Recent Publications by CFE Educators

Many echocardiographic signs of severe MR are clearly demonstrated, particularly when both TEE and TTE are used. When these signs are assiduously sought, the recognition of severe MR should pose little problem. Part of the confusion concerning MR and the grading of its severity comes from the fact that the hemodynamic consequences of a given degree of MR vary widely from one individual to another. A regurgitant volume of 50 mL might prove incapacitating to one patient while seeming inconsequential in a second patient. A regurgitant fraction of 50% is poorly tolerated in some patients and asymptomatic in others. Similarly, a regurgitant orifice 0.5 cm2 has unpredictable consequences to the organism, and, in fact, this orifice may vary considerably in size depending on hemodynamic conditions. Thus, a universal definition of the severity of MR is lacking, and there is no agreement on the units with which to quantitate it. The net effect of this confusion is not an inability to recognize severe MR but frustration in differentiating moderate MR from severe MR. We believe that precise quantitation of MR will occur when comprehensive pharmacologic interventions with either TEE or surface echocardiographic monitoring are performed to define the severity of MR by its range of responses to these agents. We have had some success with Doppler measurement of the response of pulmonary artery pressure to dynamic exercise. Patients with normal pulmonary artery pressure at rest tend to show exaggerated rises in pulmonary pressure when MR is clinically important and has resulted in left ventricular dysfunction. Anticipated progress notwithstanding, competently performed TEE is the method of choice for recognizing severe MR.

Transesophageal echocardiography is ideally suited for imaging during CPR because high-quality images can be obtained immediately and continuously without interruption of cardiac compression and ventilation. Use of TEE during CPR is increasing to help monitor resuscitative efforts, for diagnosis, to assist in understanding the physiology of blood flow, and for evaluation of new methods of CPR.

BACKGROUND

There are two competing theories of the mechanism of blood flow during cardiopulmonary resuscitation. The "cardiac pump" theory postulates that blood flows because the heart is squeezed between the sternum and the spine. The "thoracic pump" theory postulates that blood flows from the thorax because intrathoracic pressure exceeds extrathoracic vascular pressure and that flow is restricted to the venous-to-arterial direction because of venous valves that prevent retrograde flow at the thoracic inlet. To determine which mechanism is operative during actual cardiopulmonary resuscitation, 20 patients were imaged with transesophageal echocardiography during resuscitation.

METHODS AND RESULTS

Transesophageal two-dimensional and pulse Doppler echocardiography was begun within 7 minutes of initiation of cardiopulmonary resuscitation. In the 18 patients who could be analyzed, the mitral valve opened during the release phase (diastole) and closed during the compression phase (systole) of cardiopulmonary resuscitation. Mitral velocity-time integral measured 8 +/- 3 cm during diastole. There was compression of right and left ventricular cavities with significant reduction in measured left ventricular volume during cardiopulmonary resuscitation. In five patients, mitral regurgitation was present.

CONCLUSIONS

Transesophageal echocardiography performed during actual cardiopulmonary resuscitation showing mitral valve opening during cardiac release, reduction of ventricular cavity size with compression, and atrioventricular regurgitation support the cardiac pump theory of cardiopulmonary resuscitation. This study demonstrates the feasibility and usefulness of transesophageal echocardiography during cardiopulmonary resuscitation.

Although pulmonary hypertension is a well-described manifestation of systemic lupus erythematosus, there are few data regarding the pulmonary artery pressure response to exercise. We hypothesized that exercise capacity was reduced and that the pulmonary artery pressure response to exercise was abnormal in patients with systemic lupus erythematosus. To test these hypotheses, we performed Doppler exercise echocardiography in 18 patients with lupus and 10 normal control subjects. Exercise duration was significantly reduced in the patients with lupus (8.1 vs 14.4 minutes for control subjects, p or = 0.001). Pulmonary artery pressure was significantly higher in the patients with lupus at rest and during the first two stages of exercise (p 0.05). Cardiac indexes at rest were similar in the two groups, suggesting that increased pulmonary vascular resistance was the mechanism for the higher pulmonary pressure we observed. We conclude that abnormal exercise hemodynamics may contribute to reduced exercise capacity in patients with lupus.

We report two patients with systemic necrotizing vasculitis (microscopic polyarteritis) and associated recurrent pulmonary capillaritis, in whom progressive irreversible airway dysfunction began approximately 10 yr after disease onset. Their course was characterized by repeated episodes of diffuse alveolar hemorrhage, glomerulonephritis, palpable purpura, and splinter hemorrhages. The lung revealed intraalveolar hemorrhage, neutrophilic infiltration and cellular fragmentation, fibrinoid necrosis of the alveolar interstitium, and parenchymal hemosiderin deposits. No medium-sized vessel involvement, granulomatous inflammation, or bronchiolar obliteration were seen. Renal biopsies revealed focal segmental necrotizing glomerulonephritis, and a cutaneous biopsy in one case showed a leukocytoclastic vasculitis. Immunofluorescent studies of lung and kidney showed minimal or no immunoreactivity. The clinical course and serologic tests did not support another systemic vasculitis, connective tissue disease, or antiglomerular basement membrane antibody disease. The acute episodes responded to antiinflammatory and immunosuppressive therapy. Symptoms, serial pulmonary function tests, and chest imaging documented the development of a progressive irreversible obstructive airway disease. No other predisposing factors were identified. These cases demonstrate the unexpected appearance of an irreversible obstructive airway disease with lung parenchymal hyperinflation after systemic necrotizing vasculitis associated with recurrent pulmonary capillaritis and diffuse alveolar hemorrhage.

Alveolar macrophages (AM) produce various inflammatory and immunomodulatory cytokines. The objective of these experiments was to evaluate the production of IL-1ra, a specific receptor antagonist of IL-1, by AM from nonsmoking control subjects (n = 9), smoking control subjects (n = 6), and patients with interstitial lung disease (ILD) (n = 9). IL-1ra protein levels in cultured AM lysates and supernatants were determined by a specific ELISA; relative steady-state IL-1ra mRNA levels were measured using a specific cDNA probe. Before culture the isolated AM from all subject groups contained undetectable IL-1ra mRNA and no IL-1ra protein in the cell lysates as determined by ELISA. AM from nonsmoking control subjects spontaneously produced IL-1ra protein after a 20 h culture in medium, approximately 12 ng/ml with around half in cell lysates. AM from smoking control subjects produced levels of IL-1ra that were similar to the levels in AM from nonsmokers. In contrast, AM from nonsmoking ILD patients (n = 6) produced high levels of IL-1ra spontaneously (approximately 28 ng/ml), with no enhancement observed when cultured on adherent IgG. Interestingly, AM from smoking ILD patients (n = 3) produced lower levels of IL-1ra protein (approximately 11 ng/ml) that were comparable to levels noted in smoking control subjects. AM from all three types of subjects produced decreased amounts of IL-1ra in response to LPS and enhanced amounts in response to GM-CSF. In general, IL-1ra steady-state mRNA levels correlated with protein production.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies have demonstrated that noxious stimuli, intense enough to produce tissue injury, evoke a transient expression of the Fos protein product of the c-fos proto-oncogene in neurons, in regions of the spinal cord that contribute to the transmission of nociceptive messages in the rat. Since there is evidence that increases in fos-like immunoreactivity reflect increases in neuronal activity, it has thus been possible to identify populations of neurons that are activated in response to tissue injury. In this study we used immunocytochemical localization of fos-like immunoreactive (FLI) neurons to map the patterns of neuronal activity in the spinal cord at different times after peripheral nerve injury in the rat. Sciatic nerve transection induced a persistent (at least 1 month) elevation in the number of FLI neurons, predominantly in laminae 1, 2, 5, 6 and 7 of the ipsilateral lumbar enlargement of the spinal cord. In the L5 segment, the expression of fos-like immunoreactivity in the superficial dorsal horn (laminae 1 and 2) fluctuated, with peaks of Fos expression at 2 h, 2 days and 2 weeks after nerve transection. Furthermore, by 2 weeks after nerve injury, the distribution of labelled neurons in the superficial laminae of the dorsal horn shifted, with the most densely labelled cells now located in the central portion of the superficial dorsal horn. In contrast, the pattern of labelled neurons in laminae 5, 6 and 7 was relatively constant over the 4-week study period. Local anesthetic block of the sciatic nerve significantly decreased the number of FLI neurons when it was administered at either 2 days or 2 weeks post nerve injury. At 2 days, injection of the local anesthetic subcutaneously in the dorsum of neck, to control for a systemic action, also reduced expression of FLI in laminae 1 and 2; at 2 weeks, the systemic injection of the local anesthetic reduced expression of FLI throughout the gray matter of the spinal cord. These results demonstrate that peripheral nerve injury, in contrast to tissue injury, induces a prolonged increase in Fos expression in neurons predominantly in those regions of the spinal cord that are associated with the transmission of nociceptive messages. This pattern of fos-like immunoreactivity is probably the result of persistent neuronal activity in the spinal cord. The increased 'activity' in the spinal cord appears to be maintained both by abnormal activity in the injured peripheral nerve as well as by reorganization of circuits within the spinal cord secondary to the nerve injury.

We recently reported that peripheral nerve injury produced by sciatic nerve transection induces a persistent increase in the expression of the immunoreactive Fos protein product of the c-fos proto-oncogene, an indicator of neuronal activity, in the lumbar spinal cord of the rat and that local anesthetic blockade of the peripheral neuroma attenuates this long-term expression of Fos. In addition to the sustained activity of the injured afferents, the nerve transection itself results, acutely, in a massive injury-induced neural discharge. In this study we evaluated the effect of blocking this massive injury discharge on the persistence of Fos expression. Just prior to nerve transection we applied the short-acting local anesthetic, lidocaine, to the sciatic nerve. Control injections were made subcutaneously on the dorsum of the neck. We report that injection of the local anesthetic, by either route, significantly reduced the number of fos-like immunoreactive neurons at 2 days after nerve transection. The effect was only observed on neurons in the superficial dorsal horn. These results indicate that along with sustained activity of injured afferents and of reorganization of central circuits after injury, the initial brief discharge at the time of nerve injury contributes to a prolonged increase in the activity of spinal cord neurons.

The pulmonary artery pressure response to exercise has been used as an index of cardiac reserve and frequently mirrors diastolic conditions. To define this response after orthotopic heart transplantation, we exercised 27 subjects on supine bicycle ergonometers. Stroke volume and pulmonary artery pressure were monitored with contrast-enhanced Doppler imaging. Study patients had undergone orthotopic heart transplantation. Seventeen patients were screened, and eight were subsequently determined by endomyocardial biopsy to be histologically free of acute cardiac allograft rejection. A control population of nonconditioned normal volunteers was also evaluated (heart transplant patients: n = 8, age = 45.7 +/- 7.3 years, seven men; normals volunteers: n = 10, age = 49.4 +/- 12.8 years, nine men; P = NS). Total exercise time and peak heart rate were reduced in heart transplant patients: 7.6 +/- 2.5 minutes, 123 +/- 4 beats/min versus normal volunteers: 16.2 +/- 4.5 minutes, 134 +/- 4 beats/min (P 0.05). Change in stroke volume from baseline to peak exercise was greater in heart transplant patients: 29.9 +/- 4.6 ml versus normal volunteers: 3.9 +/- 5.7 ml (P 0.01). No difference was observed in the pulmonary artery pressure response to exercise. In patients with uncomplicated heart transplantation a reduction in exercise capacity is shown; however, the pulmonary artery pressure response to exercise is comparable to normal subjects. A blunted heart rate response is observed, which is partially compensated by increases in stroke volume. These findings suggest that cardiac diastolic function is preserved and that denervation of the heart accounts for impaired exercise tolerance.