Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction.

Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.

Patients with diabetes are not more likely to have atypical symptoms when seeking care of a first myocardial infarction. An analysis of 4028 patients in the Northern Sweden MONICA Study.

AIM: To describe symptoms of a first myocardial infarction in men and women with and without diabetes. METHODS: We conducted a population-based study of 4028 people aged 25-74 years, with first myocardial infarction registered in the Northern Sweden Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) myocardial infarction registry between 2000 and 2006. Symptoms were classified as typical or atypical according to the World Health Organization MONICA manual. RESULTS: Among patients with diabetes, 90.1% reported typical symptoms of myocardial infarction; the corresponding proportion among patients without diabetes was 91.5%. In the diabetes group, 88.8% of women and 90.8% of men had typical symptoms of myocardial infarction. No differences were found in symptoms of myocardial infarction between women with and without diabetes or between men with and without diabetes. Atypical symptoms were more prevalent in the older age groups (> 65 years) than in the younger age groups (< 65 years). The increases were approximately equal among men and women, with and without diabetes. Diabetes was not an independent predictor for having atypical symptoms of myocardial infarction. CONCLUSIONS: Typical symptoms of myocardial infarction were equally prevalent in patients with and without diabetes and there were no sex differences in symptoms among persons with diabetes. Diabetes was not a predictor of atypical symptoms.

The disparity between long-term survival in patients with and without diabetes following a first myocardial infarction did not change between 1989 and 2006: an analysis of 6,776 patients in the Northern Sweden MONICA Study.

AIMS/HYPOTHESIS: Long-term survival after myocardial infarction (MI) has improved in the population, but data on diabetic patients is lacking. We analysed survival for up to 18 years after a first MI in patients with or without diabetes. METHODS: The Northern Sweden MONICA Myocardial Infarction Registry was linked to the Cause-of-Death Registry for a total of 6,776 patients, 25-64 years of age, with a first MI during 1989-2006. Prehospital deaths were included. Follow-up ended on 30 August 2008. RESULTS: Sixteen per cent had diabetes. Median follow-up time was 6.8 years, and the study included 50,667 patient-years. One third of the non-diabetic patients died vs half of the diabetic patients. Median survival for non-diabetic men was 227 months and for diabetic men 123 months. Corresponding figures for the non-diabetic and diabetic women were 222 and 81 months respectively. Men with diabetes had an age-adjusted HR for all-cause mortality of 1.56 (95% CI 1.39, 1.79) vs men without diabetes. Mortality risk was higher among diabetic women, HR 1.97 (1.62, 2.39) (diabetes × sex interaction, p = 0.03). Survival increased for three consecutive cohorts and was higher in non-diabetic patients for all durations of follow-up and in all three cohorts. The interaction of diabetes x cohort was not significant over time (p = 0.5) and HRs did not differ either. CONCLUSIONS/INTERPRETATION: Long-term survival after a first MI is markedly lower in diabetic patients, especially among women, over an 18-year observation time. Although survival has improved in diabetic patients, the effect of diabetes upon mortality has not diminished.

Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section.

BACKGROUND: ECG changes, similar to those seen during myocardial ischaemia, together with symptoms of chest pain, are common during Caesarean section (CS). We hypothesized that oxytocin administration has cardiovascular effects leading to these symptoms and ECG changes. METHODS: Forty women undergoing elective CS under spinal anaesthesia were given an i.v. bolus of either 10 IU of oxytocin (Group OXY-CS, n=20) or 0.2 mg of methylergometrine (Group MET-CS, n=20), in a double-blind, randomized fashion after delivery. Ten healthy, non-pregnant, non-anaesthetized women were used as normal controls (Group OXY-NC, n=10) and were given 10 IU of oxytocin i.v. Twelve-lead ECG, on-line, computerized vectorcardiography (VCG), and invasive arterial pressure were recorded. RESULTS: Oxytocin produced a significant increase in heart rate, +28 (SD 4) and +52 (3) beats min(-1) [mean (SEM); P<0.001], decreases in mean arterial pressure, -33 (2) and -30 (3) mm Hg (P<0.001), and increases in the spatial ST-change vector magnitude (STC-VM), +77 (12) and +114 (8) microV (P<0.001), in CS patients and controls, respectively. Symptoms of chest pain and subjective discomfort were simultaneously present. Methylergometrine produced mild hypertension and no significant ECG changes. CONCLUSIONS: Oxytocin administered as an i.v. bolus of 10 IU induces chest pain, transient profound tachycardia, hypotension, and concomitant signs of myocardial ischaemia according to marked ECG and STC-VM changes. The effects are related to oxytocin administration and not to pregnancy, surgical procedure, delivery, or sympathetic block from spinal anaesthesia.

Contributions of myocardial ischemia and heart rate to ST segment changes in patients with or without coronary artery disease.

BACKGROUND: ST changes related to ischemia at different heart rates (HRs) have not been well described. We aimed to analyze ST dynamic changes by vectorcardiography (VCG) during pacing-induced HR changes for subjects with proven coronary artery disease (CAD) and without (non-CAD). METHODS: Symptomatic CAD patients scheduled for elective surgery were enrolled along with a non-CAD group. During anesthesia, both groups were placed at multiple ascending levels. VCG ST data, and in particular in ST change vector magnitude (STC-VM) from baseline, along with arterial and great coronary artery vein (GCV) blood samples were collected to determine regional myocardial lactate production. RESULTS: A total of 35 CAD and 10 non-CAD patients were studied over six incremental 10 beat/min HR increases. STC-VM mean levels increased in the CAD group from 9+/-5 to 131+/-37 microV (standard deviation) compared with non-CAD subjects with 8+/-3-76+/-34 microV. Myocardial ischemia (lactate production) was noted at higher HRs and the positive predictive value for STC-VM to detect ischemia was 58% with the negative predictive value being 88%. STC-VM at 54 microV showed a sensitivity of 88% and a specificity of 75% for identification of ischemia. CONCLUSIONS: Both HR and ischemia at higher HRs contribute to VCG ST elevation. Established ST ischemia detection concerning HR levels is suboptimal, and further attention to the effects of HR on ST segments is needed to improve electrocardiographic ischemia criteria.

Diffusely increased bone scintigraphic uptake in patellofemoral pain syndrome.

OBJECTIVES: Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The aims of this study were to determine whether bone scintigrams of patients suffering from patellofemoral pain syndrome (PFPS) show diffuse uptake and in what bony compartment of the knee uptake, if any, was localised. METHODS: Fifty eight patients with chronic PFPS were examined. All patients underwent a detailed clinical history and a thorough physical examination of the knee. Anterior and lateral static images of both knees were made using a gamma camera 3 h after injection of 550 MBq of (99m)Tc-HMDP. Two experienced radiologists visually evaluated the scans blindly and separately. As 51 patients had bilateral pain, 109 painful knees are included in the results. RESULTS: Diffuse uptake on bone scintigrams was found in 48 knees in 30 of the patients. In 33 knees the uptake was localised to only one bone compartment, in 10 knees diffuse uptake was found in two of the bones forming the knee joint, and in six knees all three bone compartments (the distal femur, the patella, and the proximal tibia) exhibited diffuse uptake. CONCLUSIONS: Scintigrams of approximately half of the patients with PFPS will show diffuse uptake in one or more of the bony compartments of the knee joint and radioactive tracer accumulation will occur as often in the proximal tibia as in the patella.

Early vectorcardiographic monitoring provides prognostic information in patients with ST-elevation myocardial infarction.

OBJECTIVE: To evaluate the prognostic value of specified vectorcardiographic data obtained during the first hours of ST-elevation myocardial infarction for cardiac outcomes up to 5 years. DESIGN: Three hundred and five patients with ST-elevation myocardial infarction and chest pain for less than 12 h were monitored with continuous vectorcardiography. RESULTS: All patients had follow-up for at least 1 year. The mortality was 5.9% at 30 days and 10.8% at 1 year. The estimated 5-year mortality was 24%. A total of 7.9% had recurrent infarction at 30 days and 11.2% at 1 year. Recurrent infarction or death occurred in 12.1% at 30 days and in 19.7% at 1 year. The presence of ST-VM (plateau) >or= 125 microV was highly predictive of the combined endpoint death or recurrent infarction at 1 year, OR 2.69 (95% CI 1.39-5.23). Multivariate analysis showed that age >or=75 years, anterior myocardial infarction, and the presence of ST-VM (plateau) >or= 125 microV, were independently associated with increased risk of recurrent infarction or death at 1 year and with death at 5-year follow-up. A start value of ST-VM

The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction.

OBJECTIVES: To evaluate tissue plasminogen activator (tPA) activity as a measure of fibrinolytic response to treatment with streptokinase (SK) and to relate this to the effect of pretreatment SK antibodies and to successful reperfusion assessed by continuous computerized vectorcardiography (VCG). SETTING: Umeå University Hospital. SUBJECTS: A total of 104 patients with acute myocardial infarction (AMI) treated with SK and no history of previous SK treatment were studied. The tPA activity was measured 4 h after the start of treatment. The effect of pre-existing neutralizing antibodies to SK was analysed with a functional assay in pretreatment samples. Reperfusion was evaluated with VCG. MAIN OUTCOME MEASURES: Successful reperfusion. RESULTS: Fifty-five patients (53%) were classified as successfully reperfused. The risk for failed reperfusion was calculated in logistic regression models. In a univariate model, a borderline significant increase in the risk of failed reperfusion was observed in intermediate levels of SK neutralizing antibodies, but not in the highest levels. In a multivariate model, only high tPA activity, >25 U mL(-1), at 4 h (OR 0.17: 95% CI: 0.06-0.51) was associated with a higher rate of reperfusion whilst longer time to treatment (OR 1.17; 95% CI: 1.02-1.35) was associated with a higher risk of failed reperfusion. There was no significant correlation between neutralizing antibodies to SK and tPA activity at 4 h. CONCLUSION: The SK treatment of AMI induced high levels of tPA activity which were associated with successful reperfusion. The effect of pre-existing SK antibodies had no significant influence on reperfusion and were not correlated to the fibrinolytic activity obtained.

Clinical significance of abnormal T waves in patients with non-ST-segment elevation acute coronary syndromes.

T-wave abnormalities are common electrocardiographic occurrences in patients with non-ST-segment elevation acute coronary syndromes. Although these abnormalities are considered relatively benign, physicians use them to guide therapies. The study objective was to examine the prognostic predictive information of T-wave abnormalities in the setting of unstable coronary artery disease. The T-wave abnormality criterion was based on a new set of normal T-wave amplitude limits differentiated by gender, age, electrocardiographic lead, and QRS axis. Four hundred sixty-eight patients suspected of an acute ischemic incident and considered ineligible for reperfusion therapy were included. Thirteen categories of T-wave abnormalities were tested prospectively. The primary 30-day end point was the combination of refractory angina, myocardial infarction, or death. Quantitative T-wave analysis in an electrocardiographic core laboratory revealed 6 of 13 prespecified categories of T-wave abnormalities that were significantly associated with an adverse outcome. T-wave abnormalities had no prognostic value when ST-segment depression was also present, but this occurred in only 7.9% of patients. T-wave abnormalities as the sole manifestation of ischemia were common (74.4%). Patients with abnormal T waves in > or =1 of 6 selected abnormality categories (70.3%) had a significantly higher risk of death, acute myocardial infarction, and refractory angina (11% vs 3%; p = 0.018). Thus, T-wave abnormalities in patients presenting with non-ST-segment elevation acute coronary syndromes are common and should not automatically be regarded as benign phenomena. Quantitative T- wave analysis provides optimal risk stratification.

Assessment of myocardium at risk in pigs with single photon emission computed tomography and computerized vectorcardiography during transient coronary occlusion.

Since myocardium at risk (MAR) is the major prognosticator of final infarct size and outcome in patients with acute myocardial infarction, it is highly desirable to estimate the size of the acutely ischemic myocardium, that is the MAR, in these patients. We assessed MAR size by Tc-99m-sestamibi-SPECT and computerized vectorcardiography using autoradiography as reference method. Transient myocardial ischemia was achieved in 12 pigs by coronary artery occlusion with PTCA catheters. During the procedure, computerized vectorcardiography was continuously recorded. After injection of Tc-99m-sestamibi and gadolinium-153-labelled microspheres, MAR size was estimated by SPECT and post-mortem autoradiography. Different cut-off levels (50-70%) were compared with respect to MAR-SPECT. Tc-99m-sestamibi-SPECT showed a good correlation with autoradiography (r = 0.94). Computerized vectorcardiography showed a good correlation with autoradiography as well as with Tc-99m-sestamibi-SPECT (STC-VM: r = 0.75 and 0.80, respectively, ST-VM: 0.75 and 0.87, respectively). It was found that 1) MAR assessed by Tc-99m-sestamibi-SPECT correlates closely with the autoradiographic reference; 2) a lower cut-off point of 60% of maximum uptake for MAR by Tc-99m-sestamibi-SPECT gives the closest correlation with the autoradiographic reference; and 3) ST-VM and STC-VM correlate well with MAR assessed by Tc-99m-sestamibi-SPECT and autoradiography.

The impact of an end-point committee in a large multicentre, randomized, placebo-controlled clinical trial: results with and without the end-point committee's final decision on end-points.

BACKGROUND: A multicentre study permits rapid recruitment of a large number of patients. However, there is a risk of heterogeneities in end-point evaluations, as complex definitions of criteria are interpreted by several local investigators from different hospitals. Reports discussing end-point evaluation are sparse. The TRIM trial was a multicentre trial of a thrombin inhibitor in patients with unstable angina or non-Q myocardial infarction. In this study, an independent end-point committee evaluated all the reported events of death, acute myocardial infarction and refractory angina pectoris in order to obtain uniform judgements of major end-points. STUDY AIMS: To describe the work of the end-point committee, to analyse its possible effect on the final study results and to discuss the impact on the design of future trials. METHOD: The end-point committee consisted of four members, one from each participating country. After the data were processed by the study monitors, completed case record forms and patient files for patients with reported end-points were mailed to the national member of the end-point committee for judgement. The end-point committee met regularly and made final decisions about the end-points. The work of the end-point committee was documented on a separate case record form. RESULTS: The end-point committee assessed 246 events of death, acute myocardial infarction and refractory angina pectoris in 187 of the 1209 patients (15.5%) in the TRIM trial. Misinterpretation of the index event, an inclusion myocardial infarction, as an early cardiac event was found in 12 patients. After end-point committee judgements, the number of patients with acute myocardial infarction or refractory angina pectoris during 30 days of follow-up was reduced from 177 to 153 (13. 6% reduction). The classification of events was changed in 53 of 187 patients (28.3%) with death, acute myocardial infarction or refractory angina pectoris. The data assessed by the safety committee was significantly different from the final database after end-point committee judgements. CONCLUSION: The end-point committee corrected misinterpretations in such a high proportion of cases that the final results differed significantly from the preliminary results delivered to the safety committee. End-point judgements by an end-point committee should be performed in multicentre clinical trials to improve the quality and reliability of study results.

Transient Increase in ST-segment Changes at Time of Reperfusion in Acute Myocardial Infarction Treated by Coronary Angioplasty.

PURPOSE: The clinical significance of early ST-segment re-elevation, a so called Òreperfusion peakÓ in patients with acute myocardial infarction (AMI) treated with thrombolysis is unclear. We examined the incidence and significance of early ST-segment re-elevation immediately upon reperfusion in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) where the time of reperfusion can be precisely established. METHODS: Thirty-two patients (6 women, 26 men, age 61.5 +/- 10.2 years) with an AMI, admitted less than four hours after the onset of chest pain, were included. Twenty-four patients were treated with primary PTCA and eight with rescue PTCA. Computerized on-line vectorcardiography was used for continuous ischemia monitoring. A reperfusion peak was defined as an increase in ST-vector magnitude (ST-VM) of > 50 µV, starting within two minutes after the re-opening of the infarct-related coronary artery and followed by an immediate decrease in the ST segment. RESULTS: Primary success was achieved in all treated patients. Twenty of the patients (63%) developed a reperfusion peak. ST-VM before coronary angiography was significantly larger (p = 0.004) and peak enzyme levels were higher (p = 0.014) in patients who developed a reperfusion peak. Thrombolytic treatment prior to rescue angioplasty, time to reperfusion, target vessel, presence of collaterals or medication on admission did not differ significantly between the groups. CONCLUSION: The occurrence of a reperfusion peak during the minutes after the onset of reperfusion is a common finding in patients with AMI treated at an early stage with angioplasty. There is a relationship with the occurrence of a reperfusion peak and the extent of the initial ST deviation (presumably reflecting the myocardium at risk) and peak enzyme levels. The importance of a reperfusion peak for clinical outcome and prognosis is so far not known.

On-line computerized vectorcardiography: influence of body position, heart rate, radiographic contrast fluid and myocardial ischemia.

UNLABELLED: On-line computerized vectorcardiography (cVCG) is increasingly being used for continuous monitoring of myocardial ischemia, however, little is known about factors other than ischemia causing electrocardiographic abnormalities. This paper describes how three important cVCG parameters, STC-VM, ST-VM and QRS-VD, are affected by different body positions, myocardial ischemia, contrast injection and increasing heart rate in patients with and without coronary artery disease. The main findings of the study are: contrast injection and different body positions caused major changes in QRS-VD but affected ST-VM and STC-VM to a minor degree. Increasing heart rate by atrial pacing produced substantial changes in all three parameters. Ischemia during angioplasty also produced changes in all three parameters, STC-VM being the most sensitive parameter. IN CONCLUSION: (1) STC-VM (> or = 50 microV) is the most valuable parameter for monitoring ischemia; (2) we propose ST-VM > or = 50 microV as criterion instead of previously used 25 microV; (3) QRS-VD cannot be used as a single marker of ischemia, and (4) electrocardiographic changes induced by increased heart rate should be taken into account during interpretation.

Sleep apnoea and nocturnal angina.

Hypoxaemia occurs with sleep apnoea and might induce nocturnal angina. Sleep apnoea was found in 9 of 10 patients with nocturnal angina pectoris. Nocturnal angina diminished during treatment of sleep apnoea by continuous positive airway-pressure, and the number of nocturnal myocardial ischaemic events measured by computerised vector-cardiography was reduced.

On-line computerized vectorcardiography monitoring of myocardial ischemia during coronary angioplasty: comparison with 12-lead electrocardiography.

BACKGROUND: With new interventions minimizing ischemic myocardial injury, accurate and reliable techniques for the detection and continuous monitoring of myocardial ischemia are essential. We compared two techniques used for the detection of myocardial ischemia during coronary angioplasty: on-line computerized vectorcardiographic (cVCG) monitoring and the standard electrocardiography (ECG) leads or the complete 12-lead ECG. METHODS: Thirty patients scheduled for routine angioplasty were included in the study. cVCG was recorded continuously. The electrodes were placed according to the lead system described by Frank and connected to a computerized system for on-line vectorcardiography. A 12-lead ECG was recorded simultaneously. The absolute variable spatial ST vector magnitude (ST-VM) and the relative variable spatial ST change vector magnitude (STC-VM) were calculated and compared with the standard 12-lead ECG for the detection of ischemia. RESULTS: The sum of deviation in ST segment in all 12 standard ECG leads correlated closely with STC-VM, irrespective of which artery was occluded. STC-VM indicated ischemia during the first balloon inflation in 87% of the patients and demonstrated ischemia in more patients than the standard 12-lead ECG. Myocardial ischemia was not demonstrated by ST-VM in five out of 26 patients with ischemia according to STC-VM. In these cases, mainly directional vector changes and fewer changes in magnitude were observed. CONCLUSION: Compared with 12-lead ECG, on-line cVCG is a more sensitive method of detecting myocardial ischemia during coronary angioplasty and the reading is easier and faster. Our results support STC-VM > or = 0.050 mV as the criterion for ischemia during angioplasty; ST-VM should be applied together with STC-VM.

Quantification of myocardium at risk and detection of reperfusion by dynamic vectorcardiographic ST segment monitoring in a pig occlusion-reperfusion model.

OBJECTIVE: The aim was to investigate whether continuous computerized vectorcardiographic monitoring of absolute spatial ST vector magnitude (ST-VM) and spatial ST change vector magnitude (STC-VM) during coronary occlusion could be used to estimate the size of myocardium at risk; and also to test whether reperfusion could be distinguished from sustained occlusion by continuous monitoring of ST vector alterations. METHODS: Computerised vectorcardiographic monitoring via Frank leads was applied in a closed chest occlusion-reperfusion pig model. Coronary occlusion over 24 h was produced in 20 animals by injecting a 2 mm ball into the left anterior descending coronary artery (n = 7), the right coronary artery (n = 8), and the left circumflex coronary artery (n = 5). Another 31 pigs were reperfused by retraction of the ball after 30 (n = 10), 60 (n = 15), or 90 (n = 6) min of left anterior descending artery occlusion. The extent of the myocardium at risk was measured by autoradiography. RESULTS: Seven animals were excluded. Irrespective of occluded coronary artery the relative parameters STC-VM over the first 30 min of occlusion correlated closely with area at risk, that is, the mean STC-VM between 10 and 30 min of occlusion (r = 0.78 p < 0.001). The absolute parameter ST vector magnitude (ST-VM) did not reflect ischaemia in 16/44 animals and did not correlate significantly with area at risk. The weight of myocardium at risk (MAR) was predictable from STC-VM: MAR weight (measured) = 0.97 x MAR weight (predicted) + 0.26 (g), r = 0.81, p < 0.001. STC-VM decline rate, time to STC-VM plateau, and cumulated sum plots of STC-VM were all able to distinguish reliably between reperfused animals and those with permanent occlusion. A paradoxical increase in STC-VM - "reperfusion peak" - was detected in 17/31 (55%) of the animals. This phenomenon was related to large amount of myocardium at risk or to a long occlusion time. CONCLUSION: Dynamic vectorcardiographic ST monitoring provides adequate estimation of myocardium at risk and enables detection of reperfusion in experimental myocardial ischaemia.

Comparison of triphenyltetrazolium chloride (TTC) staining versus detection of fibronectin in experimental myocardial infarction.

Staining with triphenyltetrazolium chloride (TTC), although controversial, has frequently been used for the delineation of myocardial infarction. This study was performed further to explore the reliability of the TTC method. In 24-h experiments pigs were subjected to closed-chest occlusion of the left anterior descending coronary artery for 30, 60 or 90 min followed by reperfusion with or without superoxide dismutase (SOD) as an adjunct. One TTC-stained slice from each heart was stabilized by microwave irradiation, gelatin-embedded, frozen in hexane chilled with dry ice and cryosectioned. Serial sections were stained with antibodies against fibronectin in order to identify irreversibly injured myocytes and with van Gieson histologically to confirm the necrotic tissue. A close correspondence of the infarct size was found between TTC stained slices and anti-fibronectin stained sections. The infarct size in the van Gieson stained sections also showed good correspondence but the area of infarction tended to be larger. In the experimental group subjected to 30 min ischaemia and with SOD as an adjunct, the estimated infarcted area in the TTC stained slices was significantly smaller than the area estimated from the anti-fibronectin stained sections. In sections viewed in the light microscope an inverse pattern of TTC and anti-fibronectin staining was observed. It was confirmed at the light microscopic level that myocytes containing an abundance of TTC deposits lacked fibronectin whereas myocytes stained with antifibronectin in general lacked TTC staining except for a zone approximately 0.5 mm wide which was located at the intersection between damaged and surviving myocytes where small TTC deposits were present. The width of the stained zone did not differ among the experimental groups. Thus, differences in estimated infarct size by the three methods used reflect problems in correctly delineating the border between living and dead myocardium rather than an interference by SOD on TTC staining.

Ischaemia and reperfusion induced transient QRS vector changes: relationship to size of the ischaemic territory.

OBJECTIVE: The aim was to investigate QRS vector changes during the first 30 min of coronary occlusion or the early phase of reperfusion with special reference to location and size of myocardium at risk. METHODS: 24 h experiments were performed in closed chest anaesthetised pigs. QRS vectors were studied by computerised vectorcardiography via Frank leads. Occlusion of the left anterior descending coronary artery followed by reperfusion was induced in 23 pigs and a sustained occlusion in 20 pigs: left anterior descending coronary artery in seven, right coronary artery in eight, and left circumflex coronary artery in five. Myocardium at risk was measured in postmortem autoradiograms. Eight animals were excluded. RESULTS: Four minutes after occlusion, QRS(mean) deviated towards the ischaemic region in 34/35 animals and returned thereafter at varying speeds. In half of the reperfused animals, deviation of QRS vectors towards the ischaemic territory was also observed during the first minutes of reperfusion. A paradoxical increase in QRS vector changes, "reperfusion peak", was recorded during the initial minutes of reperfusion in 12/19 animals. Maximum spatial QRS vector magnitude increased in all right coronary or left circumflex coronary occlusion animals compared to 6/25 in left anterior descending coronary occlusion animals. QRS vector difference, change in spatial QRS vector angle, and maximum change in QRS azimuth 4 min after occlusion correlated significantly with extent of myocardium at risk. CONCLUSIONS: Marked directional and quantitative QRS vector changes, with significant relation to size and location of myocardium at risk, were recorded during the initial minutes of ischaemia. The transient increase in QRS vector changes during the first minutes of reperfusion deserves further exploration as a new indicator of reperfusion.

Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure. A placebo controlled three-dose study.

The aim of the present study was primarily to evaluate the haemodynamic effects of the ACE-inhibitor ramipril which is active via its metabolite ramiprilat. Ramipril 1.25, 2.5 and 5 mg and placebo was administered orally to 4 groups of 12 patients with heart failure (NYHA III) in a double-blind randomised, parallel study. Haemodynamics were monitored for 24 h and blood was sampled and urine collected for up to 96 h. In the placebo-treated group the cardiac index (CI) was significantly increased (15.8%) and right atrial pressure decreased (26.6%). Ramipril 1.25 mg had insignificant haemodynamic effects compared to placebo and the 2.5 mg dose had significant effects on some haemodynamic variables. Ramipril 5 mg had pronounced and sustained effects on pulmonary artery pressure, which fell by 43.7%, and pulmonary capillary wedge pressure (PCWP; -59.1%); systemic vascular resistance was also decreased 21%. A significant effect on CI was only seen after 2.5 mg ramipril (+7.4%). The mean maximal degree of ACE inhibition was 73.2, 90.4 and 98.5%, respectively, after the three doses of ramipril. Complete inhibition of ACE-activity was seen at a mean plasma concentration of ramiprilat of 4.7 ng.ml-1. The degree of inhibition declined with a half life of about 75 h. There was a significant relation between the degree of ACE-inhibition and change in PCWP but not with the change in SVR. Ramipril was mainly eliminated in the form of ramiprilat and inactive metabolites.