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Biomedical subjects

J R Pepper

Publications and source records attributed to J R Pepper.

At least 19 recordsLinked to original sources
PubMed2001

Risk of iron overload is decreased in beating heart coronary artery surgery compared to conventional bypass.

Conventional cardiopulmonary bypass surgery (CCPB) increases the iron loading of plasma transferrin often to a state of plasma iron overload, with the presence of low molecular mass iron. Such iron is a potential risk factor for oxidative stress and microbial virulence. Here we assess 'off-pump' coronary artery surgery on the beating heart for changes in plasma iron chemistry. Seventeen patients undergoing cardiac surgery using the 'Octopus' myocardial wall stabilisation device were monitored at five time points for changes in plasma iron chemistry. This group was further divided into those (n=9) who had one- or two- (n=8) vessel grafts, and compared with eight patients undergoing conventional coronary artery surgery. Patients undergoing beating heart surgery had significantly lower levels of total plasma non-haem iron, and a decreased percentage saturation of their transferrin at all time points compared to conventional bypass patients. Plasma iron overload occurred in only one patient undergoing CCPB. Beating heart surgery appears to decrease red blood cell haemolysis, and tissue damage during the operative procedures and thereby significantly decreases the risk of plasma iron overload associated with conventional bypass.

Adult↗
PubMed2001

Quantitative myocardial cytokine expression and activation of the apoptotic pathway in patients who require left ventricular assist devices.

BACKGROUND: Molecular mechanisms underlying the deterioration of patients undergoing LV assist device (LVAD) implantation remain poorly understood. We studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and IL-6 and the terminal stage of the apoptotic pathway in patients with decompensating heart failure who required LVAD support and compared them with patients with less severe heart failure undergoing elective heart transplantation. METHODS AND RESULTS: Myocardial and serum samples from 23 patients undergoing LVAD implantation were compared with those from 36 patients undergoing elective heart transplantation. Myocardial TNF-alpha mRNA (1.71-fold; P<0.05) and protein (3.43+/-0.19 versus 2.95+/-0.10 pg/mg protein; P<0.05) were elevated in the LVAD patients. Immunocytochemistry demonstrated TNF expression in the myocytes. Serum TNF-alpha was also elevated (12.5+/-1.9 versus 4.0+/-0.4 pg/mL; P<0.0001) in the LVAD patients. IL-6 mRNA (2.57-fold higher; P<0.005) and protein (27.83+/-9.35 versus 4.26+/-1.24 pg/mg protein; P<0.001) were higher in the LVAD candidates, as was serum IL-6 (79.3+/-23.6 versus 7.1+/-1.6 pg/mL; P<0.0001). Interleukin-1beta mRNA expression was 9.78-fold higher in the LVAD patients (P<0.001). iNOS mRNA expression was similar to that in advanced heart failure patients and was not further elevated in the LVAD patients. Levels of procaspase-9 (8.02+/-0.91 versus 6.16+/-0.43 oligodeoxynucleotide [OD] units; P<0.01), cleaved caspase-9 (10.02+/-1.0 versus 7.34+/-0.40 OD units; P<0.05), intact and spliced DFF-45 (4.58+/-0.75 versus 2.84+/-0.23 OD units; P<0.05) were raised in LVAD patients, but caspase-3 and human nuclease CPAN were not. CONCLUSIONS: Elevated TNF-alpha, IL-1beta, and IL-6 and alterations in the apoptotic pathway were found in the myocardium and elevated TNF-alpha and IL-6 in serum of deteriorating patients who required LVAD support. These occurrences may have therapeutic implications and influence the timing of LVAD insertion.

Adolescent↗
PubMed2001

Changes in aortic rotational flow during cardiopulmonary bypass studied by transesophageal echocardiography and magnetic resonance velocity imaging: a potential mechanism for atheroembolism during cardiopulmonary bypass.

The human aorta is a curved conduit with a complex three-dimensional geometry. The curvature influences axial velocity distribution and introduces transverse velocity components. Rotational flow in the aorta can be demonstrated during normal pulsatile flow using transesophageal echocardiography. Cardiopulmonary bypass may affect the pattern of rotational flow in the aorta and thus influence the generation of atheroemboli. We investigated rotational flow in the descending aorta using color flow mapping and pulse-wave Doppler on transesophageal echocardiography before and during cardiopulmonary bypass. We correlated our findings with magnetic resonance velocity imaging in a model of a human aortic arch connected to a cardiopulmonary bypass circuit. Before cardiopulmonary bypass, rotational flow in the descending aorta was seen in 37 of 40 patients (93%). In the majority of these patients, rotational flow was in the clockwise direction during systole, looking in the direction of flow (30 of 37 patients, 81%, P < 0.01 vs counterclockwise rotation). During cardiopulmonary bypass, there were almost equal numbers of patients with clockwise (18 patients) and counterclockwise rotation (19 patients). Forty-seven percent of patients with clockwise rotation before cardiopulmonary bypass developed reversal in the direction of rotation to counterclockwise during cardiopulmonary bypass. Twenty-nine percent of patients with counterclockwise rotation developed reversal of the direction of rotation during cardiopulmonary bypass. The transverse velocity component increased during cardiopulmonary bypass regardless of the direction of rotation. We also demonstrated clockwise rotation in the descending aorta of a human aortic arch model connected to a cardiopulmonary bypass circuit using magnetic resonance velocity mapping. Before cardiopulmonary bypass, rotation was predominantly clockwise, while during cardiopulmonary bypass, there was no preferred direction of rotation. The geometry of the aorta, which is fairly constant in all patients, imposes handedness to aortic flow before cardiopulmonary bypass. However, during cardiopulmonary bypass, other extrinsic factors such as aortic cannula orientation may influence the direction of rotation. The change in direction of rotational flow and increase in its transverse velocity component during cardiopulmonary bypass may have implications for atheroembolism and arterial branch perfusion during extended periods of non-pulsatile flow.

Aorta↗
PubMed2001

Lung volume reduction surgery in a ventilated patient with severe pulmonary emphysema.

There are a limited number of reports in the literature cocerning lung volume reduction surgery in patients receiving mechanical ventilation. We present a case in which a ventilator-dependent patient with apparent endstage pulmonary emphysema underwent lung volume reduction with a successful outcome. Although the role of this procedure for selected nonventilated patients has been widely discussed its use in ventilated patients is still not clearly defined. We show that lung volume reduction surgery may facilitate ventilatory weaning in such cases and improve functional status.

Female↗
PubMed2001

Combination of preconditioning and delayed flap elevation: evidence for improved perfusion and oxygenation of the latissimus dorsi muscle for cardiomyoplasty.

BACKGROUND: Atrophy and fibrosis of the distal part of the latissimus dorsi muscle (LDM) wrap is a recognized complication of cardiomyoplasty that has been attributed to ischemia. Failure of the muscle wrap contributes to the late attrition seen in clinical cardiomyoplasty. In this study we examined the role of two-staged mobilization and of preconditioning by electrical stimulation on the regional perfusion and oxygenation of the LDM. METHODS: In a rabbit model (n = 36) the LDM was preconditioned as follows: group A muscles received preconditioning in situ; group B muscles were partially mobilized by dividing the intercostal perforators and then preconditioned; and group C muscles were completely mobilized and wrapped around a silicone-rubber mandrel before conditioning. Controls received no conditioning. The preconditioning regimen consisted of 2 weeks of continuous stimulation at 2.5 Hz. At completion of preconditioning the muscles were fully mobilized and mounted on a muscle-testing apparatus. Purpose-built microelectrodes measured regional PO2 and perfusion using a diffusible gas tracer technique. Muscles were weighed and processed for fiber typing and capillary counting. RESULTS: All preconditioned muscles demonstrated fiber transformation, with increased fatigue resistance. Perfusion of preconditioned muscles both at rest and during contraction was higher than control in the proximal part of the muscle. Distal regions of group B muscles had higher perfusion and capillary density than any other group (p < 0.05). Distal regions of group C had the lowest perfusion and capillary density, and showed muscle atrophy and histologic evidence of necrosis. During fatigue testing there was a decrease in the PO2 in the distal regions of the control and group C muscles (p < 0.05), whereas it was maintained at resting levels in both group A and B muscles. CONCLUSIONS: Conditioning in situ improves perfusion of the distal LDM and prevents a fall in tissue PO2 during contraction. Two-stage mobilization further improves distal perfusion and capillary density. In contrast, shortterm elevation followed by conditioning produces impaired distal perfusion, decrease in PO2, and fiber necrosis in the distal muscle. The present study suggests that partial mobilization of the LDM performed at the same time as placement of electrodes for preconditioning may prepare the LDM better for the demands of cardiomyoplasty.

Animals↗
PubMed2001

Clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve.

BACKGROUND: Hemodynamic benefits of the Toronto stentless porcine valve have been documented. Clinical well-being and freedom from major valve-related events have been less well defined. METHODS: A total of 447 patients were prospectively followed for up to 8 years (1,745.2 valve years total, 3.9 valve years/patient). The patient demographics included 66% men, mean age 65 years, New York Heart Association functional class III-IV 55%, concomitant coronary artery bypass grafting 41%. RESULTS: We found that 83.7% of patients were in New York Heart Association functional class I and 80.8% had 0 to 1+ aortic insufficiency. Mean gradient at 6 years (n = 75) was 4.4 mm Hg and mean effective orifice area (EOA) 2.4 cm2. Late adverse event rates per patient per year were: embolism 1.0%, endocarditis 0.4%, thrombosis 0%, structural deterioration 0.2%, explant 0.3%, and valve-related death 0.6%. Freedom from valve-related death at 6 years was 95.8%; from cardiac death 96.3%. Freedom from endocarditis was 98.4%, from embolism 93.9%, from structural deterioration 97.4%, and freedom from explant 98.1%. For patients older than 60 years, freedom from structural deterioration was 100%. CONCLUSIONS: These results confirm satisfactory clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve, with a low incidence of valve-related adverse events as long as 96 months after valve replacement.

Adult↗
PubMed2001

Improved reliability of post-operative ventricular pacing by use of bipolar temporary pacing leads.

The study compared the clinical reliability of using a bipolar epicardial wire (6495, Medtronic) over a unipolar type (FEP15, Ethicon) for post-operative pacing in coronary artery surgery. Atrial and ventricular wires of both types were implanted in 18 patients. Sensitivities and pacing thresholds were tested for 5 consecutive days. Results show that pacing thresholds were better maintained with the bipolar wire in both atria and ventricles. However, sensing failures were frequent in the atrial position (34% vs 9.3% compared with unipolar). By contrast, in the ventricle, no sensing failures occurred (0% vs 17.6% compared with unipolar). Furthermore, sensing magnitude was significantly better (11.13+/-1.32 vs 5.65+/-0.53 mV, P<0.001). We conclude that a single 6495 bipolar wire is effective for temporary ventricular pacing, whilst double unipolar wires remain a useful strategy for securing atrial sensing and pacing.

Cardiac Pacing, Artificial↗
PubMed2001

Scapular insertion of the rabbit latissimus dorsi muscle: gross anatomy and fibre-type composition.

This paper defines the characteristics and significance of the scapular insertion of the latissimus dorsi muscle (LDM) of the rabbit. In a study of the New Zealand White species (n = 10) the scapular insertion was found to be a consistent anatomical feature of the LDM that made up 12.3% (+/-2.3) of the total muscle weight. The fibres arise from the medial aspect of the body of the LDM and run in a caudocranial direction to be inserted into a broad, thin tendon beneath the scapula ridge. This is morphologically different from the scapular component of the human LDM which is a well-recognized but inconsistent feature and consists of no more than a small leash of fibres running around the lower pole of the scapula. The scapular insertion was deeper red in colour than the body of the muscle and fibre-typing demonstrated a mean slow-fibre composition of 49% (+/-2.6) compared to 16% (+/-1.7) for the body of the muscle (p < 0.01). Mapping of the fibre types throughout the remainder of the LDM confirmed that the body of the muscle was of fast phenotype but with significantly more slow fibres in the superomedial segment of the muscle than elsewhere. This region of the muscle contributes mainly to the scapular insertion and it is proposed that this part of the muscle takes on a predominantly postural role in stabilising the scapula during movement of the forelimb.

Adenosine Triphosphatases↗
PubMed2000

Hybrid management of coronary artery disease and coarctation of aorta.

The treatment of coarctation of aorta with an additional cardiac lesion in adults remains a difficult surgical challenge. We present here an alternative, two-stage, hybrid approach that combined stent repair of aortic coarctation followed by coronary artery bypass operation in an adult with critical coronary lesions and a poor ventricle. This method may be a potentially useful strategy in reducing the comorbidity of operation to both lesions.

Aortic Coarctation↗
PubMed2000

Oxygenation and perfusion of rabbit tibialis anterior muscle subjected to different patterns of electrical stimulation.

Dual amperometric microelectrodes were used to measure local pO2 and perfusion at multiple sites in the fast-twitch tibialis anterior muscles of anaesthetized rabbits. Six muscles were stimulated continuously at 10, 5, or 2.5 Hz. For all three frequencies, perfusion declined to about 50% of resting levels and recovered after stimulation. These changes corresponded to a rise followed by a fall in extracellular pO2. The highest levels of pO2 were reached during stimulation at 10 Hz. Eight muscles were stimulated tetanically at 100 Hz for 200 ms with duty cycles that were varied between 1.3 and 20.0%. Perfusion rose to 8.7 +/- 2.0 ml s(-1) 100 g(-1) at a duty cycle of 5% and declined with further increases in duty cycle. pO2 was depressed for duty cycles less than 10% but rose above resting levels at higher duty cycles. It is suggested that the paradoxical combination of elevated pO2 and depressed perfusion is attributable to stimulation conditions that exceed the oxygen transport capacity of a fast muscle.

Animals↗
PubMed2000

Release of GM-CSF and G-CSF by human arterial and venous smooth muscle cells: differential regulation by COX-2.

In addition to their traditional contractile function, vascular smooth muscle cells can be stimulated under inflammatory conditions to release a range of potent biological mediators. Indeed, we and others have shown that human vascular smooth muscle release the colony stimulating factors (CSF) granulocyte macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF) as well as large amounts of prostaglandins following the induction of cyclo-oxygenase-2 (COX-2), when stimulated with cytokines. Here we demonstrate, for the first time, that co-induced COX-2 activity simultaneously suppresses GM-CSF release and potentiates G-CSF release by human vascular cells. Moreover, the differential regulation of GM-CSF and G-CSF release by COX-2 was mimicked by the prostacyclin (PGI(2)) mimetic, cicaprost. These observations suggest that PGI(2), released following the induction of COX-2, differentially regulates the release of GM-CSF (suppresses) and G-CSF (potentiates) from human vascular cells.

Arteries↗
PubMed2000

Evaluation of patients undergoing lung volume reduction surgery: ancillary information available from computed tomography.

AIM: A number of imaging techniques have been used for the pre-operative assessment of patients for lung volume reduction surgery (LVRS). We evaluated whether data currently acquired from perfusion scintigrams and cine MR of the diaphragm are obtainable from high resolution CT (HRCT) of the thorax. MATERIALS AND METHODS: Thirty patients taking part in a randomized controlled trial of LVRS against maximal medical therapy were evaluated. HRCT examinations (n= 30) were scored for (i) the extent and distribution of emphysema; (ii) the extent of normal pulmonary vasculature; and (iii) diaphragmatic contour, apparent defects and herniation. On scintigraphy, (n= 28), perfusion of the lower thirds of both lungs, as a proportion of total lung perfusion (LZ/T(PERF)), was expressed as a percentage of predicted values (derived from 10 normal control subjects). On cine MR (n= 25) hemidiaphragmatic excursion and coordination were recorded. RESULTS: Extensive emphysema was present on HRCT (60% +/- 13.2%). There was strong correlation between the extent of normal pulmonary vasculature on HRCT and on perfusion scanning (r(s)= 0.85, P< 0.00005). Hemidiaphragmatic incoordination on MR was weakly associated with hemidiaphragmatic eventration on HRCT (P= 0.04). CONCLUSION: The strong correlation between lung perfusion assessed by HRCT and lung perfusion on scintigraphy suggests that perfusion scintigraphy is superfluous in the pre-operative evaluation of patients with emphysema for LVRS.

Adult↗
PubMed2000

Vascular endothelial growth factor release following coronary artery bypass surgery: extracorporeal circulation versus 'beating heart' surgery.

AIMS: The aim of this study was to examine the circulating levels of vascular endothelial growth factor, following coronary artery bypass graft surgery performed using both standard cardiopulmonary bypass or the 'octopus technique' on the beating heart. BACKGROUND: Vascular endothelial growth factor has a number of effects that are beneficial in the setting of coronary artery bypass graft surgery including cardioprotection, potent angiogenic activity and amelioration of intimal hyperplasia. Hypoxia is a powerful stimulator of vascular endothelial growth factor expression yet the ability of ischaemia, occurring during coronary artery bypass graft surgery, to induce vascular endothelial growth factor production is unknown. METHODS AND RESULTS: Serum vascular endothelial growth factor levels were determined in patients undergoing coronary artery bypass graft surgery with standard cardiopulmonary bypass (CPB-CABG group; n=20), with off-pump coronary artery bypass; (OP-CABG; n=12) and in patients undergoing non-cardiac major surgery (n=6). The effect of hypoxia on vascular endothelial growth factor release by neonatal rat cardiac myocytes in vitro was studied. In the CPB-CABG group vascular endothelial growth factor levels were significantly increased to 78.5+/-39.3 and 110.5+/-16.3 pg. microl(-1)8 and 24 h post-operatively, declining to 14.9+/-9.9 pg. microl(-1)by 48 h to pre-operative values (14.4+/-8.6 pg. microl(-1)). Significantly higher vascular endothelial growth factor levels were also present in the OP-CABG group 3, 6 and 24 h post-operatively (levels 136. 6+/-29.3, 143+/-26.12 pg. microl(-1)and 93.5+/-20.1 pg. microl(-1), respectively). However, non-cardiac major surgery did not result in elevated vascular endothelial growth factor levels post-operatively (46.36+/-9.76 vs pre-surgery levels of 26.84+/-6.1 pg. microl(-1)). Either 15 min or 3 h of hypoxia stimulated vascular endothelial growth factor release from neonatal rat cardiac myocytes in vitro. Twenty-four and 48 h post hypoxia, levels of vascular endothelial growth factor were significantly elevated by approximately 17.5- and 48.5-fold respectively. CONCLUSIONS: These data demonstrate myocardial ischaemia secondary to CPB-CABG and OP-CABG to be a potent stimulator of vascular endothelial growth factor production, which may have implications for graft endothelialization and cardiovascular haemodynamics post-operatively.

Animals↗
PubMed2000

Experience of totally implantable venous access devices (TIV ADs) in adults with cystic fibrosis over a 13-year period.

Totally implantable venous intravenous access devices (TIVADs) have an essential role in the frequent delivery of antibiotics in cystic fibrosis (CF) patients. This study at the Royal Brompton Hospital (RBH) reports the experience of TIVADs in patients attending the RBH adult CF unit implanted at the RBH and elsewhere over a 13-year period. The case notes of adult CF patients who had undergone TIVAD insertion were reviewed retrospectively. The patients were divided into those who had the insertion carried out at the RBH and those who had the device inserted elsewhere. All devices were cared for the at the RBH. A total of 115 devices in 74 patients were reviewed. The median duration of function of 109 devices was 1429 days (range 2-3989) or 3.9 years, with a total exposure of 91,188 days or 249.8 years. There was no significant difference between devices inserted at the RBH and those inserted elsewhere (P= 0.59). Thirty-four patients had devices installed without complications. Forty patients had complications in 62 devices. The incidence of complications was 34.5% at the devices inserted at RBH and 73.7% elsewhere (P<0.001). Of the 115 devices, mechanical complications occurred in 42 (36%) with a median time of diagnosis of 373 days (range 1-2554), infectious complications occurred in 16 (14%), with a median time of diagnosis of 413 days (range 40-2556) and symptomatic venous thrombosis occurred in four (3.5%). RBH-inserted devices had significantly fewer mechanical complications (P<0.001) compared with those inserted elsewhere. The group as a whole had fewer infectious complications than in most other reported series. We conclude that TIVADs provide effective and long-term intravenous access and have fewer complications if they are inserted and cared for at a centre with special expertise in their insertion and management.

Adolescent↗
PubMed2000

Cyclooxygenase-2 regulates granulocyte-macrophage colony-stimulating factor, but not interleukin-8, production by human vascular cells: role of cAMP.

Vascular smooth muscle is now recognized as an important site of mediator generation under inflammatory conditions. Indeed, the release of leukocyte activators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8, by human arterial smooth muscle cells has recently been demonstrated. However, the potential for venous cells to release GM-CSF has not been addressed. We have shown that human vascular smooth muscle cells express the "inflammatory" form of cyclooxygenase (COX), cyclooxygenase-2 (COX-2), when stimulated with cytokines. In some nonvascular cell types, the COX activity has been shown to regulate the release of GM-CSF and IL-8, although the nature of the isoform responsible was not addressed. We show that human venous smooth muscle cells, like their arterial counterparts, release GM-CSF after stimulation with IL-1beta. Similarly, both cell types released IL-8. Under the same conditions, we found that COX-2 activity suppressed GM-CSF, but not IL-8, release by both types of human vascular cells. Moreover, the prostacyclin mimetic, cicaprost, and the cAMP analogue, dibutyryl cAMP, inhibited GM-CSF release from these cells. These observations suggest that COX-2 activity suppresses GM-CSF release via a cAMP-dependent pathway in human vascular cells and illustrates a novel mechanism by which this enzyme can modulate immune and inflammatory events.

Anti-Inflammatory Agents, Non-Steroidal↗