Stig Sundberg

Rapid reversal of circadian blood pressure rhythm in shift workers.

The blood pressure and heart rates of seven normotensive shift workers were monitored automatically for 24 h with a non-invasive ambulatory method on 3 different days. The first monitoring session took place at the end of an ordinary work period of morning shifts, the second on the first day of a period of night shifts, and the third on the last day of a period of night shifts. The circadian blood pressure rhythm, which showed a normal pattern during the daytime work shift, was totally reversed from the first day of the night shift. The blood pressure rhythm closely followed the sleep-wakefulness cycle. The changes in circadian heart rate rhythm were not as pronounced as those in blood pressure but showed a similar trend.

Dose-range study of a new calcium sensitizer, levosimendan, in patients with left ventricular dysfunction.

Levosimendan, a new drug that sensitizes troponin-C to calcium and selectively inhibits phosphodiesterase III, was administered to 24 patients with ischemic heart disease and ejection fraction below 40%. In a placebo-controlled, crossover, double-blind study, each patient received two intravenous doses of levosimendan on 2 consecutive study days. The doses were 0.25 mg (n = 6), 0.5 mg (n = 11), 1 mg (n = 12), 2 mg (n = 12), and 4 mg (n = 5). After 0.25 mg and 0.5 mg, cardiac output increased by 0.49-0.67 L/min (p < 0.05) due to an increase in stroke volume of 6-11 ml. After 2 and 4 mg, cardiac output increased by 0.61-0.88 L/min due to an increase in heart rate of 6-12 beats/min. The baseline filling pressures, i.e., right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP), were within the normal range. RAP decreased significantly (p < 0.05) after 2 and 4 mg and PCWP after 0.5, 1, 2, and 4 mg. The most profound decreases were observed 10 min after infusion of 4 mg, from 5.0 to 3.2 mm Hg in RAP and from 9.8 to 6.0 mm Hg in PCWP. Total peripheral resistance decreased significantly only after 2 and 4 mg, by 13 and 21%, respectively. However, there were no statistically significant changes in pulmonary vascular resistance. It is concluded that levosimendan has a hemodynamically favorable action after 0.25 and 0.5 mg but that decreases in filling pressures probably prevented the increase in stroke volume and caused a reflex increase in heart rate after 2 and 4 mg.

VIBRATION FREQUENCIES AND AMPLITUDES IN THE ÆTIOLOGY OF TRAUMATIC VASOSPASTIC DISEASE

Abstract Forty-three Finnish lumberjacks with a history of traumatic vasospastic disease (T.V.D.) associated with the use of the chain saw were investigated. Finger-pulse plethysmography during vibration exposure revealed strong vasospasms in eighteen (42%) of the patients. The vasospasms were also triggered by body cooling and chain-saw noise. The dominant frequency of vibration in the chain saw (125 Hz) falls in the frequency region where the pacinian corpuscles are especially sensitive to vibration, and it was shown that vibration at 125 Hz was more potent than lower frequencies in producing vasospasms. At different frequencies the lowest vibration amplitudes that produced vasospasms run parallel and 20 dB above the mean threshold values of the pacinian corpuscles. It is concluded that a likely mechanism to produce the symptoms in the traumatic vasospastic disease is a chronic overexcitation of the pacinian vibration receptors that produce spastic reactions in the vasculature through a reflex linkage with the sympathetic nervous system.

Hemodynamic and neurohumoral effects of levosimedan, a new calcium sensitizer, at rest and during exercise in healthy men

Levosimendan is a novel inodilator that increases the calcium sensitivity of troponin C in a calcium-dependent way. Cardiac function (impedance cardiography, systolic time intervals), neurohumoral responses at rest and during exercise at 2 workloads, and peripheral blood flow (plethysmography) were studied in 14 healthy young men. Vehicle and 2 doses of levosimendan (6.5 micrograms/kg, low dose [LD]; and 25 micrograms/kg, high dose [HD]) were given intravenously in a crossover study. Measurements taken 15 minutes after a supine rest showed HD levosimendan shortened electromechanical systole (QS2i) by 16 ms maximally (p < 0.001), and decreased systemic vascular resistance by 25% (p < 0.001), compared with baseline values. Diastolic blood pressure fell by 9 mm Hg (p < 0.01). When the changes after vehicle were compared with the changes after HD levosimendan, the difference was 2.1 L/min after 25 micrograms/kg (p < 0.001), caused by an increase in stroke volume, with the heart rate being unaffected. Leg blood flow increased by 35% (p < 0.001). During exercise at the lower workload, HD levosimendan increased cardiac output by 1.5 L/min (p < 0.05), compared with that caused by vehicle, by an increase in heart rate, with the stroke volume being unchanged. Electromechanical systole was shortened significantly (20 ms, p < 0.001 after HD; 12 ms, p < 0.01 after LD). At the higher workload, no effects on electromechanical systole or cardiac output compared with that associated with administration of vehicle were seen, but the mean heart rate increased (p < 0.001, LD and HD) and mean diastolic blood pressure decreased (p < 0.01, HD).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic effects of a calcium sensitizer inotrope levosimendan administered intravenously in patients with normal cardiac function.

Provocation of fatal cardiac arrhythmias has limited the use of inotropic agents as heart failure therapy. Calcium sensitization of the myofilaments might increase inotropy without influencing cardiac electrophysiology unless modified by ancillary properties of the drugs. Electrophysiologic effects of a calcium sensitizer inotrope levosimendan were examined in short-term intravenous administration in humans. Variables were determined in 10 patients with normal cardiac function during a preceding control phase and levosimendan infusion yielding a high therapeutic concentration of 110 (+/-22) microg/L. Levosimendan increased heart rate by 9 beats/min (p < 0.01) on average and shortened the sinus node recovery time and AH interval. At the tested cycle lengths, levosimendan shortened the effective refractory periods in the atrioventricular node by 40-63 ms (p < 0.05), in the atrium by 22-33 ms (p < 0.001), and in the ventricle by 5-9 ms (p < 0.005) on average. Levosimendan increased ventricular monophasic action potential duration by 9-17 ms at 50% (p < 0.001) and by 5-15 ms (p = 0.07) at 90% levels of repolarization on average. The QT interval during spontaneous rhythm and atrial pacing remained unchanged although increased slightly when corrected to sinus rate (p < 0.001). The observations indicate that levosimendan in short-term administration facilitates impulse formation and conduction in cardiac slow-response tissue, enhances recovery of excitability in the myocardium, and may delay ventricular repolarization. The effects on the ventricle were not substantial, and therefore the likelihood of provoking serious cardiac arrhythmias is not estimated to be high.

Simultaneous inhibition of catechol‐O‐methyltransferase and monoamine oxidase A: Effects on hemodynamics and catecholamine metabolism in healthy volunteers

To evaluate the effects of simultaneous pharmacologic inhibition of catechol‐O‐methyltransferase (COMT) and monoamine oxidase type A (MAO‐A) on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during exercise.

Exercise hemodynamics and catecholamine metabolism after catechol‐O‐methyltransferase inhibition with nitecapone

The effect of catechol‐O‐methyltransferase inhibition with nitecapone (OR‐462) on the hemodynamic responses to exercise and catecholamine metabolism was studied in 10 healthy male volunteers (aged 19 to 26 years). Nitecapone, a new specific and selective catechol‐O‐methyltransferase inhibitor, was given at increasing single oral doses up to 100 mg. Nitecapone did not influence resting or exercise heart rate, blood pressure, systolic time intervals, or plasma catecholamine levels. It altered the metabolic profile of catecholamines as shown by (1) an increase of 140% in the plasma concentration of the monoamine oxidase–dependent metabolite 3,4‐dihydroxyphenylethyleneglycol (p < 0.001), (2) a decrease of 27% in the plasma concentration of its methylation product 3‐methoxy‐4‐hydroxyphenylethyleneglycol (p < 0.05), and (3) a 25% reduction in the urinary excretion of the methylated metabolites 3‐methoxy‐4‐hydroxymandelic acid and homovanillic acid (p < 0.05). Nitecapone was well tolerated and seemed to be hemodynamically safe in humans.

Vasodilatory effects of carvedilol and pindolol.

Summary: The effects of three different nonselective &bgr;‐blockers on central and peripheral hemodynamics as well as on pulmonary function were compared in 13 healthy subjects (19–37 years). The subjects were given carvedilol 50 mg, pindolol 10 mg, propranolol 80 mg, and placebo orally twice daily for 1 week in a double‐blind, crossover, randomized manner. Heart rate, blood pressure, arterial calf blood flow (venous occlusion strain gauge plethysmography), and pulmonary function (flowvolume spirometry) were measured at the first and at the last trial day. Heart rate and blood pressure were lower on carvedilol and propranolol than on pindolol and placebo; the maximal bradycardiac effect was 13 and 17 beats/min and hypotensive effect 9/10 mm Hg and 10/7 mm Hg on carvedilol and propranolol, respectively. Both carvedilol and pindolol increased arterial flow by about 40% (p < 0.05 and p < 0.01, respectively) and reduced peripheral resistance by about 34% (p < 0.05 and p < 0.01, respectively), the effect persisting after 1 week of treatment. None of the medications had any noteworthy effects on pulmonary function. Two subjects complained of tremor on pindolol. We conclude that carvedilol and pindolol possess distinct vasodilatory properties. Carvedilol had a stronger hypotensive effect than pindolol and was well tolerated.

Comparison of blood pressure response to heat stress in sauna in young hypertensive patients treated with atenolol and diltiazem.

Abstract A sauna bath induces a marked increase in heart rate and a decrease in peripheral vascular resistance as a consequence of heat-induced peripheral vasodilation.1,2 In normotensive patients the heat stress of a sauna does not change blood pressure (BP). However, a decrease in BP is evident in hypertensive patients,3 with a risk of hypotensive symptoms after sauna.1,4 Surprisingly little is known about the impact of cardiovascular drugs on the hemodynamic changes induced by heat stress. Because the β-blocking agent propranolol causes bradycardia, patients are warned of a hypotensive effect after sauna.4 Calcium antagonists may, by peripheral vasodilation, have an additive effect on the dilation induced by heat stress.5,6 However, no studies on this topic have been published. In the present study we compared the hemodynamic changes during and after heat stress caused by sauna bath in young hypertensives treated with the calcium antagonist diltiazem and the β1-selective adrenoceptor antagonist atenolol. We evaluated the possible additive vasodilatory effects of heat stress and calcium antagonists, and the tendency toward hypotensive reactions during and after a sauna bath.

Effects of captopril on blood pressure and respiratory function compared to verapamil in patients with hypertension and asthma

Seventeen adult patients with moderate and stable bronchial asthma and established essential hyper-tension (WHO I or II) were evaluated in a randomized, double-blind, crossover study of the effects of captopril (50–100 mg/day) and verapamil (160–240 mg/day) on blood pressure, orthostatic reactions, respiratory function, and asthmatic symptoms. The effect of both drugs 3n blood pressure was significant. Blood pressure (mean ± f 161/98 mm Hg initially) decreased to a mean of 147/90 and 160/91 mm Hg on captopril and verapamil, respectively, with normal orthostatic changes. There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1,), maximal expiratory flow at 50% of FVC (MEF50), or peak expiratory flow (PEF) measurements at the end of each treatment period. The subjective severity of asthma did not change significantly during the trial. No significant cough symptoms were reported on captopril.