Pre-operative baroreflex sensitivity and efferent cardiac parasympathetic activity are correlated with post-operative pain.

BACKGROUND: A maladaptation of the autonomic nervous system may been seen in patients with chronic pain that includes persistent changes in the autonomic tone, increased heart rate, and reduced heart rate variability and baroreflex sensitivity. Baroreflex sensitivity and acute pain intensity have been reported to be inversely correlated. However, it is unknown whether the same correlation applies with regard to post-operative pain. In the present study, autonomic function was measured in patients scheduled for minor hand surgery and correlated with early and persistent pain after the procedure. Thus, the cause (autonomic imbalance) was present before the effect (post-operative pain). Our primary hypothesis was that a lower level of pre-operative baroreflex sensitivity is correlated with increased early post-operative pain. METHODS: There were 30 patients included and scheduled for open carpal tunnel surgery. Baroreflex sensitivity and heart rate variability were measured before surgery. Efferent cardiac parasympathetic activity was estimated by power spectral analysis of heart rate variability. Post-operative pain was recorded daily for 6 weeks (early post-operative pain) and for 1 week 1 year after surgery (persistent post-operative pain). RESULTS: Pre-operative baroreflex sensitivity correlated negatively with early (P=0.05) and persistent (P=0.04) post-operative pain. Efferent cardiac parasympathetic activity correlated negatively with early (P=0.03) but not persistent post-operative pain (P=0.12). CONCLUSIONS: The findings suggest that a low pre-operative level of baroreflex sensitivity is associated with higher post-operative pain intensity. To our knowledge, this is the first study to show the correlation between baroreflex sensitivity and post-operative pain.

Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms.

Mutations in the gene for desmoplakin (DSP) may cause arrhythmogenic right ventricular cardiomyopathy (ARVC) and Carvajal syndrome (CS). Desmoplakin is part of all desmosomes, which are abundantly expressed in both myocardial and epidermal tissue and serve as intercellular mechanical junctions. This study aimed to investigate protein expression in myocardial and epidermal tissue of ARVC and CS patients carrying DSP mutations in order to elucidate potential molecular disease mechanisms. Genetic investigations identified three ARVC patients carrying different heterozygous DSP mutations in addition to a homozygous DSP mutation in a CS patient. The protein expression of DSP in mutation carriers was evaluated in biopsies from myocardial and epidermal tissue by immunohistochemistry. Keratinocyte cultures were established from skin biopsies of mutation carriers and characterized by reverse transcriptase polymerase chain reaction, western blotting, and protein mass spectrometry. The results showed that the mutation carriers had abnormal DSP expression in both myocardial and epidermal tissue. The investigations revealed that the disease mechanisms varied accordingly to the specific types of DSP mutation identified and included haploinsufficiency, dominant-negative effects, or a combination hereof. Furthermore, the results suggest that the keratinocytes cultured from patients are a valuable and easily accessible resource to elucidate the effects of desmosomal gene mutations in humans.

Association of 24-h cardiac parasympathetic activity and degree of nephropathy in IDDM patients.

In insulin-dependent diabetic patients, nephropathy is a predictor of mortality and coronary heart disease. Impaired cardiac vagal function is an important factor in the pathophysiology of sudden cardiac death in coronary heart disease. Autonomic neuropathy in diabetes in particular involves vagal function. Bedside tests and 24-h measurements of cardiac parasympathetic activity were compared in 37 insulin-dependent diabetic patients, and the relationship between 24-h vagal activity and degree of nephropathy was investigated. Nephropathy was classified according to urinary albumin excretion as normoalbuminuria, incipient, and overt nephropathy. Mean age (approximately 30 yr) was not different among groups. The 24-h measurements of parasympathetic activity appeared more sensitive than bedside tests, as 33% of patients without cardiac autonomic neuropathy in bedside tests had 24-h vagal activity values below the 95% confidence limits of 14 healthy control subjects. Patients with incipient or overt nephropathy had significantly lower mean values for vagal activity during both wake and sleep time than healthy control subjects. Increasing degree of nephropathy was associated significantly with increasing attenuation of 24-h vagal activity (P less than 0.001). The covariation of degree of neuropathy and nephropathy may suggest common pathogenetic mechanisms. The reduced 24-h vagal activity, even in the early stages of nephropathy, could be an important risk factor for cardiac death in insulin-dependent diabetic patients.

Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian BP variation has been proposed, but data have been conflicting. The aim of the present study was to describe associations between QT dispersion and circadian BP variation as well as autonomic function in type 1 diabetic patients. In 106 normoalbuminuric (urinary albumin excretion <20 microg/min) normotensive patients, we performed 24-h ambulatory BP (Spacelabs 90207) and short-term (three times in 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (deep breathing test, postural heart rate, and BP response). No patient had received (or had earlier received) antihypertensive or other medical treatment apart from insulin. In a resting 12-lead electrocardiogram, the QT interval was measured by the tangent method in all leads with well-defined T-waves. The measurement was made by one observer blinded to other data. The QT interval was corrected for heart rate using Bazett's formula. The QTc dispersion was defined as the difference between the maximum and the minimum QTc interval in any of the 12 leads. When comparing patients with QTc dispersion below and above the median (43 ms), the latter had significantly higher night BP (114/67 vs. 109/62 mmHg, P < 0.003/P < 0.001), whereas day BP was comparable (129/81 vs. 127/79 mmHg). Diurnal BP variation was blunted in the group with QTc dispersion >43 ms with significantly higher night/day ratio, both for systolic (88.8 vs. 86.2%, P < 0.01) and diastolic (83.1 vs. 79.5%, P < 0.01) BP. The association between QTc dispersion and diastolic night BP persisted after controlling for potential confounders such as sex, age, duration of diabetes, urinary albumin excretion, and HbA1c. Power spectral analysis suggested an altered sympathovagal balance in patients with QTc dispersion above the median (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P < 0.01). In normoalbuminuric type 1 diabetic patients, increased QTc dispersion is associated with reduced nocturnal fall in BP and an altered sympathovagal balance. This coexistence may be operative in the ability of these parameters to predict cardiovascular events.

The hemopoietic stem cell antigen, CD34, is encoded by a gene located on chromosome 1.

Using Southern blotting to analyze DNA from a set of human-rodent hybrids, we have mapped the CD34 gene to chromosome 1q.

Lymphopain, a cytotoxic T and natural killer cell-associated cysteine proteinase.

Through differential screening of established human leukaemia cell lines, we have identified and molecularly cloned lymphopain, a novel cysteine proteinase of the papain family. Lymphopain exhibits a remarkably restricted cellular pattern of expression, being predominantly expressed in cytotoxic T-lymphocytes and natural killer cells. The human lymphopain locus maps to chromosome 11q13, encodes a polypeptide of 376 amino acids and is conserved in the mouse. Both human and murine forms appear more closely related to protozoan papain-like enzymes than to other mammalian members of the papain family. The cellular distribution of lymphopain expression, together with the functional demonstration of lymphopain-associated proteinase activity in vitro, is suggestive of a role for lymphopain in immune cell-mediated, cell killing.

Circadian variation and influence of risk factors on heart rate variability in healthy subjects.

Quantification of variations in instantaneous heart rate (HR) can be used to evaluate cardiac autonomic function. A 24-hour standard deviation of all normal RR intervals less than 50 ms in survivors of myocardial infarction has been shown to be an independent marker of adverse prognosis. Twenty-four-hour HR variability in 140 healthy subjects aged 40 to 77 years was determined as (1) standard deviation, and (2) percentage of successive RR interval differences greater than 6%--an index of parasympathetic activity. The 24-hour standard deviation varied between 68 and 261 ms (median 139). Range for index of parasympathetic activity was 0.1 to 29.6% (median 4.4). Twenty percent of the interindividual variation in HR variability was explained by impact of risk factors. Standard deviation was uninfluenced by age, whereas parasympathetic activity decreased by increasing age. High physical training level was independently associated with significantly higher standard deviation (and parasympathetic activity) values during both day and night. Hourly figures of standard deviation decreased during the night, whereas parasympathetic activity increased and peaked early morning. Standard deviation values as low as those reported in high-risk patients were not observed, but comparable low values for, and lack of diurnal variation in, parasympathetic activity were seen in healthy subjects also. In conclusion, risk factors and, in particular, the physical training level have impact on 24-hour HR variability in healthy subjects. This may prove valuable for modification of cardiac autonomic activity in patients.

Heart rate variability in obesity and the effect of weight loss.

To investigate the effects of obesity and weight loss on cardiovascular autonomic function, we examined 28 obese patients referred for weight-reducing gastroplasty, 24 obese patients who received dietary recommendations, and 28 lean subjects. Body weight, blood pressure, and 24-hour urinary norepinephrine excretion were measured, and time and frequency domain indexes of heart rate variability (HRV) were obtained from 24-hour Holter recordings. A measure of long-term HRV, the SD of all normal RR intervals (SDANN), was used as an index of sympathetic activity and the high-frequency (HF) component of the frequency domain, reflecting short-term HRV, as an estimate of vagal activity. All 3 study groups were investigated at baseline, and the 2 obese groups were reexamined at 1-year follow-up. Obese patients had higher blood pressure, higher urinary norepinephrine excretion, and attenuated SDANN and HF values than lean subjects (p <0.01). Obese patients treated with surgery had a mean weight loss of 32 kg (28%), whereas the obese group treated with dietary recommendations remained weight stable (p <0.001). At follow-up the weight-loss group displayed decreases in blood pressure and norepinephrine excretion and showed increments in SDANN and HF values. These changes were significantly greater than those observed in the obese control group (p <0.05). Our findings suggest that obese patients have increased sympathetic activity and a withdrawal of vagal activity and that these autonomic disturbances improve after weight loss.

Importance of abstention from alcohol in alcoholic heart disease.

A case of alcohol-associated heart disease, presenting with congestive heart failure, was followed for 36 months. After abstinence from alcohol, fractional shortening rose from 13 to 60%. After 1 1/2 years of abstinence and normal physical capacity, the alcoholic abuse was resumed. Eleven months later, the patient was again in overt heart failure. Withdrawal of alcohol was again associated with significant clinical improvement, but despite being in functional NYHA class I, fractional shortening only increased from 14 to 29%. Endomyocardial morphology was unrelated to the severity of the disease. Alcoholic heart disease is partially reversible, but total abstinence is necessary to preserve cardiac function.

Atrial fibrillation and flutter after coronary artery bypass surgery: epidemiology, risk factors and preventive trials.

Atrial fibrillation and atrial flutter are common arrhythmias after coronary artery bypass grafting. Although the consequences of the arrhythmia are generally not life-threatening, it constitutes a major clinical problem often requiring conversion to sinus rhythm. Atrial fibrillation or flutter can result in hypotension, heart failure, pneumonia, and stroke. This article reviews the literature on epidemiology, electrophysiology, risk factors, and preventive trials. The major conclusions are: (1) In patients undergoing coronary artery bypass surgery, the incidence of postoperative atrial fibrillation or flutter is 20-30%, the peak incidence being on the second or third postoperative day. (2) The strongest independent preoperative predictor for atrial fibrillation or flutter is the patients' age. (3) Intra-atrial conduction delay recorded pre and peroperatively may predict development of atrial fibrillation. (4) Peroperative inducibility of atrial fibrillation by pacing the right atrium may identify patients at risk for postoperative atrial fibrillation. (5) Development of postoperative atrial fibrillation or flutter has not been associated with peroperative or postoperative events. (6) The specificity and sensitivity of age and other possible relevant factors for prediction of atrial fibrillation or flutter after coronary artery bypass grafting is low. (7) No effective prophylactic regimen has yet been established.

Atrial ectopic activity and atrial fibrillation/flutter after coronary artery bypass surgery. A case-base study controlling for confounding from age, beta-blocker treatment, and time distance from operation.

To evaluate the impact of ectopic atrial activity and cardiac autonomic function for development of atrial fibrillation or flutter we studied 128 consecutive patients undergoing elective coronary artery bypass grafting. The patients were Holter monitored during a 96-h postoperative period. Autonomic balance was estimated by heart rate variability measurement. Thirty-eight (30%) patients developed sustained atrial fibrillation or flutter. Holter recordings were analyzed in a case-base design matching for age, beta-blocker treatment, and time elapsed after the operation. The number of supraventricular ectopic beats/h was increased (P < 0.01) in the case group during each of the last 7 h before onset of atrial fibrillation or flutter. Episodes of supraventricular tachycardia 62% vs. 26%; cases vs. controls (P = 0.007), episodes of non-sustained atrial fibrillation 29% vs. 0% (P = 0.0009), and episodes of non-sustained atrial flutter 15% vs. 0% (P = 0.05) were significant predictors of atrial fibrillation or flutter. Mean heart rate/h was increased in each of the 24 h preceding the arrhythmia. However, indexes of autonomic heart function did not differ significantly between groups. Patients developing atrial fibrillation or flutter after coronary artery bypass surgery present 'warning' atrial arrhythmias: numerous supraventricular ectopic beats, paroxysmal supraventricular tachycardia, and episodes of nonsustained atrial fibrillation and flutter.

[Lowest heart rate and pauses in adults with healthy hearts]. / Laveste hjertefrekvens og pauser hos voksne hjerteraske.

The lowest heart rate measured in a one minute period (HRmin) and prevalence of pauses, was determined with eight years interval, in two 24 hour Holter Monitorings, in 183 persistently healthy adults aged 40 to 85 years. For the individual, HRmin is a stable parameter, but the level depends on sex, smoking and physical activity habits. Independently of age, HRmin less than 40 beats per minute and pauses greater than or equal to 2.0 seconds are rare events, and should be considered abnormal.

[Left ventricular hypertrophy in patients with aortic stenosis. A comparison between electrocardiography and echocardiography]. / Venstre ventrikel-hypertrofi hos patienter med aortastenose. En sammenligning mellem elektrokardiografi og ekkokardiografi.

Using echocardiography (ECHO) as the reference method, the aim of this study was to determine the sensitivity, specificity, and predictive value of the electrocardiogram (ECG) in detection of left ventricular hypertrophy (LVH) in patients with aortic stenosis. Forty-one patients, 18 men and 23 women aged 25-80 years (mean 49 years) with uncomplicated aortic stenosis were studied. ECG-LVH was estimated by standard fixed voltage criteria. ECHO-LVH was defined according to left ventricular mass (LV mass) calculated by the Penn method. In the total material, the correlation between ECG-LVH and ECHO-mass was poor (r = 0.56, p < 0.05). The sensitivity and specificity of the ECG was respectively 50% and 100%. The positive predictive value of the ECG in detection of LVH was high (100%). We conclude that the sensitivity of the ECG in detection of LV hypertrophy is unsatisfactorily low. Accordingly, it is recommended that echocardiography be performed in all patients suspected of aortic stenosis.

[Early clinical exposure--an instant success. The new medical curriculum at the University of Aarhus]. / Tidlig klinik--en øjeblikkelig succes. Beskrivelse of en ny studieordning på Aarhus Universitet.

INTRODUCTION: In the new medical curriculum at the University of Aarhus, a third term, 20-week course focussing on early patient contact was launched. MATERIAL AND METHODS: Nine prototypical and clinically important disease entities each formed the basis of one-week courses covering an introductory clinical lecture, presentation of "paper" cases, and formalised training of pertinent clinical skills. This was integrated with plenaries and group work in physiology pertaining to the disease and the patient cases. In addition, seminars were held in patient-doctor relationships, and environmental and social medicine. Introductory lectures were given on topics, such as medical ethics, taxonomy of diseases, the organisation of hospital-based health care. At the end of the term, the students resided for eight weeks at county hospitals, which do not traditionally participate in pregraduate teaching. Each student followed one particular patient, which formed the basis of a written essay. RESULTS: Early clinical lectures (87 +/- 8%, mean +/- SD) and use of clinical cases (73 +/- 8%) were well received by third term students, and 87% found that the "paper" cases facilitated their understanding of physiology. The evaluation of the hospital training was very positive (rated excellent or good by > 95%). DISCUSSION: We conclude that early introduction to clinical practice is feasible and well received by the students.

[Fatal hemostatic complications following erroneous thrombolytic therapy in patients with suspected acute myocardial infarction]. / Letale haemostasekomplikationer som følge af fejlagtig trombolytisk terapi hos patienter mistaenkt for akut myokardieinfarkt.

This report describes the fate of two young men wrongly treated with thrombolysis for suspected myocardial infarction. Both had electrocardiographic changes upon admission. Correct diagnoses of aortic dissection and haemorrhagic pericarditis was obtained within a few hours, but, due to the prolonged disturbance of haemostasis, appropriate therapy could not be instituted, and outcome was fatal for both patients. These cases underline the importance of rigid ST criteria, and procedures for neutralization of thrombolysis are proposed.

[Atrial fibrillation after coronary artery bypass surgery. The significance of preoperative vagus modulation and ectopic atrial activity]. / Atreiflimren efter koronar bypass-kirurgi. Betydningen af proeoperativ vagusmodulation og ektopisk atrieaktivitet.

To investigate the impact of pre-operative autonomic balance and atrial ectopic activity on the risk of atrial fibrillation or flutter after aorto-coronary artery bypass surgery 24-hour Holter monitoring was analyzed in 102 patients before coronary artery bypass grafting. Index for vagal tone was calculated as % successive RR-interval differences > 6%. Twenty-nine (28%) of the 102 patients developed atrial fibrillation or flutter. Independent predictors (90% confidence interval) of postoperative atrial fibrillation or flutter were identified by logistic regression analysis: the independent predictors were older age, relative risk 1.07/year (1.02-1.12), vagal index < 10%, relative risk 4.50 (1.40-14.5), > or= 10 ectopic supraventricular beats/24 hour, relative risk 3.03 (1.05-8.72), and one or more event of non-sustained supraventricular tachycardia, relative risk 3.02 (1.11-8.22). Thus, age of the patient, attenuated preoperative cardiac vagal modulation, ectopic supraventricular beats, and paroxysmal non-sustained supraventricular tachycardia are independent risk factors for the development of atrial fibrillation or flutter after coronary artery bypass surgery.

[The 24-hour heart rate variability. An important predictor of sudden death after myocardial infarction]. / 24 timers hjertefrekvensvariabilitet. En vigtig risikofaktor for pludselig død efter myokardieinfarkt.

The activity of the cardiac autonomic nervous system can be estimated by measurement of beat to beat variations in heart rate-heart rate variability (HRV). In survivors after myocardial infarction, reduced 24-hour HRV, is an independent predictor of mortality/sudden cardiac death. The attenuated HRV is presumed to indicate reduced vagal function and concomitant high sympathetic activity. In experimental studies, this combination reduces the threshold for inducing malignant tachyarrhythmias, and is very probably a clinically important factor for the evolution of ventricular arrhythmias. Measurement of HRV in ordinary 24-hour ECG recordings can, together with other non-invasive measurements, stratify arrhythmic risk in survivors of myocardial infarction.

[Late ventricular potentials after myocardial infarction]. / Sene ventrikulaere potentialer efter myokardieinfarkt.

Late potentials in the QRS complex can be detected with signal-averaged electrocardiography and are associated with delayed and disorganized ventricular activation. This article reviews the technique, describes the pathophysiological basis of late potentials, and assesses the prognostic value of late potentials for subsequent development of ventricular tachyarrhythmias and sudden cardiac death in postmyocardial infarction patients.

Cardiac involvement in juvenile neuronal ceroid lipofuscinosis (Batten disease).

OBJECTIVE: To explore the onset and progression of cardiac involvement in juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: The study population comprised an unselected group of 29 children and adolescents with genetically verified JNCL. We focused on T-wave abnormalities on an EKG, cardiac hypertrophy, and left ventricular systolic function on echocardiography, and heart rates and heart rate variability (HRV) on 24-hour EKG recordings. The surviving patients were observed for 7½ years. The 24-hour EKG recording was repeated after 3 years. RESULTS: Abnormally deeply inverted T waves were present in one-third of the initial EKG recordings and were reported as early as 14 years of age. We found coherence between the presence of repolarization disturbances of the ventricular myocardium at the initial recordings and risk of death during the observation period. At increasing age, heart rate and HRV, expressed as the vagal index (number of adjacent RR intervals deviating more than 6%), were significantly reduced, suggesting an age-dependent bidirectional effect of JNCL on heart rate: one through decreasing parasympathetic activity on the heart and the other through a direct negative influence on sinus node automaticity. Coherence between bradycardia and arrhythmia and occurrence of sinus arrests and atrial flutter with increasing age indicated an age-dependent decrease in sinus node activity also. In the early 20s, a high frequency of ventricular hypertrophy occurred. CONCLUSIONS: Progressive cardiac involvement with repolarization disturbances, ventricular hypertrophy, and sinus node dysfunction occur in JNCL. We recommend that the attention on heart involvement in JNCL and other neuronal ceroid lipofuscinosis subtypes should be intensified.