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Biomedical subjects

P A Sobotka

Publications and source records attributed to P A Sobotka.

At least 19 recordsLinked to original sources

Breath pentane and plasma lipid peroxides in ischemic heart disease.

This study examined the relationship between breath pentane and plasma lipid peroxide levels sampled simultaneously in patients with stable angina (n = 17), unstable angina (n = 23), and controls (n = 10). Plasma lipid peroxides were measured in venous blood as the adduct formed between thiobarbituric acid and malondialdehyde (MDA) using high performance liquid chromatography. Pentane was measured in end-expiratory air using gas chromatography. MDA concentrations in stable (1.81 +/- 0.84 mumol/l) and unstable (1.5 +/- 1.23 mumol/l) angina were not different. However, both groups had significantly (p < 0.005) elevated MDA levels compared to controls (0.41 +/- 0.26 mumol/l). Breath pentane was 0.20 +/- 0.12 nmol/l in controls and not different from stable angina (0.26 +/- 0.20 nmol/l) or unstable angina (0.15 +/- 0.07 nmol/l). When the data from all three groups were combined, there was no correlation between pentane and MDA (rho = -0.09, p = 0.54). In five of the unstable angina patients treated with balloon angioplasty, MDA in pulmonary arterial blood rose by 69 +/- 15% (p < 0.01), and breath pentane rose by 73 +/- 20% (p < 0.01) immediately after balloon deflation. One minute after balloon deflation MDA and pentane had returned to preinflation levels. The results suggest that basal levels of pentane are less useful than MDA as an index of lipid peroxidation in patients with coronary artery disease. However, breath pentane appears to be a sensitive index of reperfusion-induced lipid peroxidation.

Adult↗

Expired hydrocarbons in patients with acute myocardial infarction.

Pentane and isoprene concentrations were analyzed in single end-expiratory breath samples using gas chromatography. Breath analysis was performed in 15 patients with acute myocardial infarction, 15 patients with stable angina, and 15 healthy control subjects. The two patient groups were well matched for age, sex, smoking habits, hypertension and serum cholesterol levels. There was no significant difference in breath pentane concentration in the acute myocardial infarction group (0.29 +/- 0.03 nmol/l) (mean +/- SEM) compared to the group with stable angina (0.31 +/- 0.03 nmol/l) or the control group (0.36 +/- 0.04 nmol/l). However, breath isoprene concentration was higher (p < 0.01) in the acute myocardial infarction group (11.4 +/- 1.2 nmol/l), compared to both the stable angina group (7.7 +/- 0.5 nmol/l) and the control group (7.1 +/- 1.0 nmol/l). There was no difference in either the pentane or isoprene concentrations between the control group and the group with stable angina. Since pentane is thought to be an index of lipid peroxidation, the results do not support the presence of enhanced lipid peroxidation in acute myocardial infarction in the absence of thrombolytic therapy or primary angioplasty. The mechanism responsible for isoprene elevation in acute myocardial infarction is unknown.

Adult↗

Effect of acute edema on left ventricular function and coronary vascular resistance in the isolated rat heart.

The impact of acute myocardial edema on coronary flow and left ventricular performance was studied in isolated isovolumic rat hearts. After 15 min of aortic perfusion with Krebs-Henseleit buffer, hearts (10/group) were either removed for determination of water content or perfused for another 90 min. Three groups were perfused at a constant pressure of 60, 100, or 140 mmHg, and two groups were perfused at 60 or 140 mmHg with adenosine added. Compared with the 15-min group, there was a significant increase in water content in all groups except the 60-mmHg group (P < 0.005). There was a direct linear relationship between increases in coronary vascular resistance over time and water content (P < 0.0001). A decrease in developed pressure and peak +dP/dt was observed only in those groups that accumulated water. An inverse linear relationship was found between changes in developed pressure and water content (P = 0.0001). Water content had no effect on end-diastolic pressure below 5 ml/g; above 5 ml/g, a direct linear relationship was evident (P = 0.009). The results suggest that myocardial edema increases vascular resistance and decreases systolic performance. End-diastolic pressure is less influenced by edema than either systolic or coronary vascular function.

Acute Disease↗

[Relations between acute myocardial edema, coronary vascular resistance and left ventricular mechanics in isolated rat heart].

To evaluate the effect of acute myocardial edema (ME) on coronary vascular resistance (CVR) and left ventricular (LV) mechanical function, the LV water content (% of total weight) of seven groups (n = 10 each) of isolated rat heart was determined. Group I included non-perfused hearts and served as control. Group II was perfused with Krebs-Henseleit buffer only for the brief equilibration period which preceded every experiment. Group III, IV and V were perfused for 90 min at the constant pressure of 60, 100 and 140 mmHg respectively. Group VI and VII were perfused for 90 min at the constant flow of 10 and 30 ml/min respectively. The hearts were contracting isovolumically against a fluid-filled latex balloon with fixed volume. CVR and LV functional parameters were measured throughout the whole perfusion period. The water content of Group I (78.2 +/- 0.3%) was significantly lower than Group II (80.5 +/- 0.3%). A higher degree of ME was present in groups III, IV and V (80.2 +/- 0.3, 81.4 +/- 0.3 and 83.3 +/- 0.2%, respectively), as well as in groups VI and VII (80.7 +/- 0.1 and 83.4 +/- 0.2%, respectively). CVR significantly increased over time in groups III, IV and V (about +30, +35 and +50%, respectively), as well as in groups VI and VII (about +22 and +20%, respectively). LV developed pressure did not change over time in Group III (which did not show further fluid accumulation after the equilibration period); it decreased on the other hand in groups IV (about -27%) and V (about -40%). In groups VI and VII, LV developed pressure showed as increase (about +28%) and a reduction (about -29%) respectively. In conclusion, in the isolated crystalloid-perfused rat heart, ME is directly dependent on coronary perfusion pressure and/or flow. ME induces an increase in CVR and a rapid and significant depression of LV function.

Animals↗

Pentane and isoprene in expired air from humans: gas-chromatographic analysis of single breath.

Both pentane and isoprene are excreted in human breath. Although pentane is considered an index of lipid peroxidation, the significance of isoprene is unknown. Having a similar boiling point, these two hydrocarbons are difficult to separate by gas chromatography. We separated pentane from isoprene on both a Poraplot Q and a Poraplot U column, injecting single-breath samples directly into a gas chromatograph. The breath samples were pressurized to 800 mmHg to increase the amount of sample volume delivered to the column. In a group of 43 healthy volunteers, the concentrations of end-expiratory pentane and isoprene were 0.57 +/- 0.3 and 7.05 +/- 3.53 nmol/L, respectively. There was a significant linear correlation (r = 0.57, P < 0.0001) between age and pentane concentration in expired air; isoprene showed no correlation with age or pentane concentrations. The age-related increase in pentane production suggests that oxidative stress may play a role in the aging process in humans. The method described should allow for rapid, inexpensive, serial measurement of expired pentane and isoprene.

Adult↗

Elevated breath pentane in heart failure reduced by free radical scavenger.

UNLABELLED: Pentane, a product of lipid peroxidation, has been detected in situations involving ischemic injury. Such injury may be limited if lipid peroxidation can be controlled by antioxidants. The role of lipid peroxidation in chronic heart failure (CHF) was assessed by measuring breath pentane in patients with CHF vs. age matched controls. The effect of a free radical scavenger on pentane released during CHF was also measured. Pentane levels were correlated with the daily dose of captopril, a sulfhydril-containing drug used to treat CHF, which is an angiotensin converting enzyme inhibitor. To separate the scavenging effects of captopril from the pharmacologic effects of converting enzyme inhibitors, a crossover study using a nonsulfhydril inhibitor was used. Patients with CHF excreted (p < 0.005) high concentrations of pentane (5.7 +/- 2.1 vs. control 3.6 +/- 1.2 nmol/l). Patients treated with captopril also had significantly higher (p < 0.05) excretion of pentane than the control patients (4.7 +/- 1.3 vs. 3.6 +/- 1.2 nmol/l). The dose of captopril was inversely proportional to the concentration of pentane excreted (r = 0.55, p < 0.05). Pentane excretion during captopril therapy was significantly lower before (p < 0.01) and after (p < 0.02) nonsulfhydril inhibitor therapy. CONCLUSION: breath pentane is elevated in CHF and it can be reduced by a free radical scavenger. This reduction of pentane excretion is not a converting enzyme inhibitor class effect.

Aged↗

Abnormal ambulatory left ventricular ejection fraction in heart transplant arteriopathy.

The morbidity and mortality from heart transplantation has been reduced dramatically over the last several years. However, the long-term survival in heart transplant recipients is limited by arteriopathy in the allograft coronary arteries, the pathophysiology of which is poorly understood. The diagnosis of this arteriopathy is at present limited to cardiac catheterization. Noninvasive studies have proven to be of limited benefit in diagnosing this arteriopathy. The authors performed cardiac vest studies in nine heart transplant recipient patients. Six of the vest studies were abnormal; five of the patients had documented transplant coronary artery disease by cardiac catheterization. They found that the sensitivity and negative predictive value of the cardiac vest in identifying arteriopathy in transplant recipients was 100%. The authors propose that cardiac vest could be a sensitive, noninvasive screening test for identifying arteriopathy in heart transplant recipients.

Ambulatory Care↗

Implications of an audible third heart sound in evaluating cardiac function.

We prospectively compared auscultatory findings of third heart sounds with radionuclide ventriculographic analysis of systolic and diastolic function. Cardiac auscultation was done to detect an S3 in patients referred for radionuclide ventriculographic analysis of ventricular function. Of 49 adult men with the diagnosis of chronic, nonvalvular heart failure who were referred for the evaluation of heart failure, 22 (45%) at the time of the ventriculography had an S3 present on examination. For the entire study group, the radionuclide ventriculography-derived ejection fraction was 33% +/- 19.5 (mean +/- SD) with a range of 6% to 74%. The peak ejection rate was 2.05 +/- 1.09 end-diastolic volume per second with a range of 0.30 to 4.56. The peak filling rate was 1.97 +/- 1.07 end-diastolic volume per second with a range of 0.44 to 3.94, and the time to peak filling rate was 0.18 +/- 0.11 per second with a range of 0.05 to 0.61. The presence of an S3 was associated with a reduced ejection fraction and also with impaired diastolic function as determined by the peak filling rate. The sensitivity and specificity for the S3 in detecting abnormal systolic function (ejection fraction < 50%) were 51% and 90%, respectively, with a positive predictive value of 95% and a negative predictive value of only 32%. For an ejection fraction of less than 30%, the S3 had a sensitivity and specificity of 78% and 88%. The presence of an S3 was highly predictive of an abnormal ejection fraction. The absence of an S3, however, is not uncommon in patients with a mildly impaired ejection fraction.

Aged↗

The use of beta-blockade therapy in treatment of congestive heart failure.

If the activation of the sympathetic nervous system in chronic heart failure is causally related to progressive pump dysfunction, sudden death, and exercise intolerance, then selective blockade of the beta-adrenergic system may prove to be therapeutically beneficial. This report briefly reviews the evidence that there is systemic activation of the sympathetic nervous system in chronic heart failure, postulates mechanisms by which this activation might contribute to the morbidity and mortality of the syndrome, and hypothesizes further regarding how beta blockade may be beneficial in heart failure. The clinical evidence that the use of beta blockers is beneficial in the treatment of chronic heart failure is reviewed.

Adrenergic beta-Antagonists↗

High breath pentane concentrations during acute myocardial infarction.

To investigate whether reperfusion after myocardial ischaemia leads to free-radical-mediated peroxidation of membrane lipids and cell damage, we measured pentane, a product of lipid peroxidation, in the breath of 10 healthy control subjects and in 20 consecutive patients with suspected acute myocardial infarction. 10 of these patients showed no myocardial damage on electrocardiography (patient control group) and 10 satisfied standard diagnostic criteria for acute myocardial infarction. The three groups were well matched for age, sex, underlying disease, and smoking habits. The time from onset of chest pain to breath collection was similar in the patient control and acute myocardial infarction groups. The breath pentane concentration was higher (p less than 0.0001) in the acute myocardial infarction group (4.96 [1.15] nmol/l) than in the patient control (1.96 [1.04] nmol/l) and healthy control groups (1.71 [0.87] nmol/l). Lipid peroxidation during acute myocardial infarction reflects action of oxygen radicals and their potential for contribution to the pathogenesis of tissue damage.

Adult↗

Internal mammary artery revascularization in the patient on long-term renal dialysis.

Twenty-six patients on long-term renal dialysis underwent coronary artery bypass grafting. The patients were divided into two groups: group 1, (16 patients) saphenous vein bypass grafts, and group 2, (10 patients) internal mammary artery in combination with saphenous vein bypass grafts. Both groups were similar in terms of cardiac hemodynamics and previous number of myocardial infarctions, though more group 1 patients were in New York Heart Association class III or IV. Patients in group 1 received 2.9 bypass grafts per patient; patients in group 2 received 4.0 bypass grafts per patient (4 with bilateral mammary arteries). No wound healing problems occurred in either group. Blood replacement was similar for both groups (group 1, 5.5 units/patient; group 2, 5.3 units/patient). More platelets were given to group 1 patients (16.2 units/patient) than group 2 patients (3.1 units/patient). We conclude that use of the internal mammary artery in patients on long-term renal dialysis does not alter wound healing or increase blood loss in this subset of patients.

Blood Transfusion↗

Effect of inosine in the normal and reperfused rat heart.

Inosine is a positive inotropic agent and dilates coronary blood vessels. During ischemia, inosine infusion increases blood flow, resulting in decreased myocardial damage. We wished (a) to determine inosine's effect in isolated rat hearts and (b) to determine if inosine attenuates myocardial dysfunction after transient global ischemia. Developed left ventricular pressure (LVP), LV dP/dt, and coronary perfusion pressure were monitored in hearts receiving Krebs-Henseleit buffer (KHB) (n = 10) or KHB + 2 mM inosine (n = 4). KHB + 2 mM inosine significantly reduced coronary perfusion pressure by 21% but had no effect on developed LVP or LV dP/dt. Hearts receiving KHB (n = 6) or KHB + 2 mM inosine (n = 5) were subjected to 15-min global ischemia followed by 30-min reperfusion with KHB. Recovery of LVP, LV dP/dt, the incidence of arrhythmias, and the time to peak recovery of developed LVP was not different between groups. In two additional hearts, KHB + 2 mM inosine administered during reperfusion had no effect on developed LVP, LV dP/dt, or coronary perfusion pressure. Thus, unlike other preparations, inosine pretreatment did not significantly affect the time course of postischemic functional recovery of rat myocardium.

Animals↗

Effects of interleukin 2 on cardiac function in the isolated rat heart.

Adoptive immunotherapy with IL 2 is associated with severe cardiovascular toxicities including peripheral and pulmonary edema, hypotension decreased systemic vascular resistance, increased heart rate, and an increased cardiac index. The purpose of this investigation was to determine whether IL 2 alone or in combination with lymphokine-activated killer cells (LAK) cells depress cardiac function using the isolated, perfused, working rat heart preparation. Male Sprague-Dawley rats (250-350 g) were anesthetized and the hearts were removed and placed on the perfusion apparatus. Hearts were perfused with oxygenated Krebs-Henseleit buffer (KHB), or oxygenated KHB containing IL 2 alone, IL 2-Media (cell culture media supplemented with 1,500 U IL 2/ml), LYMPH (cell culture media from cultured mononuclear cells from healthy volunteers), or LAK (cell culture media from cultured lymphocytes harvested from patients receiving IL 2/LAK in the presence of 1,500 U/ml IL 2). The cells were removed before perfusion (n = 9). Cardiac output and coronary flow were measured at 20-min intervals with preload constant (afterload varied or afterload constant (preload varied). The results indicate a significant depression in cardiac function in hearts treated with LAK. This depression was evident at 20 min and was more pronounced at 60 min. Washout of the KHB plus LAK reversed this depression. Thus, IL 2-stimulated/cultured human mononuclear cells produce a soluble factor that produces a reversible severe depression of cardiac function.

Animals↗

Bifurcations and intrinsic chaotic and 1/f dynamics in an isolated perfused rat heart.

The application of the theory of chaotic dynamical systems has gradually evolved from computer simulations to assessment of erratic behavior of physical, chemical, and biological systems. Whereas physical and chemical systems lend themselves to fairly good experimental control, biologic systems, because of their inherent complexity, are limited in this respect. This has not, however, prevented a number of investigators from attempting to understand many biologic periodicities. This has been especially true regarding cardiac dynamics: the spontaneous beating of coupled and non-coupled cardiac pacemakers provides a convenient comparison to the dynamics of oscillating systems of the physical sciences. One potentially important hypothesis regarding cardiac dynamics put forth by Goldberger and colleagues, is that normal heart beat fluctuations are chaotic, and are characterized by a 1/f-like power spectrum. To evaluate these conjectures, we studied the heart beat intervals (R wave to R wave of the electrocardiogram) of isolated, perfused rat hearts and their response to a variety of external perturbations. The results indicate bifurcations between complex patterns, states with positive dynamical entropies, and low values of fractal dimensions frequently seen in physical, chemical and cellular systems, as well as power law scaling of the spectrum. Additionally, these dynamics can be modeled by a simple, discrete map, which has been used to describe the dynamics of the Belousov-Zhabotinsky reaction.

Animals↗

The value to the anesthesia-surgical care team of the preoperative cardiac consultation.

A retrospective analysis of 202 consultations for preoperative cardiology evaluation was conducted. The most common problems generating the consultation were: (1) abnormal electrocardiogram, 45 patients; (2) chest pain, 36 patients; (3) history of myocardial infarction, 27 patients; (4) dysrhythmia, 25 patients; and (5) hypertension, 23 patients. The most common diagnoses by the consultants were: (1) arteriosclerotic heart disease, 46 patients; (2) angina, 20 patients; and (3) hypertension, 40 patients. Mitral valve prolapse was the most common valvular disease (18 patients). Of the consultation requests, 108 asked for an evaluation; 79 asked for a "clearance"; 9 did not specifically ask for anything; and 6 asked a highly specific question. Most consultations provided a diagnosis (96%), addressed the problem (80%), and provided logical recommendations (96%). A minority of the consultations "cleared" a patient (28%), provided for follow-up care (41%), or suggested intraoperative monitoring techniques (41%). Out of the 189 patients who eventually had surgery, 137 patients had no change in their preoperative therapy, while 52 patients had a change in preoperative therapy. There was no difference in the incidence of complications between these two groups. An important finding was that 15% of the study group (31 patients) had disease processes (hypertension and angina) that were newly diagnosed by the consultant or felt to be not adequately treated before the consultation. It is concluded that few requesting anesthesiologists and surgeons ask for clarification of a specific problem, while most responses from the cardiology consultants provided necessary information. In addition, the preoperative cardiac consultation was found to identify medical conditions requiring long-term care and follow-up.

Adolescent↗