Coxiella burnetii infection in C.B-17 scid-bg mice xenotransplanted with fetal bovine tissue.

Two from a group of approximately 50 C.B-17 scid-bg mice were examined because of lethargy, dehydration, and rough coat. Three months prior to development of clinical signs of disease, mice of this study had been surgically implanted with fetal bovine liver, thymus, and lymph node. At necropsy, marked splenomegaly and mild hepatomegaly were observed in both animals. Large areas of necrosis and inflammation, with associated intracytoplasmic granular basophilic inclusions, were observed in histologic sections of multiple organs. Aerobic and anaerobic culturing of the liver yielded negative results. Six months after the initial case, four more reconstituted scid-bg mice from a different fetal donor had identical clinical, gross, and histologic signs of disease. To determine whether the basophilic inclusions represented an infective agent, 4-month-old immune-naive C.B-17 scid-bg mice were inoculated intraperitoneally with a liver and spleen homogenate from an affected mouse. Two weeks after inoculation, mice developed clinical signs of disease and lesions identical to those seen in the signal mice. On ultrastructural examination of the liver, pleomorphic bacteria were found in large cytoplasmic vacuoles of hepatocytes. Bacterial DNA was amplified from the liver, using primers that amplify a segment of the 16S rRNA gene from many bacterial species. Sequencing of the polymerase chain reaction (PCR) product revealed gene sequence identical to that of Coxiella burnetii, the agent of Q-fever. These results highlight the need to consider infective agents of the donor species when working with xenografted animals.

Therapeutic efficacy of oral lactobacillus preparation for antibiotic-associated enteritis in guinea pigs.

Enteritis is a potential complication of antimicrobial agent use, particularly in certain species of rodents. The organism most frequently implicated in this disease is Clostridium difficile. Anecdotal information suggests that administration of yogurt or other Lactobacillus-containing products in conjunction with antimicrobial agents will prevent or minimize the effects of antibiotic-associated enteritis. We wanted to determine whether a single subcutaneous injection of clindamycin phosphate could induce enteritis in guinea pigs and whether a commercial Lactobacillus preparation would ameliorate the clinical effects of antibiotic administration in these animals. Juvenile male guinea pigs were divided into three treatment groups. Group 1 guinea pigs (n=8) received a single saline injection followed by an oral Lactobacillus preparation twice daily; group 2 (n=8) received a single antibiotic injection followed by an oral Lactobacillus preparation twice daily; group 3 (n=8) received a single antibiotic injection. Attitude, body temperature, body weight, and feed and water consumption were recorded for each guinea pig 7 days prior to and after treatment. Fecal samples were collected and necropsies performed on each guinea pig at the time of euthanasia. C. difficile and other enteric pathogens were not isolated from any group before or after treatment, although some guinea pigs receiving the antibiotic developed enteritis. There were no significant clinical differences between guinea pigs receiving antibiotics with the oral Lactobacillus preparation, and those receiving antibiotics alone. The results of this study suggest that a single injection of clindamycin phosphate can induce enteritis in guinea pigs and that oral administration of a Lactobacillus-containing product is ineffective in preventing clinical disease in guinea pigs administered clindamycin phosphate.

Multimedia instruction of cardiac auscultation.

The cardiac physical examination is in itself a multimedia experience. It is an amalgamation of visible, palpable, and audible sensations, preceded by the collection of an appropriate historical context in which to place these multiple sensations. It is unlikely that any electronic media could ever replace the real life experience of admitting, examining, diagnosing, and effectively treating a patient with mitral stenosis who has decompensated because of the onset of atrial fibrillation with rapid ventricular response, or a patient with sudden, severe aortic regurgitation due to endocarditis. These potentially fatal conditions can be effectively treated only if the suspicion of their presence is seriously raised. Although there is no substitute for first-hand experience, attempts to provide an effective surrogate experience are worth pursuing.

Subaortic stenosis revisited: the importance of the dynamic pressure gradient.

Brachfeld and Gorlin's revised concept of subaortic stenosis derived from their recognition that the large magnitudes of the pressure gradients were incompatible with the relatively mild anatomic lesions found at surgery in 3 of their patients, and the rapidity of their arterial pulse upstroke. They proposed that a gradient caused by a superimposed systolic stenosis was responsible for the large pressure gradients and the overestimation of the severity of the discrete subaortic stenosis (DSAS). A fourth patient had no anatomic cause for the pressure gradient, and findings compatible with hypertrophic cardiomyopathy (HCM). All 4 patients had septal hypertrophy which they felt was instrumental in the brisk pulse contour and dynamic gradients across the outflow tract. In the ensuing decades, imaging techniques have been developed which permit detailed studies of ventricular ejection patterns in dynamic gradients associated with HCM and DSAS. These studies have been interpreted variously. The prevailing view is that there is a dynamic obstruction that increases progressively in severity during systole, as proposed by Brachfeld and Gorlin. An opposing view is that dynamic gradients can occur in the absence of any hindrance to ejection, and that these gradients instead result from rapid and complete emptying of the ventricle. Regardless of their cause, dynamic gradients are often superimposed upon gradients caused by DSAS and valvar aortic stenosis, leading to exaggerated estimates of severity. These dynamic gradients are uncovered when the anatomic cause of stenosis is removed, and seemingly increase the postoperative morbidity. A greater understanding of the significance of dynamic gradients and the mechanism(s) responsible for them should lead to more rational management of DSAS and HCM in the future.

Inadvertent Swan-Ganz catheter placement in the left pericardiophrenic vein.

Placement of flow-directed Swan-Ganz catheters without fluoroscopic guidance occasionally results in placement in positions other than the pulmonary artery. In the case presented, the inadvertent placement of such a catheter into the left pericardiophrenic vein was probably facilitated by distortion of the right heart and systemic venous anatomy.

Chest trauma and subvalvular left ventricular aneurysms.

Two patients were discovered to have pulsatile saccular lesions at the base of the left ventricle and mitral regurgitation following blunt trauma to the chest. These aneurysms resembled annular subvalvular aneurysms which have previously been reported as congenital defects in African blacks and as acquired lesions following endocarditis or mitral valve replacement. The first patient had two aneurysms, while the second had an aneurysm in continuity with a traumatic ventricular septal defect. These aneurysms were detected by echocardiography and magnetic resonance imaging and should be sought in patients who develop valvar regurgitation following chest trauma.

Percutaneous double-balloon angioplasty of a stenotic modified Fontan aortic homograft conduit.

A 28-year-old woman with pulmonary atresia underwent a modified Fontan procedure that utilized a valved aortic homograft; she developed stenosis of the distal anastomosis between the homograft and the pulmonary artery. Because of the increased risk of reoperation, balloon angioplasty of this stenotic lesion was performed successfully. In the subsequent 11 months she has remained asymptomatic. Balloon angioplasty was a successful alternative to reoperation in this patient.

Enhancement of mitochondrial oxidative phosphorylation capability by hypoperfusion in isolated perfused rat heart.

To define alterations in myocardial mitochondrial function due to hypoperfusion, oxidative phosphorylation was simultaneously studied in 17 control (stable perfusion pressure) rat hearts and 17 hypoperfused isolated rat hearts. Hypoperfusion for 30 minutes was achieved by a reduction in coronary perfusion pressure from 77.8 +/- 1.2 mm Hg (mean +/- SEM) to 20.2 +/- 1.8 mm Hg in the experimental group (control perfusion pressure after 30 minutes 75.6 +/- 1.2). Hypoperfusion caused a reduction in left ventricular developed pressure to 20.5 +/- 1.5 mm Hg (versus control 74.8 +/- 3.3, p less than 0.0001), a reduction of coronary flow rate to 4.9 +/- 0.3 ml/min (versus control 19.4 +/- 1.2, p less than 0.0001), and a drop in myocardial oxygen consumption to 0.06 +/- 0.005 ml O2/min (versus control 0.17 +/- 0.01, p less than 0.0001). Myocardial lactate production was increased by hypoperfusion (3.0 +/- 0.6 mumol/min) compared with controls (0.7 +/- 0.5, p less than 0.02), but myocardial creatine kinase release was similar in the hypoperfused and control groups. Hypoperfusion was associated with an augmentation of state 3 mitochondrial respiration with glutamate and malate as respiratory substrates (448.8 +/- 14.0 ng atoms O/min/mg mitochondrial protein versus controls 290.7 +/- 13.4, p less than 0.001). When rates were normalized for mitochondrial malate dehydrogenase (MDHm), state 3 respiration was still increased in hypoperfused hearts (24.1 +/- 2.1 ng atoms O/min/IU MDHm) compared with controls (15.5 +/- 1.6, p less than 0.02). The rates of dinitrophenol-uncoupled electron transport were similar to the rates of state 3 respiration in both the hypoperfused and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of left ventricular mass in normal and infarcted canine hearts using thallium-201 SPECT.

A new automated edge detection program has been developed to estimate left ventricular mass from single photon emission computed tomographic (SPECT) 201Tl images and 14 dogs were studied. Six of the 14 dogs underwent imaging before and 5 hr after coronary artery occlusion with a closed-chest technique. True left ventricular mass was determined at time of killing within 1 hr of the last 201Tl study. Left ventricular mass determined by tomography correlated well with autopsy left ventricular mass (r = 0.94; p less than 0.001, s.e.e. = 5.9 g) over a range of 62-156 g. The intraobserver variation between repeated measurements of the same SPECT study yielded an r = 0.99; p less than 0.0001; s.e.e. = 2.3 g. The reproducibility of the mass determination was assessed in four animals with two studies performed 10-14 days apart. The estimate of left ventricular mass from the two studies were highly correlated (r = 0.98; p less than 0.001) with a mean absolute difference of 4 g (3.3%). In the six dogs with a control and postinfarct study the mean total left ventricular mass by 201Tl tomography varied by less than 3.8% (r = 0.89; p less than 0.001). In conclusion, tomographic imaging with 201Tl can define left ventricular mass accurately and reproducibly in the dog model. The ability of this 201Tl tomographic left ventricular mass program to measure both normal and infarcted tissue accurately suggests the possibility of documenting interventions designed to alter left ventricular mass and of sizing acute infarcts and assessing interventions that may alter acute infarct size.

Left ventricular derived cardiac output.

Measurement of cardiac output (CO) requires right-sided cardiac catheterization. However, to save time and reduce costs, only left-sided cardiac catheterization is usually performed in most patients with suspected coronary artery disease. Thus, CO is not measured. To determine if CO can be measured from the left side of the heart, 24 patients undergoing cardiac catheterization had near-simultaneous determination of CO after indocyanine green dye was injected into the pulmonary artery and left ventricular (LV) cavity. There was close agreement between pulmonary artery and LV derived cardiac outputs (Pulmonary artery = 0.93 LV + 0.12). The pulmonary artery derived CO was 5.7 +/- 2.0 liters/min and the LV derived CO was 6.1 +/- 2.2 liter/min. Also, there was a close relation between pulmonary artery derived stroke volume (82 +/- 33 ml) and LV derived stroke volume (86 +/- 36 ml). Thus, CO can be accurately measured after injection of indocyanine green dye into the LV cavity.

Continuous external counterpressure during closed-chest resuscitation: a critical appraisal of the military antishock trouser garment and abdominal binder.

Blood flow during closed-chest CPR may result from variations in intrathoracic pressure rather than selective compression of the cardiac ventricles. During chest compression, the thoracic and abdominal cavities are subjected to positive pressure fluctuations. It has been suggested that compression of the abdomen may improve left heart outflow during CPR by limiting diaphragmatic movement or improving venous return. Abdominal compression has been performed experimentally with pneumatic abdominal binders and with the abdominal compartment of the conventional military antishock trouser (MAST) garment. The MAST garment might also improve cardiac output with CPR through an "autotransfusion" effect. In animal studies, MAST-augmented CPR has improved systolic pressures; it has not been shown to improve vital organ perfusion. In the only available clinical study, CPR with the MAST did not improve survival from prehospital cardiac arrest when compared with conventional CPR alone. If inflation of the MAST does produce blood displacement from the peripheral to the central venous circulation, such an effect may be detrimental in that the arteriovenous pressure gradients necessary for vital organ flow may be adversely affected. Inflation of the MAST during CPR may also adversely effect artificial ventilation. Selective abdominal binding also increases systolic pressures during CPR but does not improve subdiaphragmatic venous return. Although abdominal binding may increase common carotid flow, it has not been shown to improve cerebral or myocardial perfusion when compared with conventional CPR alone. These CPR adjunct techniques have not been shown to improve outcome from cardiac arrest and should remain experimental until further well-designed studies addressing regional vital organ flow and outcome of resuscitation are performed.

Modifications of cardiopulmonary resuscitation based on the cough.

The ability of cardiopulmonary resuscitation (CPR) to provide adequate vital organ blood flow during prolonged resuscitation has long been questioned, as has the mechanism of blood flow during CPR. Because coughing during cardiac arrest has been shown to produce adequate anterograde flow to maintain consciousness in man without compressing the heart, cough CPR has been used as a model of a pure "thoracic pump" mechanism on which to base modifications of CPR. In the thoracic pump mechanism, the left heart is a passive conduit for blood expressed from the pulmonary vasculature to the aorta, and there is selective flow to the brachiocephalic vascular bed because of its low pressure veins, which are protected by closure of thoracic inlet venous valves. Right heart flow from systemic veins to the lungs occurs between applications of pressure. Four alternative modalities exploiting the thoracic pump concept were studied in dogs during ventricular fibrillation with angiographic and pressure recordings: cough CPR, simultaneous chest compression and lung inflation, abdominal compression with lung inflation, and inflation of a vest and binder. The latter technique was associated with successful defibrillation and recovery after more than 30 min of circulatory support during ventricular fibrillation. Preliminary studies in a primate preparation indicate that this technique might be useful for prolonged circulatory support in man when defibrillation is not initially available or successful.

Obstruction is unimportant in the pathophysiology of hypertrophic cardiomyopathy.

There has been a longstanding controversy about the significance of intracavitary pressure gradients in hypertrophic cardiomyopathy (HCM). It has been generally assumed that the gradient is the result of an 'obstruction' that impedes left ventricular outflow and which can be relieved by operative intervention. In the first decade after the discovery of HCM (1957-66), the site of 'obstruction' was thought to be a muscular sphincter or contraction ring in the submitral region of the left ventricle, and operations designed to emulate pyloromyectomy (for hypertrophic pyloric stenosis) were developed. Following a challenge to the existence of the 'contraction ring' and an alternative non-obstructive explanation of the pressure gradient, the site of 'obstruction' was translocated to a point of apposition between the anterior mitral leaflet and the interventricular septum, a result of systolic anterior motion (SAM) of the mitral valve. Despite the translocation of the site and mechanism of 'obstruction', the operation for 'relief of obstruction' has not changed significantly. The newer site of 'obstruction' has been challenged on the grounds that the ventricle is not demonstrably impeded in its emptying; when a gradient is provoked, the ventricle empties more rapidly and more completely than it does without a gradient. In addition to a non-obstructive explanation of the gradient, other phenomena thought to be indicative of 'obstruction' can be explained by rapid and complete emptying of the ventricle (cavitary obliteration). Since the morbidity and mortality of symptomatic HCM patients without pressure gradients may exceed that of patients with pressure gradients, it is suggested that 'obstruction' may be unimportant in the pathophysiology of HCM and attention should be focused on abnormal diastolic function and life threatening arrhythmias.

The postextrasystolic murmur response to gradient in hypertrophic cardiomyopathy.

Fourteen patients with hypertrophic cardiomyopathy, 40 with aortic stenosis, and 4 with discrete subaortic stenosis had phonocardiograms during left heart catheterization that showed changes in the magnitude of the murmur in response to increases in the postextrasystolic gradient. All patients showed increases in the gradient of the left ventricular outflow tract during the postextrasystolic beat. Of the 44 patients with aortic stenosis and discrete subaortic stenosis, 42 (95%) had increases in murmur magnitude, in contrast to 9 (64%) of 14 patients with hypertrophic cardiomyopathy. Only 2 of 7 patients with hypertrophic cardiomyopathy and resting gradients of more than 25 mm Hg had murmur increases. Our study shows that the systolic murmur in hypertrophic cardiomyopathy, unlike the outflow tract murmur in aortic stenosis or discrete subaortic stenosis, does not track consistently with the magnitude of the outflow tract gradient.

Has 'obstruction' hindered our understanding of hypertrophic cardiomyopathy?

HCM is a disorder associated with significant morbidity and mortality and a propensity to cause sudden, often unexpected death. The similarity to the symptom complex of aortic stenosis and the presence of a pressure gradient justified the initial assumption that obstruction was of prime importance in HCM and that relief of obstruction was the focal point of rational therapy. However, it is our belief that the dogma of obstruction has impeded progress in and obscured the understanding of HCM and interpretation of its manifestations. The purpose of this article is to call attention to significant discrepancies in the obstructive concept that have been reinforced as new techniques emerged that have allowed further study of the disease. Since neither the presence of a gradient nor SAM can be justifiably equated with the presence of an obstruction, it is proposed that the appellation "obstruction" be reserved for those cases in which the rate of outflow or the rate or degree of ventricular emptying are demonstrably impeded, as in aortic stenosis. Therapy with beta-adrenergic-receptor and calcium channel-blocking agents have shown promise for alleviating symptoms and possibly prolonging life without systematically or predictably affecting the pressure gradient, probably because of their beneficial effects on ventricular relaxation and diastolic filling. Antiarrhythmic therapy has been effective in reducing mortality. Ideally, prevention or regression of the pathologic hypertrophy should be the major focus of future therapeutic interventions in hypertrophic cardiomyopathy.