Electrocardiogram interpretation as a basis for thrombolysis.

OBJECTIVE: To assess the skills and opinions of different grades of doctors and cardiac-trained nurses in interpreting electrocardiographic changes when deciding upon administration of thrombolysis to patients with chest pain. DESIGN: A questionnaire was distributed to staff in several local hospitals. SUBJECTS AND METHODS: Participants were asked to assess 30 electrocardiograms (ECGs) and determine whether they would prescribe thrombolytic therapy on the basis of each one, assuming an associated typical history of acute myocardial infarction (AMI) and no contra-indications to treatment. They were asked to return the questionnaire anonymously, stating only their position. RESULTS: Of the 88 questionnaires, 61 were returned by 15 senior nurses, 10 house officers, 12 senior house officers, 10 medical registrars, eight consultant physicians and six consultant cardiologists. When electrocardiograms showed unequivocal evidence of acute myocardial infarction, all consultant cardiologists gave the correct answer, but only 75.5% of house officers diagnosed AMI. Cardiologists were most in favour of thrombolysis when left bundle branch block was present. Cardiac-trained nurses showed good decision-making skills. CONCLUSIONS: Staff involved in assessment of patients with chest pain should have specific training in electrocardiographic diagnosis of myocardial infarction in order to minimise in-hospital delay when thrombolysis is indicated. The management of patients with left bundle branch block remains uncertain; cardiologists are more likely to recommend thrombolytic therapy than any of the other participants in the study.

Effects of ischaemia and reperfusion on vasoactive neuropeptide levels in the canine infrarenal aortic revascularization model.

Infrarenal aortic cross-clamping is associated with remote vascular events, including myocardial infarction and renal insufficiency. The purpose of this study was to determine whether hindlimb ischaemia and reperfusion associated with infrarenal aortic cross-clamping results in the production of vasoactive regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was used for the study. Serial blood samples were drawn, prior to, at the time of, and serially following placement of the clamp and subsequent release of the clamp and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of neuropeptide Y (NPY) (initial 10.0(1.8) pmol/l versus ischaemia 24.7(2.3) pmol/l, P < 0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5) pmol/l versus ischaemia, 7.3(1.3) pmol/l, P < 0.05). Reperfusion produced three-fold elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l, P < 0.001), two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1) pmol/l versus reperfusion maximum 2.5(0.3) pmol/l, P < 0.01) and NPY (initial 10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P < 0.001). Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased following haemorrhagic shock (initial 1.3(0.1) pmol/l versus exsanguination 3.4(0.4) pmol/l, P < 0.001), but not during ischaemia (initial 1.3(0.1) pmol/l versus ischaemia maximum 1.7(0.2) pmol/l, P = 0.7). It was concluded that vasoactive regulatory peptides are released following ischaemia, reperfusion and shock in the canine infrarenal aortic revascularization model and, therefore could contribute to remote vascular events observed with infrarenal aortic cross-clamping.

Acute ischaemic lesions in death due to ischaemic heart disease. An autopsy study of 333 cases of out-of-hospital death.

The frequency of acute coronary artery thrombus and myocardial infarction in subjects dying suddenly or unexpectedly from ischaemic heart disease (IHD) is still unclear, with previous autopsy studies reporting an incidence between 4% and 100%. In this study of 333 randomly selected out-of-hospital deaths, detailed autopsy showed IHD as the sole cause of death in 206 (62%). One hundred and seventeen acute coronary thrombi were present in 96 cases whilst four had an established acute infarct without an identifiable coronary thrombus. Thus 100 (48.5%) IHD deaths had evidence of an acute ischaemic lesion. Acute lesions were equally prevalent among males and females, but the incidence declined with increasing age and they were less frequent among those with a prior clinical history of heart disease. One hundred and forty-seven IHD deaths were witnessed. The proportion of cases with an acute ischaemic lesion increased with the duration of pre-morbid symptoms. Of those with an acute lesion, only 17% died without symptoms compared to 63% of those without an acute lesion. All cases with symptoms lasting more than 3.5 h had an acute lesion. Overall, almost half out-of-hospital IHD deaths in this study were related to an acute ischaemic lesion. Differences in the detail of the pathological examination and examination of differing sub-groups of the out-of-hospital death population probably account for the differing results of previous studies.

Endothelin-1 levels in ischaemia, reperfusion, and haemorrhagic shock in the canine infrarenal aortic revascularisation model.

Endothelin-1 (ET-1) is a potent vasoconstrictive polypeptide produced from vascular endothelial cells. The effects of ischaemia, reperfusion, and exsanguination on plasma ET-1 levels were studied and compared in the mongrel dog after infrarenal aortic cross clamping. Ischaemia produced a trend toward increased ET-1 serum levels (p < 0.07 with Bonferroni correction) that did not reach significance. Plasma ET-1 levels were significantly increased during reperfusion and even further elevations were found following exsanguination. We found a 2-3 fold increase in ET-1 levels following reperfusion (Initial 3.19 +/- 0.27 pg/ml vs. Reperfusion maximum 6.32 +/- 0.72 pg/ml, Bonferroni p < 0.01). Haemorrhagic shock was associated with a 3-4 fold increase in ET-1 levels (Initial 3.19 +/- 0.27 pg/ml vs. Exsanguination maximum 8.37 +/- 0.97 pg/ml Bonferroni p < 0.001). These data reveal that ET-1 is released during reperfusion and exsanguination and may mediate remote vascular events associated with infrarenal aortic cross clamping and acute blood loss.

Neuropeptide Y levels during ischemia and reperfusion in the canine infrarenal aortic revascularization model.

Neuropeptide Y (NPY) is a potent vasoconstrictive polypeptide colocalized with norepinephrine in sympathetic neurons. The effects of ischemia and reperfusion on plasma NPY levels were studied and compared in the mongrel dog after infrarenal aortic cross-clamping. We found a two- to threefold increase in NPY levels during ischemia (initial 10.0 +/- 1.8 pmol/L vs. maximum 24.7 +/- 2.31 pmole/L, p < 0.001). The increase in NPY remained following reperfusion (initial 10.0 +/- 0.8 pmole/L vs. maximum 23.9 +/- 2.31 pmole/L, p < 0.001). These data reveal that NPY is released during ischemia and reperfusion and may be involved in mediating remote vascular events associated with infrarenal aortic cross-clamping.

The effect of the angiotensin converting enzyme inhibitor, enalapril, on exercise tolerance and abnormalities of limb blood flow and respiratory function in patients with severe heart failure.

Ten patients with severe (NYHAIII) heart failure were compared with 10 age-matched healthy subjects in terms of oxygen uptake and minute ventilation at rest and during exercise and calf and forearm blood flow measured by venous occlusion plethysmography at rest and after a standardized exercise test. Patients performed a symptom-limited treadmill exercise test and were then treated with enalapril for 5 weeks; the various measurements were repeated at weekly intervals. Oxygen consumption (VO2) at rest was similar in the patients and controls. During exercise, patients VO2 tended to be lower at each workload, but this was not affected by enalapril treatment. Minute ventilation was higher at rest and at each exercise stage in the patients than in the control subjects, and this was significantly reduced by enalapril treatment. Compared with the controls (2.94 +/- 0.10 and 2.93 +/- 0.20 ml.100 ml-1.min-1) forearm and calf blood flow measured by venous occlusion plethysmography was reduced at rest in the patients (1.34 +/- 0.18 and 1.24 +/- 0.11 ml.100 ml-1.min-1). but was significantly increased by enalapril treatment (1.73 +/- 0.15 and 1.60 +/- 0.16 ml.100 ml-1.min-1). Submaximal leg exercise to a fixed VO2 showed attenuation of the normal vasoconstriction in the forearm and vasodilatation of the calf; enalapril treatment changed these responses significantly towards normal but a marked abnormality of flow pattern persisted.

Management of myocardial infarction: implications for current policy derived from the Nottingham Heart Attack Register.

OBJECTIVE: A register of patients with heart attacks in the Nottingham Health District has been maintained since 1973. Data from 1982 to 1984 inclusive, a period before trials of thrombolytic therapy started in Nottingham, were analysed to provide background information for the introduction of a policy of routine thrombolysis for appropriate patients. DESIGN: Data were collected prospectively on all patients transported to hospital in the Nottingham Health District with suspected myocardial infarction in the years 1982-84 and on patients treated at home during that time. SETTING: Two district general hospitals responsible for all emergency admissions in the health district. PATIENTS: 6712 patients admitted to hospital with suspected myocardial infarction and 1887 patients found dead on arrival at hospital. Approximately 1500 patients in whom a myocardial infarction was suspected were treated at home, but only 125 were identified who had a definite or probable infarction. RESULTS: Among the patients admitted within 24 hours of the onset of symptoms, the median delay from onset to hospital admission was 174 minutes; 25% of patients were admitted within 91 minutes. The only factor that seemed to affect the time taken was the patient's decision to call a general practitioner or an emergency ambulance. If a general practitioner referred the patient to hospital the median delay was 247 minutes, compared with 100 minutes when the patient summoned an ambulance. Ninety three per cent of all patients were transported by ambulance. The median time from the call for the ambulance to hospital arrival was 29 minutes. Once a patient was admitted to hospital, the time to admission and general practitioner involvement seemed relatively unimportant as predictors of outcome. Patients admitted more than nine hours after onset of symptoms with a diagnosis of definite or probable infarction had a poorer outcome than those admitted earlier (in-hospital mortality 22.4% v 13.1%). The fatality rates of those admitted to a coronary care unit or to an ordinary medical ward are similar. CONCLUSION: Although the introduction of thrombolytic therapy has brought with it an increased awareness of the need to minimise any delay in time to admission, it seems that in a predominantly urban area like Nottingham, patients with a suspected heart attack will continue to be admitted to hospital most quickly if an ambulance crew rather than a general practitioner is called. Because the ambulance crew was in contact with such patients for only a short time it seems unlikely that administration of a thrombolytic drug in the ambulance would be helpful.

The limited potential of special ambulance services in the management of cardiac arrest.

For six months a survey was made of all the patients in the Nottingham District Health Authority who died or who were brought to hospital after a cardiac arrest outside hospital. During this period just under half of the emergency ambulance shifts were covered by specially trained crews with defibrillators. During the study period the ICD coding of death certificates indicated that 894 (25%) of the 3575 deaths were due to ischaemic heart disease. During this period the ambulance service received 17,749 emergency calls, which included 445 patients who had cardiac arrests outside hospital. One hundred and forty seven of these patients were carried by ambulances equipped with defibrillators and resuscitation was attempted in 83. Seven patients survived to leave hospital. The special ambulance service was cost effective--a simple calculation suggests that the cost per life saved was approximately 2600 pounds, but it seems unlikely that special ambulance services will materially affect community fatality rates from ischaemic heart disease.

Comparison of the effects of captopril and enoximone in patients with severe heart failure: a placebo controlled double-blind study.

The effects of enoximone, a new cyclic adenosine monophosphate phosphodiesterase inhibitor, were compared with those of captopril in a double-blind study in a group of 10 patients with severe heart failure. Four weeks treatment with enoximone improved symptom-limited exercise tolerance from a mean value of 11.33 to 13.36 minutes (P less than 0.05) and 4 weeks of captopril treatment from 11.01 to 13.92 minutes (P less than 0.05). Four of the patients had a greater exercise tolerance taking enoximone, the remaining 6 while taking captopril. Both drugs reduced perceived exertion during submaximal exercise. Minute ventilation measured at rest and during submaximal exercise was also reduced by both drugs. Resting and post exercise calf blood flow was increased to a similar extent with captopril (P less than 0.03) and enoximone (P less than 0.005). There was no difference in calf blood flow and calf vascular resistance between the drugs suggesting that the peripheral haemodynamic effects of enoximone are due to peripheral vasodilatation. Enoximone is a useful drug for the treatment of patients with severe heart failure.

Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects.

There is no single, simple test with which to evaluate new treatments for heart failure. Various methods need to be used, and a study of both the acute haemodynamic and longer term symptomatic effects of flosequinan, a new direct acting arteriolar and venous vasodilator, was therefore carried out in patients with heart failure. In one group of patients flosequinan increased cardiac output and caused a fall in pulmonary capillary wedge pressure, both effects lasting for 24 hours. In a double blind, placebo controlled study in another group flosequinan improved mean exercise tolerance from 9.9 to 12.7 minutes after four weeks of treatment. The drug also reduced perceived exertion during submaximal exercise and increased calf and therefore skeletal muscle blood flow. It reduced plasma renin activity and noradrenaline concentrations. Flosequinan possesses all the important properties of a drug likely to be of value in the treatment of heart failure.

Advanced training for ambulance crews: implications from 403 consecutive patients with cardiac arrest managed by crews with simple training.

Sixty seven ambulance staff in Nottinghamshire completed a simple extended training programme in managing cardiac arrest and using a defibrillator. This enabled around one third of the ambulance emergency shifts to be manned by such a crew, with a defibrillator as part of their standard equipment. Forty four of 403 consecutive patients who suffered cardiac arrest in the community were managed by these crews and survived to leave hospital. The training programme does not include endotracheal intubation, intravenous infusion, or drug administration. The new official advanced training course for ambulance crews, which includes these skills, is inappropriate in its methods and may delay widespread introduction of emergency ambulances equipped with defibrillators.

Symptomatic assessment of patients with heart failure: double-blind comparison of increasing doses of diuretics and captopril in moderate heart failure.

Ten patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in randomised order. Four different methods were used to assess the patients' response to treatment. Both treatments improved symptom-limited exercise tolerance, higher-dose frusemide having a more favourable effect. Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments. The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments; again higher-dose frusemide had a more beneficial effect. The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea, fatigue, and general well-being.

Abnormalities of the peripheral circulation and respiratory function in patients with severe heart failure.

To investigate the peripheral circulatory and respiratory abnormalities which occur in patients with heart failure, forearm and calf blood flow were measured before and after upright exercise, and respiratory gas exchange was measured during exercise in 26 patients with severe heart failure. Compared with a group of normal subjects the patients had reduced limb blood flow at rest and the response of limb blood flow to upright exercise was also abnormal. The increase in calf blood flow after exercise and the reduction in blood flow in the non-exercising forearm were both smaller in patients than in controls. There was a significant correlation between the maximum exercise duration of the patients and calf blood flow both after exercise and at rest. Compared with another group of control subjects the patients had a higher minute ventilation during exercise and a reduced oxygen consumption. The respiratory exchange ratio during exercise was also higher in patients than in controls. This suggests that there is early onset of anaerobic metabolism during exercise in patients with severe heart failure.

Simple training programme for ambulance personnel in the management of cardiac arrest in the community.

The extended training for ambulance personnel in Nottinghamshire includes a period of training in cardiac resuscitation by defibrillation, and defibrillators are now part of the standard equipment of vehicles used on the accident and emergency service. Comparison of recent results with previous attempts in the City of Nottingham to provide a service for out of hospital cardiac arrest has shown that an elementary training course and the provision of defibrillators on emergency vehicles enables the ambulance service to save the lives of a reasonable proportion of those who suffer sudden death in the community. The extended training programme as a whole has proved acceptable to ambulance personnel and we believe that this programme could be the basis for a more widespread introduction of post basic training.

Effect of aspirin and indomethacin on exercise-induced changes in blood pressure and limb blood flow in normal volunteers.

To evaluate the possible role of prostaglandins in exercise-induced changes in blood pressure and limb blood flow we have compared the effects of aspirin and indomethacin in a double-blind placebo controlled study in a group of normal volunteers. Nine men undertook treadmill exercise after pretreatment with placebo, aspirin and indomethacin. Indomethacin caused a greater increase in systolic blood pressure during exercise than aspirin (p less than 0.05) and a smaller fall in diastolic pressure than either placebo or aspirin (p less than 0.02 and p less than 0.01). Compared with placebo both aspirin and indomethacin attenuated to a similar degree the increase in calf blood flow (p less than 0.05 and p less than 0.03) and the changes in forearm blood flow following exercise. These results suggest that although aspirin and indomethacin both inhibit prostaglandin production they have different effects on exercise-induced changes in blood pressure. They have, however, similar effects on limb blood flow.

Effects of captopril on abnormalities of the peripheral circulation and respiratory function in patients with severe heart failure.

Limb blood flow and respiratory function were compared in ten patients with severe heart failure inadequately controlled by diuretics and normal control subjects matched for age and sex. Both forearm and calf blood flow, at rest and after exercise, were lower in the patients than in the control subjects. Oxygen consumption during submaximal exercise was also lower in the patients and minute ventilation was higher. Captopril, administered in a single-blind controlled study to the patients, resulted in an improvement in these abnormalities, with the exception of oxygen consumption. It also improved exercise tolerance and reduced perceived exertion during exercise. Captopril is effective treatment for severe heart failure and improves some of the peripheral haemodynamic and respiratory abnormalities.

Home care for patients with suspected myocardial infarction: use made by general practitioners of a hospital team for initial management.

Two hundred and sixty three general practitioners were offered the use of a hospital based service consisting of a medical senior house officer, a nurse attached to a coronary care unit, and a specially equipped ambulance estate car to help with the initial management of patients with suspected myocardial infarction who might be suitable for home care. One hundred and sixty nine general practitioners registered as potential users of this service; during 22 months they called the hospital team to see 271 patients, 235 of whom the team suspected had indeed suffered a myocardial infarction. During the same period, however, these general practitioners also admitted 317 patients with suspected myocardial infarction directly to hospital. Other general practitioners admitted 323 patients and deputising doctors 258. A further 529 patients with suspected infarction were admitted without the intervention of a general practitioner. Of the patients seen by the team, 54 required immediate admission to hospital; 17 of the remaining patients who initially appeared suitable for home care later required admission to hospital. In a large city such as Nottingham the provision of hospital based facilities to help general practitioners with home management is unlikely to make an appreciable impact on the overall pattern of care of patients with suspected myocardial infarction.

The effect of aspirin on peripheral haemodynamic changes following submaximal exercise in normal volunteers.

Eight normal healthy volunteers participated in a study to determine the effect of 1800 mg of aspirin on the peripheral haemodynamic changes that occur following upright exercise. Aspirin reduced the extent of calf hyperaemia (p less than 0.05) and accentuated the reduction in forearm blood flow (p less than 0.05) following exercise. It had no effect on either calf or forearm blood flow at rest. These results indicate that aspirin, possibly by inhibiting prostacyclin production, modifies the circulatory changes following upright exercise.