SUMMARY1. Three normal subjects performed rest-exercise transitions on a cycle ergometer, from rest to unloaded pedalling (0 W), 50, 100 and 150 W. Each experiment was performed in triplicate, with randomized work load order, in two sessions. Ventilation was obtained breath-to-breath by integration of a pneumotachygraph signal, and cardiac output beat-to-beat by a new development of the Doppler technique. Results were bin-averaged in 4 s bins over the first 20 s, and compared to resting values.2. Both ventilation and cardiac output increased significantly in the first 2 s. This initial rise in ventilation was due entirely to an increase in rate, the subsequent rise mainly to increase in tidal volume. Cardiac output increased predominantly through change in rate with smaller increases in stroke volume.3. A striking feature was a tendency for ventilation and cardiac output responses to be biphasic with an initial rise followed by a slight fall at the 14 s mark, and a subsequent rise, at all work loads. Overall correlation between ventilation and cardiac output was therefore high (r = 0 92).4. Six normal subjects hyperventilated for 45 s voluntarily, (a) at rate 24/min and normal tidal volume; (b) at normal rate and tidal volume of 1-5 1; (c) at rate 24/min and tidal volume of 1-5 1. Cardiac output, averaged over 10-45 s, rose by 0 4, 0 5, and 1-0 1 min-respectively, with falls in end-tidal PCO, of 4, 6, and 8 mmHg.5. Six normal subjects hyperventilated for 60 s with rate 24/min and tidal volume of 1-4 1, and end-tidal Pco, maintained at 38 + 2 mmHg. Cardiac output, averaged from 10-60 s, rose by 1-0 I min'.6. With increased rate and tidal volume, whether isocapnic or hypocapnic, cardiac output responses showed an overshoot with a peak value at about 30 s.7. The hypothesis of 'cardiodynamic hyperpnoea' considers a possible effect of increasing cardiac output on ventilation. The effects of ventilation on cardiac output must also be considered. We propose an extended hypothesis involving stable positive feed-back.

We have used a 2.2 MHz continuous-wave Doppler blood velocity meter (Bach-Simpson BVM 202) to measure ascending aortic blood velocity and acceleration, and have obtained from the velocity signal a noninvasive measure of stroke volume and cardiac output by combining the Doppler technique with M-mode echocardiography. In two separate studies we have systematically altered the loading conditions of the heart with lower body pressure; and the inotropic state of the heart with dobutamine (5 micrograms . kg-1 . min-1), and documented the changes in mean velocity (MV), maximum acceleration (MA), stroke volume (SV), cardiac output (CO) and left ventricular end-diastolic dimension (EDD) (M-mode echocardiography). Application of lower body pressure to subjects in a 30 degrees head-up tilt position caused a systematic increase in preload, as shown by a 9% increase in EDD, which raised SV by a maximum of 33% (p less than or equal to 0.001) and CO by 32% (p less than or equal to 0.01), thus showing a classical Starling response; whilst there was relatively little increase in MA. Conversely, infusion of dobutamine, an inotropic agent, caused a 29.2% increase in MA (p less than or equal to 0.01) with minimal increase in SV. Thus, the ability to measure ascending aortic blood velocity allows noninvasive monitoring of changes in both inotropic state and Starling function, with considerable ease and rapidity.

SUMMARY Three weeks after myocardial infarction in 50 patients the effect of the infusion of a graded dose of dobutamine was compared with that of symptom limited treadmill exercise testing. The following variables were measured: blood pressure, heart rate, ST segment changes, Doppler aortic blood flow, and cross sectional echocardiographic dimensions. The heart rate and double product increased more -during exercise than during dobutamine infusion, while maximum acceleration in the ascending aorta increased more during dobutamine infusion than during exercise. Significant ST depression was recorded in 22 Patients and methods PATIENTSExercise and dobutamine stress tests were performed three weeks after acute myocardial infarction in fifty patients (mean (SD) age 56 (5), range 35-69). Nine (18%) of the patients were women. The diagnosis of acute myocardial infarction was based on at least two of three criteria: (a) a history of chest pain suggestive of myocardial ischaemia persisting for at least 30 minutes; (b) evolution ofnew pathological Q waves or persistent ST-T wave changes suggestive of non-Q wave infarction; (c) a rise in the concentrations of aspartate transaminase, hydroxybutyrate dehydrogenase, or creatine kinase to at least twice the upper limits of the reference ranges. The resting electrocardiogram showed anterior infarction in 16 patients, inferior in 22, lateral in four, true posterior in two, and non-Q wave infarction in six. Three (6%) patients had a history of a previous myocardial infarction. Patients with bundle branch block or nonischaemic valvar heart disease were excluded.Patients were randomly selected for the study before the exercise test and their written consent was obtained. 521

Endomyocardial biopsy (EMB) remains the mainstay for the diagnosis of acute cellular rejection in cardiac transplant patients. A noninvasive alternative that would supplant or reduce the number of EMBs would be a highly desirable and cost-effective tool. To evaluate one potential alternative, a pacemaker with high resolution telemetry capabilities and two fractally coated epimyocardial leads were implanted in 30 patients at five transplant centers during the heart transplant procedure. Ventricular electrograms were recorded during intrinsic and paced activity and digitized to a laptop-based data acquisition device. Electrograms were recorded at frequent intervals and systematically on days when EMBs were performed. The electrogram data were then transferred via the Internet to a central data processing site. Clinical patient management was blinded to the electrogram results and varied considerably among the five centers. Using EMB together with clinical assessment of the transplant revealed 18 cases of clinically significant rejection beyond postoperative day 27 that required antirejection therapy. The normalized parameter values extracted from the electrogram recordings during pacing (the ventricular evoked response) that were associated with significant rejection were statistically lower (86% +/- 16% versus 96% +/- 22%, P < 0.005). The application of a single-threshold diagnosis model to the parameter values allowed detection of significant rejection with a negative predictive value of 98%. This analysis also showed that as many as 55% of the routine surveillance EMBs could have been eliminated had the pacemaker monitoring technique been used as a screening tool prior to EMB. A prospective study should further define the role of this technique in the detection and management of cardiac transplant patients.

The Carillon Mitral Contour System has been studied in 3 nonrandomized trials in patients with symptomatic congestive heart failure and functional mitral regurgitation. The REDUCE FMR study is a uniquely designed, double-blind trial evaluating the impact of the Carillon device on reducing regurgitant volume, as well as assessing the safety and clinical efficacy of this device. Carillon is a coronary sinus-based indirect annuloplasty device. Eligible patients undergo an invasive venogram to assess coronary sinus vein suitability for the Carillon device. If the venous dimensions are suitable, they are randomized on a 3:1 basis to receive a device or not. Patients and assessors are blinded to the treatment assignment. The primary end point is the difference in regurgitant volume at 1 year between the implanted and nonimplanted groups. Other comparisons include clinical parameters such as heart failure hospitalizations, 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and other echocardiographic parameters. An exercise echo substudy will also be included.