Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Machine learning to predict myocardial injury and death after non-cardiac surgery.

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.

Predictors of UK healthcare worker burnout during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is putting health professionals under increasing pressure. This population is already acknowledged to be at risk of burnout. AIM: We aim to provide a 'snapshot' of the levels of burnout, anxiety, depression and distress among healthcare workers during the COVID-19 pandemic. METHODS: We distributed an online survey via social media in June 2020 open to any UK healthcare worker. The primary outcome measure was symptoms of burnout measured using the Copenhagen Burnout Inventory. Secondary outcomes of depression, anxiety, distress and subjective measures of stress were also recorded. Multivariate logistic regression analysis was performed to identify factors associated with burnout, depression, anxiety and distress. RESULTS: A total of 539 persons responded to the survey; 90% female and 53% nurses. Participants with moderate-to-severe burnout were younger (49% vs. 33% under 40 years, P = 0.004), more likely to have pre-existing comorbidities (21% vs. 12%, P = 0.031), twice as likely to have been redeployed from their usual role (22% vs. 11%; P = 0.042), or to work in an area dedicated to COVID-19 patients (50% vs. 32%, P < 0.001) and were almost 4 times more likely to have previous depression (24% vs. 7%; P = 0.012). CONCLUSION: Independent predictors of burnout were being younger, redeployment, exposure to patients with COVID-19, being female and a history of depression. Evaluation of existing psychological support interventions is required with targeted approaches to ensure support is available to those most at risk.

Dynamic Changes in High-Sensitivity Cardiac Troponin I in Response to Anthracycline-Based Chemotherapy.

AIMS: Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. MATERIALS AND METHODS: This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. RESULTS: We recruited 78 women with a median (interquartile range) age of 52 (49-61) years. The median baseline troponin concentration was 1 (1-4) ng/l and the median cumulative epirubicin dose was 394 (300-405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P < 0.001), hs-cTnI concentrations increased by a median of 50% (P < 0.001) with each successive treatment cycle. In total, 45 patients had troponin measured immediately before the sixth treatment cycle, 21 (46.6%) of whom had hs-cTnI concentrations ≥16 ng/l, indicating myocardial injury. Plasma hs-cTnI concentrations before the second treatment cycle were a strong predictor of subsequent myocardial injury. CONCLUSIONS: Cardiotoxicity arising from anthracycline therapy is detectable in the earliest stages of breast cancer treatment and is cumulative with each treatment cycle. This injury is most reliably determined from blood sampling carried out before rather than after each treatment cycle.

Radial artery vasomotor function following transradial cardiac catheterisation.

AIMS: To determine the reproducibility of flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) in the assessment of radial artery vasomotor function, and to examine the effect of transradial catheterisation on radial artery injury and recovery. METHODS: Radial artery FMD and NMD were examined in 20 volunteers and 20 patients on four occasions (two visits at least 24 hours apart, with two assessments at each visit). In a further 10 patients, radial artery FMD was assessed in the catheterised arm prior to, at 24 hours and 3 months following cardiac catheterisation. RESULTS: There were no differences in baseline radial artery diameter (2.7±0.4 mm vs 2.7±0.4 mm), FMD (13.4±6.4 vs 12.89±5.5%) or NMD (13.6±3.8% vs 10.1±4.3%) between healthy volunteers and patients (p>0.05 for all comparisons). Mean differences for within and between day FMD were 2.53% (95% CIs -15.5% to 20.5%) and -4.3% (-18.3% to 9.7%) in patients. Compared to baseline, radial artery FMD was impaired at 24 hours (8.7±4.1% vs 3.9±2.9%, p=0.015) but not 3 months (8.7±4.1% vs 6.2±4.4, p=0.34) following transradial catheterisation. CONCLUSIONS: Radial FMD is impaired early after transradial catheterisation but appears to recover by 3 months. While test-retest variability was demonstrated, our findings suggest that transradial access for cardiac catheterisation may afford a potential model of vascular injury and repair in vivo in man.

Perioperative myocardial injury in patients receiving cardiac output-guided haemodynamic therapy: a substudy of the OPTIMISE Trial.

BACKGROUND: Evidence suggests that cardiac output-guided haemodynamic therapy algorithms improve outcomes after high-risk surgery, but there is some concern that this could promote acute myocardial injury. We evaluated the incidence of myocardial injury in a perioperative goal-directed therapy trial. METHODS: Patients undergoing major gastrointestinal surgery (n=723) were randomly assigned to cardiac output-guided haemodynamic therapy (intervention group) or usual care as part of the OPTIMISE trial. At four participating sites, 288 patients were enrolled in a biomarker substudy. Serum high-sensitivity cardiac troponin I (TnI) concentration and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration were measured before and at 24 and 72 h after surgery. RESULTS: Median preoperative TnI and NT-ProBNP concentrations were 4.3 ng litre(-1) and 144 pg ml(-1), respectively. After surgery, 67 (46%) patients in the intervention group and 68 (48%) patients receiving usual care had TnI concentrations above the 99th centile upper reference limit (P=0.82). Peak serum TnI concentration was similar in the intervention and usual care groups (median [interquartile range]: 10.0 [5.3-21.5] vs 7.8 [5.0-21.8] ng litre(-1); P=0.85), and no differences were observed in serum TnI concentrations over 72 h (repeated-measures anova, P=0.51). Likewise, there were no differences in peak NT-proBNP concentration between intervention and usual care groups (645 [362-1169] vs 659 [381-1028] pg ml(-1); P=0.86) or in serial NT-proBNP concentrations over 72 h (P=0.20). CONCLUSIONS: Myocardial injury is common among patients undergoing major gastrointestinal surgery. In this study, the frequency was not affected by cardiac output-guided fluid and low-dose inotropic therapy.

Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms.

Air pollution is now recognized as an important independent risk factor for cardiovascular morbidity and mortality and may be responsible for up to 3 million premature deaths each year worldwide. The mechanisms underlying the observed effects are poorly understood but are likely to be multifactorial. Here, we review the acute and chronic effects of air pollution exposure on the cardiovascular system and discuss how these effects may explain the observed increases in cardiovascular morbidity and mortality.

The influence of the menstrual cycle, normal pregnancy and pre-eclampsia on platelet activation.

Platelet activation has a key role in mediating thrombotic and inflammatory events. This study aimed to determine the influence of the menstrual cycle, pregnancy and pre-eclampsia on in vivo platelet activation. Twelve healthy nulliparous, non-smoking women with regular menses were studied over a single menstrual cycle. Twenty-one healthy primigravida pregnant women were studied longitudinally at 16, 24, 32 and 37 weeks gestation and seven weeks post-partum. Sixteen primigravida women with pre-eclampsia were studied at time of diagnosis and at seven weeks post-partum. Platelet-monocyte aggregates and platelet-surface P-selectin expression were assessed by flow-cytometry. Soluble P-selectin and CD40 ligand (CD40L) were measured by ELISA. Markers of platelet activation did not vary over the menstrual cycle. Platelet-monocyte aggregates were greater in the third trimester of pregnancy compared to non-pregnant women (p=0.003). Platelet surface and plasma soluble P-selectin concentrations increased with gestation (p<0.0001) and were raised by 24 weeks of pregnancy compared to non-pregnant women (p< or =0.02 for both) and together with platelet monocyte aggregates, decreased post-partum (p< or =0.02). Soluble CD40L concentrations fell in pregnancy, reaching a nadir at mid-gestation (p=0.002). There were no differences in markers of platelet activation between normal and pre-eclamptic pregnancies. In conclusion, platelet activation is increased in pregnancy and increases with gestation but is unaffected by pre-eclampsia. This suggests that systemic platelet activation is a feature of pregnancy but this is not affected by established pre-eclampsia.

Dissociation of phenotypic and functional endothelial progenitor cells in patients undergoing percutaneous coronary intervention.

OBJECTIVES: Endothelial progenitor cells (EPCs) are circulating mononuclear cells with the capacity to mature into endothelial cells and contribute to vascular repair. We assessed the effect of local vascular injury during percutaneous coronary intervention (PCI) on circulating EPCs in patients with coronary artery disease. DESIGN AND SETTING: Prospective case-control study in a university teaching hospital. PATIENTS: 54 patients undergoing elective coronary angiography. INTERVENTIONS AND MAIN OUTCOME MEASURES: EPCs were quantified by flow cytometry (CD34(+)KDR(+) phenotype) complemented by real-time polymerase chain reaction (PCR), and the colony forming unit (CFU-EC) functional assay, before and during the first 24 hours after diagnostic angiography (n = 27) or PCI (n = 27). RESULTS: Coronary intervention, but not diagnostic angiography, resulted in an increase in blood neutrophil count (p<0.001) and C-reactive protein concentrations (p = 0.001) in the absence of significant myocardial necrosis. Twenty-four hours after PCI, CFU-ECs increased threefold (median [IQR], 4.4 [1.3-13.8] vs 16.0 [2.1-35.0], p = 0.01), although circulating CD34(+)KDR(+) cells (0.019% (SEM 0.004%) vs 0.016% (0.003%) of leucocytes, p = 0.62) and leucocyte CD34 mRNA (relative quantity 2.3 (0.5) vs 2.1 (0.4), p = 0.21) did not. There was no correlation between CFU-ECs and CD34(+)KDR(+) cells. CONCLUSIONS: Local vascular injury following PCI results in a systemic inflammatory response and increases functional CFU-ECs. This increase was not associated with an early mobilisation of CD34(+)KDR(+) cells, suggesting these cells are not the primary source of EPCs involved in the immediate response to vascular injury.

Acute endothelial tissue plasminogen activator release in pregnancy.

OBJECTIVE: Pregnancy is associated with marked changes in vascular physiology and an increased risk of thrombosis. The aim of the study was to assess the effect of pregnancy on the acute release of tissue plasminogen activator (t-PA) from the endothelium. METHODS AND RESULTS: Ten primigravida pregnant women were recruited in the third trimester of pregnancy (week 36 +/- 1) and compared with 20 age-matched non-pregnant women (day 9.8 +/- 0.3 of menstrual cycle). Blood flow and plasma fibrinolytic factors were measured in both forearms by venous occlusion plethysmography and blood sampling, respectively, during unilateral brachial artery infusions of bradykinin (100-1000 pmol min(-1)). Pregnant women had higher plasma plasminogen activator inhibitor type 1 (PAI-1) antigen concentrations (77.1 +/- 12.4 vs. 21.5 +/- 9.8 ng mL(-1); P = 0.004) that resulted in lower basal t-PA/PAI-1 ratios (0.2 +/- 0.1 vs. 0.6 +/- 0.1; P = 0.02) and plasma t-PA activity concentrations (0.17 +/- 0.02 vs. 0.58 +/- 0.06 IU mL(-1); P < 0.0004). In both groups, bradykinin caused dose-dependent increases in blood flow and local release of plasma t-PA antigen and activity (P < 0.005 for all). Both the plasma t-PA/PAI-1 ratios and the net release of active t-PA were markedly reduced in pregnant women (P < 0.05 for both). Area under the curve for net active t-PA release was reduced by 36%. CONCLUSIONS: Pregnancy is associated with major perturbations of endogenous fibrinolytic capacity with an overwhelming increase in plasma PAI-1 concentrations and an inadequate release of active t-PA. These prothrombotic effects may, in part, explain the increased risk of arterial and venous thrombosis in pregnant women.

Influence of menstrual cycle on circulating endothelial progenitor cells.

BACKGROUND: Endothelial progenitor cells (EPCs) are circulating mononuclear cells that participate in angiogenesis. The aim of this study was to determine the influence of the menstrual cycle on the number and function of EPCs, and to investigate their relationship with circulating concentrations of sex steroids and inflammatory mediators. METHODS: Ten healthy nulliparous, premenopausal, non-smoking women with regular menses were studied over a single menstrual cycle. Venepuncture was performed in the menstrual, follicular, peri-ovulatory and luteal phases. EPCs were quantified by flow cytometry (CD133(+)CD34(+)KDR(+) phenotype) and the colony-forming unit (CFU-EPC) functional assay. Circulating concentrations of estradiol, progesterone and inflammatory mediators (TNF-alpha, IL-6, sICAM-1 and VEGF) were measured by immunoassays. RESULTS: The numbers of CD133(+)CD34(+)KDR(+) cells were higher in the follicular phase (0.99 +/- 0.3 x 10(6) cells/l) compared with the peri-ovulatory phase (0.29 +/- 0.1 x 10(6) cells/l; P < 0.05). In contrast, the numbers of CFU-EPCs did not vary over the menstrual cycle. There were no correlations between EPCs and concentrations of either circulating sex steroids or inflammatory mediators. CONCLUSIONS: CD133(+)CD34(+)KDR(+) cells but not CFU-EPCs vary during the menstrual cycle. Our findings suggest a potential role for circulating EPCs in the normal cycle of physiological angiogenesis and repair of the uterine endometrium that is independent of circulating sex steroids or inflammatory mediators.

Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.

BACKGROUND: The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. METHODS: We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. RESULTS: Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). CONCLUSIONS: Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.

Increased arterial stiffness in patients with chronic obstructive pulmonary disease: a mechanism for increased cardiovascular risk.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with a 2-3-fold increase in the risk of ischaemic heart disease, stroke and sudden death. The mechanisms responsible for this association are not clear and appear to be independent of smoking history. OBJECTIVE: We test the hypothesis that patients with COPD have increased arterial stiffness and blood pressure in comparison with age and smoking matched controls. METHODS: In a prospective case control study, we recruited 102 patients with COPD and 103 healthy controls matched for age and smoking status. Patients were assessed by clinical history and spirometry, with arterial stiffness and blood pressure determined using radial artery applanation tonometry and sphygmomanometry. RESULTS: Patients with COPD had increased arterial stiffness compared with matched controls, with elevated augmentation pressure (17 (1) vs 14 (1) mm Hg; p = 0.005) and a reduced time to wave reflection (131 (1) vs 137 (2) ms; p = 0.004). These differences were associated with increases in both diastolic (82 (1) vs 78 (1) mm Hg; p = 0.005) and systolic blood pressure (147 (2) vs 132 (2) mm Hg; p<0.001). Serum C reactive protein concentrations were threefold higher in patients (6.1 (0.9) vs 2.3 (0.4) mg/l; p = 0.001). Data are presented as mean (SEM). CONCLUSIONS: Patients with COPD have increased arterial stiffness and blood pressure in comparison with controls matched for age and smoking status. We speculate that increased systemic inflammation and vascular dysfunction could potentially explain the excess cardiovascular morbidity and mortality associated with COPD.

Constriction to ETB receptor agonists, BQ-3020 and sarafotoxin s6c, in human resistance and capacitance vessels in vivo.

AIMS: The aim of the study was to examine the effects of the ETB receptor selective agonists sarafotoxin S6c (SFTX6c) and BQ-3020 on the forearm resistance and capacitance vessels in healthy subjects in vivo. METHODS: The local response to intra-arterial or intravenous infusion of SFTX6c (5 pmol min-1) or BQ-3020 (50 pmol min-1) was assessed, on separate occasions, in eight healthy men (aged 20-28 years). Data (mean +/- s.e.mean) were examined by ANOVA. Results are expressed as percentage change from baseline at 90 min. RESULTS: SFTX6c and BQ-3020 reduced forearm blood flow, following local intra-arterial infusion (-25 +/- 7% and -27 +/- 7%, respectively; P < 0.001) and reduced hand vein diameter, following local intravenous infusion (-30 +/- 8% and -16 +/- 7%, respectively; P < 0.001). CONCLUSIONS: We have shown that locally active infusions of the selective ETB receptor agonists SFTX6c and BQ-3020 cause arterial constriction and venoconstriction in healthy human blood vessels in vivo. These results indicate that ETB receptor stimulation may mediate vasoconstriction in humans.

Interposition of sural nerve restores function of cavernous nerves resected during radical prostatectomy.

PURPOSE: The permanent loss of erectile function when both neurovascular bundles are widely resected at radical prostatectomy as well as the successful use of autologous nerve grafts in reconstructive surgery led us to perform bilateral nerve grafts in an effort to restore erectile function in potent patients treated for prostate cancer who underwent radical retropubic prostatectomy and resection of both neurovascular bundles. MATERIALS AND METHODS: Radical retropubic prostatectomy with deliberate resection of both neurovascular bundles was recommended for high grade, locally extensive prostate cancer in 9 select, sexually active men who reported normal erectile function. After the prostate was removed but before vesicourethral anastomosis an autologous sural nerve graft was interposed between the divided ends of the cavernous nerves bilaterally. Erectile function was monitored by patient interview, questionnaire and nocturnal penile tumescence testing after the operation. RESULTS: Four to 5 months postoperatively patients noticed slowly improving spontaneous erections, as manifested by mild tumescence regularly every several hours. Nocturnal penile tumescence testing with the RigiScan device at 4 to 6 months in 2 cases revealed erections that approached minimal criteria for normalcy. Approximately 14 months after surgery a rigid erection sufficient for penetration and intercourse developed in 1 patient. He described this event as "an erection of substance-hard, not just fluffy." CONCLUSIONS: We have developed a technique using sural nerve grafts to restore continuity of the cavernous nerves, which are resected during radical prostatectomy. The early return of spontaneous partial erections in our patients suggests that interposition nerve grafts may enhance the recovery of erectile function when the neurovascular bundles are resected.

Carnitine supplementation improves myocardial function in hearts from ischemic diabetic and euglycemic rats.

BACKGROUND: Nonischemic myocardial dysfunction in patients with diabetes mellitus appears to be attenuated with long-term L-carnitine therapy. The effect of acute L-carnitine supplementation on rat hearts from euglycemic and diabetic animals subjected to ischemia and reperfusion is investigated in this study. METHODS: Study rats had diabetes mellitus induced by streptozocin (65 mg/kg intraperitoneally), and control rats had injection of saline solution (n = 12 per group). About 1 month later, the hearts were suspended on a Langendorff apparatus and perfused with either standard buffered Krebs-Henseleit solution or this standard solution supplemented with L-carnitine (5 mmol/L). After stabilization, normothermic, zero-flow ischemia was instituted for 20 minutes followed by 60 minutes of reperfusion. There were four study groups (n = 6 per group): hearts that were from euglycemic rats and that were perfused with standard buffered Krebs-Henseleit solution (E-STD); hearts that were from diabetic animals and that were perfused with the same standard buffered solution (DM-STD); hearts taken from diabetic animals and perfused with L-carnitine-enriched solution (DM-CAR); and hearts taken from euglycemic rats and perfused with the enriched solution (E-CAR). RESULTS: At 60 minutes of reperfusion, left ventricular developed pressure was significantly better in hearts from both groups (diabetic and euglycemic) with carnitine supplementation (DM-CAR versus DM-STD and E-CAR versus E-STD, p < 0.01 for both, by analysis of variance). Left ventricular end-diastolic pressure was significantly lower in the DM-CAR group compared with all other groups (p < 0.01 by analysis of variance). CONCLUSIONS: These findings suggest that acute L-carnitine supplementation significantly improves the recovery of the ischemic myocardium in diabetic and euglycemic rats.