Effectiveness of a planned strategy using cardiac rehabilitation nurses for the management of dyslipidemia in patients with coronary artery disease.

BACKGROUND: Firm evidence exists for reduction in mortality and morbidity by lipid-lowering therapy in patients with coronary artery disease (CAD), yet a significant proportion remain untreated. This prospective study determined the effectiveness of a planned strategy of management using a cardiac rehabilitation nurse in achieving (1) lower 6-month low-density lipoprotein (LDL) levels and (2) a higher proportion of patients on pharmacologic therapy. METHODS: A cardiac rehabilitation nurse arranged for the lipid profiles and initiated pharmacologic therapy as soon as possible after the diagnosis of CAD. In phase 1, this planned-strategy intervention group (n = 80) was compared with the usual-care control group (n = 189), where the management was left at the discretion of the attending cardiologist with the assignment to the 2 groups based on the weekly on-call rotations of the attending cardiologists in a nonrandomized manner. In phase 2 of the study all patients (n = 366) were enrolled in the planned strategy of management. RESULTS: There were no significant differences in the baseline lipid values between the control and intervention groups. The 6-month cholesterol and LDL values and the percentage of patients on lipid-lowering medications were significantly better in the intervention group (P =.01). In phase 2 the results obtained in the intervention group were duplicated in a much larger group of consecutive patients. The 6-month (millimoles per liter) results in the control, intervention, and phase 2 groups (respectively) were cholesterol 4.92 +/- 0.06, 4.60 +/- 0.07, 4.30 +/- 0.05; low-density lipoprotein 2.91 +/- 0.06, 2.68 +/- 0.07, 2.4 +/- 0.06; high-density lipoprotein 1.18 +/- 0.07, 1.12 +/- 0.09, 1.10 +/- 0.01; triglycerides 1.89 +/- 0.12, 1.78 +/- 0.09, 1.70 +/- 0.05; and on medications 49%, 83%, and 84%. CONCLUSION: A planned strategy of management with use of early pharmacologic therapy with a cardiac rehabilitation nurse assigned to obtain and follow lipid profiles and initiate therapy is more effective in controlling dyslipidemia than leaving the management to the cardiologist.

Possible ethnic differences in plasma homocysteine levels associated with coronary artery disease between south Asian and east Asian immigrants.

BACKGROUND: Hyperhomocysteinemia has been identified as a risk factor for coronary artery disease (CAD). South Asians appear to have a high incidence of CAD, while East Asians have a very low incidence. HYPOTHESIS: The present study was undertaken because the relative association of plasma homocysteine levels (PH) with CAD in South Asians (SA = Indian, Pakistani, Sri Lankan) and East Asians (EA = Chinese, Japanese) is not known. METHODS: Fasting PH were drawn on all patients with CAD of SA (age 62.4+/-1.1 years, 72 men, 14 women) and EA (age 61.8+/-3.0 years, 13 men, 4 women) descent. These were compared with PH available from Caucasian (CA) patients (age 61.1+/-1.1 years, 89 men, 17 women) with CAD. RESULTS: The PH in SA, EA, and CA patients were 11.0+/-0.5, 7.6+/-0.5, and 10.8+/-0.6 micromol/l, respectively (p<0.001 between EA and SA/CA). Percentages of SA, EA, and CA with elevated PH (> 12.0 micromol/l) were 33.7, 5.9, and 28.2%, respectively. There were no significant differences in the lipid subfractions between the SA and EA group. History of smoking was significantly higher in the EA (52.9 vs. 26.2%), while hypertension and diabetes mellitus had similar prevalences. CONCLUSION: Significant differences in PH of SA versus EA patients with CAD exist. The relative contribution of homocysteine in the development of CAD appears to be less in EA immigrants. In contrast, the association between CAD and PH in SA immigrants appears to be similar to that of Caucasians.

Efficiency and cost saving of 7 day per week exercise testing utilizing all electrocardiography technologists.

BACKGROUND: In most centers, exercise testing (ET) is performed by one or two trained technologists during the weekdays (0800 hours-1600 hours), leaving a void during evenings and weekends. This leads to unnecessary increased costs due to delays in management of patients. Electrocardiography technologists (ECGT) are often available for extended hours. This project was undertaken to improve the efficiency of the ET laboratory by using ECGT to perform ET during these extended hours. METHODS: Clinical utility and cost saving of a 7 day per week ET for management of patients with suspected and/or known coronary artery disease utilizing ECGT was assessed after adequate training. Of 4099 patients undergoing ET between January 1995 and December 1997, 810 tests performed by ECGT were reviewed retrospectively. RESULTS: Of the 810 patients (age mean 58.4 +/- 0.44 yrs; range 16-88; males: 508, females: 302), 806 (99.5%) underwent the Bruce protocol. The indications were: diagnostic, 61.3%, predischarge acute myocardial infarction (AMI), 17.7%, evaluation of angina, 19.6%, other, 1.4%. Only 8 (0.1%) patients had complications (prolonged chest pain, 6; nonsustained ventricular tachycardia, 2) with no AMIs or deaths. This strategy resulted in a savings of 158 bed days (Can189,600 dollars) on inpatients and 15 bed days (Can18,000 dollars) on those presenting to the emergency department. CONCLUSIONS: This study demonstrates the feasibility and safety of utilizing ECGT for ET thus extending the hours of service. This resulted in efficient patient management, with a considerable cost-saving to the hospital.

Elevation of plasma homocysteine levels associated with acute myocardial infarction.

OBJECTIVE: To study the effect of acute myocardial infarction (AMI) on plasma homocystein (Hcy) levels, to determine the optimal time to measure this risk factor for coronary artery disease. DESIGN: A prospective case study. SETTING: The Division of Cardiac Sciences, Grey Nuns Hospital in Edmonton. PATIENTS: Sixty-two patients (40 men, 22 women) admitted to hospital with AMI. INTERVENTION: Measurement of Hcy levels within 48 to 72 hours of admission and at 6 weeks after discharge from the Coronary Care Unit. In a second group of 15 patients, the Hcy levels were measured on hospital days 1 and 3. MAIN OUTCOME MEASURE: Comparison of the Hcy levels measured at the time of AMI and after discharge. RESULTS: Mean (and standard error of the mean) Hcy level measured during the AMI (13.6 [0.98] micromol/L) was significantly higher (p < 0.05) than at 6 weeks (12.1 [1.01] micromol/L). Based on the 48- to 72-hour and 6-week determinations, 31 and 21 patients, respectively, had abnormal Hcy levels (greater than 12 micromol/L) (p < 0.001). In the separate group of 15 patients, the Hcy level measured on day 3 (9.7 [0.6] micromol/L) was noted to be significantly higher (p < 0.01) than on day 1 (7.7 [0.8] micromol/L). CONCLUSIONS: There is an elevation of Hcy during AMI that may be related to an increase in the acute-phase reactant proteins. Thus, Hcy measurement should be deferred for 6 weeks in order to determine the true baseline level.

Feasibility and safety of early exercise testing using the Bruce protocol after acute myocardial infarction.

OBJECTIVE: To assess the feasibility and safety of exercise testing (ET) using a Bruce protocol (BPR) within three days of an acute myocardial infarction (AMI) with the data obtained from a prospectively managed database. BACKGROUND: Exercise testing after AMI is usually done between days 4 and 6 and often using a "low-level" protocol. Earlier testing with BPR may allow for efficient triage. METHODS: Patients were considered for early ET when off intravenous nitroglycerine with no rest angina, uncontrolled cardiac failure or arrhythmias. RESULTS: Of 300 consecutive AMI patients who underwent an ET, 216 (72.0%; M = 163, F = 53; age mean 59 +/- 0.8 SEM, range 34 to 83 years) had ET within three days of admission. There were 124 (57%) negative, 56 (26%) positive and 36 (17%) indeterminate tests. The maximum heart rate achieved was 116 +/- 1 beats/min (range 64 to 163), which was 72.2 +/- 0.8% of predicted maximum (86.6% on beta-adrenergic blocking agents at ET; exercise duration = 6.7 +/- 0.2 min). Reasons for termination: maximum effort-89 (41%); low-level test target (stage III/IV of BPR)-63 (29%); positive ST segment change-19 (9%); severe chest pain-12 (5.5%); reaching 90% predicted maximum heart rate-6 (3%); nonsustained ventricular tachycardia-1 (0.5%); other-26 (12%). Fourteen (6.5%) patients had minor complications (i.e., drop in systolic pressure, chest pain >5 min) with no cardiac arrests, AMIs or deaths. After the ET, 87 (40%) patients were discharged the same day, 73 (34%) the next day. CONCLUSIONS: The majority of ETs after an AMI can be done using the Bruce protocol within three days of admission with a very low incidence of complications. This can lead to early triage and potential cost savings.

Feasibility of direct discharge from the coronary/intermediate care unit after acute myocardial infarction.

OBJECTIVES: This investigation was designed to determine the feasibility and cost-effectiveness of direct discharge from the coronary/intermediate care unit (CICU) in 497 consecutive patients with an acute myocardial infarction (AMI). BACKGROUND: Although patients with an AMI are traditionally treated in the CICU followed by a period on the medical ward, the latter phase can likely be incorporated within the CICU. METHODS: All patients were considered for direct discharge from the CICU with appropriate patient education. The 6-week postdischarge course was evaluated using a structured questionnaire by a telephone interview. RESULTS: There were 497 patients (men = 353; women = 144; age 63.5 +/- 0.6 years) in the study, with 29 in-hospital deaths and a further 11 deaths occurring within 6 weeks of discharge. The mode length of CICU stay was 4.0 days (mean 5.1 +/- 0.2 days): 1 to 2 (12%), 3 (19%), 4 (21%), 5 (14%), 6 to 7 (19%) and > or = 7 (15%) days, respectively with 87.2% discharged home directly. Of the 425 patients surveyed, 119 (28.0%) indicated that they had made unscheduled return visits (URV) to a hospital or physician's office: 10.6% to an emergency room, 9.4% to a physician's office and 8.0% readmitted to a hospital. Of these URV, only 14.3% occurred within 48 h of discharge. Compared to historical controls, the present management strategy resulted in a cost savings of Cdn. $4,044.01 per patient. CONCLUSIONS: Direct discharge from CICU is a feasible and safe strategy for the majority of patients that results in considerable savings.

Outcomes of an ambulatory cardiac pacing program: indications, risks, benefits, and outcomes.

UNLABELLED: The purpose of this review was to evaluate the economical benefits and outcomes of an ambulatory pacing system implantation program that began in 1991 for new and replacement pacing system implantations. Patient access, incidence of complications, hospital bed day utilization, economic impact, safety, and practicality of the Ambulatory Pacing System Implantation Program was retrospectively reviewed from August 1991 to March 1994. The Ambulatory Pacing System Implantation Program includes pre-operative outpatient assessment in the pacemaker clinic, admission to the Day Medical Unit followed by same day pacing system implantation, discharge home after a short period of observation, and, in selected cases, cardiac monitoring, followed by pacemaker clinic visit 24-hours postimplantation. RESULTS: Two hundred four cardiac pacing systems, 154 new and 50 replacements (pulse generator/leads), were implanted under the guidelines of the Ambulatory Pacing System Implantation Program between August 1991 and March 1994. Eighty-seven percent of the patients were implanted with passive fixation leads, the remaining with active fixation leads; all but four of which were leads implanted in the atria. Preprocedure wait time was decreased from 16 to 2 days for elective pacing system implantation. The incidence of lead dislodgment in the first, second, and third year of the Ambulatory Pacing System Implantation Program was 20%, 12%, 5%, respectively; compared to 11% for a similar number of cases in previous years done as inpatients. The incidence of new infection was 2.4% compared to < 1% in previous years. Six of the 204 (2%) cases required admission overnight. A total savings of 1,456 bed days ($1,275,450.00; Canadian) has been realized for an equivalent number of cases when compared with previous years. The operational cost was reduced by $3,976.00 per case. CONCLUSION: It has been shown that the Ambulatory Pacing System Implantation Program has improved client access, and is a safe and economical approach to implantation of cardiac pacing systems.

Heart rate/stroke volume relationship during upright exercise in long-term diabetics.

The changes in stroke volume (SV) during upright exercise were studied in 20 insulin-dependent diabetics (IDDM) and 20 age- and sex-matched controls. None of the diabetics had any cardiovascular symptoms. In addition, tests of autonomic function were conducted in the diabetics, assessing changes in heart rate (HR) during deep breathing and the Valsalva maneuver. During exercise the SV in the controls gradually increased and then remained essentially unchanged until maximum HR was achieved. Seven of the diabetics failed to sustain an initial increase in SV (fall > 15%), eight showed a "delayed" increase in SV, and the remaining five demonstrated an increasing SV over the range from rest to peak exercise. Abnormal autonomic function results were found during deep breathing (four diabetics) and the Valsalva maneuver (four diabetics). Findings indicate that cardiac function could be abnormal in IDDM without evidence of autonomic dysfunction. This abnormality could be due to a specific cardiomyopathy.

Responses of airway rapidly adapting receptors to bradykinin before and after administration of enalapril in rabbits.

1. The present study was performed in anaesthetized, artificially ventilated, open-chested rabbits to examine whether (a) the rapidly adapting receptors of the airways were stimulated by exogenously administered bradykinin, and (b) if this sensitivity could be enhanced by the angiotensin-converting-enzyme inhibitor, enalapril. 2. Rapidly adapting receptor activity (n = 8) was recorded from the cervical vagus. Bradykinin was injected intravenously (0.25-1.0 microgram/kg) and a dose-response curve relating receptor activity to bradykinin was elicited. In the control state, the threshold dose of bradykinin required for stimulation of rapidly adapting receptors was 0.53 +/- 0.11 microgram/kg. Five minutes after the administration of enalapril maleate (2 mg intravenously), the dose-response curve was shifted to the left significantly (P < 0.01). 3. In seven other rapidly adapting receptors, enalapril (2 mg) increased the resting activity significantly (P < 0.05) over a period of 60 min. This increase was significantly different from the spontaneous variation in neural activity of rapidly adapting receptors (n = 7) recorded over a period of 60 min. 4. Bradykinin either alone (0.25-1.0 microgram/kg) or in the presence of enalapril did not stimulate the slowly adapting receptors (n = 5) of the airways. 5. These results show that (a) exogenous bradykinin stimulates the rapidly adapting receptors, (b) the sensitivity of rapidly adapting receptors to bradykinin is enhanced by enalapril and (c) enalapril increases the resting activity of rapidly adapting receptors. It is suggested that the cough reported after the administration of enalapril may be due to stimulation of rapidly adapting receptors of the airways.

Lovastatin prevents the impairment of endothelium dependent relaxation and inhibits accumulation of cholesterol in the aorta in experimental atherosclerosis in rabbits.

STUDY OBJECTIVE: The aim was to determine the effect of the HMG CoA reductase inhibitor, lovastatin, on the loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta produced by feeding a diet enriched with cholesterol. DESIGN: The study was conducted in two stages. In stage 1, New Zealand white rabbits were randomised into four groups. Group 1 (n = 15) was fed standard rabbit diet for 6 weeks. Groups 2 (n = 15), 3 (n = 12), and 4 (n = 12) were fed standard rabbit diet supplemented with 2% cholesterol for 2 weeks followed by standard rabbit diet only for the next 4 weeks. In addition, lovastatin (4 mg.kg-1.d-1) was given for the entire 6 weeks in group 3 and for the first 2 weeks only in group 4. In stage 2 a second group of animals was fed a diet supplemented with 0.5% cholesterol for 2 weeks in order to match the serum cholesterol levels in groups 3 and 4 of stage 1. EXPERIMENTAL MATERIAL: Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation (to acetylcholine), contractile responses (to noradrenaline), relaxant responses (to sodium nitrite), and sudan staining. Serum was obtained for measurement of cholesterol and triglyceride concentrations. MEASUREMENTS AND MAIN RESULTS: In stage 1, at the end of 2 weeks, the serum cholesterol was significantly lower in groups 3 and 4 than in group 2. At 6 weeks, endothelium dependent relaxation to acetylcholine (-6.0 log mol.litre-1) was impaired in group 2 compared to the other groups: group 1 78.5(SEM 5.0); group 2 43.5(7.8)%; group 3 79.4(4.6)%; group 4 84.7(3.4)%. The relaxant response to sodium nitrite was not impaired in group 2. Further, the aortic tissue cholesterol concentration in group 2 was significantly greater than that in group 1, at 355(65) v 105(10) nmol.mg-1 protein. In groups 3 and 4, the aortic cholesterol concentrations were significantly lower than those in group 2, at 74(4) and 94(17) nmol.mg-1 protein respectively. In stage 2, the serum cholesterol values were matched to those in groups 3 and 4 of stage 1. In these animals, after a further 4 weeks the aortic cholesterol was significantly greater than in group 3. CONCLUSIONS: Lovastatin attenuates the accumulation of cholesterol and preserves endothelium dependent relaxation in this model of experimental atherosclerosis. It is likely that the latter is a secondary phenomenon.

Effect of nisoldipine on atherosclerosis in the cholesterol fed rabbit: endothelium dependent relaxation and aortic cholesterol content.

STUDY OBJECTIVE: The aim was to determine the effect of the calcium channel blocker nisoldipine on the loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta produced by feeding a diet enriched with cholesterol. DESIGN: 12 week old New Zealand white rabbits were assigned randomly to four groups with the following dietary and drug regimens: group A--standard diet + 2.5% cholesterol (n = 45); group B--standard diet + nisoldipine (n = 9); group C--standard diet + nisoldipine + 2.5% cholesterol (n = 9); group D--standard diet (n = 9). After 3 weeks the cholesterol supplements were stopped and all animals were given the standard rabbit diet. The animals in groups B and C were given nisoldipine (1 mg.kg-1.d-1) by mouth for the entire 7 week period. EXPERIMENTAL MATERIAL: Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine, contractile responses to noradrenaline, relaxant responses to sodium nitrite, and sudan staining. Serum was obtained for measurement of cholesterol and triglyceride concentration. MEASUREMENTS AND MAIN RESULTS: At 7 weeks, endothelium dependent relaxation to acetylcholine was impaired in group A compared to group D, while that in group C was not. Aortic tissue cholesterol content in group A was significantly greater than in groups B, C, and D. At 15 weeks, ie, 12 weeks after reversal of the diet, endothelium dependent relaxation had recovered in the animals in group A. There was a significant reduction in the aortic cholesterol content at this stage. In two subgroups of A (groups A2 and A4) which were given nisoldipine immediately after and 4 weeks after cessation of cholesterol feeding respectively, the drug was found to have no influence upon restoration of endothelium dependent relaxation. However, the drug appeared to promote the retention of cholesterol within the aorta after cessation of cholesterol feeding. CONCLUSIONS: Nisoldipine protects against the accumulation of cholesterol and loss of endothelium dependent relaxation in the aorta of rabbits fed a diet supplemented with 2.5% cholesterol for three weeks. Administration of the drug after the lesions are established in the aorta also appears to retard the removal of cholesterol from the aorta.

A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit.

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (-9.0 to -5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (-6.0 log mol/L) was significantly (p less than 0.05) impaired in the experimental group (34.3 +/- 3.8%) compared with that in the control group (79.8 +/- 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 +/- 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 +/- 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.

Risk stratification after percutaneous transluminal coronary angioplasty.

Approximately 20-30% of patients who undergo elective percutaneous transluminal coronary angioplasty (PTCA) require a second angioplasty within 12 months. A significant proportion of patients develop clinical cardiac events during the first year following the initial procedure. The present investigation was undertaken to establish a statistical model for predicting such events. The study group consisted of 100 patients who underwent elective PTCA at the University of Alberta Hospital. All patients were prescribed nifedipine (10 mg tid) and aspirin (325 mg daily) in addition to other medications determined by the attending cardiologist. The patients were reviewed 10 weeks after the procedure and again at the end of 1 year. The follow-up was completed on 96 patients. Within the first year, forty-five experienced cardiac events (1 death, 5 myocardial infarctions, 4 bypass surgeries, 22 repeat PTCAs). These events occurred in 29 patients. An additional 16 patients experienced significant anginal symptoms. A statistical model based upon the patients' perception of symptoms immediately after the procedure, history of hypertension, vessel subjected to PTCA, ejection fraction pre-PTCA, and occurrence of intimal dissection during PTCA was used to identify patients likely to develop cardiac events. Overall, the model classified 72% of the patients (with and without events). Such a statistical model could be used to identify patients who should be subjected to an enhanced degree of cardiologic surveillance in a rehabilitation program.

Persistent impairment of endothelium-dependent relaxation to acetylcholine and progression of atherosclerosis following 6 weeks of cholesterol feeding in the rabbit.

The synthesis and (or) release of endothelium-dependent relaxant factor released by acetylcholine is impaired in New Zealand white rabbits fed an atherogenic diet. Experiments were designed to investigate whether the synthesis and (or) release of the endothelium-dependent relaxant factor from rabbit aortas are restored after reversal from an atherogenic diet to a non-atherogenic diet. Atherosclerosis was induced by feeding a diet containing lipids and 2% cholesterol for 6 weeks. Rabbits were sacrificed after 6 weeks on the atherogenic diet and 36 weeks after return to a standard laboratory diet. Synthesis and (or) release of the factor from the thoracic aorta was assayed using a bioassay system. The relaxant responses produced in the assay tissue were impaired both in the acute stage and after 36 weeks on non-atherogenic food. This impaired relaxation is probably due to a persistent functional abnormality in the aortic endothelium resulting in the failure to synthesize and (or) release endothelium-dependent relaxation factor 36 weeks after induction of atherosclerosis.

Endothelium-dependent relaxation to acetylcholine in the aorta of streptozotocin induced diabetic-rat and the BB-diabetic rat.

Experiments were designed to investigate the phenomenon of endothelium-dependent relaxation (EDR) to acetylcholine in two animal models of insulin dependent diabetes mellitus. Thoracic aortas obtained from streptozotocin diabetic rats and genetically diabetic biobreeding rats (BB rats) were used in this study. Concentration-effect curves to acetylcholine were carried out on aortic rings under isometric tension. Following the induction of diabetes with streptozotocin, half of the animals were treated with daily intermediate acting insulin and the other half maintained without insulin for a period of 12 weeks before the experiment. The diabetic BB rats were also maintained on insulin. The EDR to acetylcholine was not impaired in the aortas of streptozotocin diabetic rats (insulin treated as well as untreated) compared to nondiabetic controls. The scanning electron microscopic (SEM) appearances of the aortic endothelium did not differ among the three groups of animals. However, the EDR to acetylcholine was found to be impaired in the aortas of diabetic BB rats. (Maximum relaxation: 25.3 +/- 5.0% of the contraction to norepinephrine compared to 52.2 +/- 5.3% in controls.) The SEM appearances of the aortic endothelium in the diabetic BB rats were found to be abnormal with edema and loss of definition of cell margins compared to nondiabetic controls. The differences in EDR to acetylcholine seen between the two animal models of diabetes may be related to the different aetiologies of diabetes in the animals.

Exercise testing after myocardial infarction: relative values of the low level predischarge and the postdischarge exercise test.

This study was undertaken to compare the relative values of the low level predischarge exercise test and the postdischarge (6 weeks) symptom-limited test in 518 consecutive patients admitted with an acute myocardial infarction. Of the patients who did not develop significant ST segment depression or angina during the predischarge test, the symptom-limited test also remained negative in 91.5 and 91.9% of the patients, respectively. Similar results were obtained with ST segment elevation and the systolic blood pressure response during the two exercise tests with only 2.1 and 11.4% changing from normal to abnormal, respectively. Discriminant function analysis was done to predict the occurrence of coronary events (unstable angina, reinfarction, cardiac failure, cardiac death) with use of the data from the exercise tests together with other clinical and investigational data. The jackknife method correctly classified 71.9 and 71.4% of the patients with the data from the predischarge exercise test and symptom-limited test, respectively. Combining the data from the two tests improved the overall predictive accuracy to only 75.0%. It is concluded that the routine performance of a symptom-limited test 6 to 8 weeks after infarction does not reveal any significant additional information in those patients who have undergone a predischarge low level exercise test. Thus the 6 to 8 week test should be restricted to selected patients after myocardial infarction.

Impairment of endothelium-dependent relaxation: an early marker for atherosclerosis in the rabbit.

1. Cholesterol feeding of rabbits impairs the endothelium-dependent relaxation (EDR) evoked by acetylcholine (ACh) in the aorta. The experiments described in this paper were undertaken to examine the influence of age upon this phenomenon. 2. Rabbits aged 8 weeks and 46 weeks were fed a diet containing 2% cholesterol and other lipids for 4 weeks. Age-matched control animals were fed a standard rabbit diet. The concentrations of cholesterol and triglycerides in plasma were measured and the extent of atherosclerosis was estimated by staining the aortae with Sudan Red. Light and electron microscopy were undertaken also. 3. Rings of aorta were prepared for recording isometric tension. They were contracted with noradrenaline (NA) and EDR elicited by adding ACh. 4. The young rabbits showed weight gain, hypercholesterolaemia, prominent Sudan Red staining, together with scanning and transmission electron microscopic (SEM and TEM) features of cholesterol-induced atherosclerosis. The older animals showed significant weight loss and hypercholesterolaemia. The aortae of these animals showed no significant sudanophilia or light microscopic features of atherosclerosis. The SEM appearances were similar to the young animals fed cholesterol. 5. EDR to ACh was significantly impaired in both groups of cholesterol-fed rabbits. The maximal relaxations to ACh in young control and cholesterol-fed rabbits were 46.4 +/- 2.9% and 24.0 +/- 4.3% (mean +/- s.e. mean, n = 8, P less than 0.05) of the contractile response to NA (1 mumol 1(-1]. The corresponding results in the age control and cholesterol-fed rabbits were 31.8 +/- 3.9% and 9.1 +/- 1.5% (n = 9, P less than 0.05). 6. The young rabbits were far more susceptible to cholesterol-induced atherosclerosis than older animals and these changes were accompanied by loss of EDR. In the older animals and these changes were accompanied by loss of EDR. In the older animals the loss of the latter property was not accompanied by a significant degree of atherosclerosis although hypercholesterolaemia was present.

Endothelium-dependent relaxation in aorta of BB rat.

The study was undertaken to determine whether the phenomenon of endothelium-dependent relaxation was impaired in the spontaneously diabetic BB Wistar rat. Endothelium-dependent relaxation in the aorta of overtly diabetic animals was compared with that in nondiabetic BB rats. The relaxative responses were elicited in vitro to acetylcholine (-8.0 to -5.5 log M) and histamine (-7.0 to -3.0 log M) after precontraction with norepinephrine (-6.0 log M). The maximum relaxations produced by both acetylcholine and histamine expressed as percentages of the contractions to norepinephrine were significantly lower in diabetic than in nondiabetic rats. Scanning electron microscopy revealed that in diabetic BB rats there was consistent evidence of swollen cells, raised nuclei, and sloughing of nuclei in endothelial cells of the aorta. In nondiabetic animals these features were not evident. These findings suggest the presence of a functional and morphological defect in endothelial cells in the aorta of the BB rat.

Absence of effect of calcium antagonists on endothelium-dependent relaxation in rabbit aorta.

The effect of chronic feeding of New Zealand White rabbits with nicardipine (60 mg kg-1 daily for 5 weeks) on the endothelium-dependent relaxation (EDR) to acetylcholine (ACh) was examined in vitro. The effect of acute exposure to nicardipine and diltiazem (10 mumol l-1) in the tissue bath was also examined. A bioassay system for endothelium-dependent relaxation factor (EDRF) in which a rabbit aortic ring with endothelium removed was used as recipient and a segment of rabbit aorta with endothelium as donor (producing EDRF in response to ACh) was developed. This system enabled the effect of nicardipine on the synthesis/release and on the relaxation to EDRF to be studied separately. The maximum relaxations to ACh in control and nicardipine-fed animals were 43.6 +/- 5.5 and 53.8 +/- 6.7% (mean +/- s.e. mean) of the contractile response to noradrenaline (NA, 1 mumol l-1) (n = 6, P greater than 0.05). Similarly the EDR to ACh was not significantly altered by acute exposure (30 min) to nicardipine or diltiazem. The maximum relaxations without and with nicardipine were 32.4 +/- 4.2% and 28.0 +/- 3.1% of the contraction to NA (1 mumol l-1) (n = 11, P greater than 0.05). The corresponding data for diltiazem were 42.1 +/- 5.7 and 36.4 +/- 7.3% respectively (n = 11, P greater than 0.05). Both calcium antagonists inhibited the contraction induced by potassium (100 mmol l-1). Nicardipine and diltiazem in concentrations of 100 mumol l-1 reduced the potassium-induced contraction to 33.0 +/- 9.0% and 53.8 +/- 6.7% of control respectively (n = 6, P less than 0.05). In the bioassay experiments the infusion of nicardipine on (a) the recipient tissue only and (b) the donor and the recipient tissue had no significant effect on the relaxant response observed in the recipient tissue when superfused with Krebs-bicarbonate buffer containing ACh via the donor tissue (n = 6, P greater than 0.05). These results indicate that nicardipine and diltiazem had no significant effect on synthesis/release and the relaxant response to EDRF in the rabbit aorta. Thus the translocation of Ca2+ accompanying the EDR to ACh in the rabbit aorta is likely to utilize Ca2+ channels not blocked by these calcium antagonists.

Effects of nicardipine and diltiazem on alpha-adrenoceptor responses in canine saphenous veins.

The effects of calcium antagonists, diltiazem and nicardipine (-6.0 to -4.0 log mol/l), on the contractile responses to noradrenaline, methoxamine and BHT-920 in isolated canine saphenous vein rings, were studied with isometric tension recordings. Concentration-effect curves to the alpha-agonists were obtained in the control state and in the presence of diltiazem or nicardipine. Propranolol (-6.0 log mol/l) was present in the bath throughout. Diltiazem had no significant inhibitory effect on the responses mediated by all three agonists. Nicardipine (-5.0 and -4.0 log mol/l) produced a small but significant inhibitory effect on the responses to noradrenaline and methoxamine while it had no effect on the response to BHT-920. The effects of nicardipine were greatest on the responses to methoxamine. These calcium antagonists appeared to have only small post-synaptic inhibitory effects on the contractile responses to alpha-agonists in the canine saphenous vein with nicardipine exerting a greater inhibitory influence than diltiazem.