Are predictors for myocardial infarction the same for women and men when evaluated prior to hospital admission?

AIM: To describe predictors of myocardial infarction prior to hospital admission in women and men among patients with a suspected acute coronary syndrome without ST-elevation. DESIGN: Prospective observational study in Stockholm and Göteborg, Sweden. RESULTS: Of 433 patients who did fulfill the inclusion criteria 45% were women. Fewer women (17%) than men (26%) developed acute myocardial infarction (AMI) (p=0.054), particularly among patients with initial ST-depression, in whom AMI was developed in 22% of women and 54% of men (p = 0.001). Predictors for infarct development in women were: a history of AMI and advanced age. Among men they were: initial ST-depression or a Q-wave on ECG and elevation of biochemical markers (both recorded on admission of the ambulance crew). There was a significant interaction between gender and the influence of ST-depression on the risk for development of myocardial infarction (p < 0.05). CONCLUSION: Among patients transported with ambulance due to a suspected acute coronary syndrome and no ST-elevation fewer women than men seem to develop AMI particularly among patients with ST-depression. These results suggest that early prediction of myocardial infarction might differ between women and men with acute chest pain.

Difference in survival after out-of-hospital cardiac arrest between the two largest cities in Sweden: a matter of time?

BACKGROUND: Dramatic differences in survival after out-of-hospital cardiac arrests (OHCA) reported from different geographical locations require analysis. We therefore compared patients with OHCA in the two largest cities in Sweden with regard to various factors at resuscitation and outcome. SETTING: All patients suffering an OHCA in Stockholm and Goteborg between 1 January 2000 and 30 June 2001, in whom cardiopulmonary resuscitation (CPR) was attempted were included in this retrospective analysis. RESULTS: All together, 969 OHCA in Stockholm and 398 in Goteborg were registered during the 18-month study period. There were no differences in terms of age, gender, and percentage of witnessed cases or percentage of patients who had received bystander CPR. However, the percentage of patients with ventricular fibrillation (VF) at arrival of the ambulance crew was 18% in Stockholm versus 31% in Goteborg (P <0.0001). The percentage of patients who were alive 1 month after cardiac arrest was 2.5% in Stockholm versus 6.8% in Goteborg (P=0.0008). Various time intervals such as cardiac arrest to calling for an ambulance, cardiac arrest to the start of CPR and calling for an ambulance to its arrival were all significantly longer in Stockholm than in Goteborg. CONCLUSION: Survival was almost three times higher in Goteborg than in Stockholm amongst patients suffering an OHCA. This is primarily explained by a higher occurrence of VF at the time of arrival of the ambulance crew, which in turn probably is explained by shorter delays in Goteborg. The reason for the difference in time intervals is most likely multifactorial, with a significantly higher ambulance density in Goteborg as one possible explanation.

Prognostic value of biochemical markers, 12-lead ECG and patient characteristics amongst patients calling for an ambulance due to a suspected acute coronary syndrome.

OBJECTIVES: To evaluate whether a 12-lead ECG, together with a multi-marker strategy that used point-of-care measurements of myoglobin, creatine kinase (CK-MB) and troponin I, was able to predict patients at short- and long-term risk of death, when simultaneously considering age, gender, previous history, symptoms and clinical findings on arrival of the ambulance. DESIGN: Prospective observational study. SETTING AND SUBJECTS: Consecutive patients (n=511) in ambulances in Stockholm and Göteborg in Sweden who called for an ambulance due to chest pain or other symptoms raising a suspicion of acute coronary syndrome. INTERVENTION: In almost all patients, a diagnostic ECG, patient baseline characteristics and measurements of CK-MB, troponin I and myoglobin were recorded. RESULTS: In univariate analysis, the highest 30-day mortality (17%) was found amongst patients with the combination of ECG signs of myocardial ischaemia and the elevation of any biochemical marker. The highest 1-year mortality (20%) was found amongst patients with ECG signs of myocardial ischaemia and the elevation of any biochemical marker. Increasing age (RR 1.07; 95 CI 1.02-1.13) lack of symptoms of chest pain and a previous history of hypertension (3.02; 1.08-8.79) were independent predictors of 30-day mortality. Myoglobin was the only biochemical marker independently associated with 30-day mortality (6.66; 1.83-22.3). Increasing age (1.11; 1.06-1.16), previous history of diabetes (3.42; 1.41-8.25) heart failure (2.64; 1.26-5.52) and other symptoms than chest pain and dyspnoea (5.23; 2.14-12.76) were independent predictors of 1-year mortality. In many of the variables the confidence limits were wide. CONCLUSION: Amongst patients with a clinical suspicion of acute coronary syndrome, those with the combination of ECG signs of myocardial ischaemia and the elevation of any biochemical marker on arrival of the ambulance form a group with a particularly high risk of death. However, age as well as aspects of clinical history and type of symptoms independently contribute to prognostic information.

Elevation of biochemical markers for myocardial damage prior to hospital admission in patients with acute chest pain or other symptoms raising suspicion of acute coronary syndrome.

OBJECTIVES: To evaluate the occurrence of elevation of serum biochemical markers for myocardial damage in the prehospital setting amongst patients who called for an ambulance due to a suspected acute coronary syndrome (ACS). DESIGN: Prospective observational study. SUBJECTS: All the patients who called for an ambulance due to suspected ACS. SETTING: South Hospital's catchment area in Stockholm and in the Municipality of Göteborg, Sweden between January and November in the year 2000, were included. INTERVENTIONS: On arrival of the ambulance crew, a blood sample was drawn for bedside analysis of serum myoglobin, creatine kinase MB and troponin I. A 12-lead electrocardiogram (ECG) was simultaneously recorded. MAIN OUTCOME MEASURES: Elevation of biochemical markers prior to hospital admission. RESULTS: In all, 511 patients participated on 538 occasions. Elevation of any biochemical marker was observed in 11% of all patients. The corresponding figure for patients developing myocardial infarction was 21%; for patients with myocardial ischaemia 8%; for patients with a possible myocardial ischaemia 4% and for patients with other diagnoses 5%. Amongst those who had a final diagnosis of acute myocardial infarction (AMI), 47% had ST-elevation on initial ECG and 57% had either ST-elevation or elevation of any biochemical marker. CONCLUSION: Bedside analysis of biochemical markers in serum is already feasible prior to hospital admission amongst patients with a suspected ACS. About 20% of patients with AMI have elevated biochemical markers at that stage. When found this data might increase the possibility of diagnosing an AMI very early in the course. However, false positives were found and whether this strategy will improve the triage of these patients in the prehospital setting remains to be proven.

Continuous ambulatory monitoring of absolute right ventricular pressure and mixed venous oxygen saturation in patients with heart failure using an implantable haemodynamic monitor: results of a 1 year multicentre feasibility study.

BACKGROUND: Implantable sensors that monitor haemodynamics over time may be useful in patients with heart failure. This multicentre study assessed the feasibility of a system that has one sensor measuring absolute pressure and another measuring mixed venous oxygen saturation (SvO(2)). Both sensors were mounted on leads that were implanted in the right ventricle. METHODS: Twenty-one patients with heart failure (NYHA II-III) were included. Comparisons were made to right heart catheterizations at implant and at 2, 6 and 12 months thereafter. Patients underwent several haemodynamic provocations during the catheterizations. RESULTS: Overall, among functioning sensors, the IHM-1 values were highly correlated with reference values for all time points during all provocations, demonstrating high reproducibility and stability (r(2)=0.91, 0.79 and 0.78 for systolic, right ventricular diastolic and SvO(2), respectively). Although IHM-1 underestimated reference pressure values by 4.5 mmHg and SvO(2)by 1.6%, this difference was consistent across provocation and stable over 12 months of follow-up. Twelve of the 21 oxygen sensors failed to function and two pressure sensors had component failures. Preliminary analysis of long-term data revealed haemodynamic patterns that may be key indicators for therapeutic interventions. CONCLUSION: This multicentre feasibility study demonstrated the accuracy and stability of sensors implanted in the right ventricle. The IHM-1, using right ventricular pressures and SvO(2), with improved performance, might be useful in the study of pathophysiological mechanisms and treatment interventions in heart failure.

Effects of first myocardial infarction on left ventricular systolic and diastolic function with the use of mitral annular velocity determined by pulsed wave doppler tissue imaging.

This study was undertaken to assess the effect of a first myocardial infarction (MI) on the systolic and diastolic velocity profiles of the mitral annulus determined by pulsed wave Doppler tissue imaging and thereby evaluate left ventricular (LV) function after MI. Seventy-eight patients with a first MI were examined before discharge. Peak systolic, peak early diastolic, and peak late diastolic velocities were recorded at 4 different sites on the mitral annulus corresponding to the septum, anterior, lateral, and inferior sites of the left ventricle. In addition, the amplitude of mitral annular motion at the 4 above LV sites, the ejection fraction, and conventional Doppler diastolic parameters were recorded. Nineteen age-matched healthy subjects served as controls. Compared with healthy subjects, the MI patients had a significantly reduced peak systolic velocity at the mitral annulus, especially at the infarction sites. A relatively good linear correlation was found between the ejection fraction and the mean systolic velocity from the 4 LV sites (r = 0.74, P <.001). The correlation was also good when the mean peak systolic mitral annular velocity was tested against the magnitude of the mean mitral annular motion (r = 0.77, P <.001). When the patients were divided into 2 different groups with respect to an ejection fraction > or =0.50 or <0.50, a cutoff point of mean systolic mitral annular velocity of > or =7.5 cm/s had a sensitivity of 79% and a specificity of 88% in predicting a preserved global LV systolic function. Similar to systolic velocities, the early diastolic velocity was also reduced, especially at the infarction sites. The peak mitral annular early diastolic velocity correlated well with both LV ejection fraction (r =.66, P <.001) and mean systolic mitral annular motion (r = 0.68, P <.001). However, no correlation existed between the early diastolic velocity and conventional diastolic Doppler parameters. The reduced peak systolic mitral annular velocity seems to be an expression of regionally reduced systolic function. The peak early diastolic velocity is also reduced, especially at the infarction sites, and reflects regional diastolic dysfunction. Thus, quantification of myocardial velocity by Doppler tissue imaging opens up a new possibility of assessing LV function along its long axis.

Right ventricular function in patients with first inferior myocardial infarction: assessment by tricuspid annular motion and tricuspid annular velocity.

BACKGROUND: Unlike left ventricular function, right ventricular (RV) function has not been widely studied after a myocardial infarction (MI). The current study describes RV function determined by tricuspid annular motion and tricuspid annular velocity after MI. METHODS AND RESULTS: Thirty-eight patients with a first acute inferior MI were prospectively compared with 33 patients with a first anterior MI and 24 age-matched healthy individuals. Association of RV infarction in inferior MI was defined as the presence of >/=1-mm ST-segment elevation at the right precordial lead, V(4)R, of the electrocardiograms. From the echocardiographic apical 4-chamber views, the systolic motion of the tricuspid annulus was recorded at the RV free wall with the use of 2-dimensional guided M-mode recordings. Peak systolic and peak early and late diastolic velocities of the tricuspid annulus at the RV free wall also were recorded with the use of pulsed-wave Doppler tissue imaging. The tricuspid annular motion was reduced in inferior MI compared with that in healthy individuals (20.5 and 25 mm, P <.001). The peak systolic velocity of the tricuspid annulus was significantly reduced in inferior MI compared with that in healthy individuals (12 vs 14.5 cm/s, P <.001) and patients with anterior MI (12 and 14.5 cm/s, P <.001). Patients with inferior MI were divided into 2 subgroups: those with and those without electrocardiographic signs of RV infarction. The tricuspid annular motion was significantly lower in patients with RV infarction than in patients without RV infarction (17 and 22.7 mm, P <.001). In addition, compared with patients without electrocardiographic signs of RV infarction, patients with RV infarction also had a significantly decreased peak systolic tricuspid annular velocity (13.3 and 10.3 cm/s, P <.001) and peak early diastolic velocity (13 and 8.2 cm/s, P <.001). CONCLUSIONS: These results suggest that tricuspid annular motion and tricuspid annular velocity can be used to assess RV function in association with inferior MI.

Cardioversion of atrial fibrillation and its effect on right ventricular function as assessed by tricuspid annular motion.

In patients with atrial fibrillation, the reduced right ventricular function determined by tricuspid annular motion before cardioversion returns to normal 1 month after successful cardioversion to sinus rhythm. The simplicity of recording the tricuspid annular motion provides an easy opportunity to assess right ventricular function following electroconversion of atrial fibrillation to sinus rhythm.

Aerobic group training improves exercise capacity and heart rate variability in elderly patients with a recent coronary event. A randomized controlled study.

AIMS: Reduced heart rate variability is associated with an unfavourable prognosis in patients with ischaemic heart disease. Whether physical training can modify this risk factor is not definitely proven. Our hypothesis was that training might increase both physical capacity and heart rate variability in elderly patients recovering from an acute coronary event, i.e. acute myocardial infarction (n=38) or an episode of unstable angina (n=27). METHODS AND RESULTS: 24 h ambulatory ECG recordings were obtained from 65 patients randomized to either a 3 months supervised outpatient group training programme 50 min three times a week (n=29) or to a control group (n=36). The two groups were well balanced as regards demographic data and pharmacological treatment at the time of randomization. Body mass index and pharmacological therapy remained unchanged during the study. Heart rate variability was analysed in the time and frequency domains. At the 3 month follow-up, exercise tolerance had increased from 103 to 120 W in the training group (P<0.001), and from 102 to 106 W in the control group (ns). The time-domain heart rate variability measures SDNN (standard deviation of all filtered RR intervals over the analysed time period) and SDANN (standard deviation of the means of all filtered RR intervals for all 5 min epochs of the analysed time period) increased significantly during the daytime in the training group (P<0.01 and P<0.05, respectively), but not in the control group. A significant improvement in night-time heart rate variability was observed among controls. There was a statistically significant correlation (P<0.05) between changes in 24 h overall power (frequency domain measure) and changes in maximal exercise capacity in the training group. CONCLUSION: A regular aerobic group training programme after an acute coronary event can significantly improve exercise capacity and modify heart rate variability in a prognostically favourable direction in elderly low-to-intermediate risk patients, recovering from an acute coronary event.

Two-year results of a controlled study of residential rehabilitation for patients treated with percutaneous transluminal coronary angioplasty. A randomized study of a multifactorial programme.

AIMS: In a multifactorial lifestyle behaviour programme, of 2 years duration, to study the maintenance of achieved behaviour and risk factor-related changes. METHODS AND RESULTS: Out of a consecutive population of 151 patients treated with percutaneous transluminal angioplasty under 65 years of age, 87 were randomly allocated to an intervention group (n=46) or to a control group (n=41). The programme started with a 4 week residential stay, which was focused on health education and the achievement of behaviour change. During the first year of follow-up, a maintenance programme included regular contacts with a nurse, while no further rehabilitative efforts were offered during the second year. One patient died (control). During the second year the proportion of hospitalized patients was lower in the intervention group (4% vs 20%;P<0.05). Patients in the intervention group improved several lifestyle dependent behaviours: diet (index at 0, 12 and 24 months): 10.5+/-3. 4, 12.9+/-2.5 and 12.4+/-2.6 in the intervention group (I) vs 10. 1+/-3.2, 10.7+/-3.0 and 11.8+/-3.2 in the control group (C);P<0.05, exercise sessions per week: 2.5+/-2.3, 4.5+/-1.9 and 4.4+/-2.1 (I) vs 3.1+/-2.2, 3.5+/-2.3 and 3.7+/-2.7 (C);P<0.05, and smoking; 18%, 6% and 9% (I) vs 12%, 21% and 18% (C);P<0.05. This corresponded to improvement in exercise capacity (0, 12 and 24 months): 156+/-42, 174+/-49 and 165+/-47 W (I) vs 164+/-40, 163+/-49 and 156+/-48 watts (C);P<0.05. There were no significant differences between the two groups with regard to serum cholesterol levels at 0 and 24 months: 5. 4+/-0.8 and 5.2+/-0.9 mmol. l(-1)(I) vs 5.4+/-1.0 and 4.9+/-0.9 mmol. l(-1)(C); ns, low density lipoprotein cholesterol level: 3.6+/-0.8 and 3.4+/-0.8 mmol. l(-1)(I) vs 3.7+/-0.9 and 3.3+/-0.7 mmol. l(-1)(C); ns, triglyceride level: 2.2+/-1.6 and 1.8+/-1.3 mmol. l(-1)(I) vs 2.2+/-1.4 and 1.6+/-0.6 mmol. l(-1)(C); ns, body mass index (0, 12 and 24 months): 27.5+/-4.5, 27.0+/-4.3 and 27.4+/- 4.5 kg. m(-2)(I) vs 26.8+/-2.8, 26.9+/-2.7 and 26.9+/- 3.2 kg. m(-2)(C); ns, waist/hip ratio or blood pressure. The two groups did not differ in quality of life, or psychological factors. Return to work after 12 and 24 months was 74% and 78% (I) vs 68% and 61% (C); ns. CONCLUSION: This rehabilitation programme influenced important lifestyle behaviour and reduced some, but not all, important risk factors

Improved physical fitness and quality of life following training of elderly patients after acute coronary events. A 1 year follow-up randomized controlled study.

AIMS: Cardiac rehabilitation including exercise training is of proven value in ischaemic heart disease. However, elderly patients frequently are not encouraged to participate in such programmes. This study evaluates the physiological effects and self-reported quality of life after an aerobic outpatient group-training programme in subjects above the age of 65 years. METHODS AND RESULTS: A consecutive series of 101 patients (males 80%) aged 65-84 (mean 71) years recovering from an acute coronary event were randomized to either a supervised out patient group-training programme (n=50) or to a control group (n=51). The two groups were well balanced as regards clinical characteristics. The compliance in the training group was 87%. Exercise tolerance increased in the trained group from 104 to 122 and 111 W after 3 and 12 months respectively. The corresponding values were 102, 105 and 105 W among controls. Parameters, such as quality of life, self-estimated level of physical activity, fitness and well-being were graded higher by the trained patients than those who served as controls on the two occasions of follow-up. CONCLUSIONS: Aerobic group-training of elderly patients recovering from an acute coronary event beneficially influences physical fitness and several parameters expressing quality of life. Great care has to be taken to preserve the initial effects by continued training.

Characteristics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects.

Assessment of myocardial velocities by Doppler tissue imaging is gaining in importance. However, generally accepted reference values are still missing. In this study we examined 62 consecutive healthy subjects (mean age 46, range 22-82 years) by pulsed wave Doppler tissue imaging to characterize the systolic and diastolic velocity profiles of the left and right ventricles. The subjects were divided into 3 different age-groups: group I, younger than 40 years; group II, 40 to 59 years; and group III, 60 years and older. Recordings were made along the long axis in the apical 4- and 2-chamber views by using 4 sites (septal, anterior, lateral, and inferior) at the mitral annulus and 1 site at the tricuspid annulus. Systolic mitral annular velocity (10.3 +/- 1.4 cm/s) correlated strongly with global left ventricular function determined by M-mode echocardiographic mitral annular displacement (r = 0.70, P <.001). The systolic velocity was significantly lower in group III than in group I (9.6 vs 10.8 cm/s, P <.01). A relatively weak, but significant, correlation was found between systolic velocity and the age of the subjects (r = -0.43, P <.001). Mitral annular early diastolic velocity was also lower in group III compared with group I (11.3 vs 17.7 cm/s, P <.001), with a strong correlation with age (r = -0.81, P <.001) and other conventional Doppler diastolic parameters. Both the systolic and early diastolic mitral annular velocities at the septum were lower than at other left ventricular sites. Tricuspid annular systolic velocity (15.2 +/- 1.9 cm/s) was higher than mitral annular systolic velocity (P <.001). Unlike mitral annular velocity, systolic tricuspid annular velocity was not correlated with age. However, the diastolic tricuspid annular velocities correlated well with transtricuspid Doppler diastolic parameters. The method of recording the annular velocities was feasible in all subjects, simple and highly reproducible.

Effects of organized aerobic group training in elderly patients discharged after an acute coronary syndrome. A randomized controlled study.

The aim of this study was to compare the physiological effects of an individually adjusted outpatient group training programme to the standardized recommendations of walking in elderly patients (>65 years) discharged after an acute coronary episode. In all, 101 patients, 20 women and 81 men, aged 65-84 (mean 71) years, were randomized either to a supervised outpatient group training programme during three months (n = 50) or to a control group (n = 51). Exercise tolerance increased from 104 watts to 122 watts (p < 0.001) in the training group and from 102 watts to 105 watts (n.s.) in the control group. Self-estimated level of physical activity was higher in the patients in the training group than in the control group (p < 0.001), as was graded well-being (p < 0.05). Organized aerobic group training can easily be performed in elderly patients after acute coronary syndrome, with results of improved exercise tolerance and a higher self graded well-being.

Multifactorial evaluation of a program for lifestyle behavior change in rehabilitation and secondary prevention of coronary artery disease.

A comprehensive, multifactorial lifestyle behavior change program was developed for rehabilitation and secondary prevention of subjects with coronary artery disease. The purpose of the present report is to describe this intervention model and to analyze results achieved in a first group of consecutive participants. Main inclusion criteria for the 292 subjects were a recent history of acute myocardial infarction, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty. The program commenced with a 4-week residential stay, with the focus on health education and the achievement of behavior change in major lifestyle areas. During the year of follow-up a systematic maintenance program included regular contact with a nurse. Morbidity and mortality was low. Self-reported quality of life improved and there were significant improvements in blood lipids, exercise capacity and body mass index. There were also significant changes both in psychological variables such as Type A behavior, anger, hostility, and in major lifestyle areas such as stress reactions, diet, exercise and smoking. These changes compared favorably with data from relevant samples from the Swedish normal population. This program had a considerable effect on a number of important factors for rehabilitation and secondary prevention of coronary artery disease.

Behavioral effects of a comprehensive, multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: a prospective, randomized controlled study.

A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor-related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.

Coronary thrombosis/thrombolysis in pigs: effects of heparin, ASA, and the thrombin inhibitor inogatran.

UNLABELLED: The aim of the present study was to develop a coronary thrombolysis model using the copper coil technique in closed-chest pigs. The first goal (protocol I) was to obtain a reproducible size of myocardial infarction by controlling the coronary occlusion period, a prerequisite for evaluation of myocardioprotective interventions. The second goal (protocol II) was to study if thrombin and platelet aggregation inhibitors influence the rate of thrombolysis, the degree of reocclusion, and the time of coronary patency when added to a thrombolytic regimen (recombinant tissue-type plasminogen activator, rt-PA). Coronary thrombosis was produced by insertion of a thrombogenic copper coil into the LAD of 40 anesthetized pigs. The animals were divided into six groups as follows: Protocol I, group 1: Open-chest, lysis initiated with intracoronary rt-PA (50 mg) concomitant with intravenous heparin and acetylsalicylic acid (ASA) (n=6). Group 2: Closed-chest, lysis initiated with intracoronary rt-PA concomitant with intravenous heparin and ASA (n=10). Protocol II, group 3: Closed-chest, lysis initiated with intravenous rt-PA (n=6). Group 4: Closed-chest, lysis initiated with intravenous rt-PA concomitant with heparin (n=6). Group 5: Closed-chest, lysis initiated with intravenous rt-PA concomitant with inogatran, a low molecular weight thrombin inhibitor (n=6). Group 6: Closed-chest, lysis initiated with intravenous rt-PA immediately after intravenous administration of ASA (n=6). Protocol 1; Reperfusion was achieved in all closed- and open-chest pigs. The time to thrombolysis was 5+/-1.6 and 6+/-3.0 min (mean+/-SD) for closed- and open-chest pigs, respectively. Reocclusions were rare (one in group 1). The size of the ischemic myocardial area was 21+/-11% of the left ventricular area in group 1 and 22+/-6% in group 2. The corresponding values for infarct size as a proportion of the ischemic area were 58+/-10% and 68+/-14%, respectively. The closed-chest model was subsequently used to study the effect of the thrombin and platelet aggregation inhibitors (inogatran, heparin, and ASA) as conjunctive agents to rt-PA-induced thrombolysis (groups 3-6). To mimic its clinical use, rt-PA was administered intravenously. Time to lysis after rt-PA only (group 3) was 33+/-24 min. Concomitant treatment with heparin (group 4), inogatran (group 5), and ASA (group 6) did not significantly influence time to lysis. All adjunctive compounds did, however, prolong the time to reocclusion, which occurred in 100%, 75%, 67%, and 20% of the animals in groups 3, 4, 5, and 6. Thus, concomitant treatment with heparin and inogatran did not shorten time to lysis or reduce the reocclusion rate, and ASA turned out to be the only effective adjunct to rt-PA, significantly reducing both time to and frequency of reocclusion (p < 0.05). CONCLUSION: The described closed-chest pig model was feasible as regards the induction and lysis of a thrombus in the left coronary artery, giving reproducible areas of myocardial ischemia and infarction. This model was useful for the evaluation of pharmacological interventions in the thrombolysis process.

Myocardioprotective effects of felodipine in an antihypertensive dosage: an experimental study in pigs.

The objective of this study was to test the hypothesis that treatment with the calcium antagonist felodipine in normal clinical dosages may have a myocardio-protective effect in the event of ischemia followed by reperfusion. Comparing the cardioprotective effects of felodipine and an agent of another class allowed the influence of blood pressure reduction per se to be evaluated. Twenty open-chest pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery (LAD) followed by 240 minutes of reperfusion. Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7) was administered intravenously starting at 180 minutes before the LAD occlusion in a dose that was intended to reduce the mean arterial blood pressure (MAP) by 30%. Six pigs (vehicle group) serving as controls received a mixture of polyethylene glycol (PEG) and 5% glucose, the vehicles for felodipine and SNP, intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the preinfusion levels, respectively. Infarct size as a percentage of the area at risk was 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the vehicle groups, respectively. Felodipine, given in a dose resulting in plasma levels corresponding to the therapeutic range in patients on antihypertensive treatment, reduced infarct size following myocardial ischemia/reperfusion. Afterload reduction induced by nitroprusside did not influence infarct size. Thus, felodipine exerted a myocardioprotective effect unrelated to the mechanism of afterload reduction in clinically relevant antihypertensive dosages.

Continuous ambulatory haemodynamic monitoring with an implantable system. The feasibility of a new technique.

AIMS: This study evaluates the feasibility and safety of a completely implantable system for long-term ambulatory monitoring of important haemodynamic parameters in patients with severe cardiopulmonary disease. METHODS: The design of the implantable monitoring system is similar to a conventional single lead pacemaker. A lead with incorporated biosensors for the continuous recording of pressure and oxygen saturation signals is positioned in the right ventricle and connected to a monitor and memory device subcutaneously implanted like an ordinary pacemaker can. RESULTS: Five patients with implanted haemodynamic monitoring systems have been followed for from 7 to 16 months. Continuous measurements of activity, heart rate, mixed venous oxygen saturation and estimated pulmonary artery diastolic pressure were registered with variable resolution during daily living and predefined provocations. The memory covered a maximum of 3 weeks at low resolution. The monitored parameters showed an adequate and significant response to various haemodynamic situations. Except for the demand of recalibration of two oxygen sensors, there were no technical problems and the quality of data were excellent. CONCLUSION: Long-term ambulatory haemodynamic monitoring is feasible and potentially useful for the management of patients with severe cardiopulmonary disease.

Selective early innervation of a subset of epidermal cells in Xenopus may be mediated by chondroitin sulfate proteoglycans.

The epidermis of early Xenopus embryos is innervated by the Rohon-Beard (RB) neurons lying within the spinal cord and by extramedullary (EM) neurons lying outside of the cord. We have examined the innervation patterns of the three epidermal cell types using wholemount preparations of skin double-labelled with the HNK-1 antibody as a marker for neurons and with antibodies to chondroitin sulfate proteoglycan (CSPG). Cells of one of the three epidermal cell types, here termed conical cells, are innervated well before the other two. In wholemounts of embryonic skin incubated with antibodies to chondroitin-6-sulfate (C6S), all epidermal cells except conical cells show CSPG immunoreactivity in their basal lamina. Double-labelling of skin preparations with HNK-1 and anti-C6S confirmed that these conical cells which lack C6S immunoreactivity are the first to be innervated by RB axons. It is proposed that C6S-bearing proteoglycan initially inhibits innervation of cells whose basal lamina contain the proteoglycan, thus favoring innervation of the conical cells which lack it.