Effects of amiodarone on refractory ventricular fibrillation in acute myocardial infarction: experimental study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of a single dose of intravenous amiodarone in facilitating defibrillation of ventricular fibrillation refractory to lidocaine and epinephrine plus direct current countershocks in experimental acute myocardial infarction. BACKGROUND: Amiodarone has been hailed as the most effective single antiarrhythmic drug for the treatment of ventricular arrhythmias. However, intravenous amiodarone has only sporadically been used in the defibrillation of ventricular fibrillation in acute myocardial infarction. METHODS: Acute myocardial infarction was induced in 60 dogs by ligation of the proximal left anterior descending coronary artery for 2 h. Animals that developed spontaneous ventricular fibrillation were treated with lidocaine and epinephrine plus five direct-current countershocks. Dogs with ventricular fibrillation refractory to this regimen were randomized to further treatment with additional intravenous administration of epinephrine and bolus lidocaine plus < or = 15 direct-current countershocks (group I) or administration of amiodarone, 10 mg/kg body weight intravenously, followed by defibrillation with direct-current counter-shock (group II). RESULTS: Sixteen (27%) of the 60 dogs in which the protocol was attempted developed spontaneous ventricular fibrillation 21 min after ligation and were included in the study. Lidocaine and epinephrine plus five direct-current countershocks succeeded in converting ventricular fibrillation in one dog (6%). The other 15 dogs were randomized to group I (8 dogs) or group II (7 dogs). Defibrillation was achieved in one of the eight dogs in group I and in six of the seven dogs in group II (p < 0.005). CONCLUSIONS: In an experimental model of acute ischemia, intravenous amiodarone (10 mg/kg) influences positively the response to defibrillation of ventricular fibrillation refractory to lidocaine and epinephrine plus direct current countershocks.

Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. High Enalapril Dose Study Group.

OBJECTIVES: We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting. METHODS: Two hundred and forty-eight patients with advanced CHF (age 56.3+/-12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9+/-4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42+/-19.3 mg/day, n = 126). RESULTS: At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6+/-0.7 and had a mean systolic blood pressure (SBP) of 117+/-18 mm Hg, a mean heart rate (HR) of 85+/-16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0+/-9.8%. In group 2, patients were in NYHA class 2.6+/-0.7; their SBP was 118+/-17 mm Hg, HR 83+/-15 beats/min and LVEF 18.8+/-8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9+/-0.7) in both groups; SBP was 111+/-16 and 111+/-17 mm Hg, HR 77+/-12 and 79+/-13 beats/min and LVEF 31+/-19% and 30+/-12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF. CONCLUSIONS: No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.

Peripheral vascular endothelial dysfunction in patients with angina pectoris and normal coronary arteriograms.

OBJECTIVES: We sought to determine endothelium-dependent vasodilator function in the brachial artery of patients with microvascular angina pectoris. BACKGROUND: Previous studies suggest the presence of endothelial dysfunction of the coronary microcirculation in patients with microvascular angina pectoris. It is not known whether endothelial dysfunction in these patients is a generalized process or whether it is confined to the coronary microcirculation only. METHODS: In 11 women (mean [+/-SD] age 60.1 +/- 7.8 years) with microvascular angina (anginal pain, normal epicardial coronary arteries, positive exercise stress test), endothelium-dependent vasodilation was assessed in the brachial artery by measuring the change in brachial artery diameter in response to hyperemic flow. Results were compared with 11 age- and gender-matched patients with known three-vessel coronary artery disease and 11 age- and gender-matched healthy control subjects. In all subjects, the intima-media thickness (IMT) of the common carotid artery was also measured. RESULTS: Flow-mediated dilation (FMD) was comparable in patients with microvascular angina and coronary artery disease (1.9 +/- 2.5% vs. 3.3 +/- 3.3%, p = NS) but was significantly lower in patients with microvascular angina than in healthy control subjects (1.9 +/- 2.5% vs. 7.9 +/- 3%, p < 0.05). IMT was significantly lower in patients with microvascular angina than in those with coronary artery disease (0.64 +/- 0.08 vs. 1.0 +/- 0.28 mm, p < 0.05) and was comparable between patients with microvascular angina pectoris and healthy control subjects (0.64 +/- 0.08 vs. 0.56 +/- 0.14 mm, p = NS). IMT > or = 0.8 mm was observed in 1 of 11 patients with microvascular angina, 1 of 11 control subjects and 10 of 11 patients with coronary artery disease. CONCLUSIONS: These findings suggest that endothelial dysfunction in microvascular angina is a generalized process that also involves the peripheral conduit arteries and is similar to that observed in atherosclerotic disease. IMT could be helpful in discriminating patients with microvascular angina and atherosclerotic coronary artery disease.

Arrhythmogenic effect of high blood pressure: some observations on its mechanism.

An increase in aortic pressure is a reproducible way of causing ventricular ectopic rhythms. This study sought to determine whether it is the aortic pressure per se or the concommitant increase in afterload or preload that has a direct arrhythmogenic effect. Experiments were carried out in 17 anaesthetised dogs. For each 10 s period the pressure and the presence of a ventricular arrhythmia (at least one ectopic beat) were noted. In nine animals an aortic valve gradient was created (and released). The results were compared to those obtained by impeding the aortic flow at the ascending aorta. The mean systolic left ventricular pressure was significantly higher in the arrhythmia associated periods in 8/9 experiments when there was an aortic valve gradient and in 5/9 experiments when there was not. In 4/9 experiments the mean aortic pressure associated with arrhythmia was significantly lower with an aortic valve gradient than when there was no gradient and no arrhythmia. In 7/9 of these experiments, coronary sinus flow was measured volumetrically during the manoeuvres applied. The coronary flow was significantly lower when there was neither arrhythmia nor aortic valve gradient than when there was an arrhythmia (with or without an aortic valve gradient). In another eight experiments a pressure reservoir in the aorta was either raised or lowered while another pressure reservoir in the left atrium was moved in the opposite direction. Thus the mean aortic pressure could be increased while the left atrial pressure was decreased and vice versa. If the left atrial pressure was taken into account, the mean difference of the aortic pressure from its expected value, derived from the aortic v left atrial pressure regression equation, was significantly higher when there was an arrhythmia than it was when there was no arrhythmia in all eight experiments. On the other hand, the mean difference in the left atrial pressure from its expected value was significantly higher when there was an arrhythmia in 1/8, lower in 2/8 and not significantly different in 5/8 experiments. It is concluded that when the blood pressure is raised, it is the increase in afterload rather than an increase in aortic pressure itself or in the preload that has an arrhythmogenic effect on the ventricles.

Response of tertiary centres to pressure changes. Is there a mechano-electrical association?

STUDY OBJECTIVE: To investigate the mechanism of pressure related ventricular arrhythmias by examining them during atrioventricular (AV) block. DESIGN: Complete AV block, where all ventricular beats are ectopic, was induced by AV node ablation and/or by toxic digitalisation, and rhythm changes were studied while arterial blood pressure was repeatedly raised and lowered. SUBJECTS: 15 anaesthetised mongrel dogs, weight 15-28 kg, were used. AV block was induced in eight by chemical or mechanical ablation of the AV node. In five of these and in seven other dogs, 5.0-7.5 mg digoxin was also given. MEASUREMENTS AND RESULTS: Following AV block due to ablation, a heart rate increase (or no change) was found in 87.5% of 56 arterial pressure increases produced by elevation of an open arterial blood reservoir or by metaraminol infusion, but in only 21.8% of 55 pressure decreases caused by arterial bleeding (p much less than 0.001). Following AV block due to digitalisation, the equivalent figures were 96% of 50 pressure increases and 27.3% of 55 pressure decreases (p much less than 0.001). While arterial pressure was increased there was moderate acceleration of the escape rhythm, then appearance of premature ventricular beats, then non-sustained and finally sustained ventricular tachycardia. The reverse occurred, with some hysteresis, on decreasing the arterial pressure. In five of the digitalised animals, arterial pressure reduction to nearly zero caused reproducible sudden arrest, with resumption of the ordinary escape rhythm on increasing the pressure again. CONCLUSIONS: The findings suggest the possibility of two kinds of ectopic rhythm in AV block: the "normal" escape rhythm which is only moderately affected by arterial pressure changes; and an "abnormal" faster pressure dependent rhythm which is generated by high arterial pressure and abolished by pressure near zero, as if there were a mechano-electrical association. This abnormal rhythm may prevail completely in digitalis toxicity so that if cardiac arrest occurs, no automaticity can be expected to appear unless arterial pressure is raised.

Effect of acute changes in aortic pressure on the coronary reserve.

STUDY OBJECTIVE: The aim was to evaluate the effect of acute changes in aortic pressure on the coronary reserve and hyperaemic response. DESIGN: Aortic pressure changes were induced either by intra-aortic balloon pumping or by the production of acute aortic regurgitation. A transient 20 s occlusion of the left anterior descending coronary artery was used as the hyperaemic stimulus. EXPERIMENTAL SUBJECTS: The experiments were performed on 19 open chest anaesthetised dogs, weight 13-32 kg. MEASUREMENTS AND MAIN RESULTS: During intra-aortic balloon pumping the mean diastolic aortic pressure increased by 24.7(SEM 2.9) mm Hg (p less than 0.001), while in aortic regurgitation it decreased by 47.7(11.1) mm Hg (p less than 0.01). At the peak hyperaemic response the driving coronary pressure was 121.4(2.8) mm Hg during intra-aortic balloon pumping and 59.8(11.5) mm Hg during aortic regurgitation. The peak hyperaemic flow increased by 12.0(3.8) ml.min-1 (p less than 0.01) during intra-aortic balloon pumping, compared to the values before pumping and decreased by 14.9(4.2) ml.min-1 (p less than 0.01) during aortic regurgitation, compared to the values before aortic regurgitation. The coronary reserve, expressed as the ratio of the hyperaemic to the resting flow, increased by 0.7(0.1) (p less than 0.001) during intra-aortic balloon pumping and decreased by 0.4(0.2) (p less than 0.05) during aortic regurgitation. A positive significant correlation coefficient was found at the peak hyperaemic response between the mean aortic pressure and the total forward effective coronary flow, and between the mean diastolic aortic pressure and the diastolic component of the coronary flow, during both intra-aortic balloon pumping and aortic regurgitation. CONCLUSIONS: The results suggest that coronary reserve increases during intra-aortic balloon pumping and decreases during aortic regurgitation; these changes could be attributed to the effect of the pressure changes on the hyperaemic flow.

An extravascular hydraulic system to control blood pressure by a feedback regulation of the venous return.

Since increases in blood pressure may be effectively controlled by hydraulic feedback by reducing the venous return through the inferior vena cava in proportion to the blood pressure this principle was applied using a totally implantable extravascular system consisting of a periaortic blood pressure sensor and a pericaval cuff around the inferior vena cava. The two cuffs were supported externally by hard skeletons, filled with water, and connected directly to each other. The two devices were tested separately and together in 10 anaesthetised mongrel dogs with normal and high blood pressure induced by a metaraminol infusion. With the periaortic sensor an increase in blood pressure of 100 mmHg caused a mean(SD) isotonic volume displacement of 0.41(0.11) ml, and an increase in the pericaval balloon energy content of 100 ml.mmHg-1 caused a fall in blood pressure of 37.8(18.3)%. The whole system prevented an excessive rise in blood pressure when metaraminol was infused, with a feedback gain of about 2.8. It is concluded that blood pressure can be maintained at acceptable levels despite strong hypertensive stimuli, by this system, without additional treatment with drugs or an external energy source. The system is totally implantable and is applied extravascularly so that no anticoagulation is needed.

Thyroid hormone and immunological studies in endemic goiter.

Iodized oil (1 ml im) was given to 58 goitrous patients from a mildly iodine-deficient area in Greece. Goiter size, urinary iodine, and serum T4, T3RU, T3, rT3, TSH, thyroxine-binding globulin (TBG), and thyroid autoantibodies were measured before and 1, 3, and 6 months after the injection. Goiter size decreased. Serum T4 remained relatively constant, but TBG decreased and therefore T3RU and FTI increased. Serum T3 and rT3 initially decreased (P less than 0.001) and then increased at the sixth month (P less than 0.001), both showing roughly parallel changes. Serum TSH, initially normal (1.42 +/- 0.11 (SEM) mU/liter), decreased to 0.65 +/- 0.01 and 0.76 +/- 0.05 mU/liter at the third and sixth month (difference from baseline P less than 0.001). Thyroid autoantibodies, both against thyroglobulin and the microsomal antigen, were undetectable before treatment, but became positive in 42.8% of the patients 3 and 6 months later. Three patients developed transient hyperthyroidism. This occurred 3 or 6 months after treatment, and was associated with high titers of thyroid autoantibodies. These results indicate that: 1) transient hyperthyroidism may occur after the administration of iodized oil, possibly because of thyroid tissue necrosis and leakage of hormones, and 2) serum TBG decreases after iodized oil, a finding not previously reported and one whose cause is not known.

A pressure-time index' for assessing the severity of essential hypertension.

OBJECTIVE: A new derivative of 24 h ambulatory blood pressure monitoring (ABPM) is introduced and its association with left ventricular mass index (LVMI) in essential hypertension is examined. PATIENT: population One hundred and fifty-three previously untreated essential hypertension patients. METHODS: Patients underwent casual blood pressure (BP) readings, 24 h ABPM and left ventricular echocardiographic assessment The following 24 h awake and sleep ABP variables were calculated: mean systolic and diastolic BP, systolic and diastolic BP loads (percentage of systolic readings > 140/120 mmHg (day/ night) and diastolic readings > 90/80 mmHg (day/night)), standard deviation of systolic and diastolic ABP and nocturnal fall of systolic BP, as well as the integrated areas under the ABP curve. The area under the BP curve divided in horizontal slices was accurately modelled by a sigmoid curve. The parameters controlling the shape of the curve and in particular that regarding its 'slope' is hereafter called the 'pressure-time index'. RESULTS: 'Systolic pressure-time index 24 h' (SPTI24) is related to left ventricular mass index (multivariate analysis, P= 0.008). Using either partial correlation coefficients or a multivariate analysis, SPTI24 is related to left ventricular mass index, independently of age, casual blood pressure, mean systolic and diastolic ABP, systolic and diastolic BP loads, BP variability (standard deviation (SD), nocturnal fall of systolic BP) and integrated area under the curve (multivariate analysis, P= 0.004). CONCLUSIONS: In essential hypertension, the SPTI24 is related to LVMI independently of age, casual blood pressure, integrated area under the curve or any other derivative of 24 h ABPM, and might be used to assess the extent of hypertensive load.

Evolution of late potential parameters in thrombolyzed acute myocardial infarction might predict patency of the infarct-related artery.

The objective was to predict the patency grade of an infarct-related artery by identifying the time course of the changes of the late potential parameters before, during, and shortly after thrombolysis. The study population consisted of 51 patients with acute myocardial infarction (AMI) who received thrombolytic therapy within 3.2 +/- 1.3 hours from the onset of symptoms. Multiple signal-averaged electrocardiograms (SAECGs) were recorded before, during, and shortly after thrombolysis. A total of 489 single-averaged electrocardiographic tracings were evaluated. Late potentials were defined as: QRS duration > 114 ms, low amplitude signals (LASs) > 38 ms, and root mean square (RMS) < 20 microV. Late potentials were found in 37% of patients (21 before and 16 during the first 2 hours of thrombolysis), disappeared in all of patients within 89 +/- 75 minutes (range 25 to 350) but reappeared and persisted in 12% of patients, all with an occluded artery (grade 0). The late potential parameters (QRS, LAS, RMS) showed a gradual improvement which occurred earlier (2 vs 4 hours) and was more marked (0.01 vs 0.05) in cases with a patent artery. This improvement expressed by the late potential parameter index (LnQRS + LnLAS - LnRMS) predicts the patent artery with a sensitivity of 0.94 and specificity of 0.79. The improvement of late potential parameters jointly with close to normal initial values or the late potential parameter index and its changes constituted a satisfactory prediction of the patency grade. Thus, the signal-averaged electrocardiographic technique is capable of predicting the early success or failure of thrombolytic therapy.

Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality.

This study examined the usefulness of 01 and QRS dispersion in the prognosis of patients with advanced congestive heart failure (CHF). One hundred four patients in New York Heart Association functional classes II to IV, with a left ventricular ejection fraction of <35%, and untreated with antiarrhythmic drugs, were followed prospectively. QRS and QT dispersion were defined as the maximum difference in QRS and QT interval duration, respectively, measured on all leads of standard 12-lead electrocardiograms. The end points of the study were non-sudden and sudden cardiac mortality. During an average follow-up of 20 months, there were 13 non-sudden and 10 sudden deaths. The average QRS duration was significantly longer in nonsurvivors than in survivors (125 ¿ 34 vs 113 ¿ 34 ms, respectively, p <0.04). Similar results were obtained with 01 dispersion (95 ¿ 48 ms vs 78 ¿ 31 ms, respectively, p <0.03) and QRS dispersion (54 ¿ 17 ms vs 46 16 ms, respectively, p <0.02). Furthermore, patients who died suddenly had significantly greater QRS dispersion than patients who survived (56 ¿ 13 vs 46 ¿ 16 ms, respectively, p <0.02). In a multivariate analysis, QT and QRS dispersion were both independent predictors of non-sudden cardiac death (p = 0.01 and p = 0.001, respectively), and QRS dispersion was also an independent predictor of sudden cardiac death (p = 0.04). Death rate in patients with 01 dispersion >90 ms was 2.8-fold higher than those with 01 dispersion 90 ms (95% confidence intervals [CI] 1.2 to 6.4). Similarly, the death rate in patients with QRS dispersion >46 ms was 3.9-fold higher than in those with QRS dispersion 46 ms (95% Cl 1.6 to 9.5). These findings suggest that QT and QRS dispersion are useful predictors of mortality in patients with advanced CHF. ¿2000 by Excerpta Medica, Inc.

Effect of protracted dobutamine infusion on survival of patients in cardiogenic shock treated with intraaortic balloon pumping.

UNLABELLED: The survival of subjects with postmyocardial infarction cardiogenic shock treated with intra-aortic balloon pumping (IABP) differs significantly among various reports. Differences in the criteria for IABP application and in the timing of its initiation have been considered as the main reasons for variations in survival. This study examines whether the way patients in cardiogenic shock are treated prior to IABP may affect their survival. Fifty-five patients in severe postmyocardial infarction cardiogenic shock were classified into three groups according to the rate of dobutamine infusion prior to IABP: the "nondobutamine" (group A, n = 31), the "high-dose dobutamine" (8 to 20 micrograms.kg-1.min-1, group B, n = 17), and the "low-dose dobutamine" (up to 7 micrograms.kg-1.min-1, group C, n = 7). All subjects seen from 1978 to 1983 were recruited for group A, from 1986 to 1990 for group B, and in years 1984, 1985, and 1991 for group C, without using any other classification criteria. It was shown a posteriori that the three groups did not differ in the features of the subjects, in the severity of shock, and in the time length between onset of shock and pumping initiation. None of the 17 subjects of group B could survive under pumping, while 10 of the 31 subjects in group A and 4 of the 7 subjects in group C were weaned off pumping. CONCLUSIONS: A protracted, high-dose pre-IABP administration of dobutamine may adversely affect the survival of patients with postmyocardial infarction cardiogenic shock.

Intra-aortic ballon pump for relief of aortic regurgitation. Experimental study.

Backflow from the aorta to the left ventricle during diastole in aortic regurgitation can be reduced by expanding, during diastole, a small air balloon positioned in the ascending aorta downstream to the regurgitant valve. A spherical catheter-mounted balloon, acting as a prosthetic aortic valve for the correction of acute aortic regurgitation, was tested in 12 dogs. This "valve" was actively inflated and deflated by means of a common intra-aortic balloon pumping system (Datascope). A significant increase of end-diastolic pressure in the descending aorta, from 51.72 +/- 1.72 to 70.35 +/- 1.92 mm Hg (mean +/- standard error, p less than 0.001), was obtained, without a significant pressure gradient across the "valve". The "valve" prevented the backward flow of the descending aorta by up to 100%, so that there was a mean increase in t-e effective forward flow of 12.61 +/- 5.27% (mean +/- standard error, p less than 0.05). Coronary arterial flow changes varied during the application of the "valve." They depended directly on the changes of the diastolic component of the flow velocity wave, and this relationship was significant (x2 = 33.04, p less than 0.0001). Contractility indices were not significantly affected during the function of the "valve." It is suggested that the spherical "valve" mounted on a catheter may easily be inserted without thoracotomy for a temporary satisfactory correction of the aortic regurgitation.

Effect of the positioning of a balloon valve in the aorta on coronary flow during aortic regurgitation.

The coronary artery flow changes relative to the function of a catheter-mounted balloon valve used for relief of aortic regurgitation were studied in 10 mongrel dogs. Acute aortic regurgitation was produced by severing the aortic cusps with a long needle. Coronary flow was recorded from the left anterior descending coronary artery through an electromagnetic flowmeter. When the balloon was functioning within the cavity of the left ventricle there were no significant changes in the coronary flow and aortic pressure, except for a slight decrease in the aortic end-diastolic pressure. When it was functioning in the aortic ring the coronary flow increased 6.52 +/- 1.65 ml/min/100 gm of myocardium (p less than 0.001) and became predominantly diastolic. When it was functioning in the ascending aorta the coronary flow decreased 6.22 +/- 1.16 ml/min/100 gm of myocardium (p less than 0.001) and remained predominantly systolic. Finally, when the balloon was functioning in the thoracic aorta the coronary flow did not change significantly. With the balloon functioning in the aortic ring, ascending aorta, or thoracic aorta, there was a significant increase in the aortic end-diastolic pressure and decrease in the pulse pressure distal to the location of the balloon. It is concluded that the location of the balloon valve inserted for relief of aortic regurgitation influences the effect on coronary arterial flow.

A valveless high stroke volume counterpulsation device restores hemodynamics in patients with congestive heart failure and intractable cardiogenic shock awaiting heart transplantation.

The paraaortic counterpulsation device is a round pumping chamber with one valveless opening 20 mm in diameter and a 100 ml stroke volume. The paraaortic counterpulsation device was implanted on the ascending aorta of three male patients with intractable cardiogenic shock. Patients were assisted for 4 hours and 8 and 54 days, respectively; the first patient died as a result of nonresponding peripheral vasodilation and the other two died of septic shock. The two patients who were assisted for 8 and 54 days were conscious and able to function in a limited manner during the mechanical assistance. Discontinuation of the mechanical support for a few seconds was followed by low systolic arterial pressure (30 to 60 mm Hg) and syncopal episodes. Biochemical tests and autopsy results in these patients showed no evidence of blood cell destruction, thrombus formation, brain infarction, or other distal emboli. In conclusion, satisfactory hemodynamic effects, excellent biocompatibility, and simplicity of the implantation procedure in these patients encourage the use of the paraaortic counterpulsation device as a bridge to heart transplantation.

Long-term intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure.

STUDY OBJECTIVE: To evaluate the effects of long-term intermittent dobutamine infusion (IDI) with concomitant administration of low-dose amiodarone in patients with congestive heart failure (CHF) refractory to standard medical treatment. DESIGN: Prospective, interventional clinical trial. SETTING: Inpatient and outpatient heart failure clinic in a university teaching hospital. PATIENTS AND INTERVENTIONS: Twenty-two patients with CHF refractory to standard treatment who could be weaned from dobutamine therapy after an initial 72-h infusion were included in this study. The first 11 patients (group 1) were treated with IDI, 10 micromin, as needed (mean, once every 16 days, lasting for 12 to 48 h); the next 11 patients (group 2) received oral amiodarone, 400 mg/d, and IDI, 10 microg/kg/min, for 8 h every 7 days. MEASUREMENT AND RESULTS: There were no differences in baseline clinical, hemodynamic, and five biochemical characteristics between the two groups. The left ventricular ejection fraction was 13.5 +/- 4.5% in group 1 vs 15.5 +/- 4.9% in group 2 (mean +/- SD; p = 0.451); mean pulmonary capillary wedge pressure was 31.3 +/- 4.4 mm Hg vs 29.4 +/- 3.3 mm Hg (p = 0.316); serum creatinine was 1.9 +/- 0.4 mg/dL vs 1.6 +/- 0.5 mg/dL (p = 0.19); and serum Na was 139.6 +/- 6.2 mEq/L vs 138.4 +/- 3.1 mEq/L (p = 0.569). At 12 months of follow-up, 1 of 11 patients (9%) was alive in group 1 vs 6 of 11 patients (55%) in group 2 (p = 0.011). Furthermore, in group 2, the functional status improved significantly within the first 3 months of treatment, from New York Heart Association functional class IV to 2.63 +/- 0.5 (p = 0.0001). CONCLUSION: Long-term IDI in conjunction with amiodarone, added to conventional drugs, improved clinical status and survival of patients with severe CHF.

Redistribution of amiodarone in heart transplant recipients treated with the drug before operation.

Seven heart transplant recipients (six men and one woman) treated with oral amiodarone 194 +/- 100 mg/day before operation for a period of 30 +/- 48.5 months were studied. The myocardial concentrations of amiodarone in the transplanted heart peaked in the second posttransplantation week (87.6 +/- 80.7 microg/g myocardial tissue) and remained detectable in the twelfth week (10.2 +/- 8.4 microg/g myocardial tissue). The ratio of myocardial/plasma concentrations peaked at the end of the sixth posttransplantation week. In conclusion, amiodarone accumulated rapidly in the transplanted myocardium of heart transplant recipients treated with the drug before operation and remained detectable for at least 3 months.

Pulse pressure in normotensives: a marker of cardiovascular disease.

The purpose of the present study was to evaluate the relation of the systemic arterial pulse pressure and other parameters derived from the 24-h arterial blood pressure (BP) monitoring to the severity of coronary artery disease, carotid lesions, and left ventricular (LV) mass index in patients without arterial hypertension. One hundred ten patients with known coronary artery disease underwent coronary arteriography, 24-h arterial BP monitoring, and ultrasound imaging of the carotid arteries and the myocardium. Measurements of 24-h arterial BP monitoring (systolic, diastolic, and average BP, pulse pressure, abnormal values of systolic and diastolic BP, and heart rate), the severity of coronary heart disease (Gensini score), intima-media thickness (IMT) of the common carotid artery and LV mass index were determined in all patients. By univariate analysis, only 24-h pulse pressure was significantly related to the severity of coronary artery disease (P < .01), carotid IMT(P < .01), and LV mass index (P < .01). In a multivariate analysis, 24-h pulse pressure was also the best predictor of the severity of coronary lesions (P = .009), carotid IMT (P = .003), and LV mass index (P = .009). Gensini score was related (P < .01) to LV mass index and not to carotid IMT. In conclusion, systemic arterial pulse pressure derived from 24-h arterial BP monitoring is related to coronary artery disease, carotid IMT, and LV mass index independently of age or any other derivative of 24-h arterial BP monitoring, indicating that this parameter could be a marker of global cardiovascular risk.

Mechanical ventilation in conjunction with the intra-aortic balloon pump improves the outcome of patients in profound cardiogenic shock.

OBJECTIVE: To examine the effects of mechanical ventilation with positive end-expiratory pressure (PEEP), in conjunction with the intra-aortic balloon pump (IABP), on the outcome of patients in profound cardiogenic shock. PATIENTS: Twenty-eight consecutive patients presenting with myocardial infarction complicated by cardiogenic shock refractory to medical therapy, including dobutamine, dopamine and fluid administration. Eighteen patients were assisted by the IABP alone (IABP group), and ten patients by the IABP plus controlled mechanical ventilation with PEEP set at 10 cmH(2)O (IABP + CMV group). RESULTS: Weaning from mechanical assistance was accomplished in 8 out of 18 patients in the IABP group versus 9 out of 10 patients in the IABP + CMV group (p = 0.04). Ultimately, 5 of 18 patients in the IABP group were discharged from the hospital versus 8 of 10 patients in the IABP + CMV group (p = 0. 01). CONCLUSION: Mechanical ventilation with PEEP at 10 cmH(2)O supplements the IABP and may improve the survival rates of patients suffering from cardiogenic shock.

Treating severe cardiogenic shock by large counterpulsation volumes.

BACKGROUND: Intraaortic balloon pumping is known to be ineffective in severe cardiogenic shock. The efficacy of balloon volumes larger than those commonly used is examined. METHODS: In 18 dogs with severe experimental cardiogenic shock (systolic aortic pressure < 60 mm Hg, aortic flow < 45 mL.min-1.kg-1) the effect of three intraaortic balloon volumes (15, 30, and 45 mL) and a 60-mL paraaortic pump was examined. RESULTS: The 45-mL balloon covering the full length of the aorta induced the highest (+ 12.4 +/- 2.2 mL.min-1.kg-1; mean +/- standard error of the mean) and the 15-mL balloon the lowest increase in aortic flow (F = 14.6, p < 0.0001). Only the 45-mL balloon increased (p < 0.05) urine output and renal artery flow. The 60-mL paraaortic pump induced the highest (F = 10.72, p < 0.002) increase (+ 36.6 +/- 6.5 mL.min-1.kg-1) in aortic flow compared to the three balloons. An 80- to 100-mL paraaortic pump maintained the life of 3 patients in severe cardiogenic shock for 4 hours, 8 days, and 54 days, whereas a 40-mL conventional balloon was completely ineffective. CONCLUSIONS: Experimental and clinical data indicate that the effectiveness of intraaortic balloon pumping in severe cardiogenic shock may be improved by increasing the volume of the balloon (i.e., until it fully occupies the aorta).