Temporal Quantitative Proteomic and Phosphoproteomic Profiling of SH-SY5Y and IMR-32 Neuroblastoma Cells during All-Trans-Retinoic Acid-Induced Neuronal Differentiation.

The human neuroblastoma cell lines SH-SY5Y and IMR-32 can be differentiated into neuron-like phenotypes through treatment with all-trans-retinoic acid (ATRA). After differentiation, these cell lines are extensively utilized as in vitro models to study various aspects of neuronal cell biology. However, temporal and quantitative profiling of the proteome and phosphoproteome of SH-SY5Y and IMR-32 cells throughout ATRA-induced differentiation has been limited. Here, we performed relative quantification of the proteomes and phosphoproteomes of SH-SY5Y and IMR-32 cells at multiple time points during ATRA-induced differentiation. Relative quantification of proteins and phosphopeptides with subsequent gene ontology analysis revealed that several biological processes, including cytoskeleton organization, cell division, chaperone function and protein folding, and one-carbon metabolism, were associated with ATRA-induced differentiation in both cell lines. Furthermore, kinase-substrate enrichment analysis predicted altered activities of several kinases during differentiation. Among these, CDK5 exhibited increased activity, while CDK2 displayed reduced activity. The data presented serve as a valuable resource for investigating temporal protein and phosphoprotein abundance changes in SH-SY5Y and IMR-32 cells during ATRA-induced differentiation.

Proteomic Analysis of Circulating Extracellular Vesicles Identifies Potential Biomarkers for Lymph Node Metastasis in Oral Tongue Squamous Cell Carcinoma.

Lymph node metastasis is the most reliable indicator of a poor prognosis for patients with oral tongue cancers. Currently, there are no biomarkers to predict whether a cancer will spread in the future if it has not already spread at the time of diagnosis. The aim of this study was to quantitatively profile the proteomes of extracellular vesicles (EVs) isolated from blood samples taken from patients with oral tongue squamous cell carcinoma with and without lymph node involvement and non-cancer controls. EVs were enriched using size exclusion chromatography (SEC) from pooled plasma samples of patients with non-nodal and nodal oral tongue squamous cell carcinoma (OTSCC) and non-cancer controls. Protein cargo was quantitatively profiled using isobaric labelling (iTRAQ) and two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. We identified 208 EV associated proteins and, after filtering, generated a short list of 136 proteins. Over 85% of the EV-associated proteins were associated with the GO cellular compartment term "extracellular exosome". Comparisons between non-cancer controls and oral tongue squamous cell carcinoma with and without lymph node involvement revealed 43 unique candidate EV-associated proteins with deregulated expression patterns. The shortlisted EV associated proteins described here may be useful discriminatory biomarkers for differentiating OTSCC with and without nodal disease or non-cancer controls.

Transcriptomic and proteomic analyses of venom glands from scorpions Liocheles australasiae, Mesobuthus martensii, and Scorpio maurus palmatus.

Scorpion venom contains a cocktail of differing peptides and proteins. Previous studies focused on the identification of species-specific components in scorpion venoms, and whether there could be peptides and/or proteins conserved in the venom gland of a scorpion ancestor has been rarely investigated. Here, using a combination of transcriptomic and proteomic approaches, putative conserved toxins from the venom glands of scorpions Liocheles australasiae, Mesobuthus martensii, and Scorpio maurus palmatus were identified and compared. Similar to other studies, more than half of the conserved toxins are predominantly proteins including proteases. On the other hand, unique venom peptides, including ion channel toxins were revealed specifically in the M. martensii. The sodium channel toxin peptides revealed in M. martensii consolidated that scorpions in the Buthidae are able to envenomate their prey wih highly neurotoxic venom. This study suggested that these conserved proteins had already formed part of the arsenal in the venom gland of the common ancestor of scorpions, and likely perform important functional roles in envenomation during scorpion evolution.

Characterizing the optical response of ultra-low-noise far-infrared 60-110 µm transition edge sensors.

Far-infrared Transition Edge Sensors (TESs) are being developed for the SAFARI grating spectrometer on the cooled-aperture space telescope SPICA. In support of this work, we have devised a cryogenic (90 mK) test facility for carrying out precision optical measurements on ultra-low-noise TESs. Although our facility is suitable for the whole of the SAFARI wavelength range, 34 µm-230 µm, we focus on a representative set of measurements at 60 µm-110 µm using a device having a noise equivalent power of 0.32 aW Hz-1/2. The system is able to perform a range of measurements: (i) dark electrical characterization, (ii) optical efficiency with respect to a partially coherent beam having a modal composition identical to that of an ideal imaging telescope, (iii) optical saturation and dynamic range, (iv) fast optical transient response to a modulated thermal source, and (v) optical transient response in the presence of high-level background loading. We describe dark measurements to determine the operating characteristics of a TES and then compare the predicted optical behavior with the measured optical behavior. By comparing electrical and optical transient responses, we were able to observe thermalization in the device. We comment on the challenge of eliminating stray light.

Proteomic Analysis of the Venom of Jellyfishes Rhopilema esculentum and Sanderia malayensis.

Venomics, the study of biological venoms, could potentially provide a new source of therapeutic compounds, yet information on the venoms from marine organisms, including cnidarians (sea anemones, corals, and jellyfish), is limited. This study identified the putative toxins of two species of jellyfish-edible jellyfish Rhopilema esculentum Kishinouye, 1891, also known as flame jellyfish, and Amuska jellyfish Sanderia malayensis Goette, 1886. Utilizing nano-flow liquid chromatography tandem mass spectrometry (nLC-MS/MS), 3000 proteins were identified from the nematocysts in each of the above two jellyfish species. Forty and fifty-one putative toxins were identified in R. esculentum and S. malayensis, respectively, which were further classified into eight toxin families according to their predicted functions. Amongst the identified putative toxins, hemostasis-impairing toxins and proteases were found to be the most dominant members (>60%). The present study demonstrates the first proteomes of nematocysts from two jellyfish species with economic and environmental importance, and expands the foundation and understanding of cnidarian toxins.

Millipede genomes reveal unique adaptations during myriapod evolution.

The Myriapoda, composed of millipedes and centipedes, is a fascinating but poorly understood branch of life, including species with a highly unusual body plan and a range of unique adaptations to their environment. Here, we sequenced and assembled 2 chromosomal-level genomes of the millipedes Helicorthomorpha holstii (assembly size = 182 Mb; shortest scaffold/contig length needed to cover 50% of the genome [N50] = 18.11 Mb mainly on 8 pseudomolecules) and Trigoniulus corallinus (assembly size = 449 Mb, N50 = 26.78 Mb mainly on 17 pseudomolecules). Unique genomic features, patterns of gene regulation, and defence systems in millipedes, not observed in other arthropods, are revealed. Both repeat content and intron size are major contributors to the observed differences in millipede genome size. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute (AGO) proteins for loading small RNAs are duplicated in both millipedes, but unlike in insects, an AGO duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs-including species-specific microRNA arm switching-providing differential gene regulation is also obtained. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules found in centipedes. We identify sets of genes associated with the ozadene that play roles in chemical defence as well as antimicrobial activity. Macro-synteny analyses revealed highly conserved genomic blocks between the 2 millipedes and deuterostomes. Collectively, our analyses of millipede genomes reveal that a series of unique adaptations have occurred in this major lineage of arthropod diversity. The 2 high-quality millipede genomes provided here shed new light on the conserved and lineage-specific features of millipedes and centipedes. These findings demonstrate the importance of the consideration of both centipede and millipede genomes-and in particular the reconstruction of the myriapod ancestral situation-for future research to improve understanding of arthropod evolution, and animal evolutionary genomics more widely.

Provision of anaesthesia for porcine cardiac transplantation at the veterinary school in Trinidad and Tobago.

A successful heterotopic cardiac transplantation was performed between sibling female Yorkshire Juvenile swine. Adequate pre-medication with azaperone and a smooth induction were ensured for both pigs, which were anaesthetized simultaneously with sodium thiopentone followed by endotracheal intubation and intermittent positive pressure ventilation. Inhalation anaesthetic agents were used for maintenance, neuromuscular blockade was achieved with cisatracurium and both fentanyl and tramadol were used to provide analgesia. Invasive monitoring was used in both the donor and recipient. Central venous pressure (CVP) was maintained at > 10 cm H2O and mean arterial pressure (MAP) > 60 mmHg. Heparin was injected during the surgical dissection of the heart in the donor to prevent coronary thrombosis and prior to aortic side clamping for end-to-side anastomosis of the donor heart in the recipient abdomen. After transplantation, the cardiovascular parameters of the recipient showed a MAP of 85-105 mmHg and a CVP of 8-10 cm H2O while echocardiography of the transplanted heart confirmed an ejection fraction (EF) of 80%. A functional anaesthetic team was assembled and trained to provide anaesthesia for porcine cardiac transplantation. The transplanted heart suffered pump failure after 69 days and was excised for performance of tissue analysis.

Provision of anaesthesia for porcine cardiac transplantation at the veterinary school in Trinidad and Tobago

A successful heterotopic cardiac transplantation was performed between sibling female Yorkshire Juvenile swine. Adequate pre-medication with azaperone and a smooth induction were ensured for both pigs, which were anaesthetized simultaneously with sodium thiopentone followed by endotracheal intubation and intermittent positive pressure ventilation. Inhalation anaesthetic agents were used for maintenance, neuromuscular blockade was achieved with cisatracurium and both fentanyl and tramadol were used to provide analgesia. Invasive monitoring was used in both the donor and recipient. Central venous pressure (CVP) was maintained at > 10 cm H2O and mean arterial pressure (MAP) > 60 mmHg. Heparin was injected during the surgical dissection of the heart in the donor to prevent coronary thrombosis and prior to aortic side clamping for end-to-side anastomosis of the donor heart in the recipient abdomen. After transplantation, the cardiovascular parameters of the recipient showed a MAP of 85-105 mmHg and a CVP of 8-10 cm H2O while echocardiography of the transplanted heart confirmed an ejection fraction (EF) of 80. A functional anaesthetic team was assembled and trained to provide anaesthesia for porcine cardiac transplantation. The transplanted heart suffered pump failure after 69 days and was excised for performance of tissue analysis

Bioaccumulation, elimination, and tissue distribution of chlorpyrifos by red hybrid Tilapia in fresh and brackish waters.

Bioaccumulation, degradation, elimination and tissue partitioning of chlorpyrifos (Dursban 25E) was studied under static conditions for 3-4 days, in fresh (FW) and brackish (BW) waters by two methods: in the renewal method, fish were transferred every 24 h to FW or BW aquaria containing 0.05 mg l(-1) of the insecticide; in the spiking method, the original concentration of 0.005 mg l(-1) was spiked every 8 h. Samples of fish and water were collected at regular intervals and residues determined gas chromatographically. In the renewal experiments with 0.05 mg l(-1), bioconcentration reached its peak within 8 h of exposure in FW (1.25 mg l(-1)) and within 1 h in BW (0.95 mg g(-1)); in spiking experiments with 0.005 mg l(-1), these peaks were attained in 48 h in FW (3.8 mg g(-1)) and 8-24 h in BW (1.67 mg g(-1)). Thereafter, the concentrations declined. The concentrations of an unidentified metabolite were generally but not always correlated with that of the parent compound. Upon exposure of contaminated fish to uncontaminated waters, 72% was eliminated within the first 12 h and 4% later in 60 h in FW, and only 23% in 1 h and another 21% in the following 60 h in BW. Concentration of the metabolite was very high during the elimination. In the renewal experiment with 0.05 mg l(-1) of chlorpyrifos, tissue distribution was much higher in FW than in BW, while the reverse was true in spiking experiments with 0.005 mg l(-1) of the chemical. Testis, heart and brain had the highest levels of residues, followed by ovaries and other tissues.

The initial Trinidad experience with Cine MRI in clinical cardiology.

We describe the initial Trinidad experience with Magnetic Resonance Imaging (MRI) and Cine MRI as a diagnostic tool in clinical cardiology. Six patients from the following categories were referred for Cine MRI evaluation: congenital heart disease, valvular heart disease, aortic diseases, cardiomyopathy and intracardiac mass. All patients underwent echocardiography. MRI and Cine MRI were performed on all patients using a Siemens Magnetom 1.0 Tesla MR system at MRI Trinidad and Tobago Ltd. Selected patients underwent Angiography and/or computed tomography (CT) scanning. Clinical data and images of the six patients evaluated are described. MRI and Cine MRI provided excellent anatomical and functional details of the heart and aorta in five patients with dissection of the aorta, aneurysm of the ascending aorta, suspected left ventricular apical thrombus, infiltrative cardiomyopathy and arrhythmogenic right ventricular dysplasia. Technical difficulty was experienced with one patient who had a congenital defect (common atrium). In this study, Cine MRI provided excellent images in all but one patient. This new noninvasive technique enhanced diagnostic capabilities and facilitated management in patients with certain cardiovascular diseases.

The initial Trinidad experience with Cine MRI in clinical cardiology

We describe the initial Trinidad experience with Magnetic Resonance Imaging (MRI) and Cine MRI as a diagnostic tool in clinical cardiology. Six patients from the following categories were referred for Cine MRI evaluation: congenital heart disease, valvular heart disease, aortic diseases, cardiomyopathy and intracardiac mass. All patients underwent echocardiography. MRI and Cine MRI were performed on all patients using a Siemens Magnetom 1.0 Tesla MR system at MRI Trinidad and Tobago Ltd. Selected patients underwent Angiography and/or computed tomography (CT) scanning. Clinical data and images of the six patients evaluated are described. MRI and Cine MRI provided excellent anatomical and functional details of the heart and aorta in five patients with dissection of the aorta, aneurysm of the ascending aorta, suspected left ventricular apical thrombus, infiltrative cardiomyopathy and arrhythmogenic right ventricular dysplasia. Technical difficulty was experienced with one patient who had a congenital defect (common atrium). In this study, Cine MRI provided excellent images in all but one patient. This new noninvasive technique enhanced diagnostic capabilities and facilitated management in patients with certain cardiovascular diseases.

Stenting of partial and total coronary occlusions in Trinidad and Tobago.

In order to evaluate the efficacy and safety of coronary stenting, we reviewed the first 32 consecutive patients (34 vessels) who underwent elective coronary stenting during the period August 1999 to August 2000 inclusive at the Digital Lab installed at the Eric Williams Medical Sciences Complex, Trinidad and Tobago. Aspirin, heparin and ticlopidine were used routinely. Abciximab was used in selected cases (38%). The mean age of patients was 55 +/- 10 years. Eighty-one per cent were male, 52% were hypertensive and 21% were diabetic. Sixty-five per cent had severe angina. Prior Coronary Artery Bypass Grafting (CABG) was performed in 3% and previous Percutaneous Transluminal Coronary Angioplasty (PTCA) in 3%. Multivessel disease was present in 43%. The mean left ventricular ejection fraction was 53 +/- 12%. The culprit lesion was located in either the native left anterior descending (LAD) coronary artery (53%), right coronary artery (RCA) (31%), circumflex artery 13% and saphenous vein graft (3%). The mean baseline diameter stenosis was 91 +/- 9% and this was reduced to 13 +/- 33% after stenting. Procedural success was 100% for 26 partially occluded vs 50% for 8 totally occluded vessels. For the total occlusions, procedural success was inversely related to the duration of the occlusion. There were no cases of death, acute vessel closure, Q-wave myocardial infarction, repeat PTCA or emergent Coronary Artery Bypass Graft (CABG) during and following the procedure. Distal embolization occurred in one patient. The mean duration of hospital stay was one day (for 30 outpatient cases). One patient had recurrence of symptoms with a negative stress test. No patient underwent repeat angiography during the first year of follow-up. Coronary stents were successfully implanted at a tertiary care facility in the Caribbean with low in-hospital morbidity and mortality. Stents markedly reduced the diameter stenosis of the coronary lesion during PTCA. The incidence of clinical restenosis was low. Coronary revascularisation can be successfully achieved by coronary stenting in the Caribbean.

Stenting of partial and total coronary occlusions in Trinidad and Tobago

In order to evaluate the efficacy and safety of coronary stenting, we reviewed the first 32 consecutive patients (34 vessels) who underwent elective coronary stenting during the period August 1999 to August 2000 inclusive at the Digital Lab installed at the Eric Williams Medical Sciences Complex, Trinidad and Tobago. Aspirin, heparin and ticlopidine were used routinely. Abciximab was used in selected cases (38). The mean age of patients was 55 +/- 10 years. Eighty-one per cent were male, 52 were hypertensive and 21 were diabetic. Sixty-five per cent had severe angina. Prior Coronary Artery Bypass Grafting (CABG) was performed in 3 and previous Percutaneous Transluminal Coronary Angioplasty (PTCA) in 3. Multivessel disease was present in 43. The mean left ventricular ejection fraction was 53 +/- 12. The culprit lesion was located in either the native left anterior descending (LAD) coronary artery (53), right coronary artery (RCA) (31), circumflex artery 13 and saphenous vein graft (3). The mean baseline diameter stenosis was 91 +/- 9 and this was reduced to 13 +/- 33 after stenting. Procedural success was 100 for 26 partially occluded vs 50 for 8 totally occluded vessels. For the total occlusions, procedural success was inversely related to the duration of the occlusion. There were no cases of death, acute vessel closure, Q-wave myocardial infarction, repeat PTCA or emergent Coronary Artery Bypass Graft (CABG) during and following the procedure. Distal embolization occurred in one patient. The mean duration of hospital stay was one day (for 30 outpatient cases). One patient had recurrence of symptoms with a negative stress test. No patient underwent repeat angiography during the first year of follow-up. Coronary stents were successfully implanted at a tertiary care facility in the Caribbean with low in-hospital morbidity and mortality. Stents markedly reduced the diameter stenosis of the coronary lesion during PTCA. The incidence of clinical restenosis was low. Coronary revascularisation can be successfully achieved by coronary stenting in the Caribbean.

Coronary artery bypass graft outcome: the Trinidad and Tobago experience

The study is retrospective review of the demographic, clinical, angiographic, and operative data of the first 205 consecutive CABG operations performed by Caribbean Heart Care at the Eric Williams Medical Sciences Complex (EWMSC), Trinidad and Tobago, between November 1993 and December 1997. The aim of the study was to determine the in-hospital and intermediate-term follow-up results. The mean age of patients was 59 +/- 10 years and 78 were male. Sixty-four per cent were of East Indian descent, whereas 16 were of African descent. Forty-eight per cent of the patients were hypertensive, 46 were diabetic, 33 had hyperlipidaemia, 20 had a recent history of cigarette smoking and 16 were obese. Sixty-five per cent had a positive family history of ischaemic heart disease. The average time interval between angiography and surgery was 2.3 months. At the time of angiography, 63.5 of patients had Canadian Cardiac Society (CCS) class 3 or 4 angina. The mean ejection fraction was 61 +/- 15. Wall motion abnormalities were seen in 67 of patients. Significant stenoses of the left anterior descending artery, right circumflex artery, circumflex and ramus coronary arteries were present in 91, 78, 54 and 5, respectively. Many patients (67) had severe diffuse disease on angiography. The mean intensive care stay was 2.2 +/- 0.8 days. In-hospital mortality was 3.9 (8/205). The most frequent post-operative complication was haemorrhage (2.6). Acute renal failure occurred in 2.1; pulmonary collapse, 1.6; stroke, 1 and cardiac arrest, 1. Both sternal wound infections and systemic sepsis occurred in 0.5. Intermediate-term follow-up data were obtained for 92 (189/205). The duration of follow-up ranged from 1 to 5 years (mean 3.7 years). During the follow-up period, 7 patients (3.4) died. Angina severity was reduced from a mean CCS score of 2.61 +/- 0.95 before CABG to 1.22 +/- 0.55 at the time of follow-up (p < 0.0001). Overall 4-year mortality compared favourably with data from international studies. Among survivors, quality of life improved as evidenced by the reduction in the mean angina score.

The feasibility of a porcine model of acute coronary occlusion and reperfusion using off-pump coronary artery bypass grafting

We developed an open-chest porcine model of acute coronary occlusion and surgical reperfusion, and attempted to prevent intra-operative ischaemic ventricular fibrillation (VF) by a Retrograde Intracoronary Glyceryl trinitrate (RIG) infusion into the occluded vessel. Five Yorkshire pigs (weight 50 +/- 1.1 kg), randomized into 3 groups, underwent median sternotomy under general anaesthesia. One pig (Group 1, control) underwent sternotomy and pericardiotomy only. Four pigs underwent acute left anterior descending (LAD) coronary occlusion. Two pigs were not reperfused (Group 2). Two pigs underwent surgical reperfusion (Group 3) via left internal mammary artery (LIMA) grafting to the LAD using the Off-Pump Coronary Artery Bypass (OPCAB) technique. Ischaemic injury was assessed using 7-lead electrocardiography (ECG) and transthoracic/epimyocardial echocardiography (ECHO). Group 1: transient intraoperative hypotension and VF occurred. Successful resuscitation and 10-week survival (until sacrifice) with normal left ventricular (LV) function was achieved. Group 2: there were ECG and ECHO evidence of acute LV ischaemic dysfunction in both pigs. The surviving pig had persistent anterior hypokinesis at 8 1/2 months. The other died intra-operatively following progressive ischaemic LV dysfunction despite resuscitative attempts. Group 3: the surviving pig had normal LV function at 8 months. Initial anterior LV akinesis normalized within 7 days. The other developed post-occlusion haemodynamic instability and died intra-operatively despite reperfusion. In this porcine model, acute LAD artery occlusion modified by the novel RIG infusion technique, followed by surgical reperfusion (OPCAB) is feasible. This model would facilitate further development of OPCAB surgical expertise and understanding of the pathophysiology of ischaemia-reperfusion injury.

Two-year mortality and its determinants following acute myocardial infarction in Trinidad and Tobago.

The purpose of this study was to determine the occurrence of coronary artery disease risk factors in patients presenting with acute myocardial infarction (AMI) to a tertiary care institution in Trinidad and to determine the factors associated with increased mortality following AMI. All patients admitted to the Eric Williams Medical Sciences Complex (EWMSC) between January 1 and December 31, 1996, with a diagnosis of AMI were identified using the hospital admissions and discharge diagnosis databases. Demographic, clinical and laboratory variables were extracted from the hospital case records of patients with confirmed AMI. Sixty-one AMI patients (38 men) were admitted during the study period. Mean age at admission was 60 +/- 11 years with an ethnic case mix of thirty-nine (62%) of East Indian descent, eight (13%) of African descent, twelve (20%) mixed ethnicity and three (5%) of Caucasian descent. Thirty patients (49%) were hypertensive. Thirty-two patients (53%) were diabetic and eighteen patients (30%) gave a history of cigarette smoking. The mean left ventricular ejection fraction was 53 +/- 14%. The mean serum cholesterol from 29 patients was 228.2 +/- 49.0 mg/dl. Increasing age, female gender, an ejection fraction less than 40%, non treatment with streptokinase and in-hospital ventricular fibrillation were associated with poor survival. Multiple regression analyses identified three independent predictors of mortality. These were gender (p = 0.04), in-hospital ventricular fibrillation (p = 0.001) and an ejection fraction less than 40% (p = 0.02). Diabetes mellitus, hypertension, hyperlipidaemia and cigarette smoking were prevalent amongst patients presenting with AMI. Ventricular function was a major determinant of two-year mortality following AMI. Aggressive risk factor modification is recommended to prevent both first and recurrent coronary events.

Two-year mortality and its determinants following acute myocardial infarction in Trinidad and Tobago

The purpose of this study was to determine the occurrence of coronary artery disease risk factors in patients presenting with acute myocardial infarction(AMI) to a tertiary care institution in Trinidad and to determine the factors associated with increased mortality following AMI. All patients admitted to the Eric Williams Medical Sciences Complex (EWMSC) between January 1 and December 31, 1996, with a diagnosis of AMI were identified using the hospital admissions and discharge diagnosis databases. Demographic, clinical and laboratory variables were extracted from the hospital case records of patients with confirmed AMI. Sixty-one AMI patients (38 men) were admitted during the study period. Mean age of admittance was 60 ñ 11 years with an ethnic case mix of thirty-nine (62 percent) of East Indian descent, eight (13 percent) of African descent, twelve (20 percent) mixed ethnicity and three of Caucasian descent. Thirty patients (49 percent) were hypertensive. Thirty-two patients (53 percent) were diabetic and eighteen patients (30 percent) gave a history of cigarette smoking. The mean left venticular ejection fraction was 53 ñ 14 percent. The mean serum cholesterol from 29 patients was 228.2 ñ 49.0 mg/dl. Increasing age, female gender, an ejection fraction less than 40 percent, non treatment with streptokinase and in-hospital ventricular fibrillation were associated with poor survival. Multiple regression analyses identified three independent predictors of mortality. These were gender (p = 0.04), in-hospital ventricular fibrillation (p = 0.001) and an ejection fraction less than 40 percent (p = 0.02). Diabetes mellitus, hypertension, hyperlipidaemia and cigarette smoking were prevalent amongst patients presenting with AMI. Ventricular function was a major determinant of two-year mortality following AMI. Aggressive risk factor modification is recommended to prevent both first and recurrent coronary events.

The feasibility of a porcine model of acute coronary occlusion and reperfusion using off-pump coronary artery bypass grafting.

We developed an open-chest porcine model of acute coronary occlusion and surgical reperfusion, and attempted to prevent intra-operative ischaemic ventricular fibrillation (VF) by a Retrograde Intracoronary Glyceryl trinitrate (RIG) infusion into the occluded vessel. Five Yorkshire pigs (weight 50 +/- 1.1 kg), randomized into 3 groups, underwent median sternotomy under general anaesthesia. One pig (Group 1, control) underwent sternotomy and pericardiotomy only. Four pigs underwent acute left anterior descending (LAD) coronary occlusion. Two pigs were not reperfused (Group 2). Two pigs underwent surgical reperfusion (Group 3) via left internal mammary artery (LIMA) grafting to the LAD using the Off-Pump Coronary Artery Bypass (OPCAB) technique. Ischaemic injury was assessed using 7-lead electrocardiography (ECG) and transthoracic/epimyocardial echocardiography (ECHO). Group 1: transient intraoperative hypotension and VF occurred. Successful resuscitation and 10-week survival (until sacrifice) with normal left ventricular (LV) function was achieved. Group 2: there were ECG and ECHO evidence of acute LV ischaemic dysfunction in both pigs. The surviving pig had persistent anterior hypokinesis at 8 1/2 months. The other died intra-operatively following progressive ischaemic LV dysfunction despite resuscitative attempts. Group 3: the surviving pig had normal LV function at 8 months. Initial anterior LV akinesis normalized within 7 days. The other developed post-occlusion haemodynamic instability and died intra-operatively despite reperfusion. In this porcine model, acute LAD artery occlusion modified by the novel RIG infusion technique, followed by surgical reperfusion (OPCAB) is feasible. This model would facilitate further development of OPCAB surgical expertise and understanding of the pathophysiology of ischaemia-reperfusion injury.

Coronary artery bypass graft outcome: the Trinidad and Tobago experience.

The study is retrospective review of the demographic, clinical, angiographic, and operative data of the first 205 consecutive CABG operations performed by Caribbean Heart Care at the Eric Williams Medical Sciences Complex (EWMSC), Trinidad and Tobago, between November 1993 and December 1997. The aim of the study was to determine the in-hospital and intermediate-term follow-up results. The mean age of patients was 59 +/- 10 years and 78% were male. Sixty-four per cent were of East Indian descent, whereas 16% were of African descent. Forty-eight per cent of the patients were hypertensive, 46% were diabetic, 33% had hyperlipidaemia, 20% had a recent history of cigarette smoking and 16% were obese. Sixty-five per cent had a positive family history of ischaemic heart disease. The average time interval between angiography and surgery was 2.3 months. At the time of angiography, 63.5% of patients had Canadian Cardiac Society (CCS) class 3 or 4 angina. The mean ejection fraction was 61 +/- 15%. Wall motion abnormalities were seen in 67% of patients. Significant stenoses of the left anterior descending artery, right circumflex artery, circumflex and ramus coronary arteries were present in 91%, 78%, 54% and 5%, respectively. Many patients (67%) had severe diffuse disease on angiography. The mean intensive care stay was 2.2 +/- 0.8 days. In-hospital mortality was 3.9% (8/205). The most frequent post-operative complication was haemorrhage (2.6%). Acute renal failure occurred in 2.1%; pulmonary collapse, 1.6%; stroke, 1% and cardiac arrest, 1%. Both sternal wound infections and systemic sepsis occurred in 0.5%. Intermediate-term follow-up data were obtained for 92% (189/205). The duration of follow-up ranged from 1 to 5 years (mean 3.7 years). During the follow-up period, 7 patients (3.4%) died. Angina severity was reduced from a mean CCS score of 2.61 +/- 0.95 before CABG to 1.22 +/- 0.55 at the time of follow-up (p < 0.0001). Overall 4-year mortality compared favourably with data from international studies. Among survivors, quality of life improved as evidenced by the reduction in the mean angina score.

Inhibition of platelet deposition with local delivery of heparin using a double balloon catheter.

Heparin is an effective agent in the treatment of unstable angina and myocardial infarction. The clinical utility of heparin is limited by bleeding complications. This study was performed to determine whether static delivery of heparin could effectively inhibit further platelet deposition. Thrombogenic graft segments were incorporated into chronic arteriovenous shunts in pigs. Autologous platelets were labeled with 111Indium. Platelet deposition was quantitated with gamma camera imaging. The grafts were exposed to blood flow for 15 min in order to induce platelet deposition on the thrombogenic surface. Heparin was delivered locally either by direct exposure or with a double balloon catheter. After a 15 minute exposure period, the heparin solution was removed and subsequent platelet deposition was monitored for 90 minutes. Heparin, administered with the double balloon catheter in doses as low as 12.5 U, effectively inhibited further platelet deposition. An intravenous injection of 100 U of heparin, the highest dose use for local delivery, did not perturb bleeding time or the activated partial thromboplastin time. In conclusion, platelet deposition can be inhibited with static local delivery of heparin at doses that are not associated with systemic bleeding.