methanol to formaldehyde. In this paper we have attempted to understand what determines high selectivity in this reaction system by doping haematite with surface layers of Mo by incipient wetness impregnation. This works well and the Mo appears to form finely dispersed layers. Even very low loadings of Mo have a marked effect on improving the selectivity to formaldehyde. Haematite itself is a very poor catalyst with high selectivity to combustion products, whereas, when only 0.25 monolayers of Mo are deposited on the surface, formaldehyde and CO selectivities are greatly enhanced and CO2 production is greatly diminished. However, even with as much as seven monolayers of Mo dosed on to the surface, these materials achieve much less selectivity to formaldehyde at high conversion than do the industrial catalysts. The reason for this is that the Mo forms a 'skin' of ferric molybdate on a core of iron oxide, but does not produce a pure Mo oxide monolayer on the surface, a situation which is essential for very high yields of formaldehyde.

Cold Denaturation of Proteins in the Absence of Solvent: Implications for Protein Storage.

The effect of temperature on the stability of proteins is well explored above 298 K, but harder to track experimentally below 273 K. Variable-temperature ion mobility mass spectrometry (VT IM-MS) allows us to measure the structure of molecules at sub-ambient temperatures. Here we monitor conformational changes that occur to two isotypes of monoclonal antibodies (mAbs) on cooling by measuring their collision cross sections (CCS) at discrete drift gas temperatures from 295 to 160 K. The CCS at 250 K is larger than predicted from collisional theory and experimental data at 295 K. This restructure is attributed to change in the strength of stabilizing intermolecular interactions. Below 250 K the CCS of the mAbs increases in line with prediction implying no rearrangement. Comparing data from isotypes suggest disulfide bridging influences thermal structural rearrangement. These findings indicate that in vacuo deep-freezing minimizes denaturation and maintains the native fold and VT IM-MS measurements at sub ambient temperatures provide new insights to the phenomenon of cold denaturation.

Orbital apex disorders: a case series.

Orbital apex syndrome is an uncommon disorder characterized by ophthalmoplegia, proptosis, ptosis, hypoesthesia of the forehead, and vision loss. It may be classified as part of a group of orbital apex disorders that includes superior orbital fissure syndrome and cavernous sinus syndrome. Superior orbital fissure syndrome presents similarly to orbital apex syndrome without optic nerve impairment. Cavernous sinus syndrome includes hypoesthesia of the cheek and lower eyelid in addition to the signs seen in orbital apex syndrome. While historically described separately, these three disorders share similar causes, diagnostic course, and management strategies. The purpose of this study was to report three cases of orbital apex disorders treated recently and to review the literature related to these conditions. Inflammatory and vascular disorders, neoplasm, infection, and trauma are potential causes of orbital apex disorders. Management is directed at the causative process. The cases described represent a rare but important group of conditions seen by the maxillofacial surgeon. A review of the clinical presentation, etiology, and management of these conditions may prompt timely recognition and treatment.

Individual placement and support (IPS) for patients with offending histories: the IPSOH feasibility cluster randomised trial protocol.

INTRODUCTION: People with involvement in forensic psychiatric services face many obstacles to employment, arising from their offending, as well as their mental health problems. This study aims to assess the feasibility of conducting a randomised controlled trial (RCT) to evaluate the effectiveness of individual placement and support (IPS), in improving employment rates and associated psychosocial outcomes in forensic psychiatric populations. IPS has been found consistently to achieve employment rates above 50% in psychiatric patients without a history of involvement in criminal justice services. METHODS/DESIGN: This is a single-centre feasibility cluster RCT. Clusters will be defined according to clinical services in the community forensic services of Nottinghamshire Healthcare NHS Foundation Trust (NHCT). IPS will be implemented into 2 of the randomly assigned intervention clusters in the community forensic services of NHCT. A feasibility cluster RCT will estimate the parameters required to design a full RCT. The primary outcome is the proportion of people in open employment at 12-month follow-up. Secondary outcome measures will include employment, educational activities, psychosocial and economic outcomes, as well as reoffending rates. Outcome measures will be recorded at baseline, 6 months and 12 months. In accordance with the UK Medical Research Council guidelines on the evaluation of complex interventions, a process evaluation will be carried out; qualitative interviews with patients and staff will explore general views of IPS as well as barriers and facilitators to implementation. Fidelity reviews will assess the extent to which the services follow the principles of IPS prior, during and at the end of the trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the East Midlands Research Ethics Committee-Nottingham 1 (REC reference number 15/EM/0253). Final and interim reports will be prepared for project funders, the study sponsor and clinical research network. Findings will be disseminated through peer-reviewed journals, conferences and event presentations. TRIAL REGISTRATION NUMBER: NCT02442193; Pre-results.

Acute right ventricular dilatation in response to ischemia significantly impairs left ventricular systolic performance.

BACKGROUND: Right ventricular (RV) dilatation that occurs as a consequence of RV infarction is thought to produce hemodynamic instability by reducing left ventricular (LV) preload and compliance. We hypothesized that these geometric changes may also adversely affect LV systolic performance. METHODS AND RESULTS: Twelve 40-kg pigs were studied. Integrated conductance catheters and micromanometers were placed in both the LV and RV to allow simultaneous recordings of pressure and volume and derivation of indices of contractile function. RV ischemia was induced by balloon occlusion of the proximal right coronary artery (RCA) under 3 conditions: 1) with the pericardium intact, 2) with the pericardium intact and inotropic support, and 3) with the pericardium wide open. With an intact pericardium, RCA occlusion produced a decrease in LV end-diastolic volume associated with a marked decline in the contractile function. With the pericardium open, the same ischemic insult resulted in both LV and RV dilatation, which produced a significantly smaller negative effect on cardiac output (P=0.03), LV systolic pressure (P=0.02), LV preload-recruitable stroke work (P<0. 01), and LV end-systolic pressure-volume relations (P<0.01). Similarly, administration of dobutamine during RCA occlusion decreased the ventricular volume changes and produced a relative improvement in LV contractile performance. CONCLUSIONS: The hemodynamic compromise seen in association with acute RV dilatation within an intact pericardium is partly attributable to impaired LV systolic performance and cannot be wholly ascribed to changes in LV preload or compliance.

Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat.

OBJECTIVE: At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of the aortovenocaval (AV) fistula rat. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify cardiac mRNA expression of the endothelins and their receptors during the development of cardiac hypertrophy, while radioligand binding was employed to quantify the amount of [125I]-ET-1 binding to cardiac membranes. Tissue and plasma concentrations of ET-1 were measured by radioimmunoassay. RESULTS: In control sham operated animals, ET-1 mRNA was approximately fivefold greater in atria than in ventricles (P < 0.05), but there were no atrioventricular differences in ET-2 or ET-3 mRNA. In the AV fistula rats there was a prompt three- to fourfold increase in ET-1 mRNA in atria and a progressive five- to sevenfold rise in ventricles during cardiac hypertrophy. There were no changes in ET-2 or ET-3 transcript prevalences, except for a late rise (35 d) in ET-2 mRNA levels in left ventricle. Consistent with ET-1 mRNA measurements, immunoreactive endothelin levels were increased by 7 d in atria, but not in ventricles. In control rat hearts, ETAR mRNA levels were similar in atria and ventricles, but the prevalence of ETBR was approximately sevenfold greater in the former. ETAR mRNA prevalence increased with hypertrophy in all chambers, while ETBR transcript levels were raised only in the right ventricle. There was no significant difference in [125I]-ET-1 binding between atrial samples from 35 d control and 35 d AV fistula rats, suggesting rapid turnover of endothelin receptors balanced by increased transcription from the ETAR gene. CONCLUSIONS: During cardiac hypertrophy in AV fistula rats there is increased activity of the endothelin system mediated principally by ET-1 and the ETAR subtype.

Does parallel conductance vary during systole in the human right ventricle?

OBJECTIVES: Right ventricular (RV) contractile performance remains poorly characterised, particularly in humans. Conductance catheter techniques have the potential to overcome the geometric difficulties in RV volume measurement that have hindered systematic studies of RV pressure volume relations. The present study examines changes in parallel conductance (Vc) that may occur during the cardiac cycle in the human right ventricle. METHODS: Using signals obtained from custom-built conductance catheters, six isochronal systolic values of Vc (Vc(t)) were measured during hypertonic saline wash-in. Studies were performed in nine patients undergoing right heart catheterisation. Their ages ranged from 7 to 39 years (median = 16) and their weights ranged from 20.3 to 84.7 kg (median = 50.0 kg). Measurements of mean Vc and isochronal Vc(t) and its variability during systole were assessed. Mean Vc was measured using the Baan technique (Vc(Baan)), Vc(t) was measured from six systolic isochrones obtained during the same period of hypertonic saline wash-in. RESULTS: The temporal changes in Vc(t) were small (mean 5.8%, median = 4.4%, range = 0.6-17.9%) of total corrected end-diastolic volume (mean maximal variation of 7.7 ml). The value of Vc(t) obtained at dp/dtmax (mean = 99.1 ml; median = 104.75 ml; range 20.15-196.7 ml) was not significantly different to that obtained at dp/dtmin (mean = 100.0 ml; median = 110.87 ml; range = 20.0-204.2 ml) (P > 0.05), but both were higher than the single Vc measurement (Vc(Baan)) obtained using the standard approach (P = 0.02). The correlation between Vc(Baan) and Vc(t) for group data; (Vc(Baan) = 89.69 ml, s.d. = 43.73 ml; Vc(t) = 98.16 ml, s.d. = 50.16 ml) produces a regression slope of 0.99 for all studies (P = 0.02). CONCLUSION: We conclude that parallel conductance does vary during systole in the human right ventricle of adults and older children after repair of congenital abnormalities but there is no significant difference in Vc(t) at dp/dtmin and dp/dtmax. However, there was a significant difference when the isochronal Vc(t) measurement is compared with the standard single value technique (Vc(Baan)) obtained using the hypertonic saline wash-in method. The excellent correlation between Vc(t) and Vc(Baan) suggests that the correction of Vc for the phase of the cardiac cycle is unnecessary for most purposes when studying the human right ventricle.

The effect of changing excitation frequency on parallel conductance in different sized hearts.

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.

Postoperative nausea and vomiting following orthognathic surgery.

The purpose of this study was to assess the incidence and risk factors associated with postoperative nausea (PON) and vomiting (POV) after orthognathic surgery. A review of the clinical records of consecutively enrolled subjects (2008-2012) at a single academic institution was conducted between 9/2013 and 3/2014. Data on the occurrence of PON and POV and potential patient-related, intraoperative, and postoperative explanatory factors were extracted from the medical records. Logistic models were used for the presence/absence of postoperative nausea and vomiting separately. Data from 204 subjects were analyzed: 63% were female, 72% Caucasian, and the median age was 19 years. Thirty-three percent had a mandibular osteotomy alone, 27% a maxillary osteotomy alone, and 40% had bimaxillary osteotomies. Sixty-seven percent experienced PON and 27% experienced POV. The most important risk factors for PON in this series were female gender, increased intravenous fluids, and the use of nitrous oxide, and for POV were race, additional procedures, and morphine administration. The incidence of PON and POV following orthognathic surgery in the current cohort of patients, after the introduction of the updated 2007 consensus guidelines for the management of postoperative nausea and vomiting, has not decreased substantially from that reported in 2003-2004.

Genotypic variation among different phenotypes within aphid clones.

Most aphid species Hemiptera: Aphididae are parthenogenetic between periods of sexual reproduction. They are also highly polyphenic, with different adult morphs occurring in the life cycle, piz. winged, wingless, asexual and sexual. It is assumed that aphids born in a parthenogenetic clonal lineage are genetically identical regardless of the final adult form with the exception of sexual forms). Using the randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) we have found that different asexual adult phenotypes winged and wingless of some clones of two cereal aphid species (the grain aphid, Sitobion avenae (F.) and the bird-cherry aphid. Rhopalosiphum padi (L.) may be distinguished by the presence or absence of one or more RAPD-PCR bands. In three of nine clones examined, such differences were found, and Southern blotting and hybridization of the discriminating bands confirmed these to be of aphid origin, rather than due to endosymbiotic bacteria or contaminating fungi. The main 248 and 296 bp bands, in the two species respectively, were sequenced and found to be A/T rich. The smaller band showed 57% homology with white striated muscle over a stretch of 90 bp. Genomic DNA treated with dimethyl sulphoxide to remove secondary structures still showed differences in RAPD-PCR profiles between winged and wingless morphs within the unusual clones. This discovery may be widespread and therefore it is important to understand the phenomenon in relation to clonal organisms.

Spatial and temporal genetic variation in British field populations of the grain aphid Sitobion avenae (F.) (Hemiptera: Aphididae) studied using RAPD-PCR.

The grain aphid Sitobion avenae (F.) was collected from winter wheat and adjacent cocksfoot grass at two locations in southern England and at four times in the year (April-July). Genetic variation between individual aphids was then investigated using random amplified polymorphic DNA polymerase chain reaction. Individuals caught in wheat and cocksfoot during April provided very different and highly diagnostic banding patterns that were independent of location. This host-based genetic differentiability was less evident as the season progressed, largely as a result of genetic drift and local movement between adjacent host species, which appeared to be predominantely in the direction from cocksfoot to wheat. The diversity of putative clones fell significantly, the mean number of individuals per clone rose and clones became more exclusively associated with certain sites which suggests that long-distance migration may have less of a homogenizing effect than hitherto thought for this species.

Validation of a new intraoperative technique to evaluate load-independent indices of right ventricular performance in patients undergoing cardiac operations.

BACKGROUND: Assessment of right ventricular performance in the perioperative period is difficult because there is no generally accepted method of measuring right ventricular volume. We set out to determine whether conductance technology could provide a valuable technique for the investigation of intraoperative right ventricular function. METHODS AND RESULTS: Three validating studies were performed in 25 patients undergoing routine coronary revascularization. Study 1: The influence of conductance catheter position in the right ventricle was examined in 10 patients. Insertion of the conductance catheter through the outflow tract was associated with a larger gain constant and a smaller parallel conductance compared with insertion through the tricuspid valve. Study 2: The reproducibility of contractility measurements with the use of a conductance catheter was examined in 7 additional patients. Removal and reinsertion of the conductance catheter was not associated with any significant difference in right ventricular volume or contractile function. Study 3: Right ventricular performance before and after cardiopulmonary bypass was compared in 8 additional patients. There was a fall in the slope of the right ventricular preload recruitable stroke work from 15.6 (3.8) to 11.0 (5.1) mm Hg (P=.01) and an increase in the slope of the end-diastolic pressure-volume relations from 0.05 (0.02) to 0.11 (0.05) mm Hg/mL (P=.001). CONCLUSIONS: The conductance technique can be used to study perioperative changes in right ventricular performance. Insertion of the conductance catheter through the outflow tract provides stable and reproducible data. There is significant impairment of right ventricular contractility in the early postoperative period.

Detection of human papillomavirus in anorectal squamous cell carcinoma. Correlation with basaloid pattern of differentiation.

Polymerase chain reaction (PCR) and in situ hybridization were used to test for the presence of human papillomavirus (HPV) DNA in cases of anorectal squamous cell carcinoma. Human papillomavirus was detected by PCR with L1 consensus sequence primers in 22 of 27 cases, including 10 of 11 cases with a prominent basaloid pattern and 12 of 16 cases without basaloid patterns of differentiation. Slot blot hybridization identified HPV type 16 as the most common type, present in 7 of 10 cases of basaloid carcinoma and 10 of 12 cases without basaloid features. In situ hybridization confirmed the presence of HPV in tumor cell nuclei of five cases of basaloid carcinoma and in eight cases of squamous cell carcinoma without basaloid pattern. The authors conclude that the prevalence of HPV in cases of anorectal squamous cell carcinoma is unrelated to the presence or absence of a basaloid pattern of differentiation.

Right ventricular dysfunction during coronary artery occlusion: pressure-volume analysis using conductance catheters during coronary angioplasty.

OBJECTIVE: To study the effects of coronary artery occlusion on the pressure-volume relations of the right ventricle. DESIGN: Right ventricular pressure-volume cycles were studied using conductance catheters and micromanometers in 19 subjects undergoing coronary angioplasty in a tertiary referral cardiac centre. RESULTS: Catheter occlusions of either the left anterior descending coronary artery or the right coronary artery were associated with a decline in stroke work (mean change (SD): left-13.3 (15.8)%, p = 0.008; right -13.5(16.5)%, p = 0.04). Two patterns of change were evident: an upward shift usually associated with occlusion in the left coronary artery, and a rightward shift in the right coronary artery. In the former there was an increase in maximum ventricular volume (mean change: 3.0(2.7)%, p = 0.004) and in minimum ventricular volume (mean change: 2.3(2.7)%, p = 0.01) and a fall in peak pressure (mean change: -4.8 (5.1)%, p = 0.04). In the latter there was an increase in peak pressure (mean change 9.9(16.3)%, p = 0.04) and an increase in minimum ventricular volume (mean change 3.7(5.0)%, p = 0.02) leading to a fall in stroke volume (mean change -13.3(15.8)%, p = 0.008). CONCLUSIONS: Occlusion of the left anterior descending coronary artery or the right coronary artery is associated with a decline in right ventricular work. However, different patterns of change in indices of preload and afterload lead to different effects on overall right ventricular pump function.

Clinical application of the conductance catheter technique in the adult human right ventricle.

This study examines the use of conductance catheters to assess human right ventricular volume. Ten patients undergoing diagnostic cardiac catheterisation underwent right heart catheterisation with a conductance catheter and micromanometer, and a thermodilution catheter before and after fluid loading. Parallel wall conductance (Vc), and the multiplication factor relating conductance and thermodilution derived stroke volumes (å) were derived at each steady state. Pressure-volume cycles were analyzed at steady state and during fluid loading. Fluid loading resulted in a significant increase in cardiac output, and change in maximum and minimum cycle volume. There was no significant change in å (mean 0.40 S.D. 0.20) or Vc (mean 126.4 S.D. 59.6 ml) at higher cardiac outputs or ventricular volumes. Right ventricular pressure-volume cycles were formed demonstrating characteristic lack of clear isovolumic contraction and relaxation phases, and low cycle efficiencies (mean 0.62 S.D. 0.16). Serial cycles recorded during volume loading defined an end systolic pressure-volume relation more reliably than a stroke work end diastolic volume relation. Thus, a conductance derived volume signal can be obtained in the human right ventricle which can be interpreted as a continuous and instantaneous index of right ventricular volume, allowing the construction of real time pressure-volume cycles.

Resting right ventricular function in patients with coronary artery disease: pressure volume analysis using conductance catheters.

Right ventricular pressure volume cycles from patients with coronary artery disease were created in order to assess their characteristics and the effects of peak ventricular pressure and right and left artery coronary disease. Thirty-three patients undergoing diagnostic catheterisation for ischaemic heart disease underwent right ventricular catheterisation with a micromanometer and a conductance catheter. Simultaneous pressure and volume signals were recorded and analysed as functions of time, and of each other, forming pressure volume cycles. A total of 19/33 (58%) patients had an abnormal pressure volume loop with a clear end systolic shoulder, and an isovolumic relaxation phase. The mean peak ventricular pressure for all patients was raised (35.2 S.D. 11.8 mmHg), but there was no correlation between indices of shape and peak systolic pressure. Values of dP/dtmax were also raised, but there was no significant difference in this or any other index between patients with left or right coronary artery disease. Thus, in patients with coronary artery disease, the right ventricular pressure volume loop is frequently abnormal in a pattern that is recognised as a feature of an increased ventricular afterload.