Electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic ischemic heart disease

BACKGROUND: Bone marrow cell injection has been introduced to treat patients with ischemic heart disease. However, focal application of bone marrow cells may generate an arrhythmogenic substrate. OBJECTIVES: To assess the electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. METHODS: Bone marrow was aspirated in 20 patients (65+/-11 years, 19 male) with drug-refractory angina and myocardial ischemia. Electroanatomical mapping (NOGA, Biosense-Webster, Waterloo, Belgium) was performed during mononuclear cell isolation. Areas for cell injection were selected based on the localization of ischemia on SPECT. These areas were mapped in detail to evaluate local bipolar electrogram duration, amplitude and fragmentation. Mononuclear cells were injected in the ischemic area with the NOGA system. SPECT and electroanatomical mapping were repeated at 3 months. Holter monitoring was repeated at 3 and 6 months. RESULTS: SPECT revealed a decrease in the number of segments with ischemia (3.5+/-2.5 vs. 1.1+/-1.0 at 3 months; P<0.01) and an increased left ventricular ejection fraction (44+/-13% vs. 49+/-17% at 3 months; P=0.02). The number of ventricular premature beats remained unchanged (10+/-24x10(2)/24h vs. 8+/-23x10(2)/24h at 3 months (P=NS) and 12+/-30x10(2)/24h at 6 months (P=NS)). At 3 months follow-up, bone marrow cell injection did not prolong electrogram duration (15.9+/-4.6 ms vs. 15.6+/-4.0 ms; P=NS), decrease electrogram amplitude (3.8+/-1.5 mV vs. 3.8+/-1.5 mV; P=NS), or increase fragmentation (2.0+/-0.5 vs. 1.9+/-0.4; P=NS). CONCLUSION: Intramyocardial bone marrow cell injection does not increase the incidence of ventricular arrhythmias and does not alter the electrophysiological properties of the injected myocardium.     

Cardiovascular applications of magnetic resonance imaging and phosphorus-31 spectroscopy.

Recent advances in cardiovascular applications of magnetic resonance (MR) imaging and phosphorus-31 spectroscopy are reported. MR velocity mapping is a valuable adjunct to conventional imaging techniques, providing information on flow velocities as well as on absolute blood flow volume in the aorta and pulmonary arteries. Recently, ultrafast MR techniques have become available to evaluate myocardial perfusion with the aid of MR contrast agents as perfusion marker. Dynamic MR imaging is a powerful tool to assess cardiac function and ventricular mass. In particular, right ventricular function and mass can be evaluated with great accuracy, contributing to improved assessment of the significance of disease processes which may affect the right heart. The role of phosphorus-31 spectroscopy of the heart is expanding for the evaluation of ischemic myocardial disease and cardiomyopathies. The phosphocreatine to adenosine triphosphate ratio appears to be a marker of disease in patients with cardiac hypertrophy. In conclusion, MR imaging and phosphorus-31 spectroscopy is gaining widespread acceptance for evaluation of many cardiovascular disease processes.     

Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy

In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.Abbreviations BS blood sample - CD count density - dP/dt change in pressure over time - [¹²³I] 123-iodine - K_m affinity constant - MIBG metaiodobenzylguanidine - MB_q mega Bequerel - SPECT single photon emission computerized tomography - V_m capacity constant     

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

Continued surveillance of cancer incidence among Swedish smelter workers.

A cohort study of workers at a smeltery in northern Sweden showed an excess mortality, mostly due to deaths in cancer (especially in the respiratory organs) and circulatory diseases. Further follow-up of the cohort showed a decreasing trend in lung cancer incidence and mortality. The cohort studied has now been expanded and comprises 6,334 blue-collar workers first employed 1928-1979. They were followed in the cancer register up to 1987-01-01 and in the cause-of-death register up to 1988-01-01. The decreasing trend in lung cancer incidence and mortality continued but there was still an elevated lung cancer incidence among the workers when compared with Swedish males. The cumulative occurrence of lung cancer since time of first employment was analyzed by different employment cohorts and a higher occurrence of lung cancer was found among those earlier employed.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Stimulation-induced setting of postural muscle tone in the decerebrate rat

These studies demonstrate the presence of pontomedullary areas in the rat brainstem which, when stimulated electrically, serve to set postural muscle tone in the hindlimbs. Low amplitude stimulation of the dorsal tegmental field (DTF) was found to inhibit postural muscle tone and, in some rats, was found to decrease mean arterial pressure. Low amplitude stimulation of the ventral tegmental field (VTF) was found to increase postural muscle tone and, in all cases tested, was found to increase mean arterial pressure.