Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients.

OBJECTIVE: We evaluated the effect of two calcium channel blockers, verapamil and felodipine, on heart rate variability in hypertensive patients. DESIGN: Time and frequency domain measures of heart rate variability were obtained from 24 h Holter recording in 25 previously untreated hypertensive patients without left ventricular hypertrophy, before and after 3 months of verapamil slow-release treatment (240 mg once daily) or felodipine extended-release treatment (10 mg once daily). RESULTS: Blood pressure values decreased with both drugs. Measures of heart rate variability, comparable at baseline in the two groups, were unchanged after felodipine. After verapamil, the average RR interval, the square root of the mean of the squared differences between all adjacent normal RR intervals (r-MSSD) and the percentage of differences between all adjacent normal RR intervals > 50 ms (pNN50), measures of vagal modulation of heart rate, increased (from 735 +/- 67 to 827 +/- 84 ms, P < 0.001; from 30 +/- 10 to 44 +/- 15 ms, P < 0.001; and from 3 +/- 2 to 7 +/- 6%, P < 0.01, respectively) and were higher than after felodipine. The coefficient of variation, a measure that compensates for heart rate effects, increased only after verapamil (from 5.8 +/- 1.3% to 6.6 +/- 1.0%; P < 0.05). High frequency power and its coefficient of component variance, both representing the vagal modulation of heart rate, increased after verapamil (from 5.33 +/- 0.29 to 5.80 +/- 0.27 In units, P < 0.001 and from 1.9 +/- 0.3 to 2.2 +/- 0.25%; P < 0.05). Finally, the low to high frequency power ratio, an indicator of sympathovagal balance, with a high value suggesting a sympathetic predominance, decreased after verapamil (from 2.16 +/- 0.41 to 1.36 +/- 0.35; P < 0.001), confirming the improvement in vagal modulation of heart rate. CONCLUSION: In hypertensive patients, despite a comparable anti-hypertensive effect, verapamil, but not felodipine, has favourable effect on cardiac autonomic control.     

Efficacy and tolerance of diltiazem in primary pulmonary hypertension. Apropos of a case

The Authors report a case of a serious and symptomatic primary pulmonary hypertension, where the intravenous administration of Diltiazem, at a dosage of 0.3 mg/kg, resulted in an important improvement of haemodynamic parameters. This improvement was confirmed 4 months later on chronic oral therapy with Diltiazem, at a dosage of 180 mg per day. Six months after the beginning of therapy, the patient is totally asymptomatic. Even though further controls are needed, Diltiazem may represent an active drug in the treatment of primary pulmonary hypertension.     

The effects of doxorubicin on ventricular tachycardia

Doxorubicin, in concentrations that have no effect on fast or slow response action potentials, has been shown to suppress ouabain-induced delayed afterdepolarizations. In this study, we used standard microelectrode techniques to determine the effects of doxorubicin on isolated canine Purkinje fibers. We studied automaticity induced at normal and low membrane potentials, conduction in normal and K+-depolarized Purkinje fibers, and triggered activity induced by ouabain and by experimental myocardial infarction. Doxorubicin, 50 microM, suppressed the triggered activity and the delayed afterdepolarizations that induced it, but had no effect on the other variables. We then studied the effects of intravenous doxorubicin, 16 to 64 mg/m2 body surface area, on ouabain-induced ventricular tachycardia and the ventricular tachycardia that occurs 24 hr after ligation of the left anterior descending coronary artery in the intact dog. There was no effect on the infarct-induced arrhythmia, but concentrations of doxorubicin that had no other effect on the electrocardiogram suppressed those ouabain-induced arrhythmias that appeared to have been triggered. The automatic arrhythmias induced by ouabain were not affected. Both the latter mechanisms were verified in studies of isolated Purkinje fibers that were obtained on completion of the intact animal experiments. These results indicate that agents having high selectivity for specific arrhythmogenic mechanisms can be useful adjuncts in discriminating among the mechanisms responsible for arrhythmias in intact animals.     

Multichannel tetrapolar admittance meter (MY) for intracardiac volume measurements in animals

With an 8-electrode catheter, this instrument measures simultaneously five intraventricular sections of admittance and, also, total admittance, the latter obtained as the sum of five component sections. It injects through the two outermost electrodes of the catheter a constant current (828 microA rms) of high frequency (14 kHz). Actually, the instrument measures the mathematical inverse of the resistive component (conductance) of the impedance seen by the voltage sensing electrodes. The sensitivity per channel was adjusted to 25 V/mho, resulting in an overall sensitivity of 5.28 V/mho for the total intraventricular admittance. Nonlinearity in any single channel was less than or equal to 3.4% while, for the total admittance, it was less than or equal to 1.5%. The difference between any two individual channels when the same calibration resistor was connected, relative to the expected value, was less than or equal to 4.8%. The equipment demonstrated good performance in animal experiments and showed the possibility of detecting localized dysfunctions. Human applications still remain to be done.     

Preoperative radiation therapy for patients with T2-T3 carcinoma of the middle-to-lower rectum.

BACKGROUND: The aim of this study was to determine the effects of preoperative radiation therapy (RT) on the objective responses of patients with rectal carcinoma to their treatment. These effects were assessed with endorectal ultrasound (EUS) evaluation, histopathologic grading of postirradiation tumor mass reduction in the surgical specimen, and analysis of local and distant recurrences. METHODS: Fifty-nine consecutive patients with palpable adenocarcinoma of the rectum, classified by EUS examination as uT2-uT3 (which meant involvement of the muscular layer and the perirectal adipose tissue, respectively), received 45 grays (Gy) over 3 weeks (2 fractions per day of 1.5 Gy each) given as photons supplied through a high-energy linear accelerator (18 MeV) through 3 fields: 1 posterior and 2 opposed lateral. Surgery was scheduled 2-3 weeks after the end of RT and included a sphincter-saving resection (39 patients) and an abdominoperineal resection (20 patients). RESULTS: Greatest tumor dimension, which was evaluated with rectal endoscopy before RT and measurement of the lesion in the fresh specimen, showed a decrease among two-thirds of the patients; the decrease amounted to approximately one-third of the initial measurement. An echoendoscopic downstaging of the T component was observed among 24.5% of the patients. Complete tumor regression occurred in 8.5% of patients, whereas in 69% only the presence of rare residual cancer cells and prominent fibrosis were found at the pathologic examination of the specimen. Finally, the tumor regressed to pT0 and pT1 in 13.6% of the patients. The overall and disease free 2-year survival rates were 94.0% and 73.7%, respectively, for pT2 and pT3 patients, and 100% for those whose tumors regressed to pT0-pT1 after a median follow-up of 2 years. CONCLUSIONS: Hyperfractionated preoperative RT appears to be efficient in achieving tumor shrinkage and destroying the tumor. In this study, the subset of patients with a good response to RT therapy had an excellent clinical outcome at the time of a 2-year follow-up.     

Effects of aminophylline on respiratory drive and neuromuscular coupling in normal man and in patients with chronic airflow obstruction

Summary In order to evaluate the separate effects of aminophylline on the neural and muscular components of the respiratory control system, assessed by electromyographic activity of the diaphragm (EMGd) and mouth occlusion pressure (P_0.1), respectively, 6 normal subjects and 14 patients with mild or moderate chronic airflow obstruction (8 asthmatics and 6 COPD) were studied during CO₂ rebreathing, before and after administration of a therapeutic dose of aminophylline 5.6 mg/kg.Compared to normal subjects, before aminophylline administration both asthmatic and COPD patients exhibited a significantly greater value in EMGd response slope to CO₂. In no group did aminophylline modify P_0.1 or EMGd activity response slope to CO₂, nor did it significantly affect neuromuscular coupling, assessed by plotting change in P_0.1 against change in EMGd activity with increasing CO₂.The data appear to indicate that aminophylline in therapeutic concentrations does not modify respiratory drive or neuromuscular coupling in normal subjects, or in patients with mild or moderate chronic airflow obstruction.     

Efficiency of the heart as estimated from uncalibrated diagrams of intraventricular pressure related to conductance

Using a diagram representing the relationship of intraventricular pressure and conductance, we determined ventricular efficiency from the weighted relationship between the area encompassed by the loop (the stroke work) and the total area surrounded by the end-diastolic curve, the systolic segment of the diagram, and the end-systolic line. The basic concept underlying this calculation stems from the linear relationship between consumption of oxygen by the heart and the total area discussed above, a relationship already well established in the literature. In five animals investigated under control conditions, values ranged, as expected, from 17.5 to 30.6% (average 21.78%, SD 5.06). They showed a significant increase (P less than 0.05) after an inotropic maneuver (range 19.9-40.0%, average 31.17, SD 7.43). An attractive feature is that the diagrams need not be calibrated in absolute terms. The procedure can be easily applied during routine cardiac catheterization to obtain complementary information (ventricular efficiency) which is of value in the evaluation of cardiac performance.     

Postpartum coronary artery dissection followed by heart transplantation

A rare case of coronary artery dissection was observed in a 33-year-old woman on the fourth postpartum day. The ischemic syndrome was followed by aneurysmal dilatation of the left ventricle and progressive heart failure that necessitated cardiac transplantation. The patient is alive and well 3 years after the transplantation.     

Mortality and cancer incidence in a cohort of commercial airline pilots

We undertook a cohort study of all male pilots employed since January 1, 1950, by CP Air, now Canadian Airlines International. A total of 913 eligible pilots--630 active and 283 no longer employed--contributing 18,060 person-years of observation, were identified through company records. As of October 31, 1988, current status was obtained on 891 (97.6%). Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare, respectively, the mortality and cancer incidence of the cohort with that of the British Columbia population. Statistical significance of the SMR and SIR by comparison with the Poisson distribution (p less than 0.05 one-sided) and 90% confidence intervals (CI) were calculated. Excess deaths were observed for aircraft accidents (No. = 23; SMR = 21.29; p less than 0.001; CI 14.60, 30.20), brain cancer (No. = 4; SMR = 4.17, p = 0.017; CI 1.40, 9.50) and rectal cancer (No. = 3; SMR = 4.35; p = 0.033; CI 1.20, 11.20). Excess cancer incidence was noted for non-melanoma skin cancer (No. = 26; SIR = 1.59; p = 0.017; CI 1.10, 2.20), brain cancer (No. = 4; SIR = 3.45; p = 0.030; CI 1.20, 7.90) and Hodgkin's Disease (No. = 3; SIR = 4.54; p = 0.030; CI 1.20, 11.70). These findings, suggesting an excess risk for certain cancers in commercial airline pilots, are based on small numbers and need to be confirmed in larger cohort studies.