Bart Verheyden

Effects of aerobic training intensity on resting, exercise and post-exercise blood pressure, heart rate and heart-rate variability

We aimed to investigate the effects of endurance training intensity (1) on systolic blood pressure (SBP) and heart rate (HR) at rest before exercise, and during and after a maximal exercise test; and (2) on measures of HR variability at rest before exercise and during recovery from the exercise test, in at least 55-year-old healthy sedentary men and women. A randomized crossover study comprising three 10-week periods was performed. In the first and third period, participants exercised at lower or higher intensity (33% or 66% of HR reserve) in random order, with a sedentary period in between. Training programmes were identical except for intensity, and were performed under supervision thrice for 1 h per week. The results show that in the three conditions, that is, at rest before exercise, during exercise and during recovery, we found endurance training at lower and higher intensity to reduce SBP significantly (P<0.05) and to a similar extent. Further, SBP during recovery was, on average, not lower than at rest before exercise, and chronic endurance training did not affect the response of SBP after an acute bout of exercise. The effect of training on HR at rest, during exercise and recovery was more pronounced (P<0.05) with higher intensity. Finally, endurance training had no significant effect on sympathovagal balance. In conclusion, in participants at higher age, both training programmes exert similar effects on SBP at rest, during exercise and during post-exercise recovery, whereas the effects on HR are more pronounced after higher intensity training.

Transplacental infection and apparently immunotolerance induced by a wild-type bluetongue virus serotype 8 natural infection.

Until recently, bluetongue (BT) virus (BTV) serotypes reportedly causing transplacental infections were all ascribed to the use of modified live virus strains. During the 2007 BT epidemic in Belgium, a significant increase in the incidence of abortions was reported. A study including 1348 foetuses, newborns and young animals with or without suspicion of BTV infection, was conducted to investigate the occurrence of natural transplacental infection caused by wild-type BTV-8 and to check the immunocompetence of newborns. BTV RNA was present in 41% and 18.5% of aborted foetuses from dams with or without suspected BTV involvement during pregnancy, respectively. The results of dam/calf pairs sampled before colostrum uptake provide evidence of almost 10% transplacental BTV infection in newborns. Apparently immunotolerant calves were found at a level of 2.4%. The current study concludes that the combined serological and real-time PCR (RT-qPCR) result of pregnant dams gives no indication of the infection status of the offspring except in the case of a double negative result. In a group of 109 calves with clinical suspicion of BT, born during the vector-free period, 11% were found to be RT-qPCR positive. The true prevalence was estimated to be 2.3%, indicating the extent of transplacental infection in a group of 733 calves of one to 4 months of age without BT suspicion. Moreover, virus isolation was successful for two newborn calves, emphasizing the need for restricting trade to BT-free regions of pregnant dams possibly infected during gestation, even if they are BTV RT-qPCR negative.

Steep fall in cardiac output is main determinant of hypotension during drug-free and nitroglycerine-induced orthostatic vasovagal syncope

BACKGROUND How much of the hypotension occurring during postural syncope is cardiac output-mediated and how much can be ascribed to a fall in systemic vascular resistance are unknown. The contribution of both determinants may be influenced by the use of vasoactive drugs. OBJECTIVE The purpose of this study was to assess the determinants of hypotension during drug-free and nitroglycerine (NTG)-induced vasovagal presyncope in routine tilt table testing. METHODS In this retrospective study, a total of 56 patients (37 female; age 36 +/- 19 years) with suspected vasovagal syncope and a positive tilt test at two clinical centers were selected. In 29 patients, presyncope was provoked by 0.4 mg sublingual NTG, administered in the 60 degrees head-up tilt position. In the other 27 patients, presyncope was provoked by passive tilt alone. Finger arterial pressure was monitored continuously, and left ventricular stroke volume was computed from pressure pulsations. RESULTS After NTG administration, heart rate rose, and peak heart rate was similar in all patients. Use of NTG did not affect circulatory patterns precipitating a vasovagal response. On average in all patients, marked hypotension was mediated by an approximately 50% fall in cardiac output, whereas systemic vascular resistance was well maintained until presyncope. CONCLUSION Hypotension during routine tilt testing is cardiac output-mediated, and the mechanism appears independent of the use of 0.4 mg sublingual NTG. The study data challenge the conventional idea of systemic vasodilation as the overriding cause of hypotension during postural syncope.

Cardiovascular function and basics of physiology in microgravity

Space exploration is a dream of mankind. However, this intriguing environment is not without risks. Life, and the human body, has developed all over evolution in the constant presence of gravity, especially from the moment on when living creatures left the ocean.When this gravitational force is no longer acting on the body, drastic changes occur. Some of these changes occur immediately, others progress only slowly. In the past 40 years of human space flight (first orbital flight by Yuri Gagarin on 12 April, 1961) several hazards for the human body have been identified. Bone mineral density is lost, muscle atrophy and cardiovascular deconditioning occur; pulmonary function, fluid regulating systems of the body, the sensory and the balance system are all disturbed by the lack of gravity.These changes in human physiology have to be reversed again when astronauts return to earth. This can cause adaptation problems, especially after long-duration space flights. Also the reaction of human physiology to radiation in space poses a huge risk at this moment. In this review the accent will be on cardiovascular function in space: how normal function is modified to reach a new equilibrium in space after short- and long-duration exposure to microgravity. In order to make long-duration space flight possible the mechanisms of this physiological adaptation must be understood to full extent. Only with this knowledge, effective countermeasures can be developed.

Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans.

Key points  •  Syncope is a common clinical condition occurring even in healthy people without manifest cardiovascular disease; we determined the role of cardiac output and sympathetic vasoconstriction in neurally mediated (pre)syncope. •  Our data showed that a moderate fall in cardiac output with coincident vasodilatation occurred in the majority (64%) of the presyncopal subjects, while a marked fall in cardiac output, driven predominantly by a decrease in heart rate, with no changes in total peripheral resistance at presyncope, occurred in a smaller (36%) subset. •  Sympathetic withdrawal occurred late, after the onset of hypotension. •  Sympathetic vasoconstriction and baroreflex sensitivity during symptom‐free upright posture were well preserved and, thus, an intrinsic impairment of sympathetic neural control and vasomotor responsiveness was not the cause of neurally mediated (pre)syncope in this population. •  These results help us better understand the mechanisms for syncope in humans.

EFFECTS OF AUTONOMIC BLOCKADE ON NON‐LINEAR CARDIOVASCULAR VARIABILITY INDICES IN RATS

1 The present study assesses the effects of autonomic blockade (a‐ and b‐adrenoceptor and cholinergic) on cardiovascular function studied by heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity in rats using non‐linear dynamics. Little is known about the influence of pharmacological autonomic nervous system interventions on non‐linear cardiovascular regulatory indices. 2 In 13 conscious rats, heart rate and aortic blood pressure were measured continuously before, during and after autonomic blockade with atropine, phentolamine and propranolol. Non‐linear scaling properties were studied using 1/f slope, fractal dimension and long‐ and short‐term correlation. Non‐linear complexity was described with correlation dimension, Lyapunov exponent and approximate entropy. Non‐linear indices were compared with linear time and frequency domain indices. 3 b‐Adrenoceptor blockade did not alter the non‐linear characteristics of HRV and BPV, although low‐frequency power of HRV was depressed. a‐Adrenoceptor blockade decreased the scaling behaviour of HRV, whereas cholinergic blockade decreased the complexity of the non‐linear system of HRV. For BPV, the scaling behaviour was increased during a‐adrenoceptor blockade and the complexity was increased during cholinergic blockade. The linear indices of HRV and BPV were decreased. 4 The present results indicate that the b‐adrenoceptor system has little involvement in the generation of non‐linear HRV and BPV in rats. 5 a‐Adrenoceptor blockade mostly influenced the scaling properties of the time series, whereas cholinergic blockade induced changes in the complexity measures. 6 The absence of the baroreflex mechanism can trigger a compensatory feed‐forward system increasing the complexity of BPV.

Impact of age on the vasovagal response provoked by sublingual nitroglycerine in routine tilt testing

NTG (nitroglycerine) is used in routine tilt testing to elicit a vasovagal response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was inversely related to age (r=0.51, P=0.005). Accordingly, patients with a mean FAP fall >1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30+/-10 years compared with 51+/-17 years; P=0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r=0.75, P<0.001). It was concluded that, in older patients, sublingual NTG provokes a more gradual BP decline compared with younger patients. This gradual decline cannot be ascribed to failure of the baroreflex-buffering capacity with increasing age. Age-related differences in the laboratory presentation of a vasovagal episode depend on the magnitude of the underlying bradycardic response.

Bluetongue in Eurasian lynx.

To the Editor: Bluetongue is an infectious disease of ruminants; it is caused by bluetongue virus (BTV), has 24 known serotypes, and is transmitted by several species of Culicoides biting midges. The disease mainly affects sheep and occurs when susceptible animals are introduced to areas where BTV circulates or when BTV is introduced to naive ruminant populations. The natural host range is strictly limited to ruminants, although seroconversion without disease has been reported in carnivores (1). We report BTV infection, disease, and death in 2 Eurasian lynx (Lynx lynx) and the isolation of BTV serotype 8 (BTV-8) from this carnivorous species. The 2 Eurasian lynx, held in the same cage in a zoo in Belgium, became lethargic in September 2007; animal 1 died after 2 days, and animal 2 died in February 2008. Both had been fed ruminant fetuses and stillborns from surrounding farms in an area where many bluetongue cases had been confirmed (2). Necropsy findings for animal 1 were anemia, subcutaneous hematomas, petechial hemorrhages, and lung congestion with edema. Necropsy findings for animal 2 were emaciation, anemia, enlarged and gelatinous lymph nodes, petechial hemorrhages, and pneumonia. For each animal, microscopic examination showed edematous vascular walls; enlarged endothelial cells; and evidence of acute to subacute vasculitis in muscle, myocardium, peritoneum, and lung. Tissue samples (spleen, lung, intestine) were analyzed by using 2 real-time reverse transcriptase–quantitative PCR techniques targeting BTV segment 5 and host β-actin mRNA as a control. BTV RNA was found in all samples from animal 1; cycle threshold values (3) ranged from 28.6 to 36.2. Tissues from animal 2 were negative for BTV RNA. Although the internal control was originally designed to detect β-actin mRNA of bovine or ovine species, clear positive signals were noted in all lynx samples, which indicated that this was a reliable control procedure. Infectious virus was subsequently isolated from the lung sample of animal 1 after inoculation of embryonated chicken eggs and amplification in baby hamster kidney–21 cell cultures (4). The specificity of the cytopathic effect, observed 48 hours after passage on baby hamster kidney–21 cells, was confirmed by real-time reverse transcriptase–quantitative PCR. Virus neutralization using specific reference serum (5) proved that the isolated virus was BTV-8. Anti-BTV antibodies were detected in lung tissue fluid from animal 2 (ID Screen Bluetongue Competition assay, ID VET, Monpellier, France) (6). We describe a natural, wild-type infection of a carnivorous species. Although deaths have been documented in dogs accidentally infected with a BTV-contaminated vaccine (7), the 2 lynx in this report were neither vaccinated nor medically treated by injection. BTV-8 was first introduced to northern Europe in 2006 and has subsequently spread rapidly to many countries on that continent. During 2007, a total of 6,870 bluetongue cases were reported in Belgium (2); animal 1 died in September 2007, which corresponded to the peak of bluetongue outbreaks in that region. No deaths were reported during that period among other animals, including ruminants, held in the same zoo as the 2 lynx reported here. The time lapse between initial clinical signs and death could explain the failure to detect BTV-8 RNA in animal 2. Although speculative, the suspicion of bluetongue in this animal is based on the presence of anti–BTV-8 antibodies, vasculitis, and pneumonia, which have been found in dogs accidentally infected with BTV (7). This report raises questions about the current knowledge of the epidemiology of bluetongue. Bluetongue in lynx indicates that the list of known susceptible species must be widened, at least for serotype 8. Although infection of a susceptible host by an insect vector is the only proven natural transmission mechanism for wild-type BTV, transplacental transmission of BTV-8, resulting in the birth of seropositive (8) or virus-positive calves (9), has recently been described in cattle. Although infection by an insect vector cannot be excluded, transmission by the oral route must be strongly suspected because the lynx described in this report had been fed ruminant fetuses and stillborn animals from surrounding farms. This possibility is supported by a previous suspicion that seroconversion to BTV in carnivores was a result of oral infection (1). The possibility of oral transmission is also supported by evidence of lateral transmission of BTV infection to cattle having occurred, in the absence of insect vectors, as a result of direct contact with newborn viremic calves born to infected dams that had been imported to Northern Ireland from a bluetongue-infected region of continental Europe (S. Kennedy, unpub. data). The role of wildlife, especially carnivores, in the epidemiology of bluetongue deserves further study to elucidate their role as either dead-end hosts or new sources of infection for livestock and to help determine the risks for wildlife populations. Our findings clearly indicate that a novel transmission pathway enables the virus to cross species. Consequently, transmission to other species, including domestic animals, can no longer be excluded. Moreover, oral transmission is likely to have considerable implications for disease control, including vaccination, because BTV-8 is a fast-emerging virus with major financial consequences.

Different evolutions in heart rate variability after heart transplantation: 10-year follow-up

Background. After heart transplantation, the donor heart is extrinsically denervated. No input of sympathetic or vagal nerves can influence the heart rate, resulting in a flat power spectrum of the beat-to-beat variability. The occurrence and the significance of reinnervation remain controversial. Methods and Results. We monitored the evolution of heart rate variability (HRV) after heart transplantation, starting from a few weeks postoperatively up to 10 years after surgery. Twenty–four-hour Holter recordings of 216 heart-transplant patients were analyzed using time and frequency domain analysis of HRV. Analysis of all data revealed an increase in 24-hour and night-time total power starting from 2 years after transplantation. Low-frequency oscillations calculated over the total 24 hours, day- and nighttime increased significantly starting from year 4 and onward (year 4–8: P<0.005). No evolution was found in high-frequency power. Subgroup analysis revealed a group with a clear spectral component (n=16), a group with a small component (n=124), and a group with a flat spectrum (n=76). Only the first group revealed an evolution in both high- and low-frequency power. Conclusion. These results indicate three different types of evolution in HRV, with reinnervating patterns present in only a minority of the patients. The vast majority of the patients show no signs of reinnervation.

The Most Likely Time and Place of Introduction of BTV8 into Belgian Ruminants

Background In northern Europe, bluetongue (BT) caused by the BT virus (BTV), serotype 8, was first notified in August 2006 and numerous ruminant herds were affected in 2007 and 2008. However, the origin and the time and place of the original introduction have not yet been determined. Methods and Principal Findings Four retrospective epidemiological surveys have been performed to enable determination of the initial spatiotemporal occurrence of this emerging disease in southern Belgium: investigations of the first recorded outbreaks near to the disease epicenter; a large anonymous, random postal survey of cattle herds and sheep flocks; a random historical milk tank survey of samples tested with an indirect ELISA and a follow-up survey of non-specific health indicators. The original introduction of BTV into the region probably occurred during spring 2006 near to the National Park of Hautes Fagnes and Eifel when Culicoides become active. Conclusions/Significance The determination of the most likely time and place of introduction of BTV8 into a country is of paramount importance to enhance awareness and understanding and, to improve modeling of vector-borne emerging infectious diseases.