Knut Sevre

Association between acute hypobaric hypoxia and activation of coagulation in human beings

The risk of venous thrombosis is thought to be increased by flying. In a study of 20 healthy male volunteers who were suddenly exposed to a hypobaric environment similar to that encountered within aeroplane cabins, markers of activated coagulation transiently Increased by two-fold to eight-fold. We suggest that hypobaric hypoxia, with sedentariness and dehydration, may cause this increased risk of venous thrombosis.

Autonomic Function in Hypertensive and Normotensive Subjects: The Importance of Gender

Abstract—Baroreceptor reflex sensitivity (BRS) has been found lower and heart rate variability (HRV) parasympathetic markers have been found higher in healthy women than in healthy men. Thus, in the present study we hypothesized gender differences in the autonomic function among hypertensive subjects. Forty-one hypertensive patients and 34 normotensive subjects, age 53±1 years, were examined. Four weeks after cessation of antihypertensive therapy, HRV was assessed in 24-hour Holter ECGs, and BRS was calculated with the transfer technique. A t test was performed after log transformation of spectral values. Resting blood pressure and heart rate in the hypertensive and the normotensive groups were 150±2/100±1 (mean±SEM) and 121±2/81±1 mm Hg, respectively, and 68±1 and 60±1 bpm, respectively (P <0.0005). Compared with normotensive controls, hypertensive patients had lower total power (1224±116 versus 1797±241 ms2;P =0.03), lower low frequency power (550±57 versus 813±115 ms2;P =0.04), lower high frequency power (141±23 versus 215±38 ms2;P =0.06), lower root mean square successive difference (28.7±2.7 versus 35.7±3.0 ms;P =0.03), and PNN50 (4.9±0.6% versus 9.8±1.5%;P =0.003). BRS was also lower in the hypertensive subjects (7.6±0.6 versus 10.4±0.8 ms/mm Hg;P =0.005). When comparing the same parameters between normotensive subjects and hypertensive subjects within the same gender group, we found significant reduction (P <0.05) only within the female group. The difference in BRS within the female group was twice that within the male group. Stepwise multiple regression analysis revealed gender, age, HDL cholesterol, and blood pressure as independent explanatory variables of BRS and HRV. Our results suggest that gender is an important determinant of BRS and HRV. Autonomic function parameters were especially impaired in hypertensive women compared with hypertensive men.

The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: The VAMPHYRE Study*

The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg received 8 weeks of verapamil sustained release (240 mg) and amlodipine (5 mg) in a prospective randomized, double blind, cross-over study, both after 4 weeks of placebo. The 24-h autonomic balance was measured by analysis of 24-h heart rate variability and short-term autonomic control of BP by baroreflex sensitivity measurements. Plasma norepinephrine was sampled at rest. Blood pressure was equally reduced from 153/100 mm Hg to 139/91 mm Hg with verapamil and 138/91 mm Hg with amlodipine, P = .50/.59. The low- to high-frequency ratio (LF/HF), reflecting sympathovagal balance, was higher with amlodipine than with verapamil (4.66 v 4.10; P = .001). Baroreflex function was improved by both treatments; however, baroreflex sensitivity (BRS) was significantly higher with verapamil than with amlodipine (8.47 v 8.06 msec/mm Hg; P = .01). Plasma norepinephrine (NE) level was higher with amlodipine than with verapamil (1.59 v 1.32 nmol/L; P < .0001). Amlodipine induces a shift in sympathovagal balance, as measured by heart rate variability indices and plasma NE, toward sympathetic predominance compared with vagal predominance with verapamil. Short-term autonomic control of BP, as assessed by BRS, is more effectively improved by verapamil than by amlodipine. These contrasting effects on autonomic function suggest that the nondihydropyridine calcium antagonist verapamil may have additional beneficial effects beyond lowering BP compared with the dihydropyridine amlodipine.

Relations between insulin sensitivity, fitness and autonomic cardiac regulation in healthy, young men.

Objectives We hypothesized that insulin sensitivity and vagal cardiac control are independently related in young men after adjustment for fitness and other confounding variables. Design Male volunteers aged 21–24 years with high (borderline hypertensive; n = 20) and low–normal (normotensive; n = 21) screening blood pressure (BP) were studied cross-sectionally. Methods Mean R–R interval (RR) and heart rate variability (HRV) were computed from 30-min ECGs, and baroreflex sensitivity (BRS) and latency (phase shift) from 15-min beat-to-beat finger blood pressure (BP) and heart rate recordings. Insulin-adjusted glucose disposal rate (GDR/I) was measured with a 90-min hyperinsulinaemic glucose clamp and fitness by peak oxygen uptake (VO2peak) during a treadmill test. Results HRV, baroreflex function, GDR/I, and VO2peak did not differ between the groups. GDR/I correlated positively with time and frequency domain HRV, including high-frequency power (HF) (r = 0.40, P = 0.01) and root-mean squared successive differences (RMSSD) (r = 0.43, P = 0.005), but not BRS or phase shift. GDR/I correlated with VO2peak (r = 0.70, P < 0.0001) and was explained (R2 = 0.56) by VO2peak (β = 0.57, P < 0.0001) and RR (β = 0.29, P = 0.03), independently of HRV and measures of obesity. Conversely, RR (β = 0.55, P = 0.0004) and HRV, including HF (β = 0.44, P = 0.006) and RMSSD (β = 0.46, P = 0.004) were explained by GDR/I, independently of VO2peak. Conclusions Insulin sensitivity and autonomic cardiac control are related independently of physical fitness in young men.

Plasma catecholamines, blood pressure responses and perceived stress during mental arithmetic stress in young men

We assessed plasma noradrenaline (NA) and adrenaline (A) at rest during a hyperinsulinaemic glucose clamp and responses to a mental arithmetic stress test (MST) in relation to blood pressure (BP) responses (Finapres) and distress in 20 men with high (≥140/90 mmHg) and 21 men with normal (≤⃒115/75 mmHg) screening BP, 21-24 years of age. Perceived stress, effort and overall discomfort were scored 1-10. Catecholamines and BP increased in both groups, change in diastolic BP (ΔDBP; 9.9 vs. 3.8 mmHg, p < 0.05) and ΔDBP carryover (recovery period minus baseline) (7.2 vs. 2.2 mmHg, p < 0.01) being greater in men with high screening BP. Independently of BP status, change in systolic BP (ΔSBP) and ΔSBP carryover were related to A (both p < 0.001), and ΔDBP and ΔDBP carryover to ΔNA (both p < 0.001). The subjective score sum correlated with maximal NA (r [Formula: See Text] = 0.40) and A (r [Formula: See Text] = 0.37) (both p < 0.05). Maximal NA was independently related to stress (p < 0.05) and the subjective score sum (p < 0.01). ΔA% was greater in the high- (score ≥6) than in the low-stress category, independently of BP status (p < 0.05). High screening BP is associated with impaired BP recovery after mental stress. Plasma catecholamine responses are related to BP responses and carryover effects, and reflect perceived stress in young men.

Blood viscosity: Effects of mental stress and relations to autonomic nervous system function and insulin sensitivity

We studied effects of mental stress on whole‐blood viscosity (WBV) and blood pressure (BP), and relations between WBV and autonomic nervous system activity and insulin sensitivity. We measured WBV (rotational rheometer), plasma noradrenaline (NA), finger BP, heart rate variability (HRV) and baroreflex sensitivity (BRS; transfer technique) during hyperinsulinaemic glucose clamp and mental arithmetic stress test (MST) in 20 men with high (⩾140/90 mmHg) and 21 men with normal (⩽115/75 mmHg) screening BP, and 10 women regardless of screening BP (all normotensive). WBV and NA increased during the MST, while HRV and BRS decreased. During the MST, WBV (all shear rates) and the response (ΔWBV) (low shear) were higher in men with high compared to normal screening BP (p<0.05). In men, WBV correlated positively with NA and negatively with HRV, BRS and insulin sensitivity. The diastolic BP response (ΔDBP) was independently explained by high‐shear ΔWBV (p<0.05) and ΔNA (p<0.0001), and ΔWBV independently by ΔDBP (p<0.05). WBV is related to increased sympathetic activity, impaired vagal cardiac control and low insulin sensitivity in young adults. The haemorheological effect of mental stress is increased in young men with high screening BP and may be mediated by the acute increase in BP.

Adrenaline during mental stress in relation to fitness, metabolic risk factors and cardiovascular responses in young men

We studied plasma adrenaline (A) in relation to physical fitness, metabolic cardiovascular risk factors and cardiovascular responses. Men (age 21–24 years) with high and normal (both n = 19) screening blood pressure (BP) were studied cross‐sectionally. We measured peak oxygen uptake (VO2peak) (treadmill exercise), and plasma catecholamines, heart rate (HR), finger systolic (SBP) and diastolic (DBP) BP, and insulin‐adjusted glucose disposal rate (GDR/I) during a hyperinsulinaemic glucose clamp (rest) and mental arithmetic stress test (MST). By multiple regression, A at rest (Arest) (β = 0.37, p<0.05) and during MST (Amst) (β = 0.40, p<0.01) were associated with high screening BP. In the respective models, Arest was negatively related to body mass index (BMI) (β = −0.56, p<0.001) and Amst positively to VO2peak (β = 0.54, p<0.001). BP and HR responses correlated positively with VO2peak, but were determined by Amst in multiple regression models. Independently of BMI and VO2peak, serum high‐density lipoprotein cholesterol was positively related to A levels, whereas GDR/I was independently related only to VO2peak. Increased adrenaline secretion may be related to high BP, but may at the same time be associated with a beneficial metabolic profile.

Blood pressure and heart rate responses to cold pressor test in patients admitted to hospital due to chest pain.

Cardiovascular hyperreactivity to stress may be a risk factor for future cardiovascular events. In this study we hypothesized increased cardiovascular responses to a cold pressor test (CPT) in coronary patients admitted to hospital due to chest pain compared with patients admitted with chest pain with suspected, but not later confirmed, coronary artery disease (CAD). A total of 20 patients were included in the study. All were admitted due to chest pain. None of the patients suffered from myocardial infarction. In 10 patients (CAD+) CAD was confirmed by positive exercise ECG or coronary angiography. In the other 10 patients (CAD-) all tests were negative. The two groups did not differ significantly in resting blood pressure, body mass index (BMI), age, gender or smoking status. A 1 min CPT was performed after 15 min supine rest. Blood pressure (BP) and heart rate (HR) responses were registered. There were significantly larger heart rate (p < 0.001) and systolic blood pressure (p < 0.01) responses to a cold pressure test in patients with chest pain and coronary heart disease than in patients with chest pain only. Percentage increases in HR and systolic BP also differed significantly. Cardiovascular responses to a cold pressor test were significantly larger in CAD patients admitted to hospital due to chest pain than in patients admitted with chest pain and suspected, but not later confirmed, CAD.

Effects on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT‐1 receptor blockade

Aims. We have previously found improved insulin sensitivity in hypertensives after additional treatment with angiotensin II‐receptor blocker (ARB) compared with calcium‐channel blocker (CCB) alone, despite similar blood pressure lowering effects. In this study, we compare the effect of these two principal different vasodilating agents on the autonomic nervous system in the same patients, and test whether potential differences in these variables might explain the difference seen in insulin sensitivity. Methods. In a double‐blind crossover study, 21 hypertensive patients were randomized to receive either 100 mg losartan (ARB) or 5 mg amlodipine (CCB) in addition to an open‐labelled treatment of amlodipine 5 mg. The patients were treated for 8 weeks with either treatment regimens after a 4‐week run‐in and a 4‐week washout period. Plasma catecholamines were measured using radioenzymatic technique and baroreflex sensitivity and heart rate variability was tested at rest and during 24‐h ECG registration. Results. Plasma noradrenaline was significantly lower after additional treatment with ARB compared with CCB alone (304±29 pg/ml vs 373±43 pg/ml, p = 0.022). Heart rate variability, baroreflex sensitivity or plasma adrenaline did not differ significantly between the two treatment regimens. Conclusion. The results may suggest that improvement of insulin sensitivity by ARB is related to decreased plasma noradrenaline and potential sympatholytic effects.

Handbook of cardiac anatomy, physiology, and devices

Advances in biomedical engineering and the understanding of cardiac disease processes increase the number of technical devices used in cardiac care. At the same time, handling of new equipment is often demanding, as it requires insight in pathophysiological processes, knowledge of the specific equipment being used and technical skills. This means that there is a need for a comprehensive presentation of devices being used in concert with anatomy and physiology with emphasis on topics that are important in this particular field. The main purpose of this book is to present an up-to-date textbook for doctors and engineers working in this medical discipline. Altogether there are 33 chapters gathered under four main headings – Part 1: Introduction; Part 2: Anatomy; Part 3: Physiology and Assessment; and Part 4: Devices and Therapies. In the first part, basic features of blood, blood flow through the vessels, the heart and its pump function are presented. Part 2 gives an overview of the anatomy of the thoracic organs. This part starts with a chapter describing human heart embryology, development and maturation. Then the ‘‘adult’’ organs are thoroughly described with emphasis on the heart and great vessels. The text is richly illustrated with drawings and pictures from cadaver dissection. The content of these chapters is presented in a way that is useful for practical purposes. Part 3 first describes normal biochemical and physiological processes in the healthy heart. Then myocardial reversible and irreversible damage is reviewed. Chapter 10 outlines the autonomic nervous system. First the anatomic structures of the sympathetic and parasympathetic systems are introduced, and then the basic principles of the autonomic blood circulation control are described. This section offers an insightful summary of these important mechanisms in maintaining homeostasis of internal body environment. The overview of the autonomic nervous system is wisely followed by a chapter offered on cardiac and vascular receptors and signal transduction. The last chapters in this part are spent on diagnostic tools in cardiac care. The principles of basic examination like medical history, auscultation, blood pressure and pulse measurement are thoroughly outlined, and then the principles of ECG are carefully dealt with. At the end of this part, more advanced methods like catheterization of heart, echocardiography and cardiac MRI are presented. Part 4 starts with some historical perspectives and introduction to animal models in cardiac research, before it focuses on therapeutic devices and therapies. The description of mechanisms underlying supraventricular and ventricular arrhythmias are easy to read and well illustrated. Subsequently the electrophysiological study and transcatheter ablation technique are explained. Cardiac mapping systems are offered an own chapter. Pacemakers, biventricular pacemakers and implantable cardioverterdefibrillators (ICDs) are thoroughly presented. Methods and devices used in cardiac surgery are also presented. Cardioplegia and extracorporeal circulation are described before mechanical and biological prosthetic valves are overviewed. At the end of Part 4, less-invasive cardiac surgery techniques in coronary artery bypass grafting and treatment of septal defects are introduced. Then some emerging technologies like stem cell transplantation, genomic-based tools and catheter-delivered devices are presented. Surprisingly, percutanous transluminal coronary angioplasty (PTCA) is offered relatively little space. Personally, I also miss a section presenting the intraaortic balloon pump. The text is accompanied by two CDs with pictures and some video clips. The authors must be complemented for the easy-to-read text and the many colourful illustrations. It is obvious that the book is written by enthusiasts, and it can be strongly recommended.