High risk of thromboemboli early after bioprosthetic cardiac valve replacement.

OBJECTIVES: We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or both, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors. BACKGROUND: Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain. METHODS: The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and > 90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated. RESULTS: Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and > 90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (< 1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thromboembolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died. CONCLUSIONS: Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.

Arrhythmias and cellular electrophysiological changes during myocardial "ischaemia" and reperfusion.

Action potentials and ECGs were recorded from isolated guinea pig hearts during low flow (10% of control) and zero flow myocardial "ischaemia" and during subsequent reperfusion. During myocardial "ischaemia" ventricular tachycardia and ventricular fibrillation were significantly more frequent during low flow, than zero flow "ischaemia" (P less than 0.01). Reperfusion arrhythmias required a minimum ischaemic period of 10 to 15 min, were most frequent following 20 to 30 min of "ischaemia", being fewer following 60 min of "ischaemia" (P less than 0.05). The degree of "ischaemia" had little effect on reperfusion arrhythmias following 20 to 30 min of "ischaemia". Both types of "ischaemia" reduced action potential amplitude, Vmax, and duration, and increased conduction time. During low flow "ischaemia", electrophysiological change reached a nadir at 12 +/- 3 (mean +/- SEM) min, and in all cases spontaneous electrophysiological recovery in action potentials and conduction time preceded ventricular arrhythmias, which occurred at 18 +/- 3 min. In contrast during zero flow "ischaemia" electrophysiological changes were more marked and no recovery was observed. Refractory periods were initially prolonged by both forms of "ischaemia", followed by a marked shortening. The initial prolongation was more marked and subsequent shortening less during zero than low flow "ischaemia". Reperfusion induced electrophysiological recovery in all hearts; however reperfusion VF was preceded by further shortening of action potential duration and refractory period. These results indicate that residual flow during myocardial "ischaemia" is associated with spontaneous electrophysiological recovery and more frequent ventricular arrhythmias. The severity of "ischaemia" is less important than its duration for the development of reperfusion arrhythmias.

Effects of sotalol on arrhythmias and electrophysiology during myocardial ischaemia and reperfusion.

Isolated, buffer perfused guinea pig hearts were used to study the effects of sotalol on arrhythmias and electrophysiology during 30 min of myocardial ischaemia, induced by reducing coronary flow to 10% of control, and subsequent reperfusion. Action potentials were recorded using the floating microelectrode technique and arrhythmias were noted and defined by extracellular electrical records. Sotalol 10(-4) mol X litre-1 reduced the incidence of ventricular arrhythmias during myocardial ischaemia and reperfusion. Prior to the onset of ischaemia sotalol reduced action potential amplitude and Vmax, and prolonged action potential duration, refractory period, and conduction time, and increased pacing threshold. During myocardial ischaemia the effect of sotalol on action potential duration disappeared, and that on refractory period was diminished. The effect of sotalol on action potential amplitude and Vmax was reduced during the early (2 to 12 min) part of ischaemia, but later, at the onset of arrhythmias, tended to reemerge, while the effect on QRS width was exaggerated. Thus the cellular electrophysiological effects of sotalol on normal myocardium provided a poor guide to the mechanism of its antiarrhythmic action in ischaemic tissue.

Exogenous nitric oxide inhibits in vivo platelet adhesion following balloon angioplasty.

OBJECTIVES: The aim was to investigate the effects of an exogenous source of nitric oxide on in vivo platelet adhesion at the site of endothelial denudation after balloon angioplasty. METHODS: The study group consisted of 12 anaesthetised Large White pigs. Pigs were randomised to receive SIN-1 (3-morpholino-sydnonimine), an exogenous donor of nitric oxide, or placebo before and during balloon induced vessel wall injury. Platelet deposition was quantified using the injection of autologous 111indium labelled platelets. Platelet function was also monitored by the measurement of bleeding time and ex vivo whole blood aggregometry. RESULTS: Superficial vessel wall injury was confirmed histologically and platelet monolayer formation was demonstrated by scanning electron microscopy. Platelet deposition at the site of endothelial denudation was markedly reduced following SIN-1 administration compared to placebo: 1.266(SEM 0.063) v 1.732(0.060) log platelets x 10(5).cm-2, p = 0.001. SIN-1 raised platelet cyclic GMP concentration, from 4.47(2.48) to 6.14(2.44) pg.platelet-1 (p less than 0.01) and prolonged the bleeding time, from 135(5) to 202(6) s (p = 0.001), but had non-significant effects on ex vivo whole blood aggregometry. CONCLUSIONS: Exogenous nitric oxide, through the activation of platelet soluble guanylate cyclase, inhibits platelet adhesion in vivo following balloon angioplasty.

Effects of myocardial catecholamine depletion on cellular electrophysiology and arrhythmias during ischaemia and reperfusion.

The effect of myocardial catecholamine depletion on cellular electrophysiology and arrhythmias was assessed in Langendorff perfused guinea pig hearts during ischaemia and reperfusion. Myocardial noradrenaline was reduced to 0.17 +/- 0.04 microgram X g-1 by intracardiac injection of 6-hydroxydopamine (450 mg X kg-1 in six doses over 20 days) compared with 1.5 +/- 0.2 microgram X g-1 in vehicle injected controls. Myocardial catecholamine depletion significantly reduced the incidence of ventricular tachycardia and fibrillation during 30 min of global ischaemia and subsequent reperfusion. Myocardial catecholamine depletion prolonged action potential duration and refractory period during control perfusion and blunted ischaemia induced reduction in action potential amplitude, Vmax, and duration, but accentuated the prolongation in conduction time and QRS width. Catecholamine depletion abolished or attenuated reperfusion induced shortening of action potential duration and refractory period. Catecholamine depletion increased myocardial glycogen levels from 2.47 +/- 0.3 mg X g-1 wet weight to 4.39 +/- 0.3 mg X g-1; fasting animals for 48 h prior to study reversed this with no attenuation of the electrophysiological or antiarrhythmic action. These results provide further evidence that release of endogenous myocardial catecholamines contributes to the electrophysiological changes and arrhythmias associated with myocardial ischaemia and reperfusion.

The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty.

OBJECTIVES: Nitric oxide reduces platelet adhesion and platelet-thrombus formation following angioplasty and inhibits smooth muscle cell (SMC) proliferation in vitro. In this study we investigated the effects of the nitric oxide donor molsidomine on SMC proliferation and intimal growth following experimental angioplasty. METHODS: Bilateral carotid angioplasty was performed in 24 anesthetized pigs. Animals were randomized to receive oral molsidomine (whose active metabolite is SIN-1; 0.3 mg/kg every 8 h; n = 12) or placebo (n = 12) for 48 h before angioplasty and until the arteries were removed either 7 or 21 days (n = 12 each group) later. SMC proliferation was quantified by immunocytochemical staining with an antibody to the proliferating cell nuclear antigen (PCNA) and morphometric changes by computerized planimetry. SMC's were identified by alpha-actin staining. RESULTS: After 3 weeks treatment with molsidomine there was a significant prolongation in bleeding time [mean +/- SEM] (151 +/- 6 to 187 +/- 7 s. P < 0.01) and a sustained increase in arterial wall cyclic GMP (6.57 +/- 1.29 to 13.24 +/- 1.02 pmol/mg protein, P < 0.05). Molsidomine significantly reduced intimal proliferation when compared with placebo in arteries with an intact internal elastic lamina at 7 days (4.3 +/- 0.7 vs. 9.6 +/- 1.9 PCNA index, P < 0.005) and medial proliferation at 7 days (2.4 +/- 0.2 vs. 4.2 +/- 0.7 PCNA index, P < 0.05) and at 21 days (1.3 +/- 0.1 vs. 1.9 +/- 0.2 PCNA index, P < 0.05) after angioplasty. In arteries with rupture of the internal elastic lamina, intimal and medial SMC proliferation were similar in molsidomine- and placebo-treated animals. Intimal cell number and intimal area were uninfluenced by treatment with molsidomine in either the presence or absence of rupture of the internal elastic lamina. CONCLUSIONS: These results show for the first time that exogenous nitric oxide inhibits SMC proliferation following balloon angioplasty in vivo. The antiproliferative effects of nitric oxide are overwhelmed when injury is severe and are not associated with a reduction in intimal thickening. The inhibitory effects of nitric oxide on platelet adhesion and SMC proliferation identify a possible role for high local concentrations of nitric oxide to modify the vascular response to balloon angioplasty.

Kinetics of smooth muscle cell proliferation and intimal thickening in a pig carotid model of balloon injury.

Restenosis as a result of neointimal smooth muscle cell accumulation is an important limitation to the effectiveness of balloon angioplasty as a treatment for end-stage atherosclerosis. Quantitative animal models allow the definition of pathophysiological mechanisms and the evaluation of new therapeutic strategies. In this study we quantified the time course of neointima formation by morphometry, and smooth muscle cell (SMC) proliferation by immunocytochemistry for proliferating cell nuclear antigen (PCNA), in the pig carotid artery 0-28 days following balloon injury. This led to two distinct kinds of injury observed also in clinical studies, namely medial dilatation or deep medial tearing with rupture of the internal elastic lamina. Dilatation injury alone led to medial enlargement and neointima formation by 7 days, which did not increase further up to 28 days. Medial enlargement was similar following rupture of the internal elastic lamina; however the sum of neointima formation plus the area of medial repair ('neomedia') increased progressively up to 21 days after balloon injury. Balloon injury increased the PCNA index of smooth muscle cells in the media underlying an intact internal elastic lamina maximally after 3 days. The PCNA index in the neointima and especially in the neomedia was greater and maximal after 7 days. Endothelial regrowth occurred by 21 days in the presence or absence of medial tears. Our results establish a quantitative pig model of balloon injury which will allow the assessment of new therapeutic strategies directed at two clinically relevant types of injury. Medial tearing is associated with an enhanced and localized proliferative response and may therefore be especially important in human restenosis.

Local delivery of platelets with encapsulated iloprost to balloon injured pig carotid arteries: effect on platelet deposition and neointima formation.

Local delivery of a drug to the arterial wall during angioplasty is an approach which might reduce the incidence of occlusive events such as thrombosis and restenosis, without the risk of systemic side effects. By exploiting their natural primary haemostatic properties, platelets, with encapsulated drugs, can be targeted to a vessel wall injury site and act as a depot for sustained release. The platelet plasma membrane can be reversibly permeabilised by high voltage, short duration electrical pulses (electroporation). Drugs will diffuse into porated platelets and become trapped on resealing. We have studied the effects of autologous platelets, electroloaded with the stable prostacyclin analogue, iloprost on platelet deposition and neointima formation in a pig carotid angioplasty model. Iloprost loaded or control platelets were delivered locally and immediately to the balloon injured site using a double balloon delivery catheter. Acute platelet deposition was measured using 111-Indium, and neointima formation at 21 days post angioplasty was assessed by morphometric analysis. In pigs treated with iloprost loaded platelets, platelet deposition on the artery at 2 hours post injury was dramatically reduced (to approximately monolayer coverage), when compared with arteries from pigs treated with control platelets. In pigs with deeply injured arteries, i.e. with extensively ruptured internal elastic lamina (IEL), platelet deposition was reduced by 88% compared with control arteries (118 +/- 20 x 10(6)/cm vs. 14 +/- 2 x 10(6)/cm, means +/- SI, 2P < 0.001). In minimally injured arteries (IEL intact) a 65% reduction in platelet deposition was observed (55 +/- 24 x 10(6)/cm vs. 19 +/- 3 x 10(6)/cm. 2P < 0.002). A high concentration of free iloprost, delivered to the angioplasty site, with control platelets, had far less effect on platelet deposition, substantiating the advantage of platelet encapsulation. At 21 days post injury, morphometry of the carotid arteries after treatment with iloprost loaded platelets showed significant reductions in intimal area and intimal/medial ratios in minimally injured vessels (P < 0.05) as compared with vessels from pigs treated with control platelets. With deeply injured vessels, the mean differences (control vs. treated) for the same morphometric parameters were not significant. This novel approach of electro-encapsulating drugs within autologous platelets, and using them as highly biocompatible and biodegradable drug targeting vehicles might, with the appropriate choice of encapsulated agent, have potential for reducing the incidence of occlusion after angioplasty and thrombolysis procedures.

Antithrombotic therapy for patients with cardiac disease.

The use and type of antithrombotic therapy for patients with cardiac disease are described based on an understanding of the pathophysiologic mechanisms involved, the risk of thromboembolism, and the evidence from prospective and, if necessary, retrospective clinical trials. The indications and intensity of anticoagulant therapy in patients with valvular heart disease and prosthetic valves are first discussed. We recommend that the prothrombin time be reported as a ratio and standardized using the International Normalized Ratio. The pivotal role of platelets and the clotting system in the initiation and progression of atherosclerosis and the acute coronary syndromes is described. There is no evidence to date that antiplatelet therapy is of value in primary prevention or in patients with stable angina, but the value of aspirin in patients with unstable angina was clearly shown in two well-designed studies. Adequate prophylactic therapy to prevent the thrombotic complications of acute myocardial infarction (i.e., venous thrombosis and intracardiac thrombosis) is described, and the available data on the prevention of coronary reocclusion after thrombolysis reviewed. There is now convincing evidence from studies in animals and in patients that vascular injury during aortocoronary vein bypass graft surgery requires antitihrombotic therapy starting before the procedure to minimize acute platelet thrombus deposition and prevent occlusion. Restenosis after arterial angioplasty appears to be related to acute platelet thrombus deposition on the site of deep arterial injury. Therapeutic interventions should probably involve both anticoagulants and platelet inhibitor therapy. Implications derived from recent animal studies are discussed.

Hibernating myocardium caused by isolated, radiation induced left main stem coronary artery stenosis.

A 45 year old man presented with a five week history of worsening exertional dyspnoea and orthopnoea. He had also noted mild, bilateral ankle swelling. The patient had been diagnosed with stage III Hodgkin's lymphoma in 1968 at the age of 21. During the same year he underwent total nodal irradiation followed by chemotherapy in 1971. He had remained entirely asymptomatic over the course of the next 24 years with no evidence of relapse. Cardiac catheterisation undertaken soon after admission revealed a tight left main stem stenosis with a left dominant system. Left ventriculogram showed severe, global hypokinesia, and raised left ventricular end diastolic pressure (22 mm Hg). Urgent coronary artery bypass graft surgery was carried out. He made an uncomplicated recovery and his condition improved sufficiently to allow discharge eight days following the procedure. His heart failure slowly resolved and repeat transthoracic echocardiogram performed six months after surgery showed an unequivocal improvement in left ventricular function. Left ventricular ejection fraction continued to improve and increased from 23% at two months to 42% at two years. He currently remains entirely asymptomatic off all medication.

Acute myocardial infarction: are there missed opportunities for reperfusion? UK Heart Attack Study Investigators.

AIMS: To investigate the current use of thrombolytic therapy in the management of patients with acute myocardial infarction and to determine the potential for an increased use of thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: All hospitalised cases of acute myocardial infarction were identified in three health districts in the UK (population of 960,000) in patients under the age of 76 years during a 2-year period; 2439 patients had acute myocardial infarction, of whom 1264 (52%) received thrombolytic therapy. Failure to administer thrombolytic therapy was a result of the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%) patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as a contra-indication could, in retrospect, have received thrombolytic therapy and a further 76 would have been suitable for primary PTCA. CONCLUSIONS: The potential for increasing the use of thrombolytic therapy seems to be limited and is unlikely to make a major impact on the in-hospital mortality from acute myocardial infarction. However, primary PTCA should be considered in those who are ineligible for thrombolysis because of bleeding risk as a contra-indication.

Prevalence of inflammatory bowel disease amongst Mormons in Britain and Ireland.

The prevalence of Crohn's disease (79/10(5)), ulcerative colitis (389/10(5)) and appendicectomy (2751/10(5)) were measured in a survey of the Mormon church in Britain and Ireland. Details were obtained from 230 of the 342 branches in Britain which had a membership of 56,000 people although only 17,700 people were active members. The prevalence of Crohn's disease was comparable to that reported from various centres in Britain, but ulcerative colitis was significantly commoner amongst Mormons while the frequency of appendicectomy was significantly reduced.

Cardiorespiratory response to exercise before and after acute beta-adrenoreceptor blockade in nonsmokers and chronic smokers.

To evaluate the effects of chronic smoking on exercise performance we studied 5 smokers and 7 nonsmokers of comparable age and physical characteristics. The resting heart rate in smokers (75 +/- 3 beats/min; mean +/- SD) was significantly (P less than 0.01) higher than in nonsmokers (64 +/- 5). During exercise on a bicycle ergometer the heart rate remained significantly (P less than 0.01) higher in smokers than in nonsmokers. After exercise, the heart rate in nonsmokers settled to 78 +/- 9 beats/min at 10 minutes compared with 105 +/- 11 (P less than 0.01) in smokers. Oxygen consumption was similar in both groups throughout. Beta-adrenergic blockade reduced the exercise tachycardia in both groups but the heart rate for the same workload remained significantly (P less than 0.01) higher in smokers. Beta-blockade significantly reduced (P less than 0.05) oxygen consumption in nonsmokers but not in smokers who also incurred a significantly (P less than 0.05) greater oxygen debt and had higher serum lactate levels. These differences were attributed mainly to carboxyhaemoglobinaemia and partly to the effect of prolonged smoking on the heart and on intermediary metabolism.

Reversibility and benign recurrence of complete heart block in athletes.

In two patients, symptoms associated with complete heart block and physical training resolved with deconditioning. In one patient, symptoms recurred after resumption of training but she has remained well for 4 years without a pacemaker. This suggests that complete heart block induced by fitness is benign, even when symptomatic.

Coronary microangiography in the guinea pig, rabbit and ferret.

Using improved methods, we have developed a microangiographic technique for studying the coronary circulation in Langendorff perfused guinea pig, rabbit and ferret hearts. Striking anatomical differences were observed between these species. In the guinea pig, the interventricular septum was supplied by a large septal artery which always arose from the right coronary artery, whereas in the rabbit and ferret, the septal artery was smaller and originated from the left coronary artery. The circumflex artery was more prominent than the right coronary artery in the ferret and guinea pig, whereas the reverse pertained in the rabbit. Extensive apical collateral connections were observed between terminal branches of the left anterior descending, left ventricular branches and the septal artery in the guinea pig, while collaterals were usually absent in the rabbit and ferret. These species differences in the myocardial blood supply have wide ranging implications regarding the choice of small animals for cardiac research.

The incidence and significance of early pericardial effusion after open heart surgery.

The presence and severity of postoperative pericardial effusions were studied echocardiographically in 114 consecutive patients (70 males, 44 females; mean age 56 +/- 10 years). An effusion was present in 35 patients at 3-5 days. An effusion was less common when a drainage tube was inserted for 24-36 h in the posterior as well as the anterior mediastinum than when only an anterior drain was used. Patients with effusions differed from those without in having more supraventricular arrhythmias, more wound infections, smaller total blood drainage and longer postoperative hospital stay. Three patients with posterior pericardial effusions developed cardiac tamponade 5-18 days postoperatively. The data show that pericardial effusions are associated with postoperative complications and suggest that effusion formation can be reduced by using posterior as well as anterior chest drains.

Prospective randomized trial of single clamp technique versus intermittent ischaemic arrest: myocardial and neurological outcome.

OBJECTIVE: To explore the hypothesis that intermittent ischaemic arrest (IIA) provides better myocardial preservation but generates a larger number of cerebral microemboli (ME) and consequently a higher incidence of post-operative cerebral dysfunction compared with the single clamp technique (SCT). METHODS: Ninety-one patients with stable angina undergoing elective CABG with no clinical evidence of aortic or cerebro-vascular or neurological disease were prospectively randomized to: IIA (n = 43) or SCT with intermittent anterograde cold blood cardioplegia (n = 48). Myocardial preservation was assessed by measuring serum CK-MB, Troponin-T (TnT) and Troponin-I (TnI) and from pre- and post-operative ECGs and left ventricular (LV) function by echocardiography. Intra-operative cerebral ME were counted by transcranial Doppler of the right middle cerebral artery. All patients completed the Luria Nebraska Neuropsychological Battery (LNNB) tests for motor, visual, reading, memory and intellectual processes the day before surgery and at 1 week and 6 months post-operatively. Serum levels of the neuro-specific protein S-100 were measured. RESULTS: The two groups were comparable for age, sex, extent of coronary disease, previous myocardial infarction, diabetes, hypertension and number of arterial and venous grafts. The median number of ME detected per patient was 34 (range 4-208) and was similar in both groups. Protein S-100 levels remained normal and similar in both groups at all times except in one patient with SCT who had an operative stroke. LNNB scores were similarly depressed at 1 week and recovered in all cases at 6 months. There was no correlation between the number of ME and LNNB scores. Median peak TnI levels were 0.64 microg/l with IIA vs. 0.87 microg/l with SCT (P = NS) and TnT 0.8 microg/l vs. 1.08 microg/l (P < 0.03). SCT was however associated with longer mean ischaemic (67.6 +/- 16.1 vs. 34.5 +/- 16.5 min, P < 0.001) and mean bypass time (88.5 +/- 18.2 vs. 74.6 +/- 26.3 min, P < 0.004) than IIA. Four patients with SCT and none with IIA had ECG changes suggestive of MI (P = 0.04). CONCLUSION: During elective CABG in patients with no clinical evidence of aortic or cerebro-vascular disease the incidence of peri-operative ME and post-operative neuropsychological disturbances are comparable with both techniques of myocardial preservation. Biochemical analysis suggests that IIA provides more effective myocardial preservation.

Post-infarction ventricular septal defect: the importance of right ventricular coronary perfusion in determining surgical outcome.

Mortality from a post-infarction ventricular septal defect (VSD) can be reduced by surgery, selection for which would be helped by knowledge of factors affecting the postoperative prognosis. We reviewed our 9-year experience (1978-1987) of 40 surgically treated patients, comparing preoperative characteristics in those who died postoperatively (n = 15, 37%) and those who survived (n = 25, 63%), all still alive. Sex, age, infarct size as assessed by peak serum creatine kinase values, left ventricular end-diastolic pressure and pulmonary/systemic flow ratio (2.9 +/- 0.2 vs 3.1 +/- 0.3) were similar. Survivors had a lower incidence of inferior infarct than those who died (6, 24% vs 9, 60%, P less than 0.05), a lower incidence of cardiogenic shock (7, 28% vs 10, 67%, P less than 0.05), less elevation of right ventricular end-diastolic pressure (10.1 +/- 0.9 vs 14.7 +/- 1.0 mm Hg, P less than 0.01) and less impairment of right ventricular coronary supply as determined by a coronary angiography-derived myocardial score (0.9 +/- 0.3 vs 4.7 +/- 0.7, P less than 0.001). The data suggest that right ventricular coronary perfusion influences prognosis. The proposed angiographic score may help to identify preoperatively those patients most likely to benefit from surgery.

A microcomputer system for real-time analysis of cardiac action potentials.

A system for performing real-time analysis of cardiac action potentials has been developed using a microcomputer based on the Motorola 6800 central processor. Transmembrane potentials obtained using standard microelectrodes were digitized to 8 bits at 80 ms intervals, stored in cyclic memory buffer from which they could be selected for analysis, converted back to analogue form and displayed on an oscilloscope in real time. For each action potential, amplitude, the maximum rate of change of potential and the action potential duration at 50% repolarization and 100% repolarization were measured. In addition, conduction time (taken as the interval between the stimulus artefact and the action potential) was measured. All data were stored in memory and later printed, together with the time at which the recording was made. The system was designed for analysis of action potentials recorded using floating microelectrodes. The computer was controlled by three remote switches and a potentiometer, positioned close to the muscle bath. The program was written in Motorola 6800 assembly language and stored in erasable programmable read-only memory.

Guidelines for the early management of patients with myocardial infarction. British Heart Foundation Working Group.

In light of recent publications relating to resuscitation and pre-hospital treatment of patients suffering acute myocardial infarction of British Heart Foundation convened a working group to prepare guidelines outlining the responsibilities of general practitioners, ambulance services, and admitting hospitals. The guidelines emphasise the importance of the rapid provision of basic and advanced life support; adequate analgesia; accurate diagnosis; and, when indicted, thrombolytic treatment. The working group developed a standard whereby patients with acute myocardial infarction should receive thrombolysis, when appropriate, within 90 minutes of alerting the medical or ambulance service--the call to needle time. Depending on local circumstances, achieving this standard may involve direct admissions to coronary care units, "fast track" assessments in emergency departments, or pre-hospital thrombolytic treatment started by properly equipped and trained general practitioners.