Evaluation of the ImmuView RSV Test for Rapid Detection of Respiratory Syncytial Virus in Adult Patients with Influenza-Like Symptoms.

Rapid antigen tests may enhance the diagnostic yield of respiratory syncytial virus (RSV) infections, but studies have shown low sensitivity in adults. We evaluated the novel ImmuView RSV test in adult patients with influenza-like symptoms who were prospectively enrolled at three emergency departments in two Swedish hospitals during two influenza seasons, 2017 to 2018 and 2018 to 2019. The ImmuView RSV test was performed on nasopharyngeal swabs and results were compared to those of the BinaxNOW RSV test. In the first season, tests were performed on frozen samples, while unfrozen samples were used in the second season. For comparison, tests were also performed on selected samples from children. Of 333 included adult patients, the sensitivity of ImmuView and BinaxNOW was 27% for both tests and specificities were 98% and 100%, respectively. The interassay agreement was good (κ = 0.61). There was no significant difference in test performance between frozen and unfrozen samples. In samples from children, the sensitivities of ImmuView and BinaxNOW were 67% and 70%, respectively. In conclusion, the ImmuView RSV test showed low sensitivity and high specificity for identifying RSV in adult patients with influenza-like symptoms, comparable with the BinaxNOW RSV test. Rapid RSV testing is of limited value for diagnosing RSV infection in adults. IMPORTANCE By timely RSV diagnosis among patients with influenza-like symptoms, especially when influenza diagnostics turn negative, it is possible to prevent unnecessary antibiotic usage as well as reduce diagnostic testing, nosocomial transmission, and hospital stay. Previous rapid RSV tests have demonstrated poor sensitivity in adults, and we could demonstrate that the novel ImmuView RSV test similarly showed limited value for diagnosing RSV infection in adult patients. However, in contrast to many other studies, we investigated patient characteristics in cases with false-positive tests and we compared the performance between unfrozen and frozen samples. Thus, our results are important, as they generate new knowledge about rapid antigen tests.

The association of mode of location activity and mobility with acute coronary syndrome: a nationwide ecological study.

BACKGROUND: We aimed to study the effect of social containment mandates on ACS presentation during COVID-19 pandemic using location activity and mobility data from mobile phone map services. METHODS: We conducted a cross-sectional study using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) including all ACS presentations during the pandemic until 7 May 2020. Using a count regression model, we adjusted for day of the week, daily weather and incidence of COVID-19. RESULTS: A 10% increase in activity around areas of residence was associated with 38% lower rates of ACS hospitalizations, whereas increased activity relating to retail and recreation, grocery stores and pharmacies, workplaces and mode of mobility was associated with 10-20% higher rates of ACS hospitalizations. CONCLUSION: Government policy regarding social containment mandates has important public health implications for medical emergencies such as ACS and may explain the decline in ACS presentations observed during COVID-19 pandemic.

The brown bear as a translational model for sedentary lifestyle-related diseases.

Sedentary lifestyle accelerates biological ageing, is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, kidney failure, sarcopenia and osteoporosis. In contrast to the linear path to worsening health in humans with metabolic syndrome, brown bears have developed a circular metabolic plasticity enabling these animals to tolerate obesity and a 'sedentary lifestyle' during hibernation and exit the den metabolically healthy in spring. Bears are close to humans physiology wise, much closer than rodents, the preferred experimental animals in medical research, and may better serve as translational model to develop treatments for lifestyle-related diseases. In this review, aspects of brown bear hibernation survival strategies are outlined and conceivable experimental strategies to learn from bears are described.

Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A subgroup analysis of the VALIDATE-SWEDEHEART trial.

AIMS: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients. METHODS: This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days. RESULTS: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54-1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94-1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54-1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93-1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women. CONCLUSION: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

Physical inactivity and platelet function in humans and brown bears: A comparative study.

Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few. Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

Drivers of hibernation in the brown bear.

BACKGROUND: Hibernation has been a key area of research for several decades, essentially in small mammals in the laboratory, yet we know very little about what triggers or ends it in the wild. Do climatic factors, an internal biological clock, or physiological processes dominate? Using state-of-the-art tracking and monitoring technology on fourteen free-ranging brown bears over three winters, we recorded movement, heart rate (HR), heart rate variability (HRV), body temperature (Tb), physical activity, ambient temperature (TA), and snow depth to identify the drivers of the start and end of hibernation. We used behavioral change point analyses to estimate the start and end of hibernation and convergent cross mapping to identify the causal interactions between the ecological and physiological variables over time. RESULTS: To our knowledge, we have built the first chronology of both ecological and physiological events from before the start to the end of hibernation in the field. Activity, HR, and Tb started to drop slowly several weeks before den entry. Bears entered the den when snow arrived and when ambient temperature reached 0 °C. HRV, taken as a proxy of sympathetic nervous system activity, dropped dramatically once the bear entered the den. This indirectly suggests that denning is tightly coupled to metabolic suppression. During arousal, the unexpected early rise in Tb (two months before den exit) was driven by TA, but was independent of HRV. The difference between Tb and TA decreased gradually suggesting that bears were not thermoconforming. HRV increased only three weeks before exit, indicating that late activation of the sympathetic nervous system likely finalized restoration of euthermic metabolism. Interestingly, it was not until TA reached the presumed lower critical temperature, likely indicating that the bears were seeking thermoneutrality, that they exited the den. CONCLUSIONS: We conclude that brown bear hibernation was initiated primarily by environmental cues, but terminated by physiological cues.

KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries.

BACKGROUND AND PURPOSE: Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca(2+) concentration ([Ca(2+)](i)) by opening of K channels and release of H2S. EXPERIMENTAL APPROACH: Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca(2+)](i), and the expression of voltage-gated K channels K(V)7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels (K(Ca)1.1) was examined. Voltage clamp assessed the role of K(V)7 channels in hypoxia. KEY RESULTS: Gradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca(2+)](i) in PGF(2α) (10 µM)-contracted arteries whereas no fall in [Ca(2+)](i) was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and K(Ca)1.1 inhibited hypoxia-induced dilatation in PGF2α -contracted arteries; this inhibition was more marked in the presence of the K(v)7 channel blockers, XE991 and linopirdine, while a K(V)7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2S- and adenosine-induced vasodilatation. PCR revealed the expression of K(V)7.1, K(V)7.4, K(V)7.5 and K(Ca)1.1 channels, and K(Ca)1.1, K(V)7.4 and K(V)7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions. CONCLUSION: The K(V)7.4 and K(V)7.5 channels, which we identified in the coronary arteries, appear to have a major role in hypoxia-induced vasodilatation. The voltage clamp results further support the involvement of K(V)7 channels in this vasodilatation. Activation of these K(V)7 channels may be induced by H2S and adenosine.

Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopathy.

AIMS: Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. Limited information is available on the genesis of the underlying reversible contractile disorder. Our objective in this prospective study was to investigate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery. METHODS AND RESULTS: Thirteen consecutive patients were examined by echocardiography and coronary angiography at admission and again by echocardiography after 3 months. Amplitudes, systolic and diastolic velocities of the mitral and tricuspid annuli and conventional diastolic parameters were measured. Systolic long-axis shortening of the left ventricle (LV) and right ventricle (RV) improved from 9.6 ± 2.2 mm to 11.2 ± 1.9 mm (P = 0.02) and from 21.3 ± 3.6 mm to 24.1 ± 2.8 mm (P = 0·02), respectively. LV systolic, early and late diastolic velocities measured by pulsed-wave tissue Doppler also improved, while additional conventional diastolic parameters of the LV and RV diastolic function were unchanged. CONCLUSIONS: Takotsubo cardiomyopathy temporarily affects systolic LV and RV function, while most diastolic parameters remain unchanged.

Hyperoxia reduces basal release of nitric oxide and contracts porcine coronary arteries.

AIM: The purpose of the present study was to investigate whether changes in nitric oxide (NO) concentration is involved in hyperoxia-induced vasoconstriction in porcine conduit coronary arteries. METHODS: The effect of hyperoxia on NO release and vasoconstriction was evaluated by tension recording, microsensor measurements, and immunoblotting in porcine conduit coronary arteries contracted with U46619 or 5-hydroxytryptamine. RESULTS: In endothelium-intact segments exchanging 20% O2, 5% CO2, 75% N2 (normoxia) for 95% O2, 5% CO2 (hyperoxia) increased contraction. In segments without endothelium hyperoxia-evoked contraction was abolished, but restored by an encircling donor segment with endothelium. An inhibitor of NOS, asymmetric dimethylarginine (ADMA, 300 mum), reduced hyperoxic contraction and basal NO concentration by, respectively, 38 +/- 12% and 46 +/- 3% (P < 0.05, n = 9). A NO donor, S-nitroso-N-acetylpenicillamine (SNAP), increased NO concentration and evoked relaxation to the same levels in normoxic and hyperoxic conditions. beta-actin and endothelial NO synthase (eNOS) protein expression was similar in normoxic and hyperoxic arterial segments. Phosphorylation of eNOS was unaltered in normoxia vs. hyperoxia, but phosphorylation of eNOS-Ser(1177) was increased and phosphorylation of eNOS-Thr(495) decreased by U46619. Blockers of ATP-sensitive, voltage-dependent and calcium-activated K+ channels did not change hyperoxic contraction. However, high extracellular K+ concentration or a second and third exposure to hyperoxia decreased contraction. CONCLUSION: The present study provides direct evidence that hyperoxia reduces basal release of NO leading to depletable endothelium-dependent vasoconstriction in porcine coronary arteries independent of changes in eNOS phosphorylation.

HSP20 phosphorylation and interstitial metabolites in hypoxia-induced dilation of swine coronary arteries.

OBJECTIVE: Hypoxia induces coronary artery dilation, but the responsible mechanism is largely unknown. Many stimuli induce arterial smooth muscle relaxation by reducing ser19-myosin regulatory light chain (MLC) phosphorylation. Other stimuli can induce smooth muscle relaxation without reductions in ser19-MLC phosphorylation. This form of relaxation has been termed force suppression and appears to be associated with heat shock protein 20 (HSP20) phosphorylation on ser16. We investigated whether hypoxia-induced sustained dilation in swine coronary arteries was promoted without ser19-MLC dephosphorylation and associated with ser16-HSP20 phosphorylation. Nitroglycerin vasodilation served as control. METHODS: In a pressure myograph, the tunica media of intact pre-contracted (PGF(2alpha); 10(-5) m) porcine coronary artery segments were cannulated using a microdialysis catheter. Diameter responses and interstitial lactate/pyruvate ratios were studied during 90 min hypoxia, hypoxia + reoxygenation (60 min), nitroglycerin (100 microm, 90 min), and nitroglycerin + wash-out (60 min). The arterial segments were snap-frozen and analysed for ser16-HSP20 phosphorylation and ser19-MLC phosphorylation. RESULTS: The normalized diameter responses to hypoxia (6.1 +/- 4.3%) and nitroglycerin (12.6 +/- 1.6%) were both significantly greater than normoxic control arteries (-10.5 +/- 1.8%, anova, P < 0.05). Ser16-HSP20 phosphorylation was increased with hypoxia and nitroglycerin treatment and ser16-HSP20 phosphorylation correlated with changes in diameters (n = 29, r2 = 0.64, P < 0.001). Ser19-MLC phosphorylation was not significantly altered by hypoxia. The lactate/pyruvate ratio was significantly increased in hypoxic arteries but did not correlate with diameters or ser16-HSP20 phosphorylation. CONCLUSION: Ser16-HSP20 phosphorylation is a potential regulator of hypoxia-induced dilation in coronary arteries.

Experimental pain and psychologic status of patients with chest pain with normal coronary arteries or ischemic heart disease.

BACKGROUND: The cause of chest pain in patients with a normal coronary angiogram (NCA) remains an enigma. Also, it is unclear whether psychosocial factors play a role in the etiology of chest pain in these patients. The objective of the current study was to compare psychosocial factors, clinical pain, and responses to experimental pain in NCA patients, patients with ischemic heart disease (IHD), and healthy control subjects. METHODS: Pain intensity, threshold, and tolerance to cold pressor pain were assessed in 30 NCA patients, 30 IHD patients, and 30 healthy control subjects matched for age, sex, and sociodemographic factors. All subjects completed questionnaires measuring a number of psychosocial factors, including stress, anxiety, depression, extroversion, and neuroticism. NCA and IHD patients also completed questionnaires assessing clinical pain responses and pain-coping strategies. RESULTS: With the exception of a lower tolerance to cold pressor pain of IHD patients (P <.05), no significant differences were found between NCA and IHD patients with respect to other clinical pain measures, psychosocial measures, pain-coping strategies, and other pain-related behaviors. Healthy control subjects differed significantly (P <.05) from both IHD and NCA patients with respect to maximum cold pressor pain, depression, and state anxiety and from IHD patients with respect to intensity of cold pressor pain, threshold to cold pressor pain, and perceived stress. CONCLUSIONS: The results suggest that higher scores on various psychosocial measures in both chest pain groups are related to their pain, rather than being the cause of pain, and do not support a psychogenic explanation for chest pain in the presence of normal coronary arteries.

Axial stretch modifies contractility of porcine coronary arteries by a protein kinase C-dependent mechanism.

Large coronary arteries undergo marked circumferential and axial deformations due to changes in blood pressure and gross movements of the ventricular wall during systole and diastole. The present study was designed to investigate 1) whether axial stretch of large coronary arteries influences the sensitivity to vasoconstrictors, 2) the mechanisms mediating stretch-dependent changes in vascular sensitivity. Endothelium-denuded cylindrical segments from large porcine coronary arteries were studied under isometric conditions using a balloon-based impedance planimetric technique. In segments subjected to a pressure of 60 mmHg, 20% axial stretch caused a left-ward shift of the concentration-response curves for K+ and 5-hydroxytryptamine (5-HT). Enhancement of vascular sensitivity to 5-HT induced by axial stretch was observed also in maximally K+-depolarized coronary arteries. Protein kinase C inhibition by calphostin C (1 microM) slightly decreased the spontaneous resting tone at 60 mmHg and inhibited the leftward shift of the concentration-response curve for 5-HT elicited by axial stretch. These results suggest that axial stretch of the vessel wall enhances the sensitivity of coronary arteries to vasoconstrictors by a protein kinase C-dependent mechanism.

Vascular reactivity to nifedipine and Ca(2+) in vitro: the role of preactivation, wall tension and geometry.

The purpose of the study was to investigate the influence of preactivation, wall tension and geometry on the reactivity of porcine coronary arteries to nifedipine and extracellular Ca(2+) in vitro. Porcine large coronary arteries were mounted as ring and cylindrical preparations and studied by wire- and balloon-based techniques. The sensitivity and maximal responses to nifedipine were more pronounced in 25 mM K(+) compared to 10 microM prostaglandin F(2alpha)-contracted preparations. Vascular sensitivity to nifedipine and Ca(2+) was enhanced under isometric compared to isobaric conditions. Under isometric conditions in the presence of 25 mM K(+), coronary rings were more sensitive to nifedipine, but less sensitive to Ca(2+) compared to cylindrical segments. In cylindrical segments, circumferential and axial tension increases augmented the extracellular Ca(2+)-dependent spontaneous resting tone and the sensitivity to extracellular Ca(2+). Coronary rings showed no resting tone at various resting tensions. These results suggest that preactivation, wall tension and vessel geometry are important determinants of Ca(2+)-influxes via nifedipine-sensitive voltage-gated Ca(2+) channels. Furthermore, axial wall tension appears to be a modulator of nifedipine-insensitive transmembrane Ca(2+)-influx that may play a role for the tone and reactivity in large coronary arteries.

The influence of transmural pressure and longitudinal stretch on K+- and Ca2+-induced coronary artery constriction.

UNLABELLED: The aim of the study was to investigate transmural pressure and longitudinal stretch modulation of K+- and Ca2+-induced constriction of porcine conductance coronary arteries. In a pressure myograph set-up, left anterior descendent coronary arteries from 70 to 90 kg pigs were investigated at pressures from 20 to 120 mmHg. Longitudinal extension ratio (lambda = L/L0(-1), where L0 is the in situ length and L the examination length) varied between 0.9 and 1.1. Two protocols were carried out: (1) Outer diameter response to maximal depolarization by K+ 125 mM at 20-120 mmHg and lambda at 0.90-1.10. (2) Concentration-response curves with K+ (4.7-125 mM) and Ca2+ (0.05-4.0 mM) at four combinations of P and lambda (P = 100 mmHg, lambda = 0.9; P = 100 mmHg, lambda = 1.1; P = 40 mmHg, lambda = 0.9; p = 40 mmHg, lambda = 1.1). RESULTS: Endothelial function was preserved. A slight (<5% diameter reduction) basal tone and no myogenic response was found. Protocol 1: the constriction to K+ 125 mM was maximal in a wide pressure range from 40 to 120 mmHg. Despite the fact that K+-induced diameter changes were statistically insignificant between 40 and 120 mmHg, there was a linear trend towards smaller diameter changes in this pressure range (r = -0.54, P < 0.01). Stretch influenced constriction at 20 mmHg because lambda = 0.90 and 0.95 resulted in smaller diameter-reductions than lambda = 1.00-1.10 (P < 0.05 for all). Contrastingly, at 120 mmHg the constriction at lambda = 1.10 was smaller than the responses at lambda = 0.90-1.05 (P < 0.05 for all). Protocol 2: EC50 and EC10 values for K+- and Ca2+ were generally higher (more sensitive) at 40 compared with 100 mmHg. Stretch was of no significant importance for EC50 and EC10 at 40 and 100 mmHg. It is concluded that porcine coronary artery constriction to non-metabolized agonists is maximal at 40 mmHg with a trend towards smaller diameter changes with higher pressures. Longitudinal stretch affects responsiveness at pressure extremes.

Musculo-skeletal pathology in patients with angina pectoris and normal coronary angiograms.

PURPOSE: To evaluate the role of the musculo-skeletal apparatus in patients with angina pectoris despite normal coronary angiograms. DESIGN: A survey of patients and controls investigated by blinded observers. SETTING: A tertiary cardiologic referral centre. SUBJECTS: Thirty women and 18 men (mean age 52.9 years) with chest pain of an average duration of 3 years and 11 months were investigated. All had normal resting electrocardiograms. No patients showed evidence of left ventricular hypertrophy or valvular heart disease on echocardiography and all had a normal coronary angiogram. All had left ventricular ejection fraction > 50%, and none had signs of coronary vasospasm. Eighteen healthy persons (10 women and eight men, mean age 51.2 years) served as controls. MAIN OUTCOME MEASURES: The group frequency of chest wall complaints, spinal radiograph and physical examination findings; pressure pain thresholds. RESULTS: The patients had significantly more complaints of pain from the neck, chest, and thoracic spine, and sensations and pain radiating to the arms than the controls. The patients had more degenerative findings on radiograph than the controls, mainly at levels C4-C7. Physical examination showed that abnormal findings were significantly more frequent in patients than in the control group in the anterior and posterior chest wall, in the spine at levels Th1-Th6 and in the muscles of the neck and shoulder girdle. There were no statistically significant differences in pain thresholds or in neurological examination. CONCLUSION: The musculo-skeletal abnormalities observed in the patients could include reflex mechanisms. Whether the abnormal findings are mainly responsible for the angina pectoris symptoms or merely epiphenomena warrants further study.

Enhanced exercise-induced hyperkalemia in patients with syndrome X.

OBJECTIVES: The purpose of this study was to determine whether patients with syndrome X have altered potassium metabolism. BACKGROUND: Patients with syndrome X have angina pectoris and exercise induced ST segment depression on the electrocardiogram despite normal coronary angiograms. Increasing evidence suggests that myocardial ischemia is uncommon in these patients. Altered potassium metabolism causing interstitial potassium accumulation in the myocardium may be an alternative mechanism for chest pain and ST segment depression in syndrome X. METHODS: We compared the magnitude of exercise-induced hyperkalemia in 16 patients with syndrome X (12 female and four male, mean +/- SD age 53 +/- 6 years) and 15 matched healthy control subjects. The participants underwent a bicycle test at a fixed load of 75 W for 10 min, and blood samples were taken for analysis of potassium, catecholamines and lactate before, during and in the recovery period after exercise. In five patients with syndrome X, the test was repeated during alpha1 adrenoceptor blockade. RESULTS: Baseline concentrations of serum potassium, plasma catecholamines and plasma lactate were similar in patients and control subjects. The rate of exercise-induced increment of serum potassium was increased in the patients (70 +/- 29 vs. 30 +/- 21 micromol/liter/min in control subjects, p < 0.001). Six patients, who stopped before 10 min of exercise, showed very rapid increments in serum potassium concentration. Compared to the control subjects, patients also demonstrated larger increments in rate-pressure product, plasma norepinephrine and lactate concentrations during exercise. The rate of serum potassium increment correlated with the rate of plasma norepinephrine increment in the patients (r = 0.63, p < 0.02), but not in the control subjects (r = 0.01, p = 0.97). Blockade of alpha1 adrenoceptors decreased systolic blood pressure at baseline, but did not influence the increment of serum potassium, plasma catecholamines and lactate. CONCLUSIONS: Patients with syndrome X have enhanced exercise induced hyperkalemia in parallel with augmented increases of circulating norepinephrine and lactate. The prevailing mechanisms behind the abnormal potassium handling comprise sources distinct from alpha1-adrenoceptor activation.

Relation between zero-stress state and branching order of porcine left coronary arterial tree.

The left common coronary arterial trees of eight pig hearts were dissected. The zero-stress state (the state of the organ when the external loads are removed) of the coronary arteries was determined by first cutting the arteries into short, ring-shaped segments perpendicular to the longitudinal axis of the blood vessel and then making a radial cut. This procedure caused the ring to open into a sector whose opening angle (theta), internal and external lengths (circumferences), and wall thickness were measured. Morphometric and theta data were organized in the framework of a diameter-defined Strahler system. We investigated 4 rings from the left common coronary artery (LCCA), 185 from the left anterior descending artery (LAD) and its branches, and 159 from the left circumflex artery (LCX) and its branches. The inner circumferences of the rings ranged over six orders for the LAD arterial tree and five orders for the LCX arterial tree, corresponding to a diameter range of about one order of magnitude for both arteries. theta demonstrates viscoelastic behavior and was measured 30 min after cutting. Our results show that the inner and outer circumference and the wall thickness increase as geometric sequences with the order number. theta is found to decrease linearly toward the smaller orders with a slope of 7.3 degrees/order in the range of the six largest orders. Strain calculations showed that the inner part of the arterial wall is in compression, whereas the outer part of the wall is in tension in the no-load (zero transmural pressure) state. This study provides basic data on the zero-stress state that are necessary for understanding the mechanics of the coronary artery.

A new method for combined isometric and isobaric pharmacodynamic studies on porcine coronary arteries.

1. The principal aim of the present study was to explore the isometric and isobaric capacity of a new intravascular technique, impedance planimetry, in basic pharmacodynamic investigations on porcine isolated epicardial coronary arteries. 2. The balloon-based catheter technique provides simultaneous measurements of luminal cross-sectional area and pressure. Sources of errors that may influence the accuracy of measurements were evaluated in detail. 3. Under isometric conditions, the stretch ratio-tension diagram showed typical developments of resting and active tensions of the smooth muscle when exposed to alternating maximal K+ depolarization and mechanical stretching. The mean (+/- SEM) maximum active tension was 28.43 +/- 1.72 mN/mm, which was reached at a stretch ratio of 1.26 +/- 0.02, corresponding to a resting tension of 10.50 +/- 0.53 mN/mm (n = 7). The concentration-response relationship to K+ at optimal basal tension was characterized by a mean (+/- SEM) pD2 value of 1.67 +/- 0.01 (n = 7). 4. Under isobaric conditions in the pressure range 40-140 mmHg, the method allowed the investigation of active vascular responses to partial K+ depolarization. The maximal active response to 25 mmol/L K+ was found at the transmural pressure of 60 mmHg (n = 7). To obtain full K+ concentration-response curves, a basal tension corresponding to a transmural pressure of 120 mmHg was required. The mean (+/- SEM) pD2 value for the concentration-response relationship to K+ was 1.53 +/- 0.01 (n = 10). 5. The vascular sensitivities to cumulatively added K+ and various agonists, such as acetylcholine, 5-hydroxytryptamine and noradrenaline, obtained from the same vessel segment at the same initial conditions corresponding to 120 mmHg were significantly higher with the isometric than with the isobaric approach. 6. The results of the present study suggest that impedance planimetry could be a useful tool in pharmacological and physiological investigations of medium-sized arteries, both under isometric and isobaric conditions.

Effect of parasympathetic blockade on the signal-averaged electrocardiogram.

Low parasympathetic activity is associated with late potentials detected at a noise level of 0.4 microV in a signal-averaged electrocardiogram (SAECG) following myocardial infarction. In contrast, at a noise level of 0.2 microV, lowering parasympathetic activity influences late potential parameters in the opposite direction in healthy subjects. The aim of this study was to estimate the relationship between parasympathetic activity and the SAECG obtained at noise levels of 0.4 and 0.2 microV in healthy subjects. Two SAECG recordings in 10 healthy subjects were obtained at noise levels of 0.2 and 0.4 microV before and after parasympathetic blockade using atropine (1 mg). Signal-averaged QRS duration (SA-QRS), late potential duration (LPD) defined as duration of terminal signals below 40 microV, and root mean square voltage of the terminal 40 ms of the averaged QRS (RMS40) were measured. At a noise level of 0.2 microV SA-QRS reduced from 124 +/- 14 to 114 +/- 17 ms (P = 0.008), LPD from 37 +/- 10 to 28 +/- 14 ms (P = 0.01), and RMS40 increased from 26 +/- 22 to 41 +/- 25 microV (P = 0.006) during parasympathetic blockade compared to baseline values. At a noise level of 0.4 microV the SA-QRS (115 +/- 15 ms) and LPD (29 +/- 11 ms) were lower and the RMS40 (37 +/- 23 microV) was higher compared to the noise level 0.2 microV, and no systematic alterations of the three variables were found during parasympathetic blockade. The parasympathetic nervous system may induce a very low-amplitude late potential in the SAECG. The data suggest that parasympathetic activity and a low noise level may lead to a false late potential-positive SAECG in low arrhythmia risk subjects. Therefore, we recommend the use of a noise level of 0.4 microV or identification of high arrhythmia risk patients by late potential and low parasympathetic activity.

Regional differences in the vasorelaxant effects of nicorandil and amlodipine on isolated porcine coronary arteries.

The vasorelaxant effects of nicorandil, a K(+)-channel opener, and amlodipine, a dihydropyridine-type Ca(2+)-channel blocker, were investigated on partially and maximally K(+)-depolarized ring preparations from the porcine left anterior descending coronary artery. By comparing vascular responses in the proximal and distal parts of the epicardial segment, the scope of the study was to evaluate regional differences in the action of nicorandil and amlodipine. Nicorandil (10(-7)-10(-4) M) shifted the K+ concentration-response curves to the right and depressed the maximal contractile responses in a concentration-dependent manner, consistent with K(+)-channel opening and secondary non-K(+)-channel opening mechanisms of action. Nicorandil had a significantly more potent relaxant effect in the proximal compared to the distal arterial rings contracted with 85 mM K+. Pretreatment with methylene blue (10(-5) M) did not significantly influence the regional difference in the action of nicorandil. Amlodipine (10(-9)-10(-6) M) had a significantly more potent and effective inhibitory and relaxant effect than nicorandil under the same conditions. In contrast to nicorandil, the effect of amlodipine was more prominent in the distal compared to the proximal vessel rings. The cumulative addition of extracellular Ca2+ exhibited a more potent contractile response in the distal rather than in the proximal rings. Nicorandil totally and amlodipine partly eliminated the contractile responses to the lowest concentration of Ca2+. The inhibitory effect of amlodipine on the contractile responses to higher Ca2+ concentrations was more pronounced than that of nicorandil. The results show that there are regional differences in the responsiveness of porcine coronary arteries to Ca2+, nicorandil and amlodipine. Our findings indicate that the regional difference in nicorandil-induced vasodilation was caused neither by the K(+)-channel opening nor by the nitrate-like mechanism of action, but could be due to a direct Ca(2+)-influx blocking effect of the drug.