Spyridon D. Moulopoulos

Diastolic balloon pumping (with carbon dioxide) in the aorta—A mechanical assistance to the failing circulation

Abstract A device to provide mechanical assistance to the failing circulation is described. It consists of a catheter in a long, narrow latex tube that was inserted into the descending aorta of an anesthetized dog. The latex tube was rhythmically inflated with carbon dioxide through a pressure system, and the stroke was triggered with the aid of a timing circuit from the electrocardiogram of the animal. The stroke length and the delay after the R wave of the electrocardiogram were preset so that the latex tubing was inflated during diastole and remained deflated during systole. It was possible to increase the diastolic blood flow in the arterial system and lower the end-diastolic arterial pressure. It is hoped that the use of this device in the failing heart will result in increased diastolic blood flow, improved coronary perfusion, and decreased work for the failing left ventricle. The best indication for its use would be a failing left ventricle due to an acute coronary thrombosis.

Time Rate of Blood Pressure Variation Is Associated With Increased Common Carotid Artery Intima-Media Thickness

The extent of target-organ damage has been positively associated with the magnitude of blood pressure (BP) variability in essential hypertension. However, the clinical implications of the rate of BP changes have never been investigated. We evaluated the association between the rate of systolic BP (SBP) variation derived from ambulatory BP monitoring (ABPM) data analysis and the extent of common carotid artery (CCA) intima-media thickness (IMT) in normotensive (n=280) and in uncomplicated hypertensive subjects (n=234). The 24-hour rate of SBP variation was significantly (P<0.001) higher in hypertensive (0.608 mm Hg/min; 95% confidence interval [CI], 0.595 to 0.622) than in normotensive individuals (0.567 mm Hg/min; 95% CI, 0.555 to 0.578), even after adjusting for baseline characteristics, day–night BP changes, 24-hour heart rate (HR), SBP, and HR variability. In the entire group of patients, multiple linear regression models revealed independent determinants of CCA-IMT in the following rank order: age (P<0.001), 24-hour rate of SBP variation (P<0.001), male gender (P=0.004), cholesterol (P=0.009), and smoking (P=0.014). A 0.1 mm Hg/min increase in the 24-hour rate of SBP variation was associated to an increment of 0.029 mm (95% CI, 0.018 to 0.040) in CCA-IMT independent of BP and HR levels, BP and HR variability, and dipping status. The rate of SBP variation during the morning BP surge correlated independently (P<0.001) to larger CCA-IMT values after adjustment for baseline characteristics and other ABPM parameters. Thus, the rate of BP fluctuations is greater in hypertensive patients and correlates to increased CCA-IMT. This finding indicates that steeper BP variations may produce a greater stress on the vessel wall and consequently result in medial hypertrophy of the large arteries.

Counterpulsation: Historical Background, Technical Improvements, Hemodynamic and Metabolic Effects

The intraaortic balloon counterpulsation is performed today on the same principles that were described in its first experimental use in 1962. Experimental studies have shown significant increase of the mean aortic diastolic pressure, the diastolic pressure-time index, endocardial viability ratio, cardiac output, ejection fraction, coronary cerebral and renal blood flow, lactate utilization and myocardial oxygen supply and significant decrease of the systolic aortic pressure, left-ventricular end-diastolic pressure, left-ventricular work, tension time index, myocardial oxygen consumption and lactate production. In similar studies, intraaortic balloon pump (IABP) decreases the size of myocardial infarction. New IABP driving systems, small size sheaths and balloon catheters for percutaneous insertion made the use of the IABP easier and safer. The paraaortic counterpulsation device is suitable for chronic mechanical assistance. It is more effective than the IABP and shows excellent biocompatibility in chronic experiments. Its clinical application in 3 patients showed excellent biocompatibility and promising hemodynamic effects. In conclusion, the salutary hemodynamic effects of the IABP have been shown in several experimental studies. The technical improvements and the development and use of new devices suggest that we still need to learn more about the usefulness of the counterpulsation technique.

Effect of Acute Cigarette Smoking on Endothelium-Dependent Brachial Artery Dilatation in Healthy Individuals

The effect of short-term smoking on endothelium-dependent and endothelium-independent dilatation of the brachial artery was tested in 27 healthy volunteers using high-resolution ultrasound imaging. Short-term smoking led to a significant decrease in endothelium-dependent dilatation.

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.

Short-term estrogen administration improves abnormal endothelial function in women with systemic sclerosis and Raynaud’s phenomenon

BACKGROUND Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynauds phenomenon. The aim of this study was to evaluate the endothelium-dependent vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients. METHODS AND RESULTS The study included 12 female patients with systemic sclerosis and Raynauds phenomenon (aged 49+/-14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83+/-0.3 vs 0.46+/-0.2 mm, P= .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6%+/-7% vs 11.9%+/- 4.6%, P = .003); endothelium-independent dilatation also was reduced in patients with Raynauds phenomenon (14%+/-7% vs 23%+/-6%, P= .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7%+/-4% to 6.3%+/-4%, P= .01), whereas endothelium-independent dilatation did not change (13.4%+/-8% to 15.5%+/-7%, not significant). CONCLUSIONS Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynauds phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Short-term estrogen administration can improve endothelial dysfunction in this group of patients.

Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study

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.

Left Ventricular Performance During By-Pass or Distension of the Right Ventricle

A dog heart preparation was used to investigate the direct or mechanical effects of a right ventricular by-pass and of right ventricular distension on the performance of the left ventricle. Several other factors known to affect left ventricular performance were eliminated. The data obtained indicate impairment of left ventricular function either by right ventricular by-pass or by right ventricular distension. It is suggested that this impairment may be due to a direct effect of the volume of blood contained in the right ventricle and of right ventricular function on the common muscle bundles that encircle both ventricles.

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.

Impact of the time rate of blood pressure variation on left ventricular mass

Objectives Blood pressure (BP) changes are steeper in hypertensive than in normotensive individuals, whereas an increased rate of BP fluctuations is associated with medial hypertrophy of the carotid arteries. We evaluated the association between the rate of BP variation derived from ambulatory blood pressure monitoring (ABPM) data analysis and left ventricular mass (LVM). Methods ABPM and echocardiographic measurements of LVM were performed in 365 normotensive, 185 white-coat hypertensive (WCH) and 448 uncomplicated hypertensive individuals. Results The daytime and night-time rate of systolic blood pressure (SBP) and diastolic BP variation were significantly higher in hypertensive than in normotensive (P < 0.001) and WCH (P < 0.05) individuals. In the entire study population multiple linear regression models revealed independent determinants of LVM in the following rank order: body mass index (β + 0.266, P < 0.001), daytime SBP (β + 0.264, P < 0.001), male sex (β +0.220, P < 0.001), age (β + 0.203, P < 0.001), daytime heart rate (HR; β − 0.191, P < 0.001), daytime rate of SBP variation (β + 0.167, P < 0.001), and SBP dipping (β − 0.132, P < 0.001). A 0.1 mmHg/min increase in the daytime rate of SBP variation correlated with an increment of 7.087 g (95% confidence interval 4.775–9.399) in the LVM. The addition of the daytime rate of SBP variation in the multiple regression model for the prediction of LVM significantly increased the adjusted model R2 [R2 change 0.024 (2.4%); P for change < 0.001]. Conclusion Steeper BP variations may produce a greater stress on the left ventricular wall and may have an additive role to body habitus, BP and HR levels in the detection of cardiac hypertrophy. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP oscillations.