MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau.

Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to "pseudonormalization," because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (tau), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = -0.86) with tau and was unaffected by elevated LA pressure. Multiple regression showed that tau, but not LA or aortic pressure, was an independent predictor of RR (P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure.

A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis.

A multicenter, investigator-blinded, randomized, parallel-group study was conducted to compare oral levofloxacin 500 mg once/day for 14 days with clarithromycin 500 mg twice/day for 14 days in the treatment of acute bacterial sinusitis. Of 216 adult outpatients randomized to treatment, 190 were evaluable for efficacy. The primary efficacy measure was clinical response, based on resolution of signs and symptoms 2-5 days after therapy. A secondary efficacy measure was relapse rate 1 month after therapy. Among evaluable patients, clinical success rates (cured or improved) were 96.0% and 93.3% for levofloxacin (L) and clarithromycin (C), respectively (95% CI -9.2%, 3.7%). The confidence interval (CI) for treatment difference (C-L) included zero and its upper limit was less than 15%, indicating that levofloxacin was as effective as clarithromycin. In all, 4.1% of patients receiving levofloxacin and 7.2% receiving clarithromycin had a relapse of symptoms 1 month after therapy (95% CI-12.2%, 3.2%). Long-term success (initial success, absence of relapse at 1 month, no further antibacterial therapy 2-5 days after therapy) was 79.2% in the levofloxacin group and 76.4% in the clarithromycin group (95% CI -14.7%, 9.0%). Based on investigator-assessed treatment-emergent adverse events, overall tolerability of the drugs was similar, except for a higher frequency of taste perversion and diarrhea in the clarithromycin group. Levofloxacin had an advantage over clarithromycin based on two quality-of-life (QOL) parameters: number of times taking other drugs for targeted medical conditions and mean total cost of these drugs. No statistical significance was found in other QOL variables. These findings suggest that the efficacy and tolerability of levofloxacin 500 mg once/day are comparable with those of clarithromycin 500 mg twice/day in the treatment of acute bacterial sinusitis.

Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain. METHODS: This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics. RESULTS: Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.

Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy.

BACKGROUND: Studies in anesthetized dogs have shown that myocardial fibers shorten approximately 8%. However, in the endocardium, shortening occurs to a much greater extent at 90 degrees to the fiber orientation ("cross-fiber shortening") than it does along the fiber direction. The purpose of this study was to estimate the extent of fiber and cross-fiber shortening in the normal human left ventricle and in patients with idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Ten normal subjects and nine patients with IDC were imaged with magnetic resonance tissue tagging. Finite strain analysis was used to calculate endocardial and epicardial shortening in the fiber and cross-fiber directions using anatomic fiber angles from representative autopsy specimens as references. Anatomic fiber angles were not different between normal subjects and IDC patients. Epicardial fiber strain was -0.14+/-0.01 in normal subjects and -0.08+/-0.01 in IDC patients (P<.0001 versus normal subjects). Epicardial cross-fiber strain was -0.08+/-0.01 in normal subjects and -0.06+/-0.01 in IDC patients (P=NS). Endocardial fiber strain was -0.16+/-0.01 in normal subjects and -0.09+/-0.01 in IDC patients (P<.0001), and endocardial cross-fiber strain was -0.26+/-0.01 in normal subjects and -0.15+/-0.01 in IDC patients (P<.0001). Cross-fiber shortening was greater than fiber shortening at the endocardium in both normal subjects (P<.0001) and IDC patients (P<.05). CONCLUSIONS: In normal humans, the direction of maximal deformation aligns with the fiber direction in the epicardium but is perpendicular to the fiber direction in the endocardium. When strain in a coordinate system aligned to the fibers is estimated, cross-fiber shortening is found to be the dominant shortening strain at the endocardium. Normal fiber shortening is 15%, and this is markedly reduced in IDC. The normal transition in fiber orientation through the wall is not altered in IDC, and cross-fiber shortening is still the dominant strain at the endocardium, suggesting that interactions between myocardial layers persist in these patients.

Effects of afterload on regional left ventricular torsion.

OBJECTIVE: To determine if left ventricular torsion, as measured by magnetic resonance tissue tagging, is afterload dependent in a canine isolated heart model in which neurohumoral responses are absent, and preload is constant. METHODS: In ten isolated, blood perfused, ejecting, canine hearts, three afterloads were studied, while keeping preload constant: low afterload, high afterload (stroke volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite afterload). RESULTS: There were significant effects of afterload on both torsion (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high afterloads, at the anterior region of the endocardium only, where torsion was maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to 7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5 degrees, P = NS). Circumferential shortening at the anterior endocardium was significantly reduced both between low and high afterload (-0.19 +/- 0.02 to -0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with respect to end-systolic volume demonstrated a reduction in both torsion and shortening with afterload-induced increases in end-systolic volume. Torsion, but not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS: Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.

Frequency of hypoxanthine guanine phosphoribosyltransferase (HPRT-) T cells in the peripheral blood of cardiac transplant recipients. A noninvasive technique for the diagnosis of allograft rejection.

BACKGROUND: Histological evaluation of serial endomyocardial biopsies performed at fixed time intervals after cardiac transplantation is the universal method used for the detection of cardiac rejection and assessment of the adequacy of antirejection therapy. No noninvasive methodology thus far investigated has achieved a high enough sensitivity and predictive accuracy to be considered as a potential replacement for endomyocardial biopsy in the detection of rejection in adults. The present study exploited the finding that the rate of spontaneous mutation in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene is higher in proliferating human T cells than in resting cells. Thus, it was reasoned that in the posttransplantation setting, the frequency of HPRT- cells in peripheral blood may provide an indirect measure of alloactivated T lymphocytes. METHODS AND RESULTS: This study consisted of determining the clonal frequency of HPRT- mutant cells (FMC/10(6) peripheral blood mononuclear cells [PBMCs]) within a total of 293 peripheral blood samples representing various numbers of sequential samples from each of 27 transplant recipients. These sequential samples represented time periods when endomyocardial biopsy specimens showed either (1) no evidence of rejection (n = 5 patients), (2) a single initial episode after transplantation of early (< 1 year) or late (> 1 year) rejection (n = 12 patients), or (3) multiple rejection episodes (n = 10 patients). Statistical analyses were used to quantify the time profiles of FMC/10(6) PBMCs in serial samples among transplant recipients and to determine the association of these profiles with both the onset of first rejection episodes and, in appropriate patients, the recurrence of rejection episodes. Data showed that PBMCs from patients with no evidence of rejection uniformly gave low values of < 6 FMC/10(6) cells, a frequency similar to that seen in healthy nontransplanted volunteers. In contrast, 19 of the 22 PBMC samples that were obtained from patients whose corresponding biopsy sample was diagnosed with a histological rejection grade of > or = 3 gave values of > 6 FMC/10(6) cells, 11 of which gave values > 50/10(6) cells (range, 146 to 46,982 FMC/10(6) cells). A significant association between the onset of first rejection and an increased rate of FMC/10(6) values was noted (P = .0001). The ability of a rising trend in FMC/10(6) values to correctly identify the onset of rejection was 81.8% and to correctly identify no rejection, 100%. In addition, a significant association between recurrent rejection episodes and persistence of high FMC/10(6) values in the weeks after treated rejection episodes was noted (P = .0003). The ability of a persistently elevated trend in values of FMC/10(6) cells to correctly identify recurrent rejection was 90% and to correctly identify no rejection, 100%. CONCLUSIONS: Increasing frequencies of HPRT- mutant cells in peripheral blood correlated with the onset of first rejection, and persistently elevated HPRT- mutant cells in the weeks after a treated rejection episode correlated with recurrent rejection. This quantitative noninvasive assay may thus serve as a useful adjunct to endomyocardial biopsy for monitoring post-cardiac transplantation patients, and its use as a prospective diagnostic tool merits further study.

A noninvasive comparative study of myocardial strains in ischemic canine hearts using tagged MRI in 3-D.

Regional reduction in myocardial function has long been utilized for noninvasive detection and localization of ischemic regions in the left ventricle. In this study, we compared the ability of 13 different myocardial strain indexes to discriminate between ischemic and nonischemic tissue. Using magnetic resonance imaging with tagging and three-dimensional reconstruction, we noninvasively tracked the deformation of 24 myocardial cuboids in each of nine canine hearts with acute ischemia induced by coronary artery ligation. Monastral blue staining was used for postmortem assessment of ischemia. The ability of each index to discriminate between normal and ischemic zones was evaluated using the "t" statistic. The best discrimination was obtained by the endocardial area strain [t = 7.5 +/- 3.0 (SD)], a local measure of systolic shrinkage on the endocardial surface, and by the magnitude of the endocardial principal strain (t = 7.0 +/- 1.9). Transmural wall thickening (t = 6.1 +/- 2.3) was the third best functional index. The same three indexes correlated most closely with perfusion, as assessed by monastral blue staining. These findings imply that these are the preferable functional indexes for mapping of ischemic myocardial regions.

Different effects of fosinopril and atenolol on wave reflections in hypertensive patients.

We conducted this study to compare the effects of fosinopril versus atenolol on peripheral blood pressure, central arterial wave reflection, and left ventricular mass in a group of patients with essential hypertension. We conducted a double-blind, randomized trial of fosinopril and atenolol in 79 hypertensive patients (52 men, 27 women; mean age, 45.8 +/- 8.5 years; range, 30 to 68 years). Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. The extent of wave reflection was estimated by the augmentation index defined as the ratio of the amplitude of pressure wave above its systolic shoulder to the pulse pressure. The augmentation index, left ventricular mass index by two-dimensional echocardiography, and 24-hour ambulatory blood pressures were determined before and after 8 weeks of daily treatment with fosinopril (10 to 20 mg) or atenolol (50 to 100 mg) with or without diuretics and compared with those values in 79 normotensive control subjects. After 8 weeks of treatment, both drugs lowered 24-hour ambulatory peripheral systolic and diastolic pressures into the normal range to a similar extent (fosinopril, -18/-13 mm Hg; atenolol, -23/-17 mm Hg, both P = NS). On the other hand, whereas the elevated augmentation index in hypertensive patients compared with normotensive subjects (16 +/- 11% versus 10 +/- 8%) was completely normalized by fosinopril (-9.3 +/- 9.8%, P < or = .002), it was lowered by atenolol (-4.8 +/- 8.9%, P < .002) but to a significantly smaller extent (fosinopril versus atenolol effect, P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of regional cross-fiber shortening to wall thickening in the intact heart. Three-dimensional strain analysis by NMR tagging.

BACKGROUND: The mechanism by which small amounts of myofiber shortening lead to extensive wall thickening is unknown. When isolated fibers shorten, they thicken in the two orthogonal directions. In situ fibers, however, vary in their orientation through the wall, and each is tethered to near or distant neighbors, which allows shortening to occur both in the direction of the fibers and also perpendicular to them. This "cross-fiber" shortening may enable the wall to shorten in two directions and thereby thicken extensively in the third. METHODS AND RESULTS: Nuclear magnetic resonance tagging is a noninvasive method of labeling and tracking myocardium of the entire heart in three dimensions that does not interfere with myocardial motion. To investigate the presence and importance of cross-fiber shortening in the intact left ventricle, 10 closed-chest dogs were studied by nuclear magnetic resonance tagging. Five short-axis and four long-axis images were acquired to reconstruct 32 cubes of myocardium in each dog at end diastole and end systole. Pathological dissection was performed to determine the fiber direction at the epicardium, midwall, and endocardium of each cube. Strain was computed from the three-dimensional cube coordinates in the fiber and cross-fiber directions for epicardial and endocardial surfaces, and thickening of the full wall and its epicardial and endocardial halves was determined. Shear deformations were also calculated. Fiber strain at the epicardium and endocardium was -6.4 +/- 0.7% and -8.5 +/- 0.6% (mean +/- SEM), respectively (difference, P > .05). Cross-fiber strain at epicardium and endocardium was -0.6 +/- 0.5% and -25 +/- 0.6%, respectively (difference, P < .05). Thickening of the full wall reached 32.5 +/- 1.0%, composed of epicardial thickening of 25.5 +/- 0.6% and endocardial thickening of 43.3 +/- 1.0% (difference, P < .05). Fiber/cross-fiber shear strain was small (< 3%). Significant regional differences were present in all strains. A significant correlation was found between the extents of regional thickening and cross-fiber shortening. CONCLUSIONS: Cross-fiber shortening at the endocardium, therefore, far exceeds cross-fiber shortening at the epicardium and fiber shortening at both epicardium and endocardium. Since no active shortening can occur locally in the cross-fiber direction, the extensive endocardial cross-fiber shortening must result from interaction with differently aligned fibers at a distance. The correlation between regional thickening and cross-fiber shortening supports the hypothesis that this interaction is the mechanism for amplifying small amounts of fiber shortening to cause extensive endocardial thickening.

Variability in measures of coronary lumen dimensions using quantitative coronary angiography.

OBJECTIVES: The purpose of this study was to determine the true total variability of quantitative coronary angiographic measures and their components in the clinical setting. BACKGROUND: Many studies describe quantitative coronary angiographic variability on the basis of repeated quantitative coronary angiographic measures from the same cineangiogram. Although these studies characterize well the performance of quantitative coronary angiographic analysis methods, they do not include other potentially important sources of variability in results of this procedure, such as day to day variations in patients and equipment or variability in selection of frames for analysis. METHODS: Coronary angiograms from 20 patients who underwent diagnostic angiography followed by percutaneous transluminal coronary angioplasty an average of 2.9 days later were reviewed. A total of 30 lesions well visualized in both films were analyzed multiple times using an automated first-derivative edge-detection quantitative coronary angiographic technique. RESULTS: The coefficient of variation for quantitative coronary angiographic measures of the same lesions from separate angiograms ranged from 8.11% to 14.01%. Average diameter was the least variable and percent diameter stenosis the most variable. Day to day variations in the patient, procedure and equipment accounted for an average of 30% of the total variability. Of the remaining variability, only 13.26% was due to variability in frame selection. CONCLUSIONS: These results provide useful information for planning clinical studies using quantitative coronary angiography, identify areas where additional improvements in this technology are needed and define more clearly the applicability of quantitative coronary angiography in the setting of routine clinical practice.

Noninvasive quantification of principal strains in normal canine hearts using tagged MRI images in 3-D.

Previous studies of myocardial strains have been largely limited to invasive procedures in isolated regions. Utilizing images from tagged magnetic resonance imaging (MRI) in three dimensions (3-D), we noninvasively quantified in vivo endocardial (endo) and epicardial (epi) principal strains (PS) throughout the left ventricle (LV) and tested their uniformity. Seven normal hearts in paced reclosed-chest dogs were studied. Combining long- and short-axis images, 24 myocardial cuboids were tagged at end diastole (ED), imaged at end systole and ED, and reconstructed in 3-D. The cuboids were circumferentially arranged in three parallel approximately 1-cm-thick short-axis slices (8 cuboids/slice). By application of finite strain analysis to each cuboid, the major PS (i.e., magnitude and angle with respect to the circumferential direction of maximal shortening) was calculated for each face. when strains are averaged globally (i.e., using all regions), the average magnitude of endo PS exceeded epi PS approximately twofold: -0.24 +/- 0.07 (SD) vs. -0.11 +/- 0.05 (P < 0.05). On the other hand, the PS angle with respect to the circumferential direction at epi exceeded the angle at endo (P < 0.05) by 33 +/- 36 degrees. Average PS direction at epi, 59 +/- 32 degrees, aligned with the expected fiber direction but was perpendicular to it at endo, 26 +/- 30 degrees. However, significant regional variations were observed from wall to wall and from apex to base. When variations in location were accounted for, the pooled SD for the PS magnitudes dropped to 0.032 and for the direction to only 15 degrees. Furthermore, it was found that the anterior-posterior pair of walls contracted differently (P < 0.05) from the septal-lateral pair of walls. These observations indicate that regional myocardial function is heterogeneous and is location dependent.

Clinical predictors of myocardial damage after high voltage electrical injury.

Myocardial damage after high voltage electrical body injury is a serious and often life-threatening situation. The purpose of this pilot study was to identify early clinical predictors of myocardial damage in patients with high voltage electrical injury. Twenty-four patients with high voltage electrical injuries and no evidence of arc burns were evaluated. In 13/24 patients the diagnosis of myocardial damage was confirmed by total creatine kinase (CK) and creatine kinase MB (CK-MB) isoenzyme elevation (group A). In these patients the total CK range was 1373 to 52,544 mU/ml. In 11/24 patients CK-MB was negative (group B) indicating absence of myocardial damage. ECG changes occurred in 10/13 group A and 4/11 group B patients (p less than .095). No patient in either group gave a history suggestive of myocardial ischemia after the electrical injury. The pathways of electricity through the body, as mapped by a line drawn between the wound(s) of entrance and exit, were vertical in all group A patients, i.e., from upper to lower body segment, vs. 5/11 group B patients with evidence of a vertical pathway (p less than .003). Group A patients also had greater body surface burns (16.0 +/- 2.7%) vs. group B patients (4.0 +/- 1.6%, p less than .001). The presence of a vertical pathway and the magnitude of percent surface burns were found to be the most significant clinical predictors of myocardial damage in multiple logistic regression analysis (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Relative importance of four pressoregulatory mechanisms after 10% bleeding in rabbits.

Four physiological mechanisms are known to be important for recovery of arterial pressure (AP) after acute hemorrhage. These are the sino-aortic baroreflex (SA), the vagally mediated cardiopulmonary baroreflex (CP), the renin-angiotensin system (RA), and the vasopressin system (VP). We evaluated in anesthetized rabbits the relative importance of these mechanisms by repeating rapid, 10% arterial hemorrhage (6.5 ml/kg) once before and once after eliminating one of them and comparing the posthemorrhage hypotension. The study was conducted in two series. In the first series, we randomly grouped 24 rabbits into four groups, i.e., a sinoaortic baroreceptor-denervated group (SA) a vagotomized group (CP), a renin-angiotensin-blocked group (RA), and a vasopressin-blocked group (VP). In control conditions, AP fell to 88% at 2 min and 92% at 6 min after completing the hemorrhage. Significantly greater hypotension (e.g., 74% at 6 min) occurred only in the SA group. In the second series, we randomly classified 18 rabbits into three groups, i.e., an autonomic ganglion-blocked group (AB) plus a RA group and a VP group as before. Hypotension significantly greater than control (68% opposed to 91% at 6 min) occurred only in the AB group. We submit that as far as restoration of arterial pressure after rapid, mild hemorrhage in the rabbit is concerned, the arterial baroreceptor reflex system plays a far more important role than the vagally mediated cardiopulmonary baroreflex, the vasopressin system, or the renin-angiotensin system triggered directly by a fall in renal arterial pressure.

Transient atrial dysfunction after conversion of chronic atrial fibrillation to sinus rhythm.

Although conversion of atrial fibrillation (AF) to sinus rhythm can usually be accomplished by electrical or drug therapy, effective atrial systole may not be restored. To investigate the return of atrial transport function and its relation to the duration of the arrhythmia, Doppler echocardiography was performed after conversion in 18 patients with acute AF (less than or equal to 1 week duration), 14 patients with chronic AF (greater than 1 week duration) and 15 control patients. Flow velocities during rapid filling (E wave) and atrial systole (A wave) were measured in both left and right ventricles. Patients in the acute AF group had left ventricular A waves (49 +/- 4 cm/s) and A/E ratios (0.97 +/- 0.1) similar to those of the control patients (55 +/- 7 cm/s, 0.87 +/- 0.08, respectively). In contrast, patients in the chronic AF group had much smaller A waves (19 +/- 5 cm/s) and A/E ratios (0.30 +/- 0.08) than those in the other 2 groups (p less than 0.001). Five patients with chronic AF (36%) had complete left atrial paralysis (A/E = 0) despite normal sinus P waves. Measurements in the right ventricle showed similar differences among the groups. Patients with chronic AF who maintained sinus rhythm showed an increase in A/E ratio to control levels, from 0.45 +/- 0.1 to 0.93 +/- 0.1 (p = 0.003) at 48 days (average) after conversion. Thus, atrial transport function is normal after brief periods of AF, but reduced or absent when conversion is achieved after the arrhythmia has been sustained greater than 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

Nausea and vomiting during acute myocardial infarction and its relation to infarct size and location.

Nausea and vomiting occurring during myocardial ischemia is believed to be associated with inferior wall infarction. However, data supporting such an association are limited, and an alternative hypothesis that cardiac vomiting is related to infarct size has also been advanced. The 2 hypotheses were tested in a cross-sectional study of 265 patients consecutively admitted to the coronary care unit. Nausea or vomiting was a good predictor of myocardial infarction (p less than 0.0001). The odds of having an infarction was 3.14 times greater for patients with nausea or vomiting than for those without these symptoms. Nausea was not a good predictor for inferior wall infarction (p = 0.14): 51% of patients with inferior infarcts had nausea or vomiting and 66% with anterior infarcts had these symptoms. Using peak serum creatine kinase level as an index of infarct size, nausea or vomiting was a good predictor of larger infarction. While 55% of all patients with infarction had nausea or vomiting, for patients with infarctions that produced a peak creatine kinase level of more 1,000 IU/liters, 78% had nausea or vomiting. Sex was a marginally important variable. After adjusting for sex, the presence of nausea or vomiting still predicted infarct size (p less than 0.001). Thus, cardiogenic nausea and vomiting are associated with larger myocardial infarctions but do not suggest infarcts in a particular location.

Augmentation of pressure in a vessel indenting the surface of the lung.

The lungs and intrathoracic cardiovascular structures compete for space within the thorax, interacting through their adjacent surfaces via the pleural space. Theoretical analysis and in vitro model studies (detailed here) established that when a vessel indents the lung surface, the increase in intravascular pressure with positive pressure lung inflation can be greater than the change in the pleural surface pressure measured outside of the interaction area. We define this phenomenon as intravessel pressure augmentation. We determined the average intravessel pressure gain as the slope of the linear regression of the pressure in a vascular structure or balloon indenting the lung on the pleural surface pressure measured by a flat disk-shaped device (disk). The analysis showed that the disk pressure overestimates the pleural pressure. Therefore, the derived pressure gain underestimated the pressure augmentation. In five dogs, the disk and a 2-ml balloon were placed in the lateral pleural space, and a segment of IVC was ligated at both ends and filled with saline. The dogs were ventilated with fixed tidal volumes, while the positive end-expiratory pressure was changed. The pressures were compared at the end of expiration. For the IVC segment, the pressure gains under four different tidal volumes were significantly greater than one [95% confidence interval of mean value (CIM) = 1.57 +/- 0.16, P less than 10(-4)], and for the small balloon, this was the case for three of four tidal volumes (95% CIM for all four volumes 1.13 +/- 0.04, P less than 10(-4)). We conclude that the surface interaction of the lungs with adjacent cardiovascular structures causes appreciable pressure augmentation in those structures during ventilation with the positive end-expiratory pressure.

The cellular electrophysiologic changes induced by high-energy electrical ablation in canine myocardium.

High-energy electrical ablation is a new experimental approach to control arrhythmias. In this study, the cellular electrophysiologic effects of high-energy shocks (5 to 40 J) delivered in vitro to 14 epicardial tissues from 11 dogs were studied in an attempt to understand the nature and extent of injury as well as potential arrhythmogenic mechanisms. In addition, this preparation was used to test the importance of cathode-anode configuration, current density, and fiber orientation in the induction of tissue injury in vitro. Electrophysiologic abnormalities were noted up to 10 mm from the electrode wall, and their extent was determined in part by current density and the cathode-anode orientation. A decrease in resting membrane potential, action potential amplitude, and dV/dT occurred in all tissues after high-energy shocks, which was worst nearest the cathode and of graded severity at increasing distances from the cathode. The most severe effects were noted with high current densities and in tissues located between the cathode and anode. In addition, impaired impulse conduction and abnormal repolarization were documented. Histologic study demonstrated contraction band necrosis immediately after delivery of high-energy shocks. The extent and distribution of the contraction bands was in part dependent on the energy delivered and the cathode-anode configuration. These findings suggest potential mechanisms for arrhythmogenesis and altered regional hemodynamic abnormalities that occur in vivo.