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Biomedical subjects

A J Bryan

Publications and source records attributed to A J Bryan.

At least 37 records · Page 2Linked to original sources
PubMed1998

The end of the cold era: from intermittent cold to intermittent warm blood cardioplegia.

BACKGROUND: A major reduction in the energy demand of the myocardium results from the electromechanical arrest, and cooling contributes to a lesser degree to this reduction. It is from this assumption that strategies of myocardial protection, utilizing warm blood cardioplegic induction, followed by cold cardioplegia with terminal warm reperfusion before removal of the aortic cross clamp, became established as optimal myocardial protection. Continuous normothermic perfusion 'closed the loop' by avoiding myocardial ischemia and linking warm induction and terminal reperfusion. A series of laboratory and clinical data confirmed the benefits of warm heart surgery on myocardial function and metabolism. The disadvantages of continuous warm blood cardioplegia including disturbance of the operative field, led surgeons to administer warm hyperkalaemic blood intermittently as a new cardioplegic strategy. METHODS: This review examines the laboratory and clinical data with reference to the intermittent warm blood cardioplegia, to establish its experimental basis and place in clinical practice. CONCLUSIONS: Experimental observation and clinical application have established intermittent warm blood cardioplegia as a practical, effective and cheap myocardial protection technique, particularly with reference to coronary artery surgery.

Animals↗
PubMed1998

Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery.

OBJECTIVE: The influence of the addition of magnesium on myocardial protection with intermittent antegrade warm blood hyperkalaemic cardioplegia in patients undergoing coronary artery surgery was investigated and compared with intermittent antegrade warm blood hyperkalaemic cardioplegia only. METHODS: Twenty-three patients undergoing primary elective coronary revascularization were randomized to one of two different techniques of myocardial protection. In the first group, myocardial protection was induced using intermittent antegrade warm blood hyperkalaemic cardioplegia. In the second group, the same technique was used except that magnesium was added to the cardioplegia. Intracellular substrates (ATP, lactate and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. RESULTS: There were no significant changes in the intracellular concentration of ATP or free amino acid pool in biopsies taken at the end of the period of myocardial ischaemia. However, the addition of magnesium prevented the significant increase in the intracellular concentration of lactate seen with intermittent antegrade warm blood hyperkalaemic cardioplegia. Upon reperfusion there was a significant fall in ATP and amino acid concentration when the technique of intermittent antegrade warm blood hyperkalaemic cardioplegia was used but not when magnesium was added to the cardioplegia. CONCLUSIONS: This work shows that intermittent antegrade warm blood hyperkalaemic cardioplegia supplemented with magnesium prevents substrate derangement early after reperfusion.

Adenosine Triphosphate↗
PubMed1998

External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.

Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis. These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors, and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF). Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation. We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation. However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.

Animals↗
PubMed1998

Endothelin-1 and endothelin receptors in porcine saphenous vein-carotid artery grafts.

The regional distribution of endothelin-1 (ET-1) and its receptor subtypes (ETA and ETB) in porcine saphenous vein into carotid artery interposition grafts was studied 1 month after surgery and compared to ungrafted saphenous vein and carotid artery. ET-1 immunoreactivity was identified by immunohistochemistry and ET receptor subtypes were studied using in vitro autoradiography. In vein grafts, there was a higher density of ETA compared to ETB receptor binding in both the tunica media and the neointima. ETA binding to the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Dense ETA and ETB binding was also associated with adventitial microvessels in the graft, and ETB binding was also identified to neutrophils, which accumulated at the subendothelium and within the adventitia. ETA receptors may play a role in vein graft thickening at the medial and neointimal vascular smooth-muscle cell level, whereas ETB receptors may play a role in microangiogenesis. The high levels of ETA receptors in the tunica media of ungrafted saphenous vein, relative to the carotid artery and vein graft, may also render this conduit susceptible to neointimal formation. These data indicate that studies of the effect of ET receptor antagonists on the pathobiology of vein graft disease are warranted.

Animals↗
PubMed1997

Left ventricular volume reduction surgery.

Left ventricular volume reduction has recently been introduced as a surgical treatment for end stage dilated cardiomyopathy. This operation involves the resection of a slice of viable left ventricular myocardium in order to reduce the wall tension imposed upon the contracting heart chamber. Early results are encouraging, but clinical evaluation on a larger scale is required. In the present article, we describe the indications, surgical principles and results of left ventricular volume reduction surgery with reference to our group's experience.

Animals↗
PubMed1997

Towards the prevention of vein graft failure.

Improved outcome after coronary bypass surgery over the last decade has been attributed largely to the increasing use of arterial conduits and their superior patency rates over that of saphenous vein grafts. In spite of this trend, autologous saphenous vein has remained an important and convenient conduit for a variety of operative scenarios, and is still used for more than 70% of grafts. As a result, vein graft failure continues to represent a significant clinical and economic burden upon the health care service. Between 15 to 30% of saphenous vein grafts occlude within the first year of surgery, increasing to over 50% after 10 years. By this time, more than 10% of patients will require further intervention to alleviate symptoms arising from occluded grafts and progression of native disease. Graft occlusion arises either from early thrombosis or the later onset of 'vein graft disease' and subsequent atherosclerotic changes.

Animals↗
PubMed1997

Staged minimally invasive direct coronary artery bypass and percutaneous angioplasty for multivessel coronary artery disease.

OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) using the left internal mammary artery (IMA) to the left anterior descending (LAD) coronary artery can be performed with low operative risk. MIDCAB can be combined with percutaneous transluminal coronary angioplasty (PTCA) to treat patients with multivessel disease. We report here our experience with staged MIDCAB and PTCA in the management of a selected group of patients. METHODS AND RESULTS: 11 patients (9 males, mean age 64.6+/-8.7 years) with multivessel coronary artery disease received left IMA grafts to the LAD using the MIDCAB approach. There were no postoperative morbidity or mortality. All patients were extubated within 4 h of leaving the operating room with a mean ITU stay of 12.8 h. All patients but two underwent coronary angioplasty during the same hospital admission, 3.8+/-1.3 days after the MIDCAB procedure. Angiography confirmed IMA grafts patency in all patients, and complete revascularisation by PTCA of other coronary arteries was possible in all patients but one. Mean hospital stay was 5.9 days, and all patients remain free of angina at a mean follow-up period of 11.4 months. CONCLUSIONS: Staged MIDCAB and angioplasty is an experimental approach for the management of selected patients with multi-vessel coronary artery disease. Further experience is needed to clarify patient selection and the long-term outcome of this approach.

Aged↗
PubMed1997

Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery.

Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution (n = 19), decreased the intracellular concentrations (micromol/g wet weight) of taurine (from 9.8 +/- 0.8 to 7.7 +/- 0.7, P < 0.05) and glutamine (8.7 +/- 0.5 to 7.2 +/- 0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5 +/- 0.5 and 7.4 +/- 0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution (n = 16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4 +/- 0.5 to 6.5 +/- 0.7) and glutamine (8.0 +/- 0.7 to 5.8 +/- 0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.

Adenosine Triphosphate↗
PubMed1997

Nitric oxide synthase and adenylyl and guanylyl cyclase activity in porcine interposition vein grafts.

BACKGROUND: A high proportion of autologous saphenous vein grafts occlude as the result of intimal thickening. Blood vessels synthesize substances that may inhibit such intimal thickening. These include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are stimulated by prostacyclin and nitric oxide, respectively. The prostacyclin-cAMP and nitric oxide-cGMP axes were therefore investigated in porcine vein grafts. METHODS: Saphenous vein-carotid artery interposition graft procedures were carried out in pigs. One month after the operation, ungrafted saphenous veins, vein grafts, and carotid arteries were excised, the formation of cAMP and cGMP was assessed by radioimmunoassay, and the nitric oxide synthase content was determined by autoradiography. RESULTS: The formation of cAMP and nitroprusside-stimulated cGMP was significantly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. Calimycin-stimulated cGMP synthesis (nitric oxide release dependent) and the endothelial nitric oxide synthase content (autoradiography) were significantly elevated in vein grafts compared with ungrafted saphenous veins but were significantly less than those in carotid arteries. CONCLUSIONS: Adenylyl and guanylyl cyclase activity are down-regulated in vein grafts, which may contribute to the development of intimal and medial thickening. Nitric oxide release and endothelial nitric oxide synthase content are up-regulated in vein grafts, which is indicative of an adaptation to the arterial conditions of shear stress and pulsatile pressure.

Adaptation, Physiological↗
PubMed1997

Biochemical markers of myocardial injury during cardiac operations.

The evaluation of myocardial damage in relation to cardiac operation from a clinical and a research perspective is of great importance, particularly for the evaluation of different cardioprotective strategies. Although measurements of serum biochemical markers have often been used, their value has been limited by their lack of sensitivity and specificity in the presence of skeletal muscle damage. A newer range of markers are now available that may reliably indicate both perioperative myocardial infarction, as well as more subtle degrees of subclinical myocyte injury. In this review, the application of biochemical markers for clinical and research purposes during cardiac operation is considered.

Biomarkers↗
PubMed1997

Dynamic evaluation of the 21-mm Medtronic Intact aortic bioprosthesis by dobutamine echocardiography.

BACKGROUND: High residual transvalvular gradients have been reported with the use of small Medtronic Intact aortic valve prostheses. The aim of this study was to evaluate the hemodynamic performance of 21-mm prostheses using dobutamine Doppler echocardiography. METHODS: Ten patients (7 women; mean age, 79 years) who had undergone aortic valve replacement with 21-mm Medtronic Intact prostheses 19.1 +/- 9.9 (standard deviation) months previously were studied. Dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 10 and 20 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed and continuous-wave Doppler studies were performed at rest and at the end of each stage. Effective orifice area, performance index, and discharge coefficient of each valve were calculated, and peak and mean velocity and pressure drop across the prostheses were measured. Cardiac output was determined by Doppler measurement of flow in the left ventricular outflow tract. RESULTS: Dobutamine stress increased heart rate and cardiac output by 68% and 65%, respectively (both p < 0.005), and mean transvalvular gradient increased from 19.1 +/- 5.1 mm Hg at rest to 33.2 +/- 7.7 mm Hg at maximum stress (p < 0.0001). Regression analyses demonstrated that maximum-stress gradient was independent of all variables except resting gradients (p < 0.004). Body surface area had no effect on the changes in cardiac output, effective orifice area, or transprosthetic gradient at maximum stress. CONCLUSIONS: These data show that the 21-mm Medtronic Intact aortic prosthesis exhibits acceptable hemodynamic performance. Transvalvular gradients remained within a clinically acceptable range, both at rest and at maximum stress. Moreover, overall hemodynamic performance suggests that patient-prosthesis mismatch is unlikely to be a problem of clinical importance when this prosthesis is used.

Aged↗
PubMed1997

Influence of normothermic systemic perfusion during coronary artery bypass operations: a randomized prospective study.

OBJECTIVES: Normothermic cardiopulmonary bypass has been proposed as a more physiologic technique than hypothermic bypass for the maintenance of the body during cardiac surgery. The aims of this study were to investigate the effects of systemic perfusion temperature on clinical outcome after coronary revascularization. METHODS: Three hundred patients (mean age 60 +/- 9 years, 88% male) were prospectively randomized into three groups: hypothermia (28 degrees C, n = 100), moderate hypothermia (32 degrees C, n = 100), and normothermia (37 degrees C, n = 100). All patients received cold antegrade St. Thomas' Hospital crystalloid cardioplegic solution, and patients in the normothermic group were actively rewarmed during cardiopulmonary bypass (nasopharyngeal temperature 37 degrees C). RESULTS: No differences were found between groups with respect to mortality (1%), intraaortic balloon pump use, perioperative infarction rates, focal neurologic deficits (1%), intubation time, intensive care unit stay, and postoperative hospital stay. Further stepwise regression analysis identified age and intensive care unit stay as important predictors of the variability in postoperative stay (both R2 = 0.114; p < 0.001), whereas perfusion temperature remained a nonsignificant explanator. Normothermic perfusion necessitated larger doses of phenylephrine to maintain arterial pressure above 50 mm Hg during cardiopulmonary bypass (p < 0.0001 vs 28 degrees C, p < 0.01 vs 32 degrees C) but less requirement for electrical defibrillation during reperfusion (p < 0.05 vs 32 degrees C, p < 0.01 vs 28 degrees C). Total chest drainage was not different between groups, but patients undergoing normothermic cardiopulmonary bypass required less transfusion of blood (p < 0.05 vs 28 degrees C and 32 degrees C) and platelets (p < 0.04 vs 32 degrees C, p < 0.001 vs 28 degrees C) in the postoperative period. CONCLUSIONS: Cardiopulmonary bypass temperature did not influence early clinical outcome after routine coronary artery bypass operations. Normothermic systemic perfusion was associated with an increased requirement for vasoconstrictors and reduced requirements for electrical defibrillation and transfusion of blood products.

Bicarbonates↗
PubMed1997

Cardiac troponin T and troponin I release during coronary artery surgery using cold crystalloid and cold blood cardioplegia.

OBJECTIVE: To evaluate and compare myocardial protection using cold crystalloid and blood cardioplegia by measuring release of cardiac Troponin T and Troponin I during coronary artery surgery. METHODS: Forty two patients undergoing myocardial revascularization were prospectively randomised into two groups in whom myocardial protection was achieved with either antegrade cold (4 degrees C) crystalloid (CCP) (n = 21) St. Thomas' I cardioplegic solution. Serial venous blood samples were collected for measurement of cardiac Troponin T and Troponin I, prior to induction of anesthesia and at 4, 12, 24 and 48 h after removal of the aortic cross clamp. RESULTS: There were no hospital deaths in the two groups and one patient in each group suffered a perioperative myocardial infarction. Rising levels of Troponin T and Troponin I were found in all patients. Serum concentrations increased as early as 4 h after removal of the aortic cross clamp, and reached a peak at 12 h postoperatively in both groups. These levels subsequently declined, but remained higher than preoperative values at 48 h. There were no differences between the two groups with respect to serum Troponin T and I release at 4, 12, 24 and 48 h, area under the respective curves, and peak Troponin T and I release. Serum Troponin levels were significantly higher in patients with unstable angina and in two patients who suffered a perioperative myocardial infarction. CONCLUSION: Serum release of cardiac Troponin T and Troponin I is significantly raised in low risk patients undergoing myocardial revascularization. This release is similar when either cold crystalloid or cold blood cardioplegia are used. This may imply that both methods offer identical protection to the myocardium in a low risk group of patients.

Aged↗
PubMed1997

The influence of surgical preparation on cyclic nucleotide synthesis in an organ culture of human saphenous vein.

OBJECTIVES: To investigate adenosine cyclic 3'5' monophosphate (cAMP) and guanosine cyclic 3'5' monophosphate (cGMP) synthesis in freshly isolated and surgically prepared human saphenous vein before and after culture. SETTING: Bristol Heart Institute, Bristol, U.K. METHODS: Freshly isolated and surgically prepared human saphenous vein was obtained from patients undergoing coronary artery bypass graft surgery. cAMP and cGMP synthesis, was assessed by radioimmunoassay in response to specific simulators in segments of saphenous veins after collection and following 14 days culture. RESULTS: Immediately after collection there was a significant reduction in the synthesis of cAMP (forskolin and prostaglandin E1-stimulated) and cGMP (sodium nitroprusside-stimulated) in surgically prepared compared to freshly isolated saphenous veins. In contrast, following 14 days in culture, cAMP and cGMP synthesis was significantly elevated in surgically prepared compared to freshly isolated saphenous veins. CONCLUSIONS: These data indicate that surgical preparation results in a marked reduction in cyclic nucleotide synthesis in saphenous vein which may be relevant to the pathophysiology of early vein graft failure. The normalisation of both cAMP and cGMP synthesis in surgically prepared veins following 14 days culture indicates that cyclic nucleotide synthesising capacity may not be a major determinant of neointima formation in this experimental model.

Acetylcholine↗