Troponin levels in patients with myocardial infarction after coronary artery bypass grafting.

BACKGROUND: The objective of this study was to evaluate serum cardiac troponin T and I levels in patients in whom electrocardiogram, myocardial scan, and serum CK-MB levels of the MB isoenzyme of creatine kinase indicated perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG). METHODS: We studied 590 patients who underwent CABG at the Montreal Heart Institute between 1992 and 1996. Postoperative cardiac troponin T levels (493 patients), troponin I levels (97 patients), and activity of the MB isoenzyme of creatine kinase, electrocardiograms, clinical data, and clinical events were recorded prospectively. The diagnosis of perioperative PMI was defined by a new Q wave on the electrocardiogram, by serum levels of the MB isoenzyme of creatine kinase higher than 100 IU/L within 48 hours after operation, or both. RESULTS: After CABG, 22 patients in whom troponin T levels (22/493, 4.5%) and 6 patients in whom troponin I levels (6/97, 6.2%) were measured had sustained a perioperative MI according to current diagnostic criteria. In these patients, troponin T levels higher than 3.4 microg/L 48 hours after CABG best detected the presence of perioperative MI, with an area under the receiver operating characteristic curve of 0.95, a sensitivity of 90%, a specificity of 94%, a positive predictive value of 41%, a negative predictive value of 99%, and a likelihood ratio of 15. Serum troponin I levels higher than 3.9 microg/L 24 hours after CABG confirmed the perioperative MI with an area under the receiver operating curve of 0.86, a sensitivity of 80%, a specificity of 85%, a positive predictive value of 24%, a negative predictive value of 99%, and a likelihood ratio of 5. CONCLUSIONS: Serum troponin T levels higher than 3.4 microg/L 48 hours after CABG correlated best with the diagnosis of perioperative MI. Serum troponin T levels greater than 3.9 microg/L 24 hours after CABG also correlated with the diagnosis of perioperative MI, although a larger experience is needed to confirm the validity of the chosen cutoff value.

Can L-arginine improve myocardial protection during cardioplegic arrest? Results of a phase I pilot study.

BACKGROUND: L-arginine appears to improve myocardial protection during cardioplegic arrest in animal models. METHODS: To study the clinical effect and safety of L-arginine in humans, a phase I pilot study was performed with 50 patients who underwent coronary artery bypass grafting. We randomly assigned half to a treatment group, which received 1 g of L-arginine administered during the first 30 minutes of cardioplegic arrest induced by either warm or cold blood cardioplegia, and half to a control group, which did not receive L-arginine supplementation. RESULTS: Age, sex, and preoperative clinical status were similar in both groups. Seventeen patients of each group were administered intermittent warm antegrade blood cardioplegia, whereas the solution needed to be cooled to obtain complete standstill of the remaining eight hearts in each group. An internal thoracic artery graft to the left anterior descending coronary artery was performed in all patients. There was no death and no myocardial infarction in the treatment group, but there were one death and two infarctions in the control group. The amount of serial release of troponin I during the first 72 hours after the operation was similar between the L-arginine group and the control group (p > 0.05). Peak serum troponin levels averaged 4.9 +/- 1.0 microg/L in the arginine group and 3.9 +/- 1.0 microg/L in the control group (p > 0.05). A multivariate analysis of variance showed no effect of L-arginine (p > 0.05) but a significant effect of the temperature of the cardioplegic solution on the release of troponin I (p < 0.05). Serum troponin I levels averaged 2.2 +/- 0.4 microg/L, 4.5 +/- 0.4 microg/L, and 6.9 +/- 0.4 microg/L in the patients with cold cardioplegia and 1.4 +/- 0.3 microg/L, 2.4 +/- 0.3 microg/L, and 3.3 +/- 0.3 microg/L in the patients with warm cardioplegia 1, 2, and 6 hours, respectively, postoperatively. CONCLUSIONS: The administration of 1 g of L-arginine during the first 30 minutes of blood cardioplegic arrest did not result in a decrease in the postoperative release of cardiac enzyme; however, cold cardioplegic arrest significantly increased the release of cardiac troponin I postoperatively. There was no significant side effect related to the addition of L-arginine to the cardioplegic solution.

In elective coronary artery bypass grafting, preoperative troponin T level predicts the risk of myocardial infarction.

OBJECTIVE: Several combinations of risk factors for death or cardiac events after coronary artery bypass grafting have been described. We studied the prognostic value of the preoperative serum levels of cardiac troponin T. METHODS: We studied 468 patients who underwent elective coronary artery bypass grafting. Preoperative and postoperative levels of cardiac troponin T and creatine kinase MB, electrocardiograms, clinical data, and events were recorded prospectively. No acute ischemic changes were present on the electrocardiogram before the operations, and preoperative creatine kinase MB serum levels were within normal limits in all patients. RESULTS: Ninety-seven (97/468, 21%) patients had serum levels of troponin T greater than 0.02 microg/L within 24 hours before coronary artery bypass grafting. Hospital mortality was similar in this group and in the patients with preoperative levels less than 0.02 microg/L (1% in each group). Nine patients (9/97, 9%) with elevated levels of troponin T before the operation had a perioperative myocardial infarction compared with 12 patients (12/371, 3%) among the group with lower troponin T levels (p = 0.015, RR = 2.9). Congestive heart failure occurred in 10 (10/97, 10%) and 8 (8/371,2%) patients, respectively (p = 0.0009, RR = 4.8). Intensive care unit (p = 0.002) and postoperative hospital length of stay (p = 0.09) were all longer in patients with the elevated preoperative troponin T level. In a logistic regression analysis, troponin T level before the operation was the variable most strongly correlated with postoperative myocardial infarction (p = 0.003). CONCLUSION: Preoperative troponin T stratification before coronary artery bypass grafting identifies a subgroup of patients with increased risk of postoperative cardiac complications.

Early noninvasive identification of failed reperfusion after intravenous thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: This study sought to evaluate a biochemical approach to the early noninvasive assessment of reperfusion. BACKGROUND: In patients with an acute myocardial infarction, a rapid noninvasive method of detecting failure of intravenous thrombolytic therapy to restore early Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery (IRA) is needed. METHODS: Serial blood samples were collected to assay creatine kinase-MB fraction (CKMB mass), cardiac troponin T and myoglobin concentrations in 105 patients with a myocardial infarction who underwent early angiography after intravenous streptokinase. The ratios of the 60- and 90-min concentrations to prethrombolytic values were used to determine an index that could identify failure to achieve TIMI grade 3 flow in the IRA at 90 min. RESULTS: Significant increases in serum concentrations of markers at 60 min were more likely with TIMI grade 3 flow (59 patients) than with TIMI grade 0 to 2 flow (46 patients). Ratios < or = 5 at 60 min after thrombolysis detected failure to achieve 90-min TIMI grade 3 flow with 92% to 97% sensitivity, 43% to 60% specificity and 63% to 76% positive and 86% to 94% negative predictive values. Ratios < or = 10 at 90 min showed 88% to 95% sensitivity, 49% to 65% specificity and 61% to 69% positive and 86% to 94% negative predictive values for TIMI flow grade < 3. The overall predictive values were thus similar for all three markers. CONCLUSIONS: In acute myocardial infarction treated with intravenous streptokinase, a simple measurement of increased serum concentrations of CKMB mass, cardiac troponin T or myoglobin at 60 and 90 min can accurately predict failure to achieve TIMI grade 3 flow in the IRA at 90 min.

The role of cardiac troponin T and other new biochemical markers in evaluation and risk stratification of patients with acute chest pain syndromes.

BACKGROUND AND HYPOTHESIS: Increased serum creatinine kinase (CK) and CK-MB enzyme levels have been used for years to detect myocardial infarction (MI). However, serum myoglobin and CK-MB mass or protein levels may indicate MI earlier; cardiac troponin T is the most specific marker of myocardial injury and it can detect even minor myocardial necrosis. The diagnostic and prognostic utility of the traditional and new markers of cardiac injury in the emergency evaluation of patients with acute chest pain syndromes were therefore compared. METHODS: One hundred and fifteen consecutive patients with an acute coronary syndrome, and 64 controls recruited during the same period, were examined. The time elapsed from onset of symptoms to blood collection was recorded. Cardiac markers were measured in specimens collected upon arrival (0 h), and 2 and 5-9 h, and later in cases of longer observation. The major cardiac events occurring up to 40 months after the index examination were recorded. RESULTS: cTnT levels provided unique information: they were the most specific indicators of myocardial damage and identified unstable angina patients at high risk of future major events. Up to 6 h after the onset of chest pain, the new markers were elevated more frequently than the traditional ones and permitted earlier MI recognition. The worst prognosis (nonfatal myocardial infarction or death) was noted in subjects with chest pain at rest within 48 h before the index examination and elevated cTnT levels. CONCLUSIONS: The new markers, particularly cardiac troponin T, offer considerable advantages and they should be more widely used in the diagnosis and risk stratification of acute coronary syndromes.

Myocardial distribution of cardioplegia administered by antegrade and retrograde routes to ischemic myocardium.

OBJECTIVE: To study the distribution of a cardioplegic solution delivered by antegrade and retrograde routes to ischemic myocardium. Retrograde administration has been suggested to improve protection of the ischemic myocardium. However, there are insufficient data on perfusion of ischemic and necrotic zones by the retrograde route. DESIGN: A laboratory study in dogs. METHOD: In 12 dogs, 500 mL of hyperkalemic crystalloid cardioplegia containing 0.5 mCi of thallium-201 was injected antegradely or retrogradely through the coronary sinus after 3 hours of occlusion and 2 hours of reperfusion of the left anterior descending coronary artery. Myocardial distribution of the cardioplegic solution was measured by computer planimetry in the normally perfused zone, in the ischemic area and in the necrotic zone. RESULTS: The mean (and standard deviation) area at risk of ischemia (% of the left ventricle) delimited by Evans blue perfusion was smaller in dogs receiving a retrograde injection than in those receiving an antegrade injection (34% [3%] v. 42% [4%], p = 0.15). The infarct size (% of the area at risk indicated by triphenyltetrazolium dye) averaged 25% (11%) and 20% (7%) respectively (p = 0.36). The ratio of thallium-201 activity in ischemic to normal myocardium averaged 76% (13%) in the retrograde and 89 (12%) in the antegrade groups (p = 0.75). The ratio of thallium activity of infarct to normal myocardium averaged 56% (8%) in the retrograde group and 93% (19%) in the antegrade group (p = 0.18). Large areas of hypoactivity in the left ventricular myocardium were noted on scintigraphic imaging in all dogs that received retrograde perfusion. CONCLUSIONS: The retrograde injection of cardioplegia through the coronary sinus does not improve the distribution of cardioplegic solution in the acutely ischemic myocardial area nor in the zone of acute infarction in the dog. Because some cells may remain viable in the border zone and into the necrotic area, retrograde cardioplegia may result in suboptimal protection and incomplete prevention of further damage to the myocardium.

'True' fasting serum insulin level, insulin resistance syndrome and coronary artery disease.

BACKGROUND: Increased fasting serum insulin level not associated with hypoglycemia is considered to be a practical indicator of the insulin resistance syndrome, a frequent risk factor for atherosclerosis in industrialized countries. However, in most studies, insulin was measured by using antibodies which cross-react with proinsulin and 31/32, 32/33 split products of insulin. We re-examined the correlations between the insulin resistance syndrome and 'true' fasting serum insulin level. METHODS: We studied 242 post-menopausal women (age 63 +/- 8 years), a population in whom insulin resistance syndrome is particularly frequent. Serum insulin was measured by a recent specific microparticle immunoassay. RESULTS: There was a significant correlation between elevated 'true' fasting serum insulin level and various constituents of the insulin resistance syndrome, such as obesity, dyslipidemia (hypertriglyceridemia, increased apolipoprotein B and decreased high-density lipoprotein cholesterol and apolipoprotein A1 concentrations), increased serum glucose, uric acid levels, and plasminogen activator inhibitor type I concentration, as well as increased frequency of diabetes. There was also a correlation between insulin level and various manifestations of coronary artery disease: patients in the highest quartile of 'true' insulin level had significantly more entirely occluded coronary arteries than in the lowest one. Similarly, in the highest insulin quartile more patients had occluded arteries with lumen diameter stenoses greater than 50% (P < 0.05) and more of them had history of previous myocardial infarction approaching the level of significance (P = 0.0587) than in the lowest one. Most of these correlations were also noted in nondiabetic people. CONCLUSIONS: An increase of 'true' fasting serum insulin level is a useful practical index to identify patients with the insulin resistance syndrome exposed to increased risk of coronary artery disease.

Effect of L-arginine on metabolic recovery of the ischemic myocardium.

BACKGROUND: The release of nitric oxide is decreased after myocardial ischemia and reperfusion. Whereas the precursor L-arginine can stimulate the release of nitric oxide, its effect on metabolic recovery after myocardial ischemia is unknown. METHODS: To study the effect of L-arginine on metabolic recovery after myocardial ischemia, cardioplegia infusion, and reperfusion, 33 dogs were placed on cardiopulmonary bypass and subjected to a sequence of 30 minutes of normothermic global ischemia, 30 minutes of warm blood cardioplegic arrest, and 30 minutes of reperfusion. A pH probe was inserted in the anterior wall of the left ventricle, and tissue pH was measured throughout the experiment. Coronary blood flow in the left anterior descending coronary artery and the circumflex coronary artery was measured. Blood samples from the coronary sinus were taken to measure blood pH and levels of lactate, creatine kinase, and troponin T. RESULTS: In the control group of 9 dogs, tissue pH averaged 6.4 +/- 0.1, 6.5 +/- 0.1, and 6.8 +/- 0.1 after the end of global ischemia, cardioplegia, and reperfusion, respectively. Tissue pH averaged 6.4 +/- 0.1, 6.6 +/- 0.1, and 6.9 +/- 0.1, respectively, in the experimental group of 9 animals with 2 mmol/L of L-arginine added to the cardioplegic solution. Tissue pH averaged 6.2 +/- 0.1, 6.7 +/- 0.1, 7.1 +/- 0.1, respectively, in the third group of 9 animals that received an additional infusion of L-arginine (10 mg.kg-1.min-1) during reperfusion. Tissue pH recovered faster in groups with L-arginine (p = 0.00001). A hyperemic response of coronary blood flow was shown at reperfusion in animals in the control group only. In 6 dogs, L-NAME (N-nitroarginine methyl ester), an inhibitor of nitric oxide synthesis, was injected and resulted in a slower pH recovery on reperfusion compared with that of animals that received L-arginine. CONCLUSIONS: The addition of L-arginine to the cardioplegic solution and the systemic circulation during reperfusion resulted in a significant increase in coronary blood flow during cardioplegia infusion and in a faster recovery of myocardial tissue pH, possibly by increasing coronary blood flow through the release of nitric oxide.

Metabolic recovery after global myocardial ischemia: effects of blood cardioplegic solutions.

OBJECTIVE: To determine the effect of whole blood cardioplegia (WBC) and a mix of crystalloid in blood (CB) hyperkalemic cardioplegic solutions on recovery of the myocardium following global ischemia. DESIGN: Twenty-one dogs were placed on normothermic cardiopulmonary bypass, and a pH probe was inserted in the anterior wall of the left ventricle. Global myocardial ischemia was obtained by clamping the ascending aorta until a decrease in myocardial tissue pH of 0.4 units from baseline value was obtained, at which time cardioplegic solutions were perfused over 30 mins. The aorta was then unclamped and 30 mins of reperfusion was allowed. RESULTS: The aortic cross-clamping time necessary to decrease myocardial tissue pH 0.4 units from baseline averaged 13 +/- 8 mins. Whereas myocardial tissue pH returned to baseline value (6.9 +/- 0.1) after an average of 24 mins with cold (15 degrees C) and warm (35 degrees C) WBC, it took an average of 48 mins to reach control levels when warm CB solutions were used. Moreover, tissue pH decreased temporarily from 6.97 +/- 0.35 to 6.77 +/- 0.37 (P < 0.05) at initiation of normothermic myocardial reperfusion in cold WBC protected animals, and myocardial pH remained normal in the warm WBC group but remained severely acidic in warm CB animals (6.6 +/- 0.3). CONCLUSIONS: Metabolic recovery after global ischemia was faster with WBC cardioplegic protection. Normothermic blood reperfusion in cold WBC protected animals caused a significant but temporary tissue acidosis.

Clinical trial of retrograde warm blood reperfusion versus standard cold topical irrigation of transplanted hearts.

BACKGROUND: A prospective, randomized clinical study involving 34 patients undergoing heart transplantation compared myocardial preservation of donor hearts maintained with continuous reperfusion with retrograde warm blood cardioplegia during surgical implantation versus the standard cold topical irrigation. METHODS: Hearts in both groups were arrested with a standard crystalloid solution and maintained in a cold saline solution during transportation. In the retrograde group, cardioplegia was administered through a catheter in the coronary sinus during surgical implantation. An average of 471 +/- 30 mL of hyperkalemic crystalloid solution diluted 1:4 in warm blood from the oxygenator was infused. In the standard group, the heart was kept cold by topical irrigation of cold saline solution and was reperfused only when the ascending aorta was unclamped. RESULTS: Preoperative characteristics of donors and recipients were similar in the two cohorts. Ischemic time average 139 +/- 12 minutes in the retrograde group compared with 130 +/- 11 minutes in the standard group (p = 0.57). Cardiopulmonary bypass time averaged 89 +/- 4 minutes in the retrograde group and 110 +/- 12 minutes in the standard group (p = 0.12). Defibrillation at reperfusion was performed in 4 patients (4/17, 24%) in the retrograde group and 12 patients (12/18, 67%) in the standard group (p = 0.01). There were no deaths in the retrograde group (0/17), whereas in the standard group, 3 patients (3/17) died of early graft failure (p = 0.11). Four early graft failures occurred in the standard group (p = 0.06). Two patients (2/17, 12%) were weaned from bypass with ventricular assist devices in the standard group. The number of subendocardial necrotic cells in the first two weekly endomyocardial biopsy specimens averaged 2.7 +/- 0.8 cells/mm2 in the retrograde group and 5.9 +/- 2.4 cells/mm2 in the standard group (p = 0.12). CONCLUSIONS: Retrograde warm blood reperfusion appears to improve the initial recovery of transplanted hearts. The technique is easy to use and may be a useful approach to graft protection during surgical implantation.

Fasting hyperinsulinism, insulin resistance syndrome, and coronary artery disease in men and women.

A large segment of the population gradually develops insulin resistance, and the related metabolic syndrome is one of the most frequent causes of atherosclerosis. Searching for a practical indicator of insulin resistance, we studied the correlations between fasting serum insulin level, the general manifestations of insulin resistance syndrome, and various aspects of coronary artery disease in 797 men and 322 women. After we classified patients according to the quartiles of serum insulin level, we noted in the top quartile the presence of practically all manifestations of insulin resistance syndrome in persons of both sexes (e.g., increased waist/hip ratio, body mass index, glucose, uric acid, triglycerides, apolipoprotein B and decreased high-density lipoprotein cholesterol levels as well as apolipoprotein A-I/B ratios, and so forth). We also noted a higher prevalence of hypertension, diabetes mellitus, and type IV hyperlipidemia. Significantly more women in the fourth than in the first quartile had angiographically documented significant stenosis of the coronary arteries (p = 0.0016, odds ratio 2.9, 95% confidence interval 1.5 to 5.6) and previous myocardial infarction (p = 0.0297, odds ratio 2.1, 95% confidence interval 1.1 to 4.1). Men in both the first and the fourth quartile had a more disturbed lipid profile and a higher prevalence of significant stenoses of coronary arteries and/or previous myocardial infarction than women; there was a tendency toward a lower prevalence of alcohol consumption (p = 0.0503), a higher prevalence of gout (p = 0.0634), and previous myocardial infarction (p = 0.0791) in men in the fourth than in the first quartile.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe familial HDL deficiency in French-Canadian kindreds. Clinical, biochemical, and molecular characterization.

A decreased level of HDL cholesterol (HDL-C) is the most common lipoprotein abnormality seen in people with premature coronary artery disease (CAD). In many cases, HDL-C reduction in patients with CAD may be the result of increased apo B-containing lipoprotein production by the liver with secondary hypoalphalipoproteinemia. Primary hypoalphalipoproteinemia is seen in approximately 4% of people with CAD. We report findings in four subjects with severe familial HDL deficiency (HDL-C << 5th percentile for age and sex; 0.08 to 0.38 mmol/L) in three French-Canadian kindreds with autosomal codominant inheritance. By inclusion criteria, all four subjects had normal fasting triglycerides and none were diabetic. HDL particle size by gradient gel electrophoresis revealed small HDL particles (estimated Stokes' diameter, 8.14 to 8.30 nm). Apo AI analysis by polyacrylamide gel electrophoresis and use of isoelectrofocusing gels in affected subjects revealed normal molecular weight (28.3 kD) and normal isoelectrofocusing point but a relative increase in proapoliprotein AI, with near-normal levels of proapolipoprotein AI in plasma, suggesting normal secretion of apo AI. Quantitative Southern blot analysis of the apo AI-CIII-AIV gene cluster reveals no gene rearrangements or allele deletion. Haplotypes of the apo AI gene, determined by use of the restriction enzymes Pst I, Xmn I, and Sst I and of the apo AII gene by use of the enzyme Msp I, did not reveal segregation of the low HDL-C trait with either the apo AI or the AII gene. Sequence analysis of the promoter region of the apo AI gene reveals heterozygosity for guanine-to-adenine substitution at position 76 in two kindreds with no evidence of segregation with the low HDL trait. None of the patients had mutations of the lipoprotein lipase gene common in subjects of French-Canadian descent. Haplotype analysis of the lipoprotein lipase gene did not show segregation with the low HDL trait. Plasma lecithin: cholesterol acyltransferase (LCAT) activity was found to be within normal levels in affected subjects and in nonaffected first-degree relatives. None of the affected subjects had clinical manifestations of Tangier disease. Two of the four cases examined, both men, had severe CAD and had undergone revascularization procedures. The third is a younger brother of one of these probands and the fourth is a 30-year-old woman, and both were free of clinical CAD. However, in none of the families did the low HDL trait unequivocally cosegregate with CAD.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of cold and warm blood cardioplegia assessed by myocardial pH and release of metabolic markers.

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 degrees +/- 2 degrees C) and cold (n = 7; mean myocardial temperature, 12 degrees +/- 1 degree C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly (p < 0.05) from 7.1 +/- 0.3 to 6.53 +/- 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 +/- 0.3 to 6.64 +/- 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant (p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference (p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermittent antegrade warm versus cold blood cardioplegia: a prospective, randomized study.

A prospective, randomized study was performed in 200 patients undergoing coronary artery bypass grafting to compare the myocardial protection obtained with intermittent antegrade warm versus cold blood cardioplegia. Preoperative and surgical characteristics of the two cohorts were similar. Intermittent antegrade infusion of warm blood cardioplegia failed to achieve sustained electromechanical arrest of the heart in 13%. The only difference in clinical outcomes was the more frequent spontaneous return to sinus rhythm after the unclamping of the aorta in the warm group (88% versus 70%, p = 0.002). Mortality (1% each) and myocardial infarction (2% and 4%) rates were similar. Rates of increase in serum activity of the isoenzyme of creatine kinase (CK-MB), CK-MB mass concentration, and cardiac troponin-T level as well as total release of troponin T were significantly lower in the warm group, and fewer patients in this group had a clinically significant increase in serum CK-MB mass (20% versus 39%, p = 0.005) and troponin T (20% versus 56%, p = 0.00001). Thus, intermittent antegrade warm blood cardioplegia is appropriate and clinically safe; the lower release of biochemical markers of myocardial damage suggests improved protection during first-time coronary artery bypass grafting.

Cardiac troponin T and creatine kinase MB isoenzyme as biochemical markers of ischemia after heart preservation and transplantation.

An ischemic preservation period of less than 4 to 6 hours for the donor heart is considered safe in heart transplantation. To determine the severity of myocardial cell damage, we measured serum creatine kinase MB isoenzyme activity, creatine kinase MB isoenzyme mass concentration, and troponin T release in 14 patients during the first 48 hours after heart transplantation. All donors had normal cardiac function at echocardiographic evaluation. The heart was arrested with cold crystalloid cardioplegic solution and preserved in a hypothermic solution. All patients survived the first week after transplantation. Total ischemic time averaged 126 +/- 33 minutes (range 88 to 195 minutes). Maximal creatine kinase MB isoenzyme activity, creatine kinase MB isoenzyme mass concentration, and troponin T serum values after transplantation averaged 130 +/- 44 IU/L, 140 +/- 121 ng/ml, and 3.3 +/- 1.4 ng/ml, respectively. No significant correlation was found between ischemic time and peak levels of creatine kinase MB isoenzyme activity (r = 0.22), creatine kinase MB isoenzyme mass (r = 0.37) and troponin T (r = 0.12). A moderate correlation between ischemic time and the initial slope of time-activity curve of creatine kinase MB isoenzyme mass (r = 0.66, p = 0.01) and of troponin T release (r = 0.55, p = 0.03) was observed. Ischemic time and donor age were significantly related to creatine kinase MB isoenzyme mass (R2 = 0.61) and to troponin T (R2 = 0.47) initial release slopes. In conclusion, during a short period of ischemic preservation, myocardial cell damage appears to be mild and best reflected by the elevation and the time-activity curves of release of cardiac troponin T and creatine kinase MB isoenzyme mass.

The place of ferritin among risk factors associated with coronary artery disease.

BACKGROUND: Prospective studies of East Finnish men demonstrated an increased risk of myocardial infarction in association with elevated serum ferritin levels (> or = 200 micrograms/l). The present study was designed to explore whether serum ferritin concentrations are related to angiographically determined coronary artery disease or to a past history of myocardial infarction. METHODS: We studied 225 men and 74 women, most of them of French-Canadian origin, undergoing elective coronary arteriography, and classified them according to the presence, absence, and severity of angiographic findings. A history of myocardial infarction was defined as clinical and electrocardiographic and/or enzymatic evidence of a myocardial infarction occurring more than 12 weeks previously or akinesia of the left ventricle. Serum ferritin was measured with the Baxter Stratus II immunoassay system. RESULTS: There were no significant differences in ferritin levels between patients with > or = 50% diameter stenosis (195 men, 48 women) and those with intact or minimally affected arteries (31 men, 26 women) either in men or in women. There was no correlation between the quartiles of serum ferritin and the severity of coronary artery disease. There were no differences in ferritin levels in patients with (95 men, 25 women) or without (71 men, 43 women) a history of myocardial infarction. However, serum lipid levels were significantly related to all the above conditions. CONCLUSION: In a French-Canadian population, serum ferritin levels, unlike serum lipids, were not related to the presence or severity of angiographically determined coronary artery disease, nor to a history of myocardial infarction.

Relation of coronary artery disease in women < 60 years of age to the combined elevation of serum lipoprotein (a) and total cholesterol to high-density cholesterol ratio.

After age 40 years, coronary artery disease (CAD) is the leading cause of death in both women and men, yet in women the factors associated with, or leading to, CAD have been less extensively studied. This study examined the strength of association of a number of risk factors to CAD in groups of women < 60 years of age with (n = 108) and without (n = 66) angiographically documented significant narrowing of coronary arteries. In univariate analyses, there were significant differences between control subjects and patients with regard to age (49 +/- 6 vs 52 +/- 7 years) and total lipids and apolipoproteins measured. The relative frequency of cigarette smoking and diabetes was higher and that of estrogen replacement therapy lower in patients with CAD than in control subjects. In multivariate analysis the following factors were independently associated with CAD (adjusted odds ratios and 95% confidence intervals): total cholesterol to high-density lipoprotein (HDL) cholesterol (1.91; 1.56 to 2.34); lipoprotein (a) (10.66; 3.51 to 32.35); estrogen replacement (0.24; 0.11 to 0.54); age (1.12; 1.04 to 1.18); and smoking (1.50; 0.98 to 2.29). The nonadjusted odds ratio of CAD, based on combined tercile values of lipoprotein (a) serum level and total cholesterol to HDL cholesterol ratio, was very low (0.15; 0.06 to 0.36) when both values were within the first tercile, but very high (16.63; 3.54 to 78.07) when both were in the third tercile.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma endothelin-1 levels in stable and unstable angina.

Plasma levels of endothelin-1 are elevated in acute myocardial infarction with higher levels in complicated infarctions. Measurements of levels in unstable angina could help clarify whether the elevation is the consequence of cell necrosis or is in some way related to the pathophysiology of acute coronary syndromes. Plasma endothelin-1 levels were determined by radioimmunoassay in 29 patients with unstable angina and 6 with a myocardial infarction. Blood samples were obtained at admission before drug administration and 6 and 72 h later. Levels were also determined in 27 control subjects and in 29 patients with stable angina. Admission levels were similar in unstable angina, 0.635 +/- 0.052 pg/ml [log(1 + x)], and myocardial infarction, 0.746 +/- 0.122, and significantly higher than in controls, 0.428 +/- 0.047, and stable angina patients, 0.449 +/- 0.052 (p < 0.01). In unstable angina, levels decreased progressively to normal at 6 h, 0.557 +/- 0.049 pg/ml, and 72 h 0.474 +/- 0.054, as opposed to an increase to 0.868 +/- 0.109 (p < 0.05) after 6 h in myocardial infarction followed by a decrease to 0.597 +/- 0.122 at 72 h. The elevation in unstable angina did not correlate with other clinical or laboratory characteristics. Unstable angina is associated with an increase in endothelin-1 plasma levels during the acute phase, suggesting a role of this endothelium-derived vasoactive peptide in the pathophysiology of acute coronary artery syndromes.

Risk factors of venous aortocoronary bypass graft disease noted at late symptom-directed angiographic study.

One hundred and nineteen consecutive patients who had undergone venous aortocoronary bypass surgery 95.1 +/- 46.0 months earlier and in whom symptom-directed late graft angiography was performed were studied. Patients were designated 'controls' if their graft(s) appeared intact or revealed only minimal irregularities; they were designated 'cases' if one or several grafts showed at least 25% stenosis or complete occlusion. Controls and cases did not reveal significant differences in the frequency of classic nonlipoprotein risk factors or medication, including the use of acetylsalicylic acid. In multivariate analysis, significant graft narrowing or occlusion was most strongly related to elevated serum apolipoprotein B and lipoprotein(a) levels, as well as to the age of the grafts.

Actions of intravenous magnesium on ventricular arrhythmias caused by acute myocardial infarction.

Although the antiarrhythmic properties of magnesium are well recognized, its mechanisms of antiarrhythmic action are poorly understood. This study was designed to characterize the effects of magnesium on ventricular tachyarrhythmias related to acute myocardial infarction (MI) in dogs. When the circumflex coronary artery was occluded repeatedly for 10 min at 30-min intervals, ventricular fibrillation (VF) occurred in 30, 35 and 33% of dogs during occlusions 1, 2 and 3, respectively. Magnesium pretreatment reduced the incidence of VF to 14% during occlusion 3 (P less than .05 compared to occlusions without magnesium pretreatment). Neither the prevalence of ventricular ectopic complexes 24 h after MI nor arrhythmia inducibility 4 days after infarction were significantly altered by i.v. magnesium. Magnesium significantly attenuated the ST segment elevation (an index of ischemic injury) and ventricular conduction slowing caused by MI. Because magnesium has been reported to reverse the effects of hyperkalemia, we evaluated the role of this action by infusing potassium directly into a coronary artery (to mimic ischemia-induced hyperkalemia) and administered i.v. magnesium. Potassium infusion markedly slowed intraventricular conduction, an effect fully reversed by discontinuing potassium administration but unaffected by i.v. magnesium. We conclude that magnesium has antiarrhythmic actions only during the early phases of an experimental MI, and that these actions are associated with attenuation of indices of ischemic injury and conduction slowing. These properties of magnesium are similar to those of calcium antagonists, and suggest that magnesium's calcium antagonist properties may be important in its antiarrhythmic actions.