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Biomedical subjects

J R Pepper

Publications and source records attributed to J R Pepper.

At least 55 records · Page 3Linked to original sources
PubMed1999

A prospective study of wound infection in coronary artery surgery.

OBJECTIVE: The incidence of wound infection in coronary artery surgery is low, but there is an appreciable mortality associated with sternal infection. In other fields of surgery there is evidence that an all disposable paper gown and drape system has protective advantages over a fabric system. Using an established wound scoring system (ASEPSIS), we investigated this in a prospective, randomised trial of patients undergoing cardiac surgery. METHODS: 505 patients undergoing isolated coronary artery surgery in a single hospital over an 18 month period were randomised to either a disposable, paper drape system or re-usable fabric drapes. Allocation was stratified according to whether or not the patient had had previous coronary artery surgery. Patients were followed for 3 months. Total infection scores for each wound were calculated from daily scores collected in hospital together with the scores at six weeks and three months. RESULTS: The two randomised groups were otherwise well matched. Full follow-up information was available for 464 (92%) patients. There was no evidence of any difference in rates of sternal or leg wound infection between the two groups (P = 0.87 and 0.62, respectively). Women were more likely to have infected sternal wounds (P = 0.17) and significantly more likely to have infected leg wounds (P = 0.04). Patients with sternal wound infections had a significantly higher body mass index (P = 0.001). High Parsonnet scores and increased time on ventilation were significantly associated with leg wound but not sternal infections. For both wound sites, patients with infections had spent longer in the operating theatre. CONCLUSION: In a randomised controlled study of patients undergoing coronary artery surgery we found that the use of paper drapes and gowns conferred no benefit over a reusable fabric in terms of post-operative wound infection. Although females and diabetics are more likely to experience this complication, an important additional risk factor is an extended operating time.

Coronary Disease↗
PubMed1999

The effects of cardioplegia on coronary pressure-flow velocity relationships during aortic valve replacement.

OBJECTIVE: The acute physiological response of the coronary circulation to aortic valve replacement (AVR) has not been fully elucidated. This study aimed to characterize the changes in coronary perfusion pressure-flow velocity relationships, and to test whether this relationship is affected by cardioplegic method. METHODS: Nineteen patients (mean age 67 +/- 12 (SD) years, 9 males) undergoing aortic valve replacement who received either cold blood cardioplegia (CBC, n = 9) or warm blood cardioplegia (WBC, n = 10), were prospectively studied before and 30 min after the operation, using transesophageal Doppler echocardiography combined with high fidelity left ventricular (LV) and aortic pressures. We thus determined: (1) Diastolic flow velocities in proximal anterior descending coronary artery (LAD), and simultaneous aorta to LV pressure differences. (2) The slope (LAD proximal linear resistance) and pressure intercept (zero flow pressure) of this relationship. (3) Overall LAD linear resistance as the ratio of mean diastolic flow velocity to mean pressure difference between aorta and left ventricle. (4) LV myocardial stroke work. RESULTS: Following operation, myocardial stroke work fell from 5.2 +/- 2.7 to 3.0 +/- 1.7, mJ cm(-3) (P = 0.001), LAD mean diastolic flow velocity increased from 47 +/- 19 to 74 +/- 21, cm s(-1) (P = 0.0002). LAD overall linear resistance fell (0.75 +/- 0.24 vs. 1.26 +/- 0.26, mmHg cm(-1) s, P = 0.001). LAD proximal linear resistance, however, remained unchanged (P = 0.21), but the zero flow pressure fell (18 +/- 12.6 vs. 27 +/- 12.2, mmHg above LV end diastolic pressure, P = 0.013). With similar fall in myocardial work postoperatively, there was a greater fall in zero flow pressure after WBC than CBC (48 +/- 28 vs. 19 +/- 13,% of pre-op, P = 0.012), and a greater increase in flow velocity time integral (127 +/- 81 vs. 53 +/- 59,%, P = 0.039). CONCLUSION: Instantaneous diastolic LAD pressure-flow velocity relations in the early postoperative period can be explained more satisfactorily in terms of zero flow pressure and proximal linear resistance than simple resistance alone. The fall in zero flow pressure alone explains the increase in LAD flow velocity immediately after aortic valve replacement. The extent of this fall is greater after warm rather than cold blood cardioplegia.

Aged↗
PubMed1999

Effect of coronary occlusion on left ventricular function with and without collateral supply during beating heart coronary artery surgery.

OBJECTIVE: To study the effects of coronary occlusion and collateral supply on left ventricular (LV) function during beating heart coronary artery surgery. DESIGN: Prospective intraoperative study, performed at baseline, during wall stabilisation, coronary artery occlusion, and 2 and 10 minutes after reperfusion. Transoesophageal M mode echocardiograms, simultaneous high fidelity LV pressure, and thermodilution cardiac output were measured. LV anterior wall thickening, thinning velocities, thickening fraction, regional work, and power production were derived. Asynchrony during the isovolumic periods was quantified as cycle efficiency. SETTING: Tertiary referral cardiac centre. PATIENTS: 14 patients with stable angina, mean (SD) age 62 (7) years, undergoing left anterior descending artery grafting using the "Octopus" device. RESULTS: Collaterals were absent in nine patients and present in five. Epicardial stabilisation did not affect LV function. Results are expressed as mean (SD). Coronary occlusion (15.6 (2) minutes) depressed anterior wall thickening (1.4 (0.6) v 2.6 (0.6) cm/s) and thinning velocities (1.4 (0.5) v 3.0 (0.6) cm/s), regional work (2.2 (0.8) v 4.6 (0.6) mJ/cm2), and power (21 (4) v 33 (5) mW/cm2) in patients without collaterals (p < 0.05 for all), but only wall thinning (3.5 (0.5) v 4.8 (0.5) cm/s, p < 0.05) in patients with collaterals. All returned to baseline within 10 minutes of reperfusion. Cycle efficiency and regional work were impaired at baseline and fell during occlusion, regardless of collaterals. Within 10 minutes of reperfusion both had increased above baseline. CONCLUSIONS: Coronary occlusion for up to 15 minutes during beating heart coronary artery surgery depressed standard measurements of systolic and diastolic anterior wall function in patients without collaterals, but only those of diastolic function in patients with collaterals. Regional synchrony decreased in both groups. All disturbances regressed within 10 minutes of reperfusion.

Analysis of Variance↗
PubMed1999

Intraoperative cardiac troponin T release and lactate metabolism during coronary artery surgery: comparison of beating heart with conventional coronary artery surgery with cardiopulmonary bypass.

OBJECTIVE: To compare cardiac troponin T release and lactate metabolism in coronary sinus and arterial blood during uncomplicated coronary grafting on the beating heart with conventional coronary grafting using cardiopulmonary bypass. DESIGN: A prospective observational study with simultaneous sampling of coronary sinus and arterial blood: before and 1, 4, 10, and 20 minutes after reperfusion for analysis of cardiac troponin T and lactate. Cardiac troponin T was also analysed in venous samples taken 3, 6, 24, 48, and 72 hours after surgery. SETTING: Cardiac surgical unit in a tertiary referral centre. PATIENTS: 18 patients undergoing coronary grafting on the beating heart (10 single vessel and eight two-vessel grafting) and eight undergoing two-vessel grafting with cardiopulmonary bypass. RESULTS: Cardiac troponin T was detected in coronary sinus blood in all patients by 20 minutes after beating heart coronary artery surgery before arterial concentrations were consistently increased. Peak arterial and coronary sinus cardiac troponin T values on the beating heart during single (0.03 (0 to 0. 05) and 0.09 (0.07 to 0.16 microg/l, respectively) and two-vessel grafting (0.1 (0.07 to 0.11) and 0.19 (0.14 to 0.25) microg/l) were lower than the values obtained during cardiopulmonary bypass (0.64 (0.52 to 0.72) and 1.4 (0.9 to 2.0) microg/l) (p < 0.05). The area under the curve of venous cardiac troponin T over 72 hours for two-vessel grafting on the beating heart was less than with cardiopulmonary bypass (13 (10 to 16) v 68 (26 to 102) microg.h/l) (p < 0.001). Lactate extraction began within one minute of snare release during beating heart coronary surgery while lactate was still being produced 20 minutes after cross clamp release following cardiopulmonary bypass. CONCLUSIONS: Lower intraoperative and serial venous cardiac troponin T concentrations suggest a lesser degree of myocyte injury during beating heart coronary artery surgery than during cardiopulmonary bypass. Oxidative metabolism also recovers more rapidly with beating heart coronary artery surgery than with conventional coronary grafting. Coronary sinus cardiac troponin T concentrations increased earlier and were greater than arterial concentrations during beating heart surgery, suggesting that this may be a more sensitive method of intraoperative assessment of myocardial injury.

Aged↗
PubMed1999

Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass : relationship to increased thrombin generation and heparin concentration.

Several recent studies have proposed that coagulation is triggered during cardiopulmonary bypass surgery by extrinsic pathway activation involving factor VIIa generation, but the methodology was indirect. Therefore, 12 patients were studied during routine cardiac and cardiopulmonary bypass surgery. Samples were taken before, during, and after bypass from the perfusate, from the aorta (retrograde cardiac drainage), pericardium, and collected suction fluid originating from the whole operative field. These samples were analyzed by enzyme-linked immunosorbent assay for 2-chain factor VIIa, by prothrombin F1+2 assay, by thrombin-antithrombin (TAT) assay, and for heparin concentration. Factor VIIa, F1+2, and TAT levels in samples from the pericardium were greatly elevated (mean, 0.92 to 1.01, 227 to 334, and 399 to 526 microg/L, respectively; preoperative mean, 0.33, 32.3, and 1.90 microg/L, respectively; P<0. 05 for all), whereas levels in suction fluid were less consistently high. Factor VIIa and both F1+2 and thrombin-antithrombin levels in samples from the aorta, pericardium, and suction fluid were significantly correlated (r=0.57, P<0.001, n=111; and r=0.51, P<0. 001, n=105, respectively), and all were inversely correlated with heparin levels (r>-0.35, P<0.001, n>92). There was no evidence of factor VIIa generation in the circuit during bypass surgery, and both F1+2 and thrombin-antithrombin levels rose only approximately 2-fold, probably because heparin levels were higher than they were in the pericardium (P<0.05). We concluded that appreciable activation of factor VII occurs on the pericardium and that this is associated with increased thrombin generation. Ineffective local heparinization may be partly responsible. These results suggest that pericardium-induced activation of factor VII should be the target of anticoagulant strategies during cardiopulmonary bypass surgery.

Aged↗
PubMed1999

Plasma catecholamines, pharmacotherapy and mood of subjects with cardiovascular disorder.

This study investigated whether drug therapy explains why the concentration of arterial plasma catecholamines in patients who have received an orthotopic heart transplant (OHT) or coronary bypass and graft (CABG) is greater than in those with heart failure (HF). The results suggest that the differences in plasma catecholamine concentrations in these groups of patients could not be attributed to administration of any of the drugs studied here. An additional finding is that the use of aspirin is associated with a higher concentration of plasma noradrenaline, but not adrenaline. Patients who were taking aspirin also had a more positive mood, as rated by the Profile of Mood States; this was mainly because they had a lower fatigue score than did patients who were not taking this drug. In contrast, several agents (warfarin, Ca2+-channel blockers and 'mixed cardiac' drugs), which had no effects on catecholamine overspill, were linked with negative mood; this was expressed consistently as a higher tension score. These findings suggest that drugs which are administered for their effects in the periphery could also influence patients' psychological status. With the possible exception of aspirin, this does not involve changes in spillover of catecholamines in the periphery.

Adult↗
PubMed1999

Plasma hypoxanthine levels during crystalloid and blood cardioplegias: warm blood cardioplegia increases hypoxanthine levels with a greater risk of oxidative stress.

BACKGROUND: PATIENTS undergoing cardiopulmonary bypass (CPB) are subjected to severe oxidative stress, and frequently show evidence of acute lung injury post surgery. Associations between acute lung injury, oxidative stress, and aberrant ATP catabolism have been made and prompted us to consider whether the purine metabolites xanthine and hypoxanthine alter significantly during CPB when different types of cardioplegia are used. METHODS EXPERIMENTAL DESIGN: retrospective follow up study on stored plasma samples from patients randomly selected to receive either warm blood, cold blood, or crystalloid cardioplegia. SETTING: adult intensive care unit of post graduate teaching hospital. PATIENTS: thirty-eight patients undergoing aortic valve replacement, with or without artery grafting. Operation was carried out by a single surgeon. INTERVENTIONS: all patients received either a homograft aortic valve or a stentless porcine valve. RESULTS: No significant differences in xanthine levels at any time points during CPB, or between the different cardioplegic groups. Hypoxanthine levels were, however, significantly higher in patients receiving warm blood cardioplegia (74.84+/-16.715 microM, p=0.0151), and was most marked at time point 3 when the aortic cross clamp was released. PATIENTS receiving crystalloid cardioplegia showed higher levels of hypoxanthine (44.56+/-10.16 microM) than those receiving cold blood cardioplegia (21.57+/-7.106 microM). CONCLUSIONS: Considering these data together, it suggests that aberrant ATP catabolism, characteristic of ischaemia/reperfusion, is further disturbed during warm blood cardioplegia leading to a marked increase in plasma hypoxanthine levels. This has the potential to further increase oxidative stress during CPB.

Aged↗
PubMed1999

Toward a rational management of concomitant carotid and coronary artery disease.

BACKGROUND: Patients with angina undergoing carotid endarterectomy have a high perioperative mortality. Our aim was to assess the outcome of carotid endarterectomy in patients with concomitant coronary artery disease, in particular, to examine the timing of carotid endarterectomy and CABG. METHODS: A retrospective study was performed at a tertiary and secondary referral centre for cardiovascular disease. Over a five-year period 71 carotid endarterectomies and 6,590 coronary artery bypasses were performed. Significant (>70%) internal carotid stenoses were found in 35 (0.5%) patients due for CABG. Of these, 23 patients underwent Combined procedures (Carotid and CABG), 9 Reverse staged (CABG then Carotid), and 3 Prior staged carotid endarterectomies (Carotid then CABG). 36 other carotid endarterectomies were in patients evaluated cardiologically, but did not require CABG (Isolated group). Risk factors, 30 day perioperative outcome including hospital inpatient stay and early follow-up are reported. RESULTS: The Combined group 30-day perioperative mortality rate was 4.3% and permanent stroke rate 8.6%. There were no major complications in Reverse or Prior staged cases. Isolated group mortality was 2.7% with no strokes. Risk factors were more prevalent in the combined group; 56% previous myocardial infarction, 39% hypertension, 35% a history of raised cholesterol and 46% intermittent claudication. All cases were followed up for a mean of 18.4 months, with no carotid stroke related events. Overall hospital stay for staged patients was a mean 19.3 days (SE=2.4) days compared to mean 9.8 days for combined patients (SE=0.97, p<0.001). CONCLUSIONS: Patients with combined cardiac and carotid disease benefit from assessment of both systems in order to stage CABG and carotid endarterectomy. Risk factors were more prevalent in the combined group; a combined procedure offered a median difference of 8 days less hospital inpatient stay compared to the staged cases. Our experience suggests that carefully planned management of concomitant coronary and carotid disease can achieve better results.

Aged↗
PubMed1998

The use of an implantable left ventricular assist device in a patient with cardiogenic shock following acute myocardial infarction.

We report the successful long-term use of an implantable left ventricular assist device in a 42-year old patient who suffered cardiogenic shock after an acute anterior myocardial infarction unresponsive to recanalisation of the infarct-related artery and intra-aortic balloon counterpulsation. Attempts to wean our patient from the assist device were not successful and the patient underwent cardiac transplantation after 35 weeks on device assistance. The intermediate and long-term use of an implantable left ventricular assist device may be lifesaving in post-myocardial infarction cardiogenic shock and may allow sufficient time for any stunned myocardium to recover. Should there be no recovery, the device acts as a bridge to cardiac transplantation.

Adult↗
PubMed1998

Cyclo-oxygenase-2 regulates inducible ICAM-1 and VCAM-1 expression in human vascular smooth muscle cells.

Prostaglandins are well characterised inflammatory mediators, whose formation is regulated by constitutive (COX-1) or inducible (COX-2) isoforms of cyclo-oxygenase. We have previously demonstrated that IL-1 beta causes an induction of COX-2 in human vascular smooth muscle (1). This present study investigates the ability of different cytokines to induce ICAM-1 and VCAM-1 on human vascular smooth muscle, and tests whether co-induced COX-2 would regulate their expression. IL-1 beta induced ICAM-1, and COX activity, while it had no affect on VCAM-1. Conversely, IL-4 induced VCAM-1, while it had no effect on PGE2 release or ICAM-1 expression. Inhibition of IL-1 beta induced COX-2 and elevated ICAM-1 expression, an effect reversed by exogenous PGE2. Furthermore, IL-1 beta inhibited IL-4 induced VCAM-1 expression, which was also reversed by COX-2 inhibition. These results demonstrate that COX-2 limits adhesion molecule expression on human vascular smooth muscle cells and suggest that COX-2 can play a protective role in cardiovascular and inflammatory diseases.

Cells, Cultured↗
PubMed1998

Analysis of wave reflections in the arterial system using wave intensity: a novel method for predicting the timing and amplitude of reflected waves.

The timing and amplitude of reflected arterial waves in the ascending aorta were studied by analysis of the aortic pressure waveform and were compared with those derived using wave intensity analysis. Wave intensity analysis considers aortic pressure changes to be the result of forward and backward wavelets carrying energy. Wave intensity (dI = dPdU) is calculated from changes in pressure (dP) and flow velocity (dU), and its sign indicates the direction of travel of propagating wavelets (positive for forward-traveling waves and vice versa). We measured aortic pressure and flow velocity in 14 patients, mean age 60+/-9 years, with three-vessel coronary artery disease at the time of surgical revascularization. The travel time of the reflected wave derived from analysis of the aortic pressure waveform (tp) was measured from the foot of the aortic pressure waveform to the inflection point of the aortic pressure (derived objectively from the zero of second derivative of aortic pressure). From wave intensity analysis, the travel time of the reflected wave was measured to the onset of the wave intensity of the backward-traveling wave dI_ (t(i)), and to the onset of the separated backward pressure wave (t(b)). All patients showed an aortic pressure waveform characterized by an inflection point on the rising limb of the aortic pressure, followed by a secondary rise in pressure, representing the return of reflected waves. Wave intensity analysis consistently showed a negative peak in mid systole, the timing of its onset corresponding closely to the inflection point of the aortic pressure. The travel time of the reflected wave derived from the analysis of the aortic pressure waveform (t(p)) was 121+/-21ms and showed close agreement with ti (118+/-28 ms) and t(b) (115+/-29ms), with mean differences of 4 and 6ms, and 95% confidence intervals of difference (-2 to 7 ms) and (1 to 12ms), respectively. The augmentation index, a measure of the secondary increase in aortic pressure due to reflected waves, was significantly correlated with the magnitude of dI_ (r = 0.63, P < 0.001). Wave intensity is a quantity that indicates the rate of energy flux due to wave travel and since its value is positive for forward-traveling waves and negative for backward-traveling waves, its calculation allows the timing of reflected waves to be accurately predicted. Furthermore, the magnitude of wave intensity in backward-traveling waves (dI_) is related to the augmentation index and may provide a measure of the amplitude of the reflected wave. This analysis of the arterial system is done in the time domain and therefore can be easily applied to assess temporal changes in arterial characteristics.

Aorta, Thoracic↗
PubMed1998

Psychological adjustment after cardiac transplantation.

Psychosocial function improves after cardiac transplantation but the extent of improvement is not established. Neither are the factors established that account for variability in function between patients following successful transplantation. We therefore compared illness-related dysfunction in patients following orthotopic cardiac transplantation (OCT) with that in angina-free patients following coronary artery bypass graft (CABG) and stable patients in heart failure awaiting transplantation (HF). We also measured two factors that might contribute to variation in function: emotional distress and concern with physical symptoms. Psychosocial function was as good in OCT as in CABG patients and, in both, was better than in HF patients. Differences in emotional distress and in physical symptoms showed a similar pattern and contributed to, but did not completely account for, differences in function. Concern with physical symptoms contributed to variability in functional impairment in HF but not CABG patients; transplantation strengthened this relationship. The results show that successful cardiac transplantation enhances psychosocial function to a level comparable with that after CABG, and suggest targets for psychological or educational intervention to improve quality of life after transplantation in patients whose recovery is inhibited by concern about physical symptoms.

Adaptation, Psychological↗
PubMed1998

Muscle transformation in cardiomyoplasty: the effect of conditioning and mobilisation on perfusion, oxygenation and fatigue resistance in the latissimus dorsi muscle.

BACKGROUND: In the clinical application of transformed skeletal muscle to cardiac assistance there is evidence that the latissimus dorsi muscle (LDM) wrap can undergo atrophy, which would prevent it from providing a sustained functional improvement. Possible causes are ischaemia and degeneration related to the conditioning process. We studied the nutritional and structural changes occurring under different stimulation regimes with the aim of improving the conditioning protocol. METHODS: Microelectrodes were used to measure regional perfusion and oxygenation in the rabbit LDM during mobilisation and subsequent repeated contraction. Group A muscles (n = 10) were conditioned for 6 weeks at 10 Hz, Group B muscles (n = 10) for 2 weeks at 2.5 Hz. Each muscle was then mobilised and tested in a hydraulic apparatus which recorded the pressure generated in a closed circuit. RESULTS: Muscles of Group A and Group B demonstrated transformation of fibre type, with a predominance of type I (62 +/- 4%) fibres in Group A and type IIa (68 +/- 9%) fibres in Group B. There was no evidence of muscle degeneration. After 10 min of fatigue testing the pressure produced was 53 +/- 5% of initial values in Group A and 51 +/- 8% in Group B, compared to 8 +/- 1% in the control group (P < 0.001). Maximum rate of relaxation was faster in Group B than in Group A (46 +/- 3% vs. 36 +/- 3% of control muscle, P < 0.05). Mobilisation resulted in a decrease in the distal perfusion of the control muscles (P < 0.05) and PO2 decreased by 8.7 +/- 1.7 mmHg during a fatigue test, which resulted in rapid loss of contractile function to 46 +/- 1% of the initial value within 1 min. In both Groups A and B the perfusion of all regions of the muscles both before and after mobilisation was greater than that of controls. During the same fatigue test, the PO2 of the distal regions was maintained and the contractile function fell more slowly to between 70 and 80% of initial values within 1 min. CONCLUSION: We showed that ischaemia in the distal region of the control LDM could result from mobilisation and repeated contraction. Muscle transformation improved perfusion and prevented a fall in tissue PO2 during a sustained series of contractions. Muscles that were conditioned at 2.5 Hz shared the improved perfusion of the fully transformed muscle, but had faster relaxation characteristics. Short periods of in situ conditioning prior to mobilisation may help to avoid ischaemic changes in distal parts of the LDM while achieving fatigue resistance in the grafted muscle at an earlier postoperative stage.

Animals↗
PubMed1998

Production of nitric oxide during surgery involving cardiopulmonary bypass.

OBJECTIVES: Surgery involving cardiopulmonary bypass induces an inflammatory response due to the contact of blood with the extracorporeal circuit. In some patients, this inflammatory response leads to multiple organ failure and death. Inflammatory states may increase the production of nitric oxide, either by increasing the activity of constitutive enzyme systems or by inducing of inflammation-specific systems. We hypothesized that surgery involving cardiopulmonary bypass would increase the production of nitric oxide in association with the inflammatory response. DESIGN: Prospective, single center, observational study. SETTING: University-affiliated, tertiary referral cardiothoracic center. PATIENTS: Eleven adult patients undergoing routine myocardial revascularization. INTERVENTIONS: Surgery for myocardial revascularization. MEASUREMENTS AND MAIN RESULTS: Observations were made after induction of anesthesia, before bypass, after completion of the bypass, and on return to the recovery area. Parameters measured included hemodynamics, exhaled nitric oxide concentrations, plasma nitrate/nitrite concentration, plasma and bronchoalveolar lavage myeloperoxidase concentrations, and protein carbonyl conversion. All patients survived surgery. Oxygenation index fell significantly after bypass. Plasma myeloperoxidase increased significantly during the study period. Plasma carbonyl conversion also increased, although not significantly. Plasma nitrate/nitrite and airway nitric oxide concentrations did not change through the course of the study. CONCLUSION: Surgery involving cardiopulmonary bypass induced a demonstrable inflammatory response, but this response was not associated with increased nitric oxide production.

Aged↗
PubMed1998

Cytokine and lipopolysaccharide stimulation of endothelin-1 release from human internal mammary artery and saphenous vein smooth-muscle cells.

Many pathologic conditions are associated with elevations in the production of endothelin-1 (ET-1) in the blood vessel wall. Because many of these conditions are cytokine-driven we examined the effects of a mixture of cytokines and lipopolysaccharide on ET-1 production in human vascular smooth-muscle (VSMC) cells derived from the internal mammary artery (IMA) and saphenous vein (SV). Incubation of VSMCs from IMA and SV with a combination of tumor necrosis factor-alpha (10 ng/ml), interferon-gamma (1,000 U/ml), interleukin-1 beta (500 U/ml) and lipopolysaccharide (10 micrograms/ml) for up to 48 h markedly elevated the expression of mRNA for ET-1 and the release of ET-1 into the culture medium. We conclude that low levels of ET-1 mRNA and peptide production in human VSMCs are markedly increased by exposure to cytokines and LPS. This suggests that during inflammatory states the VSMC, as well as the endothelium, may be a site of significant ET-1 production in the blood vessel wall.

Cells, Cultured↗
PubMed1998

Intraoperative release of troponin T in coronary venous and arterial blood and its relation to recovery of left ventricular function and oxidative metabolism following coronary artery surgery.

OBJECTIVE: To investigate the intraoperative release of troponin T during uncomplicated coronary artery surgery and to determine its relation to ischaemic time and to recovery of left ventricular function and oxidative metabolism. DESIGN: A prospective observational study. SETTING: Cardiac surgical unit in a tertiary referral centre. METHODS: Troponin T, creatine kinase, and lactate were analysed from arterial and coronary sinus samples taken before operation, and 1, 4, 6, 10, 20, 35, and 45 minutes after cross clamp release. Net myocardial troponin T release and lactate extraction were derived from their respective arteriovenous differences. Haemodynamic measurements were made using a thermodilution pulmonary artery catheter. PATIENTS: 45 patients, mean (SD) age 62 (9) years, with two or three vessel coronary artery disease and chronic stable angina undergoing routine coronary artery surgery. RESULTS: Before operation, troponin T concentrations were not raised, but within one minute of cross clamp release they increased progressively in both coronary sinus and arterial blood for the entire 45 minutes of reperfusion studied. Coronary sinus troponin T concentrations were consistently higher than arterial concentrations at all time points (p < 0.001), indicating net troponin T release by the myocardium. Peak net troponin T release and area under the curve of net troponin T release correlated closely with ischaemic time (r = 0.58 and r = 0.61, p < 0.0001 for both). Area under the curve of arterial troponin T concentration was also significantly correlated with ischaemic time (r = 0.44, p < 0.01). Patients with cross clamp times longer than 72 minutes (upper quartile for ischaemic time) had greater troponin T release, delayed reversion to lactate extraction, and lower left ventricular stroke work index three hours after surgery, compared with patients who had short (< 50 minutes, lower quartile) and intermediate (51-71 minutes, interquartile) cross clamp times. Peak net troponin T release and area under the curve of arterial troponin T concentration were inversely correlated with left ventricular stroke work index three hours after surgery (r = -0.57, r = -0.38, p < 0.01). CONCLUSIONS: Troponin T concentrations increased in every patient after cross clamp release, and were consistently higher in coronary sinus blood than in arterial blood, indicating net myocardial release of troponin T during the period of reperfusion. Intraoperative net troponin T release has functional significance, as it is closely related to ischaemic time and reflects delayed recovery of left ventricular function and oxidative metabolism; therefore, its measurement may contribute to the perioperative assessment of myocardial injury sustained during coronary artery surgery.

Biomarkers↗