Carotid body size on CTA: correlation with comorbidities.

AIM: To test the hypothesis that computed tomographic angiography (CTA) can identify carotid body enlargement in patients with sympathetically mediated diseases. MATERIALS AND METHODS: A retrospective chart review of all patients obtaining CTAs of the cervical vasculature at University of Utah Health Sciences Center over a 6-month period was performed. Widest axial measurements of both carotid bodies were performed on a picture archiving and communication system (PACS). Statistical analysis was then performed to compare the mean carotid body size between control patients and patients with diabetes mellitus, hypertension, and congestive heart failure. RESULTS: Measurements were performed on 288 patients, with 134 controls. Of the remaining 154, 72 patients had diabetes mellitus, 46 had congestive heart failure, and 130 had hypertension. The control patients had a mean carotid body diameter of 2.3 mm. There was a statistically significant (p < 0.01) 20-25% increase in mean diameter with diabetes mellitus (2.8 mm), hypertension (2.7 mm), and congestive heart failure (2.7 mm; p < 0.01). CONCLUSIONS: This study found a 20-25% larger mean carotid body size in patients with diabetes mellitus, hypertension, and congestive heart failure relative to controls. However, this small enlargement should not mimic other carotid body diseases, such as a paraganglionoma. Moreover, these findings further support the proposed functional relationship between the carotid body and sympathetically mediated disease states.

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.

Impaired hypoxic ventilatory drive in diabetic patients with autonomic neuropathy.

The mortality of diabetic patients with autonomic neuropathy (DAN) is higher than that in those without autonomic neuropathy (DM). To test the hypothesis that this may be due to respiratory rather than cardiac dysfunction, we evaluated ventilatory responses to isocapnic-hypoxic and hyperoxic-hypercapnic conditions in 14 diabetic patients (8 DAN and 6 DM) and compared the results with those in 8 normal subjects. In all groups tested there was a significant linear correlation between end-tidal CO2 and minute ventilation and between end-tidal CO2 and mouth occlusion pressure (p100), as an index of the drive to breathe. There were no significant differences between the slopes and intercepts in the groups tested. A significant linear correlation was found between the O2 saturation and both minute ventilation and p100. There were no significant differences in the relationship between minute ventilation and O2 saturation, but the slopes and the intercepts of the regression lines of p100 vs. O2 saturation were significantly different in the DAN compared with those in normal subjects and DM. Additionally, five of eight patients with DAN lost their ventilatory drive and ventilatory responses to hypoxemia compared with only one of six DM. These findings suggest that a disorder in the ventilatory response to hypoxemia exists in some DAN.

Decreased alpha 2-adrenergic receptors on platelet membranes from diabetic patients with autonomic neuropathy and orthostatic hypotension.

Platelet adrenergic receptors were studied in normal subjects and diabetic patients with autonomic neuropathy to determine the relationship between adrenoreceptor status and orthostatic hypotension. The binding of [3H]clonidine and [3H]yohimbine to platelet membranes was measured in diabetic patients with autonomic neuropathy and orthostatic hypotension (n = 12) and without orthostatic hypotension (n = 11), diabetic patients without autonomic neuropathy (n = 12), and normal subjects (n = 9). Mean basal and standing plasma norepinephrine levels were not different in the four groups, and there was no relationship between orthostasis and norepinephrine responses. The diabetic patients with orthostatic hypotension had a significantly greater fall in mean blood pressure [31 +/- 2.8 (+/- SE) mm Hg] than any of the other three groups. Diabetic patients with diabetic autonomic neuropathy and orthostatic hypotension had a 30-40% decrease in number of platelet alpha 2-adrenergic receptors, as demonstrated by [3H]clonidine and [3H]yohimbine binding. The maximum number of binding sites for clonidine was 34 +/- 2.8 (+/- SE) fmol/mg protein in normal subjects, 27.4 +/- 3.4 in diabetic patients with neuropathy, 26 +/- 2.5 in diabetic patients with autonomic neuropathy without orthostatic hypotension, and 20.4 +/- 3.8 fmol/mg protein in diabetic patients with autonomic neuropathy with orthostatic hypotension (P less than 0.001). The maximum number of binding sites for yohimbine was 112 +/- 12.6 in normal subjects, 127 +/- 10 in diabetic patients without orthostatic hypotension, and 87 +/- 12.4 fmol/mg protein in patients with diabetic autonomic neuropathy with orthostatic hypotension (P less than 0.001). Reduced platelet alpha 2-receptors are associated with postural hypotension in diabetic autonomic neuropathy. If applicable to the postjunctional alpha 2-adrenergic receptor on sympathetic neurons, reduced vascular responses to changes in posture would be expected despite normal or enhanced norepinephrine secretion.

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.

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.

Errors in the determination of left ventricular functional parameters.

Gated blood-pool scans of the left ventricle are routinely employed for determination of the left ventricular ejection fraction. Recently, attempts have been made to evaluate other left ventricular functional parameters. These values include peak emptying rate (PER), time to peak emptying rate (TPER), peak filling rate (PFR), and time to peak filling rate (TPFR). In studying these parameters clinically, we identified many software errors and assumptions that impact on these values. These errors may also affect the determination of left ventricular ejection fraction (EF). We conclude that before any serious investigation of left ventricular functional parameters is undertaken, a detailed evaluation and standardization of the acquisition and edge detection algorithms must be performed.

Breath pentane is a marker of acute cardiac allograft rejection.

Breath pentane, a product of lipid peroxidation that serves as a noninvasive marker of tissue inflammation and injury, was measured as a potential marker of acute cardiac allograft rejection. We prospectively studied 37 consecutive outpatients with stable cardiac allograft function. Breath pentane levels were measured with gas chromatography, and the results were compared the findings from routine surveillance endomyocardial biopsy. Data analysis was performed with the receiver operating characteristic curve and negative and positive predictive values. Statistical methods include analysis of variance and two-sample t-tests. Histopathologic findings consistent with rejection were present on endomyocardial biopsy in 52% of the subjects. Pentane levels in healthy control subjects did not differ from those of patients undergoing transplantation without rejection. Average pentane excretion for subjects with mild rejection (4.2 +/- 2.8 nmol/L) or moderate rejection (5.4 +/- 2.6 nmol/L) exceeded that seen in subjects who did not have rejection (1.7 +/- 0.9 nmol/L) (p < 0.02). A pentane cutoff value of 2.43 nmol/L, chosen to give the highest negative predictive value, had a sensitivity of 0.80. We concluded that breath pentane excretion is a sensitive noninvasive screening test for the detection of cardiac allograft rejection.

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.

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.

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.

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.

Signal-averaged electrocardiography. Promising tool for predicting sudden cardiac death.

Signal-averaged electrocardiography has shown great promise as an adjunct in identifying patients at risk for sudden cardiac death. Clearly, much research remains to be done. Methods and criteria must be standardized so studies can be compared and the most effective ways in which to use this technology can be determined.

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.

[Relations between acute myocardial edema, coronary vascular resistance and left ventricular mechanics in isolated rat heart]. / Relazione tra edema miocardico acuto, resistenze vascolari coronariche e meccanica ventricolare sinistra nel cuore di ratto isolato.

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.