[Cardiac surgery in Cameroon. Results at one year of the pilot phase]. / Chirurgie cardiaque au Cameroun. Résultats à un an de la phase pilote.

In the framework of implementation of his national program for control and prevention of cardiovascular diseases, Cameroonian government has set up a cardiac surgery project. We report in this manuscript results of one year follow up of the patients operated during the pilot phase. From September 22 till 26, 2008, 11 patients have been operated in Cameroun. Surgical procedures were 5 mitral mechanic valve replacement, 2 aortic mechanic valve replacement, 1 atrial septal defect closure, 2 pace maker implantation. No intrahospital death was observed. One patient died at 11th month after the operation due to mitral valve thrombosis and attributed to lack of compliance. One patient presented low cardiac output, pneumonia and a pleural effusion. 2 patients presented 2 minor complications consisting of pericarditis and superficial wound infection. The results of the pilot phase of cardiac surgery in Cameroon are effective. However, the sustainability of the program require human, material capacity building, and funding mechanism as well.

Effects of aging and cardiac denervation on heart rate variability during sleep.

BACKGROUND: Cardiac vagal predominance increases the RR interval and RR high-frequency (HF) variability during non-rapid eye movement (non-REM) sleep (stages I through IV) in young subjects. Aging suppresses deep sleep, but effects of age-related changes in sleep architecture on RR are unknown. Whether mechanical effects of changes in the breathing pattern on the sinus node during sleep affect RR variability is unclear. METHODS AND RESULTS: Polygraphic sleep recordings and RR and RR spectral profiles were determined in 8 young (22.5+/-3.3 years) and 8 older (55.0+/-7.3 years) healthy volunteers. HF oscillations in RR of 8 cardiac-denervated heart transplant recipients determined mechanical effects of respiration on the sinoatrial node during sleep. Transition from wakefulness to non-REM sleep increased the RR interval in young and older subjects and increased the HF variability of RR in the young (P:<0.05) but not in the older subjects. Older subjects disclosed a faster RR (P:<0.01) and a lower HF variability (P:<0.05) during non-REM sleep than the young subjects. Aging did not affect light and REM sleep but decreased deep sleep (stage IV) from 39+/-23 to 6+/-6 minutes (P:<0.001). Reduction in sleep stage IV with aging blunted the increase in RR and in RR HF variability during non-REM sleep (r>0.55, P:<0.05). Transition from wakefulness to non-REM sleep doubled the markedly reduced HF variability of RR in the heart transplant recipients (P:<0.05). CONCLUSIONS: Disappearance of deep sleep with aging impairs nocturnal increase in cardiac vagal activity. Mechanical effects of changes in breathing pattern during sleep favor increases in HF oscillations of the RR interval during non-REM sleep.

Differential characteristics of neural circulatory control: early versus late after cardiac transplantation.

BACKGROUND: Reappearance of low-frequency (LF) (+/-0.10 Hz) oscillations in RR interval (RR) after cardiac transplantation is indicative of sympathetic efferent reinnervation. We hypothesized that restored LF oscillations in RR in heart transplant recipients (HTRs) are linked to oscillations in muscle sympathetic nerve traffic (MSNA). METHODS AND RESULTS: RR, RR variability, and MSNA were recorded 5+/-2 months (n=7, short-term HTRs) and 138+/-8 months (n=7, long-term HTRs) after heart transplantation and compared with matched hypertensive patients (n=7). A coherence function determined the coupling between LF oscillations in MSNA and RR. RR variance did not differ between short-term and long-term HTRs. However, LF variability was only 1+/-0.5 ms(2) in the short-term HTRs but was 15+/-8 ms(2) in the long-term HTRs (P<0.05). Normalized LF variability was also higher in the long-term HTRs (40+/-14 normalized unites) versus the short-term HTRs (6+/-3 normalized united, P<0.05) but did not differ from the LF variability of the hypertensive patients. Long-term HTRs were taking less cyclosporine (P<0.01) but had higher MSNA than the short-term HTRs (62+/-7 versus 31+/-7 burst/min, respectively, P<0.05). Coherence between LF oscillations in MSNA and RR was similar in the long-term HTRs (0.59+/-0.11) and the hypertensive patients (0.60+/-0.07) and was 3-fold greater than in the short-term HTRs (0.20+/-0.06, P<0.05). CONCLUSIONS: Cardiac reinnervation after long-term heart transplantation is characterized by a restoration of the coherence between LF oscillations in RR and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time elapsed after cardiac transplantation may be a major determinant of sympathetic excitation in heart transplant recipients.

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

Circadian rhythms of blood pressure after liver transplantation.

Twenty-four-hour systolic blood pressure, diastolic blood pressure, and heart rate profiles were recorded in 17 liver-transplanted patients by noninvasive ambulatory monitoring and were analyzed with the periodogram method. These recordings were compared with those of control subjects matched for age, sex, and daytime ambulatory blood pressure. Abnormal blood pressure patterns were found in seven of the 17 patients, whereas the other 10 patients had circadian blood pressure profiles that were not different from those of control subjects. These two groups of liver-transplanted patients did not differ in age, sex, oral dose of cyclosporine, specific serum cyclosporine level, and proportion of patients receiving azathioprine and antihypertensive medications. In contrast, the daily oral dose of prednisolone was significantly higher (p < 0.001) in the seven patients with abnormal circadian blood pressure patterns. Moreover, only the daily oral dose of prednisolone was inversely correlated with the magnitude of the nighttime systolic and diastolic blood pressure decrease (r = -0.64 and r = -0.66, p < 0.01). In contrast to blood pressure, patients and control subjects had similar circadian heart rate variations. We conclude that exogenous glucocorticoid administration may have a dose-dependent effect on the nighttime blood pressure fall and may play an important role in the pathogenesis of the abnormal circadian blood pressure profiles observed in liver-transplanted patients.

Quantitative analysis of the 24-hour blood pressure and heart rate patterns in young men.

To characterize the normal nycterohemeral blood pressure and heart rate profiles and to delineate the relative roles of sleep and circadian rhythmicity, we performed 24-hour ambulatory blood pressure monitoring with simultaneous polygraphic sleep recording in 31 healthy young men investigated in a standardized physical and social environment. Electroencephalographic sleep recordings were performed during 4 consecutive nights. Blood pressure and heart rate were measured every 10 minutes for 24 hours starting in the morning preceding the fourth night of recording. Sleep quality was not significantly altered by ambulatory blood pressure monitoring. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour cycle. The typical blood pressure and heart rate patterns were bimodal with a morning acrophase (around 10:00 AM), a small afternoon nadir (around 3:00 PM), an evening acrophase (around 8:00 PM), and a profound nocturnal nadir (around 3:00 AM). The amplitude of the nycterohemeral variations was largest for heart rate, intermediate for diastolic blood pressure, and smallest for systolic blood pressure (respectively, 19.9%, 14.1%, and 10.9% of the 24-hour mean). Before awakening, a significant increase in blood pressure and heart rate was already present. Recumbency and sleep accounted for 65-75% of the nocturnal decline in blood pressure, but it explained only 50% of the nocturnal decline in heart rate. Thus, the combined effects of postural changes and the wake-sleep transition are the major factors responsible for the 24-hour rhythm in blood pressure. In contrast, the 24-hour rhythm of heart rate may reflect an endogenous circadian rhythm, amplified by the effect of sleep. We conclude that modulatory factors different from those controlling nycterohemeral changes in blood pressure influence the 24-hour variation in heart rate.

Twenty-four-hour blood pressure and heart rate profiles in humans. A twin study.

To delineate the relative roles of genetic and environmental factors on physiological variations of blood pressure and heart rate, we performed 24-hour ambulatory blood pressure monitorings with simultaneous polygraphic sleep recordings in 28 monozygotic and 16 dizygotic healthy young male twin pairs investigated in a standardized physical and social environment. Blood pressure and heart rate were measured every 10 minutes for 24 hours. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour span. Surprisingly, monozygotic twins as a group tended to have higher blood pressure values than dizygotic twins, and this difference reached the level of significance for daytime systolic blood pressure (P < .005). Although environmental influences largely controlled the mean levels and characteristics of the 24-hour systolic blood pressure variations, significant genetic effects were demonstrated for the mean levels and 24-hour patterns of diastolic blood pressure and heart rate. For both diastolic blood pressure and heart rate, the genetic effects concerned largely the same characteristics of the 24-hour profiles: the 24-hour mean, the daytime mean, the value of the evening acrophase, and the value of the major acrophase. Moreover, there was a strong genetic influence for the amplitude of the 24-hour rhythm of heart rate.

Diurnal variations in cardiovascular function and glucose regulation in normotensive humans.

To define the physiological relationships between cardiovascular function, glucose regulation, and insulin secretion, we submitted nine young normotensive subjects to ambulatory blood pressure monitoring and blood sampling at 20-minute intervals for 24 hours to measure glucose, insulin, C peptide, cortisol, and growth hormone. Subjects ingested three identical carbohydrate-rich meals in the morning (8:30 AM), early afternoon (2 PM), and evening (8 PM). On the following day, they underwent an intravenous glucose tolerance test for quantification of insulin sensitivity. Significant postmeal increases in systolic pressure averaging 18 +/- 10 mm Hg in the morning, 18 +/- 8 mm Hg in the early afternoon, and 26 +/- 19 mm Hg in the evening were observed. Postprandial variations in diastolic pressure and heart rate were significant only for the morning meal. The magnitude of the postprandial increases in systolic pressure was correlated with the amount of insulin secreted in the morning but not later in the day. Pulses of growth hormone consistently occurred 3 to 4 hours after the morning and midday meals, as well as after the onset of sleep. Our findings indicate that under normal conditions, there is a quantitative relationship between postprandial insulin secretion and blood pressure.

Arterial baroreflex control of the sinus node during dobutamine exercise stress testing.

The contributions of increases in circulating catecholamines, changes in central command, and muscle afferents on baroreflex control of the sinus node during exercise are unclear. We used a dobutamine infusion to induce hemodynamic changes comparable to those of moderate physical exercise in the absence of changes in central command and muscle afferents in 13 healthy subjects. Dobutamine (up to 9 microg/kg body weight per minute) increased systolic blood pressure, shortened the RR interval, increased systolic blood pressure variability, but blunted RR interval variability (P<0.05 versus placebo). Consequently, dobutamine decreased the coherence between variations in systolic blood pressure and RR interval and decreased arterial baroreflex sensitivity from 12+/-2 to 3+/-1 ms/mm Hg (P<0.01). The largest increases in systolic blood pressure with dobutamine were paralleled by the greatest impairments in arterial baroreflex sensitivity (0. 50

Long-term acceptability of perindopril: European multicenter trial on 856 patients.

The acceptability of perindopril in the long-term treatment of patients with mild to severe essential hypertension was assessed in a large European multicenter trial including 856 patients. Diastolic blood pressure (DBP) at inclusion was 95-125 mm Hg after 1 month of placebo. Normalization of blood pressure was defined as a DBP less than or equal to 90 mm Hg. Treatment was started with perindopril 4 mg once daily and increased when necessary to 8 mg daily. If DBP was not controlled, a second drug (hydrochlorothiazide) and finally a third drug were added. After 1 year of treatment in all 690 evaluable patients, supine systolic and diastolic blood pressure decreased by 29 mm Hg (from 172 +/- 1 to 143 +/- 1 mm Hg, p less than 0.001) and 19 mm Hg (from 105 +/- 1 to 86 +/- 1 mm Hg, p less than 0.001), respectively. Perindopril monotherapy normalized blood pressure in 55% of patients and total percentage of normalization was 78%. The overall incidence of withdrawals for side effects was 6.8%, the most common side effect being cough (2.2%). The most frequent complaints reported were cough (7.0%), headache (5.6%), asthenia (5.1%), mood and/or sleep disturbance (5.1%), and dizziness (3.2%). The small changes observed in hematologic and biochemical parameters were not clinically relevant.

Sleep quality and continuous, non-invasive beat-to-beat blood pressure recording.

OBJECTIVE: To investigate the effects of continuous, non-invasive, beat-to-beat finger blood pressure monitoring on sleep in healthy men. DESIGN: After 1 night of habituation to the laboratory environment, which consisted of the placement of electroencephalographic equipment without recording, polygraphic sleep recordings were performed during two consecutive nights (nights 1 and 2) in 15 healthy men (mean +/- SD age 25 +/- 6 years). Blood pressure was recorded continuously for 24 h from the end of night 1 to the end of night 2. RESULTS: The blood pressure recording procedure caused a decrease in the amount of rapid eye movement (REM) sleep and increased the duration of nocturnal awakenings. Consequently, sleep efficiency was decreased by approximately 5%. The blood pressure measurements did not affect the duration of light and of deep sleep. Although the respective predominance of deep sleep and of REM sleep at the beginning and at the end of the sleep period were preserved during the night of blood pressure recording, the blood pressure recording procedure hampered the rise in REM sleep during the final two thirds of the sleep period. CONCLUSION: In healthy young men continuous, non-invasive, beat-to-beat finger blood pressure monitoring induced modest reductions in sleep efficiency of similar magnitude to those observed previously with non-invasive ambulatory blood pressure monitoring.

Acute central and renal haemodynamic responses to tertatolol and propranolol in patients with arterial hypertension following head injury.

We compared the central and renal haemodynamic effects of tertatolol, a new non-cardioselective beta-adrenergic blocking drug without partial agonist activity, with those of an equipotent dosage of propranolol in two groups of 10 patients each with acute cerebral injury who had developed systemic hypertension. After tertatolol, 5 mg orally, mean arterial pressure was unchanged, heart rate decreased by 22% (P less than 0.01) and cardiac index by 24% (P less than 0.01), while renal blood flow remained unchanged (-5%, NS). After 160 mg propranolol orally, mean arterial pressure was unchanged, heart rate decreased by 12% (P less than 0.01), cardiac index by 16% (P less than 0.01) and renal blood flow by 17% (P less than 0.01). There was a moderate rise in norepinephrine levels after tertatolol only. Thus in this particular model of acute hypertension, tertatolol acted as a potent beta-blocking agent but differed from propranolol by preserving renal perfusion.

Does non-invasive ambulatory blood pressure monitoring disturb sleep?

OBJECTIVE: To assess the effects of non-invasive ambulatory blood pressure monitoring upon sleep in healthy men. METHODS: Spontaneous variations in the quality of sleep were assessed by taking polygraph recordings in 44 healthy men aged 17-69 years. Subjects were allowed one night to become accustomed to the laboratory environment, and then their sleep was recorded for 4 consecutive nights. On day 4 blood pressure was measured every 10 min for 24 h. RESULTS: The blood pressure recording procedure caused a small but significant decrease in the amount of slow-wave sleep and an increase in the duration of nocturnal awakenings. As a result, sleep efficiency was decreased. The number of nocturnal awakenings was not affected by the blood pressure measurements. The effects of ambulatory blood pressure monitoring were qualitatively similar in young and older volunteers. CONCLUSION: Non-invasive ambulatory blood pressure monitoring induces modest sleep disturbances which are unlikely to artifactually distort the physiological 24-h blood pressure profile.

Does cardiac denervation affect the short-term blood pressure variability in humans?

OBJECTIVE: To explore the repercussion of cardiac denervation on the short-term blood pressure variability in humans, in order to assess the extent to which the variability of blood pressure is linked to the variability of heart rate. METHODS: Beat-to-beat blood pressure and RR interval time were recorded in 16 heart-transplanted patients and were compared with those of 10 healthy control subjects in the resting supine, sitting and standing positions. Blood pressure and RR interval variabilities were assessed by spectral analysis. RESULTS: The total blood pressure power and the sitting very low-frequency, low-frequency, low-frequency and high-frequency blood pressure variability were similar in the heart-transplanted patients and in the controls, despite a marked reduction in the RR interval variability in the heart-transplanted patients. However, the heart-transplanted patients had lower standing low-frequency blood pressure variability than the control subjects. Moreover, very low-frequency and low-frequency RR interval variabilities reappeared in the long-term heart-transplanted patients but not in the short-term heart-transplanted patients (range of time after transplantation 53-124 and 3-25 months, respectively). CONCLUSIONS: Short-term RR interval fluctuations are not mandatory for the maintenance of normal blood pressure variability in the supine and sitting positions, but may contribute to the increase in the low-frequency blood pressure variability which occurs normally in the standing position. Moreover, the long-term heart-transplanted patients had increased RR interval variability, which may have been caused by the reappearance of limited autonomic cardiac modulation. However, this increased RR interval variability did not affect the corresponding blood pressure variability.

Low-dose antihypertensive therapy with 1.5 mg sustained-release indapamide: results of randomised double-blind controlled studies. European study group.

OBJECTIVE: In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release (SR) formulation of indapamide was developed to optimize the drug's efficacy : safety ratio. The aim of this work was to evaluate the benefit of a low-dose diuretic by consolidating the efficacy and safety results of two clinical trials with a similar design. PATIENTS AND METHODS: Clinical data were obtained in two European randomized double-blind studies with 690 mild to moderate hypertensive patients (95 mmHg < or = supine diastolic blood pressure < or = 114 mmHg using a mercury sphygmomanometer) treated respectively for 2 and 3 months, with a mean age of 53 and 57 years, 44 and 57% males, mean supine diastolic blood pressure of 100.6 and 102.5 mmHg and mean supine systolic blood pressure of 161.0 and 164.5 mmHg. RESULTS: The first study, a dose-finding study with indapamide SR at 1.5, 2 and 2.5 mg versus placebo and the immediate-release (IR) formulation of indapamide, showed that the 1.5 mg dosage of the new indapamide formulation had an improved antihypertensive efficacy : safety ratio. The second study confirmed the equivalence of blood pressure reductions with 1.5 mg indapamide SR and 2.5 mg indapamide IR, and better acceptability with 1.5 mg indapamide SR, particularly in the number of patients with serum potassium levels < 3.4 mmol/l, which was reduced by more than 50%. The long-term efficacy of 1.5 mg indapamide SR was observed through a 9-month open-treatment follow-up to the second study. CONCLUSION: The 1.5 mg SR formulation of indapamide has an improved antihypertensive efficacy : safety ratio, which is in accordance with international recommendations for the use of low-dose antihypertensive drugs and diuretics in first-line therapy of hypertension.

Ambulatory blood pressure and neuroendocrine control after diet-assisted gastric restrictive surgery.

BACKGROUND: Long-term weight control after conventional diet is disappointing but may be improved when diet is assisted by gastric restrictive surgery (GRS). OBJECTIVE: To determine the effects of GRS on ambulatory blood pressure (ABP) and neuroendocrine BP control in 28 morbidly obese subjects. METHODS: A BP and heart rate were recorded every 10 min for 25 h before and 4 months after GRS. Effects of marked reductions in body weight on the renin-angiotensinaldosterone system, on plasma insulin and on sympathetic activity were also determined. RESULTS: Body mass index decreased from 43 +/- 1 to 34 +/- 1 kg/m2 and systolic (S) BP decreased by 7 +/- 2 mmHg during daytime (P=0.01) and by 8 +/- 3 mmHg during the night (P=0.02). Pulse pressure, a marker of reduced arterial compliance, decreased by 5 +/- 1 mmHg throughout the 24 h period (P < 0.001). Diastolic BP remained unchanged. Heart rate decreased more during the night (-13 +/- 2 bpm, P<0.0001) than during daytime (-5 +/- 2 bpm, P=0.03). Reductions in SBP were largest in subjects with highest initial BP values (r = -0.63, P<0.001) but were unrelated to weight loss. GRS decreased fasting glycaemia, plasma insulin, plasma C peptide and 24 h urine sodium (n=20) and noradrenaline (n=19) excretion (P<0.01). CONCLUSIONS: Diet-assisted GRS favourably affects neuroendocrine BP control in obese patients. Reductions in sodium intake, insulin levels and sympathetic tone combined with possible improvements in arterial compliance induce persistent 24 h reductions in SBP and pulse BP. Reductions in BP are largest in subjects with highest initial BP values and are unrelated to the amount of weight loss, thereby emphasizing the importance of even moderate reductions in weight on BP control.

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study.

OBJECTIVE: To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). DESIGN: The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. SETTING: European hospitals, general practitioners and cardiologists. PATIENTS: Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. INTERVENTIONS: Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. MAIN OUTCOME MEASURES: LVMI variation in the perprotocol population. RESULTS: Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. CONCLUSIONS: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

Reappearance of a normal circadian rhythm of blood pressure after cardiac transplantation.

Twenty-four-hour blood pressure (BP) and heart rate profiles were recorded in 19 patients 1 and 7 months after cardiac transplantation using noninvasive ambulatory monitors and were analyzed using the periodogram method. These recordings were compared with those of control subjects matched for age, sex and daytime ambulatory BP. One month after transplantation, the nighttime decrease in systolic and diastolic BPs were attenuated in the patients as compared to the control subjects (p less than 0.001). The daily oral dose of prednisolone was inversely correlated with the magnitude of the nighttime decreases in systolic and diastolic BPs (r = -0.47 and -0.53, p less than 0.05). In contrast, 7 months after transplantation, the nighttime decrease in systolic and diastolic BPs reappeared in the patients and was of similar magnitude as that in the control subjects. When the immunosuppressive regimens during the 2 periods of recordings were compared, the reduction in the daily oral dose of prednisolone administered to the patients 7 months after transplantation was correlated with the observed increase in the day-night systolic and diastolic BP difference (r = 0.61, p less than 0.01 and r = 0.51, p less than 0.05). Thus, data show the reappearance of normal circadian BP profiles in patients with long-term heart transplants, and suggest that glucocorticoid administration may contribute to the abnormal nocturnal BP profiles observed 1 month after transplantation.

Administration of dazoxiben, a selective thromboxane synthetase inhibitor, in the adult respiratory distress syndrome.

Experimental studies suggest that thromboxane A2 could play a role in the pulmonary hypertension of the adult respiratory distress syndrome (ARDS). We therefore investigated the hemodynamic and gasometric effects of dazoxiben, a selective thromboxane synthetase inhibitor, in seven patients who had developed ARDS. The patients were studied for 120 minutes after a single intravenous bolus of 1.5 mg of dazoxiben per kilogram of body weight. During this period, there was no change in pulmonary hemodynamics, a moderate increase in arterial oxygen pressure, and a slight decrease in venous admixture. Therefore, administration of dazoxiben in patients with ARDS does not decrease pulmonary hypertension. This study does not support the role of thromboxane A2 as an important mediator in pulmonary hypertension in human ARDS, at least once the syndrome has been recognized.

Ketanserin, a serotonin antagonist. Administration in patients with acute respiratory failure.

Increased release of serotonin (5-hydroxytryptamine, 5-HT) can play a significant role in the development of acute respiratory failure. The hemodynamic effects of ketanserin, a selective inhibitor of 5-HT2 receptors, were studied in eight patients who developed acute respiratory insufficiency after an episode of circulatory shock. Administration of ketanserin was associated with reductions in systemic and pulmonary artery pressures, without significant change in heart rate or cardiac output. Concomitant decreases in hemoglobin and protein concentrations suggested an associated increase in plasma volume. These changes were attributed to an increased peripheral pooling of blood related to vasodilation. Arterial oxygenation and pulmonary shunt were unaffected. These results indicate ketanserin represents a promising vasoactive agent for treatment of acute respiratory failure in critically ill patients.