[Evaluation of coronary rehabilitation. Ambulatory aftercare improves recovery].
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Biomedical subjects
Publications and source records attributed to R Nordlander.
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Long-term monitoring of central haemodynamics with implanted monitoring systems might be valuable in managing heart failure patients. Such systems offer an opportunity for repeated 'semi-invasive' cardiac output determinations according to the Fick principle. Five patients, four with chronic heart failure and one with chronic pulmonary disease, underwent supine exercise testing during cardiac catheterization at 0, 2, 6 and 11 months after implantation of a right ventricular mixed venous oxygen saturation sensor connected to an implantable haemodynamic monitor. The monitor provided a continuous measure of oxygen saturation via a radio-telemetry link to a metabolic cart capable of measurement of breath-by-breath oxygen consumption. Cardiac output was computed using oxygen consumption, mixed venous oxygen saturation, arterial oxygen saturation by pulse oximetry and haemoglobin oxygen capacity. Biosensor-derived oxygen saturation compared to blood samples from the pulmonary artery showed an excellent correlation over time, r2 = 0.94 (implant), r2 = 0.91 (6-11 months). There was a strong correlation between semi-invasive-determined cardiac output using the biosensor and the invasive technique, which persisted over the entire follow-up period. Repeated semi-invasive cardiac output measurements using an implanted haemodynamic monitoring system in chronic heart failure patients is feasible and the data may be of value for optimizing therapy.
Sinus node recovery time assessment is used to diagnose clinically significant sinus node dysfunction (SND) when Holter has failed to prove a relationship between sinus bradyarrhythmias and symptoms, but consensus has not been reached as to the value of including assessment after pharmacologic blockade of the autonomic nervous system. This issue was addressed in the present study performed on 52 patients with syncope or presyncope/dizziness (n = 48), sinus bradyarrhythmias (n = 45), or both (n = 41). Group 1 consisted of 13 patients with a proven relationship between symptoms and sinus bradyarrhythmias. Group 2 consisted of 39 patients with suspected SND. The protocol included three pacing periods at two pacing rates and was performed at baseline (n = 52), after single doses of atropine and propranolol (0.02 mg/kg and 0.1 mg/kg, respectively) (n = 41), and again after a second dose (n = 29). The sensitivity of prolonged recovery times was 77% in group 1. Among group 2 patients, 56% had prolonged recovery times at baseline (79% when including the results after the first dose of drugs). The second dose did not contribute diagnostic information, but it caused significant adverse reactions in 7 of 29 patients (P < 0.001). These 7 patients were all older than 60 years. Assessment of sinus node recovery time after pharmacologic blockade of the autonomic nervous system thus increases the sensitivity of the method in patients with suspected SND and normal baseline results. However, only 50% of the initially suggested doses of atropine and propranolol is sufficient and eliminates the risk for significant adverse reactions.
OBJECTIVES: Coronary venous retroinfusion (CVR) has been used experimentally in large animals for selective drug delivery into ischaemic myocardium. It would be an advantage if CVR could also be used in isolated perfused rat heart models. The aim of the present paper is to develop a regional ischaemic model in the isolated perfused rat heart combined with CVR. METHOD: Pharmacokinetic study: The spatial distribution of retrogradely infused felodipine (used as a tracer) during regional myocardial ischaemia was investigated. Following occlusion of the left coronary artery, felodipine was administered over a period of 5 min by CVR. Ischaemia-reperfusion study: Following 30 min of stabilisation, 14 rat hearts were subjected to 60 min of regional ischaemia followed by 60 min of reperfusion. Felodipine (0.7 nmol/kg, n = 7) or vehicle (n = 7) was administered by means of CVR. The infusion was given during the last 5 min of ischaemia at a rate of 0.6 ml/min. RESULTS: Pharmacokinetic study: By means of CVR, the compound was distributed specifically into the ischaemic myocardium. The highest tissue concentration was obtained when the coronary vein was occluded during CVR. The maximal concentration in the ischaemic myocardium was 20-70 times that in the non-ischaemic areas. A transmyocardial gradient was noted with higher drug concentration in the subepicardial zone. Ischaemia-reperfusion study: At the end of reperfusion, the recovery of coronary flow, left ventricular developed pressure and double product (DP; LVDP x HR) was 101 +/- 7% (mean +/- s.e.m.), 99 +/- 8% and 98 +/- 4% of the pre-ischaemic values, respectively. This was significantly different from the vehicle group (78 +/- 5, P < 0.05, 74+/- 6, P < 0.01 and 78 +/- 3, P < 0.05). CONCLUSION: CVR could easily be accomplished in the isolated perfused rat heart. The drug was specifically delivered into the ischaemic myocardium. Felodipine exerted a myocardioprotective effect in isolated rat hearts subjected to 60 min of regional ischaemia followed by 60 min of reperfusion.
To verify that atrioventricular (AV) synchronous pacing (DDD) with short AV delay improves the condition of patients with severe congestive heart failure, we implanted DDD pacemakers in 10 patients with severe heart failure (New York Heart Association [NYHA] class III to IV). One day after pacemaker implantation, the AV delay was optimized by Doppler echocardiographic measurements over the aortic outflow tract. Patients were evaluated regarding NYHA class, stroke volume, cardiac output, ejection fraction, and quality of life at 1, 3, and 6 months after pacemaker implantation. Although the optimized AV delay was associated with short-term improvement in stroke volume and cardiac output (baseline stroke volume = 22 +/- 7 ml, day 1 = 28 +/- 12 ml; p = 0.03: baseline cardiac output = 1.9 +/- 0.6 L/min, day 1 = 2.2 +/- 1.1 L/min; p = 0.10), the mean stroke volume, cardiac output, NYHA class, and ejection fraction did not change significantly after 1, 3, and 6 months of pacing compared with baseline values. Three patients improved in NYHA class during the follow-up. A consistent improvement in stroke volume, cardiac output, NYHA class, and ejection fraction was observed in only 1 patient. In conclusion, we found no beneficial effects of AV-synchronous pacing with optimized AV delay in patients with severe heart failure.
A new noninvasive screening method for diagnosing sinus node dysfunction (SND) was evaluated. Sinus cycle variations from 1-minute electrocardiograms (ECG) were described by two variables: the variation range around the mean cycle length (percentage) and the maximal change between any two consecutive cycles (milliseconds). SND was diagnosed when both variables were increased. Part 1: Validation of this method against Holter and sinus node recovery time assessment in 69 patients with proven or possible sick sinus syndrome (SSS). Part 2: Application of the method to 60 patients with clinically significant cardiovascular and pulmonary disorders (group 3), but without any pretest suspicion of SND. Part 1: Sinus cycle variations and sinus node recovery times were abnormal in similar proportions, 55% and 63%, respectively. The sensitivities in proven SSS were 72% and 71%, respectively. Sinus node function was concordantly classified in 80% of 64 patients undergoing both tests. When sinus cycle variations were abnormal the probability of a prolonged recovery time was 89%. Part 2: Asymptomatic SND was found in 12% of patients in group 3. Thus, analysis of short-term beat-to-beat variations in the surface ECG has a sensitivity of approximately 70% and a specificity of 100% for diagnosing SND.
Pulmonary arterial diastolic pressure is an important parameter for hemodynamic monitoring in congestive heart failure. It is traditionally obtained through a pulmonary arterial catheter. If it could be obtained from a sensor in the right ventricle, chronic monitoring would be possible without the use of a pulmonary arterial catheter. This study is based on the hypothesis that pulmonary valve opening and pulmonary arterial diastolic pressure occur at the time of maximum positive rate of pressure development (dP/dt) in the right ventricle, when the pressures should be equal. Thus, right ventricular pressure at the time of maximum dP/dt (PAD index) should be a reasonable estimate of pulmonary arterial diastolic pressure. Eight patients with heart failure were catheterized and exposed to hemodynamic stress. Right ventricular and pulmonary arterial pressures were simultaneously recorded from a Millar (Houston, TX) catheter with two pressure transducers. The distal transducer was positioned in the bifurcation of the pulmonary artery and the proximal transducer was placed in the right ventricle. Pulmonary arterial diastolic pressure and PAD index were stored beat by beat on a bed-side computer. Acceptable recordings were obtained in all patients. Recordings from the individual patients showed a good covariation between PAD index and pulmonary arterial pressure during different hemodynamic manuevers, except during infusion of dobutamine, when the correlation was not as good. Pulmonary arterial diastolic pressure may be estimated from a transducer in the right ventricle, thus eliminating the need for a permanent pulmonary arterial catheter in an implantable hemodynamic monitoring system. Further studies are needed to verify the correlation on a long-term basis.
Right ventricle venous oxygen saturation was studied in 10 heart failure patients over 24 h using a lead equipped with an oxygen biosensor inserted temporarily. At the same time a pressure sensor, incorporated in the same lead to measure right ventricular pulse pressure and maximum positive and negative rate of pressure development (RV dP/dt), was tested to see whether it would interfere with the oxygen sensor. Data from the biosensor lead were continuously compared with mixed venous oxygen saturation obtained from a fibreoptic Swan-Ganz catheter with the tip in the pulmonary artery. For reference, blood samples were drawn at regular intervals from this catheter. A provocative protocol was used to cause haemodynamic changes. There was good correlation between oxygen saturation in the right ventricle (biosensor-derived) and mixed venous oxygen saturation in the pulmonary artery (fibreoptic-derived) (r = 0.86) and between sensor-obtained right ventricular oxygen saturation and oxygen saturation in the blood samples from the pulmonary artery (r = 0.90). Changes in central haemodynamics were also well reflected by changes in pulse pressure and dP/dt derived from the pressure sensor. As it was not possible to obtain absolute pressures no attempt was made to compare the pressure changes with conventional haemodynamics. These 24 h haemodynamic measurements suggest that a biosensor-equipped lead placed in the right ventricle could be a valuable tool for long-term monitoring of mixed venous oxygen saturation and pressure in patients with congestive heart failure.
Lipid peroxidation is one of the major mechanisms involved in free radical-mediated postischemic myocardial injury. In the present study, a newly synthetized lipid peroxidation inhibitor H290/51 [cis-7methyl-9-methoxy-5,5a,b,10b- tetrahydroindeno(2,1-6 indole)] was evaluated for its effects on myocardial functional recovery during reperfusion after 30-min global ischemia in isolated cold-arrested rat hearts. Administration of 200 and 800 nM H290/51 at initiation of global ischemia markedly improved the functional recovery, whereas 50 nM H290/51 had no significant effects. The percent recovery of cardiac output (CO), left ventricular developed pressure (LVDP), and LVdP/dtmax at the end of the 30-min reperfusion period in the working mode was much higher in the groups receiving 200 and 800 nM H290/51 than that in vehicle group (CO 73 +/- 5 and 60 +/- 5 vs. 23 +/- 7%; LVDP 79 +/- 5 and 73 +/- 8 vs. 43 +/- 10%; LV dP/dtmax 78 +/- 5 and 69 +/- 4 vs. 45 +/- 10%). The indenoindole compound H290/51 reduced ischemia/reperfusion-induced cardiac dysfunction.
The influence of coronary venous retroinfusion and a vasoselective calcium antagonist felodipine on the microsphere loss in a porcine model of myocardial ischaemia and reperfusion was studied. Sixteen open-chest pigs underwent 45 min of myocardial ischaemia induced by occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Either felodipine (felo-retro group, 7 nmol kg-1, n = 6) or the corresponding amount of vehicle (vehicle-retro group, n = 5) was infused retrogradely into the coronary veins over 30 min, starting 5 min before reperfusion. In a third group, the same amount of felodipine was administered intravenously (felo-iv group, n = 5). Myocardial regional blood flow was measured with radiolabelled microspheres (phi = 15 microns) injected before ischaemia to investigate a possible loss during ischaemia. In the felo-retro group, the apparent blood flow in the ischaemic areas, expressed as a percentage of the corresponding values in the non-ischaemic areas (%-flow), were 73 +/- 15, 73 +/- 11 and 75 +/- 19 in the subendocardial, midmyocardial and subepicardial layers, respectively. The corresponding percentage flows were 64 +/- 11, 70 +/- 11 and 62 +/- 9 in the vehicle-retro group and 75 +/- 18, 77 +/- 15 and 76 +/- 11 in the felo-iv group. The differences between the groups were not statistically significant. It is concluded that in this open-chest preparation microsphere loss observed in the ischaemic and reperfused myocardium is not increased by coronary venous retroinfusion or by a concomitantly administered vasodilative agent like felodipine.
Thirteen healthy men (age range 24-59 years) received three single doses (30, 75, and 150 mg/day) of aspirin for seven days, followed by a wash-out period of three weeks, in a randomized order. The arachidonic acid metabolite 12-L-5,8,10-heptadecatrienoic acid (12-HHT) was taken as a measure of platelet cyclooxygenase activity. There was a large inter-individual variation in 12-HHT production prior to and during aspirin treatment. After one week of treatment the mean reduction was 69, 72 and 83% for the doses 30, 75 and 150 mg/day respectively. When the degree of cyclooxygenase inhibition was expressed per microgram aspirin administered per kg bw, a positive correlation was established to the activity before medication. It was found that doses exceeding 1500 micrograms per kg bw is required to achieve a predictable reduction in cyclooxygenase activity. Thus, by determining the pre-treatment cyclooxygenase activity in an individual it should be possible to adjust the enzyme activity to any desired level below 40% of its initial value. 150 mg aspirin/day for one week had a stimulating effect on the platelet basal production of 12-HHT when measured three weeks after the cessation of treatment. This rebound phenomenon was also observed up to six weeks after a single dose of 600 or 1200 mg of aspirin.
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Thirty-seven patients with chronic, stable angina pectoris were included in a randomized, double-blind cross-over study to assess the efficacy of once- and twice-daily dosage regimens of 60 mg isosorbide-5-mononitrate, in a controlled-release formulation (5-ISMN Durules, Astra). After 2 weeks of treatment, during a symptom-limited bicycle ergometer exercise test performed 3 h after the dose, the time to 1 mm ST segment depression was observed to be longer by once-daily than by a twice-daily dosage regimen (614 +/- 165 vs 561 +/- 148 s; P < 0.01). The time to the end of exercise was also significantly prolonged by once-daily dosage, as compared with placebo (693 +/- 158 and 645 +/- 173 s, respectively; P < 0.05), which was not observed with the twice-daily regimen. Both dosage regimens still had a significant effect on the prolongation of the time to onset of angina 9 h after the dose: 420 +/- 164 s by placebo, 492 +/- 161 s by once-daily dosage; P < 0.01, and 466 +/- 154 s by twice-daily dosage; P < 0.05. Anginal attack rate and nitroglycerin consumption was significantly lower during the once-daily dosage period as compared with placebo; this difference was not evident during the twice-daily administration of the drug. Controlled-release 5-ISMN 60 mg given once daily was effective in angina pectoris patients for at least 9 h after the dose and showed no clinical signs of tolerance after 2 weeks of the treatment. Attenuation of the clinical effect was observed with the twice-daily (in 12 h intervals) dosage regimen, presumably caused by constantly high 5-ISMN plasma concentration.
The protective effect of the nitric oxide (NO) substrate L-arginine on myocardial ischaemial/reperfusion injury was studied in pigs. Four groups were subjected to 45 min ischaemia and 4 h reperfusion. One control group received coronary venous retroinfusion of saline, the second retroinfusion of L-arginine (1 mg.kg-1.min-1), the third retroinfusion of L-arginine plus the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA), and the fourth systemic i.v. infusion of L-arginine (1 mg.kg-1.min-1). The infarct size in the L-arginine retroinfusion group was 35 +/- 5% of the myocardial area at risk compared to 76 +/- 5% in saline treated controls (P < 0.001). In pigs receiving the combination of retroinfused L-arginine and L-NNA the infarct size was similar to that of controls (79 +/- 4%). Systemic i.v. infusion of L-arginine did not influence the infarct size. Administration of L-NNA+L-arginine slightly increased arterial blood pressure during ischaemia but the groups did not differ in blood pressure, heart rate, rate-pressure product, left ventricular dP/dt or coronary blood flow during the reperfusion period. Coronary vasodilatation by acetylcholine was significantly compromised in the saline retroinfusion group, but not in the L-arginine retroinfusion group as compared to pigs not subjected to myocardial ischaemia. The results show that coronary venous retroinfusion of L-arginine reduces myocardial infarct size and preserves endothelial function via a local action which seems to be related to maintained nitric oxide formation.
To investigate if an nonphysiological prolongation of the AV interval is common during activity sensor modulated atrial rate adaptive (AAIR) pacing, 21 patients with sinus node disease treated with fixed rate atrial (AAI) or AAIR pacemakers were examined. Spike-Q intervals were compared at different heart rates obtained by overdrive pacing at rest and during exercise (Study I), measured during exercise at unresponsive (AAI), optimal (AAIR) and over responsive programming (AAIR+) of the activity sensor (Study II), and finally examined by 24-hour Holter recording in AAI and AAIR pacing modes (Study III). Study I: The spike-Q interval increased significantly with increasing heart rate at rest, but not during exercise. At rest the spike-Q interval was significantly higher at all heart rates compared to exercise. There was a significant positive correlation between the maximal spike-Q interval at rest and the maximal spike-Q interval during exercise (r = 0.63). Study II: The spike-Q interval was shortest in the AAI and longest in the AAIR+ mode in all patients. Study III: During AAI or AAIR pacing the spike-Q interval was longest at night and shortest in the morning. The mean spike-Q interval was longer in AAIR than in AAI pacing. No statistical difference between the maximal spike-Q intervals observed during the two modes was, however, found. Variations in spike-Q interval are generally caused by changes in autonomic tone or medication with drugs with antiarrhythmic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Tissue and plasma concentrations of felodipine, a dihydropyridine (DHP) calcium antagonist, retroinfused through the coronary venous system were studied in 27 pigs. The animals underwent 45-min myocardial ischemia followed by 4-h reperfusion. Felodipine (7 nmol/kg body weight) was administered in the coronary vein for 30 min, 5 min before reperfusion. Concentrations of felodipine in the ischemic and nonischemic myocardium and in plasma were determined by gas chromatography. In the ischemic area, felodipine concentration at start of reperfusion was 304 +/- 285, 171 +/- 160, and 52 +/- 47 nmol/kg (mean +/- SD) in the subepicardial, midmyocardial, and subendocardial layer, respectively. Corresponding concentrations in the nonischemic area were 15 +/- 13, 17 +/- 14, and 16 +/- 15 nmol/kg (p < 0.05 vs. ischemic area). Subepicardial concentration was highest at start of reperfusion, whereas concentrations in other layers peaked at the end of retroinfusion. The transmural concentration gradient of felodipine in the ischemic area decreased progressively during the reperfusion period. The nonischemic tissue concentration increased slightly during the reperfusion period. The plasma concentration was very low throughout the study (peak = 3.2 +/- 1.4 nM at 30 min). Coronary venous retroinfusion of felodipine resulted in profound accumulation of the drug, specifically in ischemic myocardium. The plasma concentration was low and did not affect systemic hemodynamics. Coronary venous retroinfusion is considered an advantageous technique for selective drug delivery.
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