Consecutive pathological and immunological alterations during experimentally induced swine dysentery - a study performed by repeated endoscopy and biopsy samplings through an intestinal cannula.

The development of intestinal lesions after inoculation with Brachyspira hyodysenteriae was followed by repeated endoscopy and biopsy sampling through a caecal cannula. Seven eight-week-old pigs were cannulated and inoculated, two were cannulated but not inoculated, and two pigs were inoculated but not cannulated. Endoscopy, biopsy, and blood sampling to determine SAA (serum amyloid A), haptoglobin, cortisol, and WBC counts were performed at scheduled time-points. At the third day of disease, endoscopy showed a hyperaemic, perturbed mucosa and excessive amount of mucus. Histologically, crypt hyperplasia, depletion of goblet cell mucus, and erosions were noted. Simultaneously, elevated acute phase proteins and circulating monocytes, and decreased number of intraepithelial CD3(+) cells were observed. After five days the pigs recovered. Intestinal lesions were demarcated and interspersed among apparently normal mucosa and blood parameters returned to initial values. Endoscopy through an intestinal cannula made it possible to follow the development of intestinal alterations in vivo and describe the sequential events during the course of swine dysentery. The number of animals used in a study could thus be minimised and the precision of the experiment increased.

Blood concentrations of amino acids, glucose and lactate during experimental swine dysentery.

The aim of this study was to examine blood concentrations of amino acids, glucose and lactate in association with experimental swine dysentery. Ten pigs (approximately 23kg) were orally inoculated with Brachyspira hyodysenteriae. Eight animals developed muco-haemorrhagic diarrhoea with impaired general appearance, changes in white blood cell counts and increased levels of the acute phase protein Serum Amyolid A. Blood samples were taken before inoculation, during the incubation period, during clinical signs of dysentery and during recovery. Neither plasma glucose nor lactate concentrations changed during the course of swine dysentery, but the serum concentrations of gluconeogenic non-essential amino acids decreased during dysentery. This was mainly due to decreases in alanine, glutamine, serine and tyrosine. Lysine increased during dysentery and at the beginning of the recovery period, and leucine increased during recovery. Glutamine, alanine and tyrosine levels show negative correlations with the numbers of neutrophils and monocytes. In conclusion, swine dysentery altered the blood concentrations of amino acids, but not of glucose or lactate.

Synthesis of proglycogen and macroglycogen in skeletal muscle of standardbred trotters after intermittent exercise.

REASONS FOR PERFORMING STUDY: The degradation of glycogen and its two forms, proglycogen (PG) and macroglycogen (MG) has been studied in horses performing different types of exercise, but no information is available about the resynthesis of PG and MG after exercise. OBJECTIVES: To determine the resynthesis of PG and MG in skeletal muscle after intermittent uphill exercise. METHODS: At a training camp 9 well-trained Standardbred trotters performed a training session comprising a warm-up period, 7 repeated 500 m bouts of exercise on an uphill slope and a recovery period. Muscle biopsies (m. gluteus medius) for analysis of PG, MG, glucose and glucose-6-phosphate were taken at rest, at the end of exercise and 1, 4, 8, 24, 48 and 72 h post exercise. Blood samples for analysis of glucose, lactate and insulin were collected before exercise, immediately after the last bout of exercise and then as for the muscle biopsies. RESULTS: The MG and PG concentration pre-exercise was 311 - 47 and 305 +/- 55 mmol/kg dwt respectively. The exercise caused a decrease in PG (A 63 +/- 26 mmol/kg dwt) and MG (delta 136 +/- 68 mmol/kg dwt). Immediately after the last sprint plasma glucose and lactate increased compared to values pre-exercise. During the first hour post exercise there was a further decrease in MG in 7 out of 9 horses. The rate of glycogen resynthesis during 1-24 h was higher for MG than for PG. The rate of muscle glycogen resynthesis thereafter was slower and did not differ between MG and PG up to 72 h. CONCLUSION: After repeated bouts of exercise on a slope, resynthesis of glycogen is a slow process and the resynthesis of proglycogen differs from that of macroglycogen. The fraction most depleted during exercise (MG) had no resynthesis during the first hour of recovery but then had the highest rate of resynthesis during the remainder of the first 24 h period. POTENTIAL RELEVANCE: If the time between exercise sessions during training is too short the recovery period will be inadequate for complete restoration of muscle glycogen.

Pro- and macroglycogenolysis in skeletal muscle during maximal treadmill exercise.

The purpose was to investigate the degradation of proglycogen and macroglycogen in skeletal muscle during intense exercise. Ten Standardbred trotters performed a maximal treadmill exercise test comprising a warm-up period, an exercise period, starting at 7 m/s with increments of 1 m/s every 60 s until the onset of fatigue (mean +/- s.d. 246 +/- 32 s) and a walking recovery period. Muscle biopsies were taken at rest, immediately after exercise and 15 min postexercise. The exercise caused a marked anaerobic metabolism as shown by the decrease in both muscle ATP and creatine phosphate and increase in muscle lactate. Free muscle glucose increased immediately postexercise and a further increase was noted 15 min later. There was a significant decrease (P<0.05) in proglycogen (57.1 +/- 22.2 mmol/kg dw) and macroglycogen (63.0 +/- 65.5 mmol/kg dw) during exercise. The proglycogen concentration tended to increase 15 min after exercise (19.9 +/- 27.3 mmol/kg dw; P = 0.06). The results from this study demonstrate that both proglycogen and macroglycogen contribute equally to glycogenolysis during intense exercise and suggest that glycogen resynthesis starts in the proglycogen pool.

Work capacity and central hemodynamics thirteen to twenty-six years after repair of tetralogy of Fallot.

Exercise tests and cardiac catheterization were performed in 53 patients, 13 to 26 years after intracardiac repair of tetralogy of Fallot. At the time of repair, the median age was 7 years, and 60% of patients with cyanosis had had a previous palliative procedure. The right ventriculotomy was closed without a patch in 21 patients (40%), a patch restricted to the right ventricle was inserted in 18 patients (34%), and in 14 (26%) the patch extended across the pulmonary anulus. At follow-up, 94% of the patients were free of symptoms. Symptom-limited work capacity was 87% of the predicted value (95% confidence limits, 82% to 94%). Work capacity was inversely related to age at follow-up, to right ventricular systolic pressure at rest, and to presence of moderate or severe pulmonary valve regurgitation. Cardiac output in relation to oxygen uptake was reduced in 74% of patients during exercise. In 12 patients (23%), systolic pressure at rest in the right ventricle was 50 mm Hg or higher. Systolic pressure during exercise in the right ventricle was lower in patients without a patch than in those with a patch and was abnormally high in all groups compared with healthy subjects. The ratio of right to left ventricular pressure was significantly lower than measurements taken immediately after repair. An intracardiac left-to-right shunt was present in 6 patients (11%). Three patients required invasive treatment as a result of our follow-up. We conclude that work capacity was moderately reduced 13 to 26 years after repair of tetralogy of Fallot and was adversely influenced by right ventricular hypertension and pulmonary valve regurgitation. Intermittent lifelong surveillance is advocated, because patients without symptoms may have hemodynamic abnormalities that necessitate intervention.

Late sudden deaths after repair of tetralogy of Fallot. Electrocardiographic findings associated with survival.

Of 141 hospital survivors after intracardiac repair of tetralogy of Fallot, eight died suddenly 6-23 years later. Compared with the other 133 patients, these eight were older at operation, with higher post-repair systolic right ventricular pressure and more often complete atrioventricular block; ventricular arrhythmia was diagnosed before death in three cases. In follow-up totalling 2255 patient years, the linearized rate of sudden death was 0.35%/year. The instantaneous risk of sudden death showed continuous increase with the length of follow-up. Of 80 survivors electrocardiographically evaluated 13-26 (median 20) years postoperatively, none had complete block, but 79 had complete right bundle branch block, including seven with left anterior hemiblock. Ventricular extrasystoles were recorded in 1% at rest, in 34% during exercise and in 83% during 24-hour ambulatory monitoring, with Lown Grade > or = II in 27%. Old age and possibly presence of fibrosis and/or fibroelastosis in right ventricular outflow Lown Grade. A patient with Lown grade III died suddenly 2 years after our follow-up. Old age at repair thus was associated with increased risk of late sudden death and with frequent ventricular arrhythmia in long-term survivors.

Pulmonary function thirteen to twenty-six years after repair of tetralogy of Fallot.

Lung function was evaluated in 68 patients 13 to 26 (median 19) years after repair of tetralogy of Fallot. Age at repair was 7 years (9 months to 42 years) and 51% had a palliative shunt. An outflow patch was inserted in 56%. Median vital capacity was 84% of predicted, forced expiratory volume in 1 second 83%, maximal voluntary ventilation at 40 breaths/min 70%, and diffusing capacity for carbon monoxide 77% of predicted. Scintigraphy demonstrated abnormal pulmonary perfusion in 86%. Average right lung perfusion was 57% (predicted 52%). Regional hypoperfusion could in some patients be explained by previous palliative shunt, pulmonary artery obstruction, or presence of aortopulmonary collaterals. Median symptom-limited work capacity was 82% (95% confidence limits 78% to 90%) of predicted. Twenty-eight physically active patients had high values for symptom-limited work capacity, vital capacity, forced expiratory volume in 1 second, and maximal voluntary ventilation at 40 breaths/min compared with those of inactive patients. Lung function variables were related to physical exercise and previous palliative shunt. Moderate or severe pulmonary valve incompetence had negative but not significant influence on lung function. There was no significant influence of acyanosis before repair, use of transannular patch, duration of follow-up, or smoking. We found moderately reduced work capacity and lung function late after repair of tetralogy of Fallot that did not cause symptoms. Lung function variables were high in young active male patients and low in patients with previous palliative shunt. A better lung function in active patients indicates that physical activity should be encouraged after repair of tetralogy of Fallot.

Effort dyspnea after coronary bypass surgery.

One hundred consecutive patients were followed up for 6-36 months after coronary artery bypass surgery (CABS) for angina pectoris. Of the 98 survivors, 35 reported effort angina. Of the 63 angina-free patients, nine (14%), also had to interrupt ordinary activities such as walking upstairs/uphill, though now because of dyspnea. In exercise tests all nine denied chest pain, the limiting symptom being dyspnea. Chest radiograms were normal in these nine cases, and spirometry was largely unchanged from the preoperative findings (normal in 3 cases). Exercise tolerance was normal or near normal in six patients. The other three underwent pulmonary scintigraphy and cardiac catheterization at rest and during supine exercise. The scintigrams revealed no pulmonary emboli. Catheterization showed hypokinesis and raised pulmonary capillary wedge pressure during exercise in all three patients. The cause of the left myocardial failure was not established. Long-term evaluation of CABS should take into account both effort angina and effort dyspnea.

Effort dyspnea after coronary artery bypass grafting.

Two series of consecutive patients with disabling effort angina were studied prospectively. From the first series, 94 survivors were followed up 9 months after coronary artery bypass grafting. Thirty-five patients (37%) reported that they still suffered from effort angina. Another 26 patients (28%) also used to stop when walking uphill/upstairs but because of dyspnea and 2 (2%) because of leg fatigue. A symptom-limited exercise test performed in 24 of the 26 with dyspnea revealed effort angina in 2 patients and high-degree dyspnea (mean grade 6.6 of 10) in 22. The exercise capacity was less than normal in 16 of these 22 patients. The number of peripheral anastomoses did not differ between the 26 dyspnea patients and the 31 free from effort restriction, nor did the incidence of perioperative infarctions or treatment with diuretics and beta-blocking drugs at follow-up. The second series of 95 survivors confirmed the high prevalence of disabling dyspnea after coronary artery bypass grafting (24%) and showed that it was not predictable. We conclude that physical fitness is restored in less than half the patients undergoing coronary artery bypass grafting.

Identifying severe aortic valvular stenosis by bedside examination.

Sixty-seven consecutive symptomatic patients with aortic valvular stenosis (AS) and no or slight aortic incompetence were prospectively examined bedside by a senior cardiologist before an invasive pre-operative investigation. A history of effort syncope had the highest predictive value (pos), 100%, for a significant degree of AS (defined as a calculated valve area less than or equal to 0.9 cm2 or a peak systolic pressure difference across the valve of greater than or equal to 40 mmHg). The absence of effort syncope had a predictive value (neg) of 40%. The corresponding figures for peak intensity of the murmur in mid-systole were 93 and 82%, respectively. For the combination of effort syncope and/or mid-systolic peak intensity of the murmur (borderline findings included) the predictive values were 90% (pos) and 94% (neg), respectively. No other combination of symptoms and physical finding was more discriminating. This combination of criteria for prediction of a significant stenosis was prospectively applied to the next 39 AS patients. The criteria were fulfilled by 29 patients and all were found to have a significant AS as were four of the 10 patients not fulfilling the criteria. These four falsely negative patients had a valve area/peak pressure difference of 0.5, 0.8, 0.8 cm2 and 43 mmHg. The inter-observer variation was studied in a third series by two senior cardiologists independently examining 22 AS patients. They were concordant in all with regard to a history of effort syncope and in all but one (0.6 cm2) with regard to the timing of the peak murmur. Bedside examination of an AS patient by an experienced cardiologist has a good predictivity for severity, and the inter-observer variation is low. Non-invasive laboratory investigations have only a supplementary role. However, as many patients have effort angina, a pre-operative invasive procedure including coronary arteriography is often unavoidable.

Does post-exercise ST depression reflect local ischemia or some global effect in the left ventricle?

As exercise-induced ST depressions are most frequent and marked in lead V5 independent of which single coronary artery is obstructed, some other mechanisms of ST depressions than local ischemia should be searched for. Left ventricular hemodynamics during exercise was studied in two groups of patients with severe effort angina, 19 with and 12 without ST depression after exercise (STAE). During supine exercise until angina, stroke index became significantly lower (37 vs. 52 ml/m2) and left ventricular end-diastolic pressure (LVEDP) significantly higher (40 vs. 30 mmHg) in the STAE group. The best discriminator was the early diastolic pressure (LVeDP) (22 vs. 11 mmHg), which is interpreted as a sign of a more ischemic ventricle in the STAE group. The sum of STAE in all leads is correlated to LVeDP but not to LVEDP during exercise. The link between the significant ischemia in various locations and STAE appearing most frequently and markedly in V5 seems to be some global mechanism as the occurrence of STAE and the height of the R wave were positively correlated in the various leads. As STAE in coronary heart disease shows similar configuration and distribution as in aortic valvular stenosis and digoxin medication of healthy subjects, a possible link could be the compensatory increase in contractility in non-ischemic parts of the ventricle.

Hemodynamics in diabetic renal failure.

Cardiac performance was assessed by left ventricular catheterization in ten insulin-dependent diabetics with non-dialysis-requiring uremia. None of the patients had a history or clinical signs of ischemic or valvular heart disease or congestive heart failure. Cardiac output at rest was normal in all patients. During exercise, one patient had somewhat low cardiac output and nine showed impaired ability to increase stroke work. This impairment was accompanied by elevation of the left ventricular end-diastolic pressure. The abnormal cardiac performance could not be ascribed to the degree of anemia or uremia or to volume overload. Arterial hypertension possibly contributed. The observations suggest that in diabetic patients with moderate uremia there is also left ventricular dysfunction. Renal transplantation should therefore be considered for these patients earlier than is customary for uremics without diabetes.

Cardiac performance in various stages of renal failure.

Cardiac catheterisation was performed to evaluate cardiac function in 12 patients with various stages of renal failure. All patients were studied at rest and during supine exercise to subjective exhaustion. Eight patients had a normal arteriovenous oxygen difference at rest and during exercise whereas three had a low arteriovenous oxygen difference and one a high arteriovenous oxygen difference. Left ventricular stroke work did not increase normally at transition from rest to exercise in most patients with serum creatinine concentrations greater than 500 mumol/l. The left ventricular end diastolic pressure was abnormally raised during exercise in all patients (range 20-42 mm Hg) and also at rest in most of them (range 8-36 mm Hg), indicating myocardial dysfunction. These observations suggest that patients have abnormal cardiac performance at a relatively early stage of renal failure.

Electrocardiographic prediction of the severity of aortic valvular stenosis.

The ECG at rest and at 4 min after a symptom-limited exercise test was studied in 52 patients who were catheterized because a significant aortic valvular stenosis was suspected. The calculated valve area ranged from 0.2 to 1.1 cm2/m2 BSA. QRS amplitude criteria did not discriminate between slight and severe stenoses but a negative or biphasic T wave in lead V6 did, especially after exercise. Thirty-three of the 37 patients with an area of less than or equal to 0.5 cm2/m2 BSA showed negative/biphasic TV6 after exercise but only 4 of the 15 with an area of greater than or equal to 0.6 cm2/m2 BSA. Thus, this criterion had a sensitivity for stenoses less than or equal to 0.5 cm2/m2 BSA of 89%, a specificity of 73% and a predictive value of a positive test of 89% (the pre-test likelihood being 71%). The left ventricular pressures measured during supine exercise in 38 patients did not correlate to the TV6 patterns after exercise.

ST depression and left ventricular haemodynamics during exercise in patients with angina pectoris.

The mechanism of ischaemic ST depression and the cause of its low sensitivity to coronary artery stenosis are not well understood. Of 30 patients with severe stable effort angina, 19 (63%) showed ischaemic ST depressions after exercise (the STAE group) and 11 did not. The highest load during the symptom-limited exercise test and the heart rate on that load did not differ between the two groups. The clinical characteristics and angiographic findings were also similar, but the findings at heart catheterization differed during exercise (in supine). Although the load was similar, the stroke index was significantly lower (38 vs. 53 ml/m2 BSA) and the left ventricular end-diastolic pressure rose to a significantly higher value in the STAE group (40 vs. 32 mmHg). When STAE occurred, they were exclusively or concomitantly present in chest lead 5. These findings suggest that ischaemic STAE may not reflect regional ischaemia but the consequent left ventricular dysfunction. The mechanism may, for example, be that a sufficiently elevated left ventricular diastolic pressure causes a global subendocardial ischaemia.

Rate of progression of severity of valvular aortic stenosis.

Twenty-six patients with valvular aortic stenosis were followed up for an average period of 9 years after the initial evaluation when the valvular disease had been considered too mild for surgical treatment. The valve area was 0.7-1.9 (mean 1.2) cm2 at the first study and 0.3-2.0 (mean 0.9) cm2 at the second. The mean annual decrease was about 0.1 cm2 in ten and less in the remaining patients. Advanced age and low physical working capacity at the first investigation were associated with rapid progression of the severity of the stenosis, but rapid progression was not predictable. At follow-up the combination of 1) calcifications of the valve on chest X-ray, 2) low physical working capacity and 3) negative/biphasic T wave in V6 after exercise was present in 100% of the severe stenoses (much less than 0.6 cm2) and in 10% of the mild (much greater than 1.0 cm2). The rate of progression of valvular aortic stenosis in adults is usually slow, but moderate stenoses may become severe within a few years.

Prediction of left main coronary artery stenosis by exercise electrocardiography.

The possibilities of predicting left main coronary artery stenosis (LMCAS) by the T wave pattern in exercise ECG were studied in a consecutive series of patients with stable angina pectoris and were compared to the predictive ability of ST criteria. After exclusion of patients with interfering diagnoses and digitalis treatment, 146 patients remained; 16 of them had LMCAS. Appearance or increase of a biphasic or negative T wave in leads V2-6 2 min after exercise detected 63% of the LMCAS, and the predictive value of a positive test was 36%. The sensitivity of the ST criteria was only 38% and the predictive value 26%. The observer concordance was 98% for the T wave and 84% for the ST criteria. These T wave criteria are at least as sensitive and predictive as the ST criteria and easier to apply.

Aortic valve replacement in patients over 70 years.

Twenty-seven patients 70 years of age or more were operated upon with aortic valvular replacement with an early mortality rate of 7%. No more patients died during a mean follow-up period of 28 months. The Björk-Shiley standard tilting disc valve was implanted in 15 cases and the new convexo-concave model in 12 cases. Sixty-seven per cent of the patients had narrow aortic roots (21 and 23 mm prosthesis diameters) compared with 40% of younger patients. Thrombo-embolic complications occurred in 2 patients who had not received anticoagulant treatment. No such complications were recorded in the remaining 23 surviving patients treated with anticoagulants. All the surviving patients (except one who was re-operated because of a thrombotic encapsulation of the disc) were markedly improved postoperatively. High age alone is no longer an absolute contra-indication for aortic valve replacement. The convexo-concave Björk-Shiley tilting disc prosthesis is suitable in these patients because of its low resistance of flow at small diameters. The importance of anticoagulant treatment even in elderly patients is emphasized.

Haemodynamic changes after tricuspid valve surgery. A recatheterization study in forty-five patients.

Changes of the central haemodynamics at rest and during exercise were evaluated in 45 patients who underwent tricuspid valve surgery. Tricuspid valve disease was associated with left heart valvular lesions in 42 patients, while isolated tricuspid valve lesions were present in 3 patients. The pre-operative evaluation showed marked impairment of cardiac function expressed by cardiomegaly, low physical working capacity, hypokinetic central circulation, elevated right atrial pressure and pulmonary hypertension in the majority of patients. Nineteen patients underwent tricuspid valve replacement and 26 tricuspid annuloplasty. The left heart valvular lesions were corrected by prosthetic valve replacement in all patients but one, who underwent mitral commissurotomy. The Björk-Shiley tilting disc valve prosthesis was used for all valve replacements. At postoperative evaluation the patients were classified in 3 groups: (1) Group TVR- 19 patients with well-functioning tricuspid valve prostheses; (2) Group TAP - 16 patients with good functional results in tricuspid annuloplasty; and (3) Group TAP-Failure - 10 patients in whom significant tricuspid incompetence was observed. The overall response to surgery in groups TVR and TAP was about the same, leading to an increase in working capacity and cardiac output and a decrease in heart volume, right atrial pressure and pulmonary hypertension. In the TAP-failure group, this response was limited to an increase in cardiac output and mainly attributable to the corrected left heart lesions. Sustained pulmonary hypertension, failing left ventricular myocardium, residual left heart lesions and anatomical tricuspid valve changes were the likely causes of TAP-failure, which could not be predicted from the pre-operative evaluation.