Effects of respiratory alkalosis and acidosis on myocardial excitation

The adipokinetic activities, relative to isoproterenol as 1,000, in sedated, phenoxybenzamine pretreated unfasted mice were: norepinephrine 540, epinephrine 330, N-t-butylnorepinephrine 130, isoetharine 30 and N-cyclopentylbutanefrine 10. These relative activities correlate (r=0.88) with the medians of some previously defined beta1-adrenoceptor activities, but not (r=less than 0.1) with the medians of some previously defined beta2-adrenoceptor activities. These findings are in accord with the previously suggested view that an alpha, beta1-, beta2-, adrenoceptor concept is in better accord with experimental evidence that is an alpha- and beta-adrenoceptor one.     

Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease

BACKGROUND: Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography. METHODS AND RESULTS: We studied 28 subjects: 18 patients with coronary artery disease (66 +/- 8 years) and 10 age-matched healthy volunteers (64 +/- 13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non-infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4 +/- 0.4 versus 2.6 +/- 0.7, respectively; P = NS). Quantitative PET estimates of hyperemic blood flow (r = .81, P < .00001), flow reserve (r = .78, P < .00001), and an index of the "minimal coronary resistance" (r = .78, P < .00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4 +/- 0.4 versus 1.8 +/- 0.5, respectively; P = .04). CONCLUSIONS: In patients with coronary artery disease, non-invasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.     

Effects of ergotamine on myocardial blood flow in migraineurs without evidence of atherosclerotic coronary artery disease

The effects of intravenous ergotamine (0.25 mg) on basal and hyperemic (dipyridamole) myocardial blood flow (MBF), measured with positron emission tomography and H2(15)O, were assessed in 15 migraineurs in a double-blind, randomized, placebo controlled, crossover study. Ergotamine produced a 27% reduction in hyperemic MBF (2.62 +/- 0.11 vs 3.72 +/- 1.05 ml x min(-1) x g(-1); p <0.05), a 31% reduction in the coronary vasodilator reserve (1.81 +/- 0.50 vs 2.71 +/- 1.15; p <0.01), and a 55% increase in minimal coronary resistance (42.2 +/- 15 vs 26.7 +/- 8 mm Hg x min x ml(-1) x g(-1); p <0.001), suggesting vasoconstriction of the coronary microcirculation.     

Regional myocardial blood flow during hyperemia induced by contrast agent in patients with coronary artery disease

Regional myocardial specific blood flow (regional specific flow) was measured at rest and during contrast hyperemia after the intracoronary injection of xenon-133. The changes in regional specific flow were transient, resulting in some compromise in one of the underlying restraints of the inert gas washout method, namely, the presence of a steady state. Therefore, to determine the clinical utility of this technique, regional specific flow values obtained with this method were correlated with the presence and severity of coronary artery disease as assessed from the coronary arteriogram and left ventriculogram. Regional specific flow during contrast hyperemia was 186+/- 11 (mean +/- 1 standard error of the mean) ml/min per 100 g in control patients and 115+/-5 in patients with coronary artery disease. There was an inverse relation between regional specific flow during contrast hyperemia and the percent coronary stenosis when the stenosis was 40 percent or greater (r = 0.70, P less than 0.001). Regional specific flow was significantly less in patients with asynergy (77 +/- 10 ml/min per 100 g) than in patients with normal ventricular function (105 +/- 5) distal to coronary stenoses of greater than 75 percent. Thus regional specific flow measured during contrast hyperemia using the xenon washout technique and the Anger camera differentiated patients with normal coronary arteriograms from those with coronary artery disease. With this technique, good correlation was shown between regional specific flow and the percent coronary stenosis and presence of ventricular wall abnormalities. The information obtained with this method may provide prognostic information concerning suitability for surgical intervention.     

Modifications of the coronary blood flow and of myocardial lactate metabolism due to pacing in coronary disease

The variation of coronary sinus blood flow during pacing-induced tachycardia shows no direct correlation with the number of affected coronary arteries. As a functional test, total coronary blood flow is a parameter with low sensitivity in characterizing patients with coronary artery disease and thus appears unsuitable in the selection of patients for medical or surgical treatment. The thermodilution technique remains useful for the assessment of the effects of new drugs on the heart, for the evaluation of a therapeutic intervention, and for the selective measurement of regional myocardial perfusion in the anterior interventricular vein.     

Prevalence of coronary blood flow reserve abnormalities among patients with nonobstructive coronary artery disease and chest pain

BACKGROUND: Very little is known about the mechanisms underlying adverse reactions to radiocontrast medium. On the basis of the clinical features of the adverse reactions, it has generally been considered that an IgE-dependent mechanism is not involved in these adverse reactions, and only a few studies have demonstrated the presence of IgE antibody to radiocontrast medium in patient sera. METHODS: We assayed for IgE antibody to ioxaglic acid (Hexabrix), a representative radiocontrast medium, in the sera of patients who had developed adverse reactions to ioxaglic acid. A conjugate was prepared by coupling succinyl ioxaglic acid to human serum albumin. Enzyme immunoassay and radioimmunoassay for the detection of IgE antibody to ioxaglic acid in patient sera were constructed by physical adsorption or by covalent coupling of the conjugate on solid supports. RESULTS: When the radioactivity or the absorbance exceeding the mean plus 3 SD for normal healthy subjects was regarded as positive, IgE antibody was detected in the sera of 47.1% of the patients who had a past history of adverse reactions to ioxaglic acid and 16.2% of those who had experienced adverse reactions to ioxaglic acid within 24 h before the blood collection, although the IgE antibody levels were low. On the other hand, IgE antibody to ioxaglic acid was not detected in the sera of patients with no history of adverse reactions to ioxaglic acid. Inhibition experiments revealed the presence of IgE antibody specific to ioxaglic acid in the serum defined as positive for IgE antibody to ioxaglic acid. The presence of IgE antibody to ioxaglic acid did not always correlate with the activation of mast cells due to the occurrence of adverse reactions to ioxaglic acid. CONCLUSIONS: A small amount of IgE antibody to ioxaglic acid was detected in the sera of some patients with a history of adverse reactions to ioxaglic acid, and these adverse reactions may be partly explained by the presence of IgE antibody in the serum of at least some patients.     

Vasodilation with adenosine or sodium nitroprusside after coronary artery bypass surgery: a comparative study on myocardial blood flow and metabolism

The effects of adenosine and sodium nitroprusside (SNP) on central hemodynamics and myocardial blood flow and metabolism were investigated postoperatively after elective coronary artery bypass (CABG) surgery in ten sedated and mechanically ventilated patients in the intensive care unit. During three consecutive 15-min periods, SNP (0.8 +/- 0.1 micrograms.kg-1 x min-1), adenosine (88.9 +/- 13.3 micrograms.kg-1 x min-1), and then again SNP (0.7 +/- 0.1 micrograms.kg-1 x min-1) were infused to control postoperative hypertension at a mean arterial pressure of approximately 80 mm Hg. Systemic and pulmonary hemodynamics and global (coronary sinus flow, CSF) as well as regional (great cardiac vein flow, GCVF) myocardial blood flow and metabolic variables were measured. During adenosine infusion, in comparison to SNP, heart rate was unchanged, stroke volume index and cardiac index increased (24% and 32%, respectively), and the systemic vascular resistance index decreased (-26%). Mean pulmonary arterial pressure (24%) as well as pulmonary capillary wedge pressure (27%) and central venous pressure (18%) were higher with adenosine compared to SNP. Adenosine also increased CSF and GCVF (108% and 103%, respectively) without altering the CSF/GCVF flow ratio compared to SNP. Furthermore, adenosine increased the coronary oxygen content (51%) and decreased the arterio-great cardiac vein oxygen content difference (-48%) without changing regional myocardial oxygen consumption, indicating a more pronounced hyperkinetic myocardial circulation compared to SNP. In addition, adenosine infusion decreased arterial PO2 (-11%) and increased the intrapulmonary shunt fraction (57%). The PR interval time of the electrocardiogram was prolonged (12%) and the ST segment was more depressed during adenosine infusion compared to SNP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of prostacyclin on myocardial hemodynamics and metabolism after coronary artery bypass grafting

OBJECTIVE: To evaluate the impact on clinical behavior of a 3-day workshop designed to increase trainees' rates of smoking cessation counseling and reminders about Pap smears in routine consultations. DESIGN: Randomized control trial. SETTING: Accredited teaching practices of the Royal Australian College of General Practitioners' Training Program. SUBJECTS: Thirty-four trainees and 1,500 consecutive adult patients ages 16-65 years. METHOD: Trainees randomly allocated to the experimental group participated in a 3-day interactive workshop on disease prevention during their 13-week family medicine term. Audiotapes of consultations with adults conducted by trainees at the beginning and end of the rotation were analyzed blind to compare assessment of patients' smoking status and, for women, date of last Pap smear. A questionnaire mailed to each patient after the consultation also allowed identification of smokers and women overdue for a smear. Consultations with these patients at risk were analyzed for preventive counseling. Inter- and intrarater reliability was calculated for audiotape analysis. RESULTS: Preworkshop rates of questions about smoking were low, occurring in 22% of consultations. While trainees allocated to the experimental workshop were more likely to ask a routine question about smoking at the end of the term than those in the control group (P = 0.01), two-thirds of smokers remained undetected irrespective of trainee group and fewer than one in five were advised to stop smoking. Reminders about Pap smears did not change as a result of training and remained low in fewer than 20% of consultations. kappa values demonstrated high reliability of audiotape analysis. CONCLUSION: This direct measurement of clinical behavior revealed that low levels of preventive care provided by trainees are resistant to skills training without reinforcement in clinical practice. In view of the importance of prevention in routine consultations, we recommend continued evaluation of more intensive educational programs. Those withstanding rigorous evaluation could be considered for implementation in similar training contexts seeking to improve the frequency and quality of disease prevention in primary medical care.     

Impact of impaired coronary flow reserve and insulin resistance on myocardial energy metabolism in patients with syndrome X

To evaluate the role of a decreased coronary flow reserve in the genesis of angina pectoris in patients with syndrome X, we studied myocardial hemodynamics and metabolism at rest, during pace stress, and in the recovery period after pacing in 18 consecutive patients with syndrome X and in 10 control subjects. By means of positron emission tomography or the intracoronary flow-wire method, patients were subclassified as having microvascular angina (MA, n = 8) when coronary flow reserve was reduced (<2.5) or no microvascular angina (non-MA, n = 10) when coronary flow reserve was preserved (> or =2.5). At rest, coronary sinus blood flow was increased in MA patients. During pace stress, coronary sinus blood flow increased by 39 +/- 6% in MA patients versus 67 +/- 12% in non-MA patients and 69 +/- 7% in controls (p <0.05). Patients with non-MA revealed fasting hyperinsulinemia, increased arterial concentration of free fatty acids, and a similar tendency for beta-hydroxybutyrate. Oxygen extraction and carbon dioxide release did not differ between groups. Net myocardial lactate release was not observed in any patient during pace stress and myocardial energy metabolism was preserved in all patients with syndrome X. During pacing, myocardial uptake of free fatty acids and beta-hydroxybutyrate was increased in non-MA patients. Myocardial uptake of free fatty acids correlated positively and myocardial glucose and lactate uptake correlated inversely with arterial concentrations of free fatty acids in all subjects. Metabolic evidence of myocardial ischemia is uncommon in patients with syndrome X, irrespective of a globally reduced coronary flow reserve. Although patients with syndrome X can be subclassified according to presence of a microvascular or a metabolic disorder, angina pectoris and ST-segment depressions coexist with a preserved global myocardial energy efficiency in all patients.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Influence of residual antegrade coronary blood flow on the long-term prognosis of medically treated patients with myocardial infarction and single-vessel disease

This is a review article concerning an influence of trematodes infections on a defence system of snails. Changes in: snails' plasma composition, a number of hemocytes, size of a hemopoietic organ, molecules secreted by hemocytes and defence cells activities caused by the infections are discussed in detail. The differences in humoral and cellular response between susceptible and resistant strains of snails as well as between young and old snails are also presented in the article. Finally, the problem of an existence of the specific immunological memory in snails is analyzed.     

Incremental value of myocardial perfusion scintigraphy in prognosis and outcomes of patients with coronary artery disease

The concept of incremental value in prognosis and outcome of patients with coronary artery disease is important to the field of noninvasive imaging. Because these tests are expensive, they should be held to the standard of demonstrating a statistical improvement over the information provided by clinical assessment and treadmill testing. Responding to the demand for cost-effective applications of myocardial perfusion scintigraphy, a large amount of research has recently been devoted to defining specific patient subsets in which incremental value exists for scintigraphy. Subsets thus far demonstrated to benefit incrementally include those men and women referred for possible coronary artery disease, with known coronary artery disease, and after percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, unstable angina, or recent infarction. Incremental cost savings also apply to these subsets except for patients with normal ECGs at rest and less than 15% likelihood for significant coronary artery disease.     

Prognostic value of myocardial hypoperfusion indexes in patients with suspected or known coronary artery disease

BACKGROUND: We evaluated the prognostic value of exercise 201Tl indexes of myocardial hypoperfusion in patients with suspected or known coronary artery disease. METHODS AND RESULTS: Patients were divided into two groups: group I consisted of 332 patients with diagnostic electrocardiographic stress test results and group II consisted of 144 patients with nondiagnostic (inadequate or uninterpretable) stress electrocardiograms. At the 2-year follow-up, 20 hard events (16 cardiac deaths and 4 nonfatal myocardial infarctions) and 80 soft events (coronary revascularization procedures) occurred in group I. Considering total events, thallium imaging provided significant prognostic information in addition to clinical and exercise stress test data in the total study population (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, thallium imaging added incremental prognostic value only in those with positive electrocardiographic stress test results (p < 0.01). When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). In group II at the end of follow-up, 15 hard and 39 soft events had occurred. In these patients occurrence of total (p < 0.001), hard (p < 0.05), and soft (p < 0.001) events was higher in those with abnormal thallium scintigraphic results than in those without. Moreover, no clinical and exercise variable, except history of myocardial infarction, was significantly related to outcome, whereas both indexes of extent and severity of hypoperfusion were significant. CONCLUSIONS: The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give unique prognostic information in patients with nondiagnostic electrocardiographic stress test results. Thallium imaging provides incremental prognostic information even in patients with diagnostic electrocardiographic stress test results but not in the low-risk subset of patients without previous infarction who have negative electrocardiographic stress test results.     

Indices of protein and nitrogen metabolism in newborn calves in experimental metabolic acidosis and alkalosis

The content of indices of protein and nitrogen metabolism in the blood of newborn calves has been studied under the conditions of experimental metabolic acidosis and alkalosis. It has been found that the state of experimental metabolic acidosis of the calves for the first 36 hours of their life is accompanied by the decrease in the content of protein and its basic fractions. Under experimental metabolic alkalosis the concentration of the mentioned indices considerably grows, and it even exceeds physiological values. The obtained results also evidence for the considerable role of hemoglobin buffer system of the newborn calves in regulation of organism acid-base-state.     

Effects of electrostimulation of the vagus afferent endings in patients with coronary artery disease

BACKGROUND: In rats, low-frequency electroneurostimulation (ENS) of the ear afferent vagus endings and brainstem structures via transauricular electroacupuncture increases the parasympathetic tone of the autonomic nervous system. We examined the effects of ENS applied in the preoperative period in patients with coronary artery disease (CAD) who underwent coronary artery bypass grafting operations. METHODS: ENS was performed in a group of 10 patients with CAD who were classified as Canadian Cardiovascular Society class IV before operation. A second group of 10 patients with a similar degree of CAD comprised a control group. The efficacy of the procedure was evaluated on the basis of improvement in the patient's clinical course before and after operation. The presence of major inducible stress protein (HSP 70i) and the ATP content of the myocardium was determined in atrial tissue (part of the right heart auricle) from both groups of patients. Tissue from patients with Wolff-Parkinson-White (WPW) syndrome served as a control, non-ischemic, cardiac tissue. RESULTS: A course of 10 ENS procedures improved the patients' preoperative clinical course, producing a rapid reduction in their angina. By the end of the course, the patients no longer developed angina either at rest or after a moderate physical load, and their dependence on treatment with vasodilators had decreased considerably. Atrial tissue from patients with CAD who were treated with ENS was similar to that from patients with WPW in lcaking HSP 70i and in ATP content. In contrast, tissue from the control group of patients with CAD contained HSP 70i and had an increased content of ATP. The antianginal effect of neurostimulation lasted for at least 2-3 weeks after completion of the procedures. The postoperative recovery of patients treated with ENS was characterized by stable hemodynamics and sinus rhythm. CONCLUSION: We conclude that ENS had a central vagotonic/sympatholytic influence on the heart, leading to the development of three main effects in patients with CAD: relief of anginal symptoms, diminution of some biochemical myocardial signs of the disease, and an increase in the heart's tolerance of operative reperfusion damage.     

Retrograde coronary artery flow in aortic valve disease

Retrograde coronary artery flow was observed angiographically in 43 patients with aortic stenosis and/or regurgitation. In the 24 patients with pure or predominant aortic stenosis, retrograde flow was seen in all 24 during end-systole. In the eight patients with pure aortic regurgitation, retrograde flow was seen mainly during end-diastole (6/8). Among the 11 patients with stenosis and regurgitation, retrograde flow was both end-systolic and enddiastolic. Dominant left coronary arteries were seen in 13 patients; 13 showed retrograde flow in the dominant arteries. Dominant right coronary arteries were seen in 25 patients: all 25 showed retrograde flow equally in the right and left coronary. Five of the 43 patients could not be evaluated for dominance because of coronary artery occlusions. The severity of retrograde flow did not correlate with usual clinical, hemodynamic or tension-stress parameters: angina, electrocardiographic abnormality, end-diastolic pressure or volume, end-systolic pressure or volume, ejection fraction, severity of aortic regurgitation, peak or mean valve gradient, aortic valve area, myocardial tension and stress calculations, or DPTI:SPTI. In summary, retrograde coronary artery flow was seen in all 43 patients with severe aortic valve disease. The time in the cardiac cycle when retrograde flow occurred was related to the type of valve disease. Retrograde flow was seen mainly in the coronary arteries supplying the left ventricle and may result from increased regional myocardial stresses.     

Prevalence of extracranial carotid and vertebral artery disease in Chinese patients with coronary artery disease

Electrotonic responses recorded extra- or intracellularly from peripheral nerve preparations show a "sag" to hyperpolarizing current pulses. The biophysical nature of this "inward rectification" is still under discussion since the phenomenon has not been noted at voltage-clamped single nerve fibres, and since Cs+, which reduces inward rectification, is not a specific ion channel blocker. In this study, we found that low micromolar concentrations of ZD 7288, a specific blocker of the hyperpolarization-activated cationic current (Ih) in the soma of central mammalian neurons, result in a complete block of inward rectification in the electrotonic responses of isolated rat spinal dorsal roots. In addition, ZD 7288 enhanced the activity-dependent slowing of conduction seen in compound C fibre action potentials of isolated rat vagus nerves and augmented the post-tetanic hyperpolarization following trains of action potentials in unmyelinated and myelinated axons. The data suggest that ZD 7288 is a potent blocker and a useful research tool for the study of hyperpolarization-activated inward rectification (Ih) of peripheral nerve preparations.     

Salutary effects of myocardial ischemia in coronary artery disease

A novel fine wire bone transport system for use with Ilizarov frames has been used in Bristol. It uses parallel wires instead of crossed wires. Its stiffness has been tested and compared with a crossed wire construct. In its basic form it is not as stiff to bending and shear loading, however, by modification it can be made at least as stiff. A parallel wire construct does not transfix as much soft tissue as a crossed wire construct when used in the leg. This is advantageous, because soft tissue transfixion causes pain and limb swelling, which impair patient mobilization.