Greater Decrease In Heart Rate Research Articles

Ambulatory blood pressure monitoring and postprandial hypotension in elderly patients with isolated systolic hypertension. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

The present analysis was undertaken to evaluate postprandial (PP) changes in blood pressure (BP) assessed with ambulatory BP monitoring (ABPM) in elderly subjects with isolated systolic hypertension (ISH) on conventional measurement. A total of 530 patients (335 women and 195 men, aged 60-100 years, median 70 years) who performed an ABPM during the placebo run-in period of the Syst-Eur trial were included into the analysis. The PP changes in BP and heart rate (HR) were calculated by subtracting the mean systolic BP (SBP), diastolic BP (DBP) and HR in the 2 h preceding the main meal from the corresponding means covering the 2 h after the meal. The reproducibility of the postprandial fall in BP and heart rate (PPH) was assessed by contrasting the first and second ABPM in a subgroup of 147 patients who performed two ABPM's during the placebo run-in period. The mean SBP and DBP decreased and reached the nadir 2 h after the main meal while HR did not change. When PPH was assessed by comparing BP in the 2 h before and after the meal, both SBP and DBP decreased significantly (respectively -6.6 mm Hg, -5.4 mm Hg; P < 0.001). In 67.6% of all patients a decrease in SBP was observed and in 24.1% it exceeded 16 mm Hg. The corresponding values for DBP were 71.3% and 24.5% (DBP decreased more than 12 mm Hg). A greater fall in DBP was associated with a greater decrease in HR (r = 0.20, P < 0.001), while changes in SBP and HR were not interrelated. Regression analysis did not identify any significant covariate of PPH. Group means of PPH could be reproduced without significant changes in their values, but the within-subject reproducibility of the PP changes was low. There were no differences in PPH according to the place of residence of the patients. In conclusion, the descriptive analysis of the meal-induced changes in ABPM in elderly subjects with ISH showed that in every day circumstances most of them experience falls in both SBP and DBP within 2 h after the meal.

Inhibition of Nitric Oxide Synthase Causes Profound Enhancement of the Bezold-Jarisch Reflex

The Bezold-Jarisch reflex function was evaluated in rats made hypertensive by the chronic oral intake of a nitric oxide synthase inhibitor N ω-nitro- l-arginine methyl ester (L-NAME, averaging 35 mg/kg/day), for 3, 6, and 12 days (n = 9/group) and in untreated control rats (CR, n = 9/group). L-NAME–treated rats showed a marked hypertension (MAP: 148 ± 3, 182 ± 4, and 179 ± 4 mm Hg, respectively) compared with CR (110 ± 2 mm Hg). The 6- and 12-day groups showed tachycardia (447 ± 20 and 466 ± 13 beats/min, respectively) when compared with CR (355 ± 10 beats/min). When compared with CR, left ventricular hypertrophy was observed in rats treated with L-NAME for 6 and 12 days. The Bezold-Jarisch reflex, a decrease in heart rate (HR) accompanied by a decrease in diastolic arterial pressure (DAP), was evoked in a dose dependent manner by the intravenous injection of 5-hydroxytryptamine (5-HT, 5 to 10 μg/kg). Relative to responses observed in CR, 5-HT at 10 μg/kg caused a four- to fivefold greater decrease in HR and a two- to threefold greater decrease in DAP in all the L-NAME treatment groups. Using a Langendorff technique, we observed a significant increase in the responsiveness of the pacemaker to acetylcholine (1.25 to 80 μg/mL). These data suggest that the pharmacological inhibition of the nitric oxide synthase causes profound changes in the mechanisms of cardiovascular regulation as shown by a marked enhancement of the Bezold-Jarisch reflex in L-NAME-treated rats. The enhancement of this reflex seems to be in great part due to the hyperresponsiveness of the cardiac pacemaker to cholinergic stimulation.

Mibefradil in the Treatment of Chronic Stable Angina Pectoris: Comparative Studies With Other Calcium Antagonists

The ability of mibefradil, a new T-channel-selective calcium antagonist, to improve exercise tolerance and silent ischemic parameters in patients with chronic stable angina was compared in 3 separate trials with 2 other commonly used calcium antagonists: diltiazem SR (120 mg/twice daily) and amlodipine (10 mg/day). Compared with amlodipine, mibefradil 100 mg given once daily over a 3-week period resulted in a statistically significantly larger increase from baseline in total exercise tolerance test (ETT) duration (treatment difference of 40.9 sec, p = 0.04), time to onset of angina (treatment difference 61.2 sec, p <0.001), and time to onset of ischemia (treatment difference of 54.4 sec, p = 0.004). The decrease in weekly anginal episodes was 58% with mibefradil versus 19% with amlodipine, and the reduction in nitroglycerin consumption was 58% with mibefradil versus a 10% increase with amlodipine. The decrease in the number of silent ischemic episodes detected by a 48-hour Holter recording was significantly larger (p = 0.03) with mibefradil 100 mg (88%) compared with amlodipine 10 mg (38%). Similarly, a larger decrease in the duration of silent ischemia was observed with mibefradil (69%) compared with that seen with amlodipine (38%). The preliminary results of a second trial comparing mibefradil with amlodipine were consistent with the first demonstrating that the improvement for all 3 ETT parameters was larger for mibefradil (ETT duration: 55.2 sec; delay in onset angina: 74.2 sec; time to onset of ischemia: 63.6 sec), but in this trial the treatment differences did not reach statistical significance. In the trial comparing mibefradil (100 mg once daily) with diltiazem SR (120 mg twice daily), both compounds had equivalent effects on all ETT parameters tested. Mibefradil produced a 21% increase in exercise duration compared with a 20% increase with diltiazem. Although mibefradil yielded larger increases in the time to onset of angina and the time to onset of 1-mm ST-segment depression (42% and 38%, respectively) than did diltiazem (34% and 25%, respectively), the treatment differences did not reach statistical significance. Both mibefradil and diltiazem SR were associated with at least a 70% reduction from baseline in anginal frequency and nitroglycerin consumption. Mibefradil-treated patients showed greater decreases in heart rate and the rate-pressure product at each stage of the ETT than patients treated with amlodipine or diltiazem SR. All 3 drugs were well tolerated. However, compared with mibefradil, amlodipine and diltiazem SR produced a higher incidence of leg edema. In conclusion, the effectiveness of mibefradil in improving all 3 ETT parameters was greater than that of amlodipine and equivalent to that of diltiazem SR. Moreover, mibefradil provided greater reductions in the heart rate and cardiac workload than did the other 2 drugs.

The method of subliminal psychodynamic activation: do individual thresholds make a difference?

The present experiment investigated the effects of subliminal psychodynamic stimuli on anxiety as measured by heart rate. Following an anxiety-inducing task, male and female subjects were tachistoscopically shown, at their subjective thresholds, one of five subliminal stimuli, MOMMY AND I ARE ONE, DADDY AND I ARE ONE (symbiotic messages). MOMMY HAS LEFT ME (abandonment message), I AM HAPPY AND CALM (positively toned but nonsymbiotic phrase), or MYMMO NAD I REA ENO (control stimulus). It was hypothesized that men would exhibit a greater decrease in heart rate after exposure to the MOMMY stimulus than the control message. No definitive predictions were made for women. The abandonment phrase was expected to increase heart rate. A positively toned message was included to assess whether its effects would be comparable to those hypothesized for the MOMMY message. The results yielded no significant effects for stimulus or gender and so provided no support for the hypotheses.

Cholesterol Changes in Smoking Cessation Using the Transdermal Nicotine System

Background. Cigarette smoking is a well-known major risk factor in coronary heart disease. Smoking cessation results in a positive change in atherogenic factors. High-density lipoprotein cholesterol has been observed as increasing with smoking cessation. Since the use of nicotine transdermal replacement has become so widespread, this study examined the effect, if any, of the transdermal nicotine system on selected cardiovascular parameters in patients who were abstinent from cigarette smoking, and possible dose effect. Methods. Eight cardiovascular outcome measures were evaluated at baseline and Week 6 in both abstinent and nonabstinent patients randomized to four treatment groups; transdermal nicotine system 7 mg, 14 mg, and 21 mg per day, and placebos. Results. In abstinent patients, systolic blood pressure and heart rate decreased from baseline (while still smoking, before the start of the study) to the end of transdermal treatment, while weight increased. Similarly, HDL increased while LDL decreased and triglycerides increased. In nonabstinent patients, weight also increased from baseline to Week 6 while heart rate decreased. No other variables showed significant change. In abstinent patients, effect of nicotine dosage was observed with greater weight gain in placebo than 21 mg TTS patients and greater decrease in heart rate in placebo than 21 mg TTS patients. Conclusions. In summary, the abstinent patients showed a positive effect of smoking cessation on cardiovascular risk factors even while using the transdermal nicotine system. These findings are favorable since the transdermal nicotine system has become a useful method of nicotine replacement in smoking cessation programs.

Role of dorsal medullary reticular formation in maintenance of vasomotor tone in rats

Recent investigations of central nervous system structures involved in the generation of vasomotor tone have focused on the rostral ventrolateral portion of the medulla, whereas other medullary areas have not been considered to have primary importance. The present study was designed to determine the role of the medullary reticular formation, dorsal to the ventrolateral medulla, in the maintenance of vasomotor tone. The effects of microinjections of the inhibitory amino acid glycine into this medullary region on systemic arterial pressure, heart rate and renal nerve activity were determined in male rats anaesthetized with propofol and treated with atropine to block vagal influences on the heart. Unilateral injections (24 of 57 sites) of glycine into the dorsal medulla caused significant decreases in arterial pressure (−10 ± 1.0 mmHg) and renal sympathetic nerve activity (−12 ± 1%) whereas heart rate was not significantly affected. Bilateral injections (12 of 20) of glycine caused significantly greater decreases in heart rate (−10 ± 1 bpm) and renal nerve activity (−25 ± 4%) than were elicited by unilateral injections. In contrast, although arterial pressure decreased significantly from control values (−10 ± 1 mmHg), these responses were not different from the arterial pressure changes caused by unilateral injections. These results demonstrate that, in the propofol anaesthetized rat, neurons in the dorsal medullary reticular formation contribute to the maintenance of vasomotor tone.

Interaction between oral verapamil and β-blockers during submaximal exercise: Relevance of ancillary properties

The interaction between verapamil and beta-blockers may involve negative chronotropic, inotropic, and dromotropic effects. Three randomized, double-blind, crossover trials evaluated standardized submaximal exercise hemodynamics after oral verapamil (120 mg) and beta-blocker, alone and in combination, in groups of eight healthy men. The beta-blockers were propranolol (80 mg), metoprolol (100 mg), and pindolol (5 mg). During submaximal exercise, each beta-blocker produced similar reductions in heart rate. Likewise, each verapamil and beta-blocker combination caused greater decreases in heart rate and prolongation of PR interval than did either drug alone. Only the verapamil and propranolol combination produced greater reduction of systolic blood pressure and prolongation of rate-adjusted PR interval. All verapamil and beta-blocker combinations caused frequent adverse events, predominantly exercise fatigue and resting first-degree heart block. Although the verapamil and metoprolol or pindolol combinations produced lesser negative dromotropic or inotropic effects compared with verapamil and propranolol, coadministration of verapamil and any beta-blocker should be performed cautiously.

Cortical Influences on Diving Bradycardia in Muskrats (Ondatra zibethicus)

Muskrats (Ondatra zibethicus) freely diving for food in an indoor tank were monitored with a video camera and a VCR unit. The EKG was telemetered from the animals and recorded on the audio channel of the VCR tape. Heart rate responses to voluntary dives were analyzed and compared with those from escape andforced dives. Heart rate responses from decorticate and sham-operated muskrats were also recorded to elucidate the role that the cerebral cortex plays in the dive response. In intact animals voluntary, escape, and forced submergence resulted in progressively greater decreases in heart rate. At 5 s into the dive, heart rate had fallen by 56% in voluntary dives, 65% in escape dives, and 73% in forced dives. Intensification of the bradycardia in escape and forced dives to a lower heart rate than that seen in voluntary dives was mediated by the cerebral cortex. Heart rate in decorticate muskrats in escape and forced dives did not fall below that seen in voluntary dives. However, there appeared to be a recovery of cortical function in decorticate muskrats because intensification of bradycardia in forced dives reappeared with time after surgery. Diving bradycardia was not due to fear or stress but occurred as a result ofsubmersion per se, although there was a marked cortical influence on the response in that bradycardia was intensified in escape and forced dives.

Les bêta-bloquants aggravent-ils la cardiotoxicité de la bupivacaïne ?

Bupivacaine is known to impair the electrophysiology of the heart as well as haemodynamic parameters. Administration of calcium channel blockers prior to bupivacaine enhances its cardiotoxicity. This study assessed the effects of bupivacaine at toxic dose in dogs with previous beta-adrenergic receptor blockade. It included 12 dogs anaesthetized with thiopentone, allocated in a control group (n = 6) receiving a bolus of bupivacaine (4 mg · kg −1) and a study group (n = 6) treated with the sequence propranolol (0.2 mg · kg −1) and bupivacaine (4 mg · kg −1), 15 min later. Infranodal conduction (HV conduction times and QRS durations) was worsened in both groups. Previous propranolol administration had no potentiating effects on these parameters. Conversely the latter was responsible of a greater decrease in heart rate, and increase in atrio-ventricular conduction time (77.9 % vs 18.7 %, p < 0.05), as well as a more severe hypotension. Moreover, 3 out of the 6 animals in the study group suffered a cardiac arrest between the 5th and the 10th min. It is concluded that in anaesthetized dogs the cardiac and circulatory effects of a toxic dose of bupivacaine are increased in case of preexisting blockade of beta adrenergic receptors.

Nasotracheal intubation in the neonate: Physiologic responses and effects of atropine and pancuronium

Thirty infants with birth weights from 580 to 3450 gm (25 to 40 weeks gestation) were prospectively studied during nasotracheal intubation. The infants were randomized to receive atropine 0.01 mg/kg, atropine 0.01 mg/kg plus pancuronium 0.1 mg/kg, or no medication (controls) prior to intubation. There was a significant decrease in transcutaneous PO2 (27.3 torr, P less than 0.02), associated with significant increases in mean arterial blood pressure (57%, P less than 0.01) and intracranial pressure (mean increase 18.9 cm H2O, P less than 0.01) with intubation in all three groups of infants. Only in control infants and infants receiving atropine was there significant decrease in heart rate (52.2 and 36.2 bpm, respectively, P less than 0.01) during intubation. Control infants experienced a significantly greater decrease in heart rate and demonstrated the lowest mean heart rate, compared with the other two groups. Pancuronium plus atropine was associated with lesser increases in intracranial pressure and with the least changes in heart rate in response to intubation. There was no significant difference between the groups for changes in systemic blood pressure or transcutaneous PO2. Further studies are required to determine the clinical consequences, if any, of these responses, and the use of pretreatment in the neonate requiring intubation.

Time-course effects of two barbiturates on cardiovascular activity and temperature in the squirrel monkey

Heart rate (HR), mean arterial blood pressure (BP) and core temperature (TEMP) were recorded from conscious, chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous injections of methohexital and secobarbital. Methohexital (0.3–17.0 mg/kg) and secobarbital (1.0–30.0 mg/kg) decreased HR, BP and TEMP in a dose-dependent manner. Methohexital resulted in a greater decrease in blood pressure than secobarbital, but the latter caused greater decreases in heart rate and temperature. The duration of all effects of methohexital was substantially briefer than the effects of secobarbital at the higher doses studied. The data show that these two barbiturates differ not only in duration of action but also in the magnitude of effect on cardiovascular activity in the squirrel monkey.

Differences in hemodynamic effects of nitroprusside and prazosin in severe chronic congestive heart failure: Evidence for a direct negative chronotropic effect of prazosin

To compare the hemodynamic effects of prazosin and nitroprusside in patients with severe congestive heart failure, nine patients with heart failure refractory to conventional therapy received oral prazosin and intravenous nitroprusside administered so as to produce a similar decrease in left ventricular filling pressure in each patient. By this comparison, both drugs produced similar decreases in mean right atrial pressure, mean pulmonary arterial pressure and systemic and pulmonary vascular resistance. However, with nitroprusside, cardiac index increased more (+ 0.97 versus +0.73 liters/min per m 2, P < 0.01) and mean arterial pressure decreased less (−13.7 versus − 18,3 mm Hg, P < 0.05) than with prazosin. Both drugs produced similar changes in stroke volume index (+11.7 cc/beat per m 2 with nitroprusside and +12.5 with prazosin) and stroke work index (+8.1 g-m/m 2 with nitroprusside and +6.6 with prazosin). Therefore, the differences In the hemodynamic responses observed with the two agents were due to the significantly greater decrease in heart rate with prazosin (−8 beats/min) than with nitroprusside (−2 beats/min, P < 0.05). These clinical data support experimental evidence suggesting that there is a significant negative Chronotropic action of prazosin independent of its peripheral vascular effects.